Phlebitis and Thrombophlebitis of Superficial Vessels: Clinical Guidelines

List of Abbreviations

VKA – vitamin K antagonists

OAC – anticoagulant therapy

ASA** – acetylsalicylic acid**

ATIII – antithrombin III

APS – antiphospholipid syndrome

aPTT – activated partial thromboplastin time

GSV – great saphenous vein

VTE – a collective term encompassing superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism

PSVT – purulent superficial thrombophlebitis

DUSLS – duplex ultrasound scanning of lower extremity veins

BMI – body mass index

SSV – small saphenous vein

LMWH – low-molecular-weight heparins (ATC: B01AB Heparin group)

RR – relative risk

NSAIDs – non-steroidal anti-inflammatory drugs (ATC: M01A, Anti-inflammatory and antirheumatic products, non-steroids)

s.c. – subcutaneous

AASV – anterior accessory saphenous vein

DOACs – direct oral anticoagulants (ATC group: B01AF Direct factor Xa inhibitors; B01AE Direct thrombin inhibitors)

PTS – post-thrombotic syndrome

RUOG – Russian Association of Obstetricians and Gynecologists

GFR – glomerular filtration rate

aHR – adjusted hazards ratio

SPJ – saphenopopliteal junction

SFJ – saphenofemoral junction

DVT – deep vein thrombosis

NSTVT – non-varicose superficial vein thrombosis

SVT – superficial vein thrombophlebitis

PE – pulmonary embolism

CVD – chronic venous diseases

ASH - American Society of Hematology

NCCN (National Comprehensive Cancer Network) – National Comprehensive Cancer Network, USA.

PICC (Peripherally Inserted Central Catheter) – peripherally inserted central venous catheter

RCOG - Royal College of Obstetricians and Gynaecologists

Terms and Definitions

Varicose veins of the lower extremities (varicose transformation of subcutaneous veins) – dilated subcutaneous veins with a diameter of more than 3 mm in the standing position. They usually have a nodular (saccular) and/or tortuous (serpentine) appearance.

Varicose thrombophlebitis – thrombophlebitis (thrombosis) of varicose-altered superficial veins.

Venous thromboembolic complications – a collective term encompassing superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism.

Duplex ultrasound scanning of lower extremity veins – a method of ultrasound examination of veins in which, if necessary, simultaneous use of two or three scanning modes is possible.

Crossectomy (Trojanov-Trendelenburg operation) – high ligation (directly at the deep main trunk) of the great (or small) saphenous vein with mandatory ligation of all junctional tributaries and excision of the superficial vein trunk within the surgical wound.

Junctional ligation (high ligation) – high ligation (directly at the deep main trunk) of the great (or small) saphenous vein without ligation of junctional tributaries and excision of the superficial vein trunk within the surgical wound.

Deep vein thrombosis – a condition characterized by blood clot formation in the deep veins.

Superficial vein thrombophlebitis (superficial vein thrombosis) – a pathological condition characterized by the formation of thrombotic masses in superficial veins with the development of a concomitant inflammatory reaction of the venous wall, subcutaneous tissue, and skin.

Pulmonary embolism (PE, pulmonary thromboembolism) – the lodging of an embolus in the pulmonary arteries, the source of which is the veins of the systemic circulation.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Superficial vein thrombosis/thrombophlebitis – a pathological condition characterized by the formation of thrombotic masses in superficial veins with the development of a concomitant inflammatory reaction of the skin and subcutaneous tissue.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The thrombotic and concomitant inflammatory process can affect not only varicose, but also non-varicose veins. In this regard, it is important to distinguish between thrombosis of varicose superficial veins (varicothrombophlebitis) and thrombosis of non-varicose superficial veins (TNSV). The prognosis of the disease and the treatment tactics for patients in these cases have significant differences. The most frequent risk factor for SVT is the presence of lower extremity varicose veins. Transformation of superficial veins in patients with SVT is detected with a frequency of up to 80%; on the other hand, SVT develops in 4–59% of patients with varicose vein disease [1–5]. In Russia, according to the SPECTRUM study, the frequency of SVT development in patients with chronic venous disease was 7% [6]. Among the possible risk factors for SVT are age, obesity, tobacco smoking, including the use of tobacco heating systems or vaporizers (vapes), a history of DVT or SVT, pregnancy and the postpartum period, oral hormonal contraceptives, hormone replacement therapy, immobilization, recent surgeries and trauma, and oncological diseases [3]. Thus, for example, during the first month after childbirth, the risk of developing SVT increases significantly [7]. Oncological disease is detected in 10–18% of patients with SVT [8–10]. Hereditary thrombophilia, in particular the mutation in the coagulation factor V (Leiden) gene, the prothrombin G20210A gene mutation, antithrombin III (AT III), protein C, and protein S deficiency significantly increase the risk of SVT [11–21]. In the absence of varicose veins, autoimmune diseases, and oncological pathology, the Leiden mutation increases the risk of SVT by approximately 6 times, the prothrombin G20210A gene mutation by 4 times, and combined variants by 12.9 times [15]. Among patients with SVT, the prevalence of various hemostatic disorders (resistance to activated protein C and deficiency of antithrombin III, protein C, or protein S) reaches 59% [14]. In patients with thrombotic involvement of varicose veins, dyslipidemia plays a special role, increasing the risk of recurrent SVT by 5.4 times [21]. A possible risk factor for SVT may be autoimmune diseases accompanied by an elevated level of anticardiolipin antibodies. In patients with recurrent SVT, an elevated level of anticardiolipin antibodies is detected in 33.3% of cases [22]. The most dangerous complications of SVT are the spread of the thrombus to the deep veins (deep vein thrombosis) and the development of pulmonary embolism. The frequency of deep vein thrombosis reaches 18.1% (95% CI: 13.9%, 23.3%), and the frequency of symptomatic pulmonary embolism in SVT is 6.9% (95% CI: 3.9%, 11.8%) [23]. It is important to consider the risk of SVT extension into the deep venous system, which ranges from 7% to 32% [2,3,24]. Most frequently, SVT spreads to the deep veins via the saphenofemoral junction (SFJ) [24,25]. It is believed that the closer the proximal level of the thrombus in the superficial vein is to the junction, the higher the risk of the process extending into the deep veins, and a location within 1 cm of the junction zone is associated with the highest risk [26]. Meanwhile, to date, there are no convincing data to assert that in SVT, thrombosis localized in the junction area is the primary source of pulmonary embolism. One study showed that SVT within 3 cm of the SFJ does not increase the likelihood of pulmonary embolism [27]. A simultaneous deep vein thrombosis, including in the contralateral limb, can be a source of pulmonary embolism in a patient with SVT [28].

1.3 Epidemiology of the Disease or Condition

In a 2014 population-based study, the annual incidence of SVT in a cohort of 265,687 individuals was 0.64% (95% CI 0.55%-0.74%) [29].

Furthermore, the incidence was slightly higher in women than in men and increased with age for both sexes. Specifically, the annual incidence of SVT in women aged 18–39 years was 0.13% (95% CI 0.02–0.23), and in those aged >75 years, 2.19% (95% CI 1.59%–2.78%); in men of the same age groups, this figure was 0.04% (95% CI, 0.00–0.1) and 0.95% (95% CI, 0.41–1.48), respectively. Concomitant symptomatic deep vein thrombosis was diagnosed in this study in 24.6% of patients with SVT (95% CI 18.3%-31.7%), and symptomatic PE in 4.7% (95% CI 2.0%-9.0%). In an earlier population-based study from 1973, the annual incidence of SVT in women aged 20–39 years was 0.31%–0.51%, and in those older than 70 years, 2.2% [30]. In men of the same age groups, these figures were 0.05%–0.13% and 1.6%–1.8%, respectively. In the USA, the frequency of SVT is estimated at 1 case per 1000 population per year (0.1%), with 125,000 cases of SVT registered annually [31]. The average age of patients with SVT ranges from 54 to 65 years, with the disease more frequently affecting women [32,33]. In a Dutch retrospective cohort study, the incidence of SVT (without clear localization distinction into upper and lower extremities) was 1.31 (95% CI, 1.25-1.37) cases per 1000 population per year. The incidence was lower in men (1.16; 95% CI, 1.01-1.24) compared to women (1.67; 95% CI, 1.58-1.76) and increased with age: 0.73 (95% CI, 0.66-0.79) in individuals under 40 years versus 2.95 (95% CI, 2.56-3.38) in individuals over 80 years [34].

The true prevalence of the disease may exceed the cited figures because many patients with limited forms of SVT do not seek medical care.

1.4 Features of Coding the Disease or Condition

Phlebitis and thrombophlebitis (I80):

I80.0 - Phlebitis and thrombophlebitis of superficial vessels of lower extremities.

I80.8 - Phlebitis and thrombophlebitis of other sites

Embolism and thrombosis of other veins (I82):

I82.1 - Migratory thrombophlebitis

Venous complications in pregnancy (O22):

O22.2 - Superficial thrombophlebitis in pregnancy

Venous complications in the puerperium (O87):

O87.0 - Superficial thrombophlebitis in the puerperium

1.5 Classification of the disease or condition

The classification of SVT includes division by stages (depending on the phase of the course and manifestations of the inflammatory reaction) and by the degree of risk of thrombus extension into the deep veins.

1.5.1. Superficial vein thrombophlebitis and post-thrombotic changes

When formulating a diagnosis, it is necessary to distinguish between superficial vein thrombosis (SVT) and post-thrombotic changes in superficial veins.

The term "post-thrombotic changes of superficial veins" can be used in the diagnosis to designate a prior history of superficial thrombophlebitis (when treatment or follow-up is not required), to describe the clinical manifestations of a previous SVT (induration, pigmentation in the area of affected veins), and to describe venous changes on ultrasound examination. In case of post-thrombotic changes, specifying the stage of SVT and the risk grade of thrombus extension to the deep veins is not required. The conventional boundary between subsiding thrombophlebitis and post-thrombotic changes is 45 days.

Local indurations in the area of post-thrombotically altered superficial veins and their post-thrombotic changes on duplex ultrasound of lower extremity veins (DUSLEV) can persist for a long time (6 months or more), but do not require treatment or follow-up.

1.5.2. Stages of superficial vein thrombophlebitis depending on the phase of the course and manifestations of the inflammatory reaction:

When formulating the diagnosis of a patient with SVT, it is necessary to use the following staging of SVT: acute, subsiding, subsided.

From a tactical standpoint, it is necessary to divide SVT into stages depending on the activity and dynamics of the inflammatory reaction manifestations and the time elapsed since the onset of thrombosis. The stage of SVT affects: the need for hospitalization, the choice of the goal and type of surgical intervention, the determination of indications for anticoagulants (agents from the ANT group: antithrombotic agents), and the determination of indications for NSAIDs. Stages of SVT:

⁻ acute SVT (0–7 days from the onset of the disease), usually accompanied by pronounced manifestations of inflammation of the skin and soft tissues near the affected vessels;

⁻ subsiding SVT (1–3 weeks from the onset of the disease), characterized by the regression of soft tissue inflammation manifestations near the affected vessels;

⁻ subsided SVT (more than 3 weeks from the onset of the disease) is characterized by the absence of soft tissue inflammation manifestations, but the persistence of painless or slightly painful indurations along the affected vessels, as well as the possible presence of skin hyperpigmentation over them.

The stage of "subsided thrombophlebitis" denotes the period during which clinical manifestations of inflammation are absent or mild, and symptomatic therapy is not required, but an increased risk of venous thrombosis recurrence persists, and anticoagulant therapy may be advisable. The division into the aforementioned stages is conventional. The decision on which stage the process is in should not be based solely on the duration of the disease. This decision is made by the attending physician, taking into account the severity and dynamics of inflammation in the given patient.

1.5.3. Risk of thrombus extension to the deep veins

When formulating the diagnosis of a patient with SVT, it is necessary to use the following grading of the risk of thrombus extension to the deep veins: low, moderate, high.

From a tactical standpoint, it is necessary to divide patients with SVT into groups according to the risk grade of thrombus extension to the deep veins. The risk grade of thrombus extension to the deep veins affects: the need for hospitalization (taking into account the stage of SVT), the need for prescription and dosage of anticoagulants (ANT: antithrombotic agents), and indications for surgical intervention taking into account the stage of SVT and the risk grade of thrombus extension to the deep veins. The risk grade is primarily determined by the localization of the proximal border of thrombosis [33, 35–37].

• Low risk of thrombus extension to the deep veins:

- isolated thrombophlebitis of varicose and non-varicose tributaries of main superficial veins;

• Moderate risk of thrombus extension to the deep veins:

- thrombophlebitis of the trunk of a main saphenous vein or pre-ostial tributaries with the proximal border of the thrombus distal to 3 cm from the junction (the anterior accessory saphenous vein may be considered as a main vein);

- thrombosis of the suprafascial segment of a perforating vein up to the fascial level;

• High risk of thrombus extension to the deep veins:

- thrombophlebitis of the trunk of a main saphenous vein or pre-ostial tributaries of any extent with the proximal border of the thrombus at a distance of 3 cm from the junction or closer;

- thrombosis of the subfascial segment of a perforating vein.

There are no data to evaluate the dependence of the risk of thrombus extension to the deep veins on the stage of SVT (activity of the inflammatory process). At the same time, it has been proven that even with complete subsidence of clinical manifestations and laboratory markers of inflammation, the risk of venous thrombosis recurrence and pulmonary embolism (PE) development is higher than the population risk of a first thrombotic event. The risk of VTE recurrence is maximal during the 3 months (sHR 71.4 [95% CI, 60.2–84.7]) and remains elevated for several years after an episode of SVT (at 5 years, sHR 5.1 [95% CI 4.6–5.5]) [38]. Indicating the risk grade of thrombus extension to the deep veins and the stage of SVT is not required in the presence of post-thrombotic changes in superficial veins.

Additional risk factors for the recurrence and progression of SVT and the development of VTE are given in section "7. Additional information (including factors affecting the outcome of the disease or condition)".

1.5.4. Formulation of the diagnosis

When formulating the diagnosis of a patient with SVT, it is necessary to divide SVT into stages and indicate the risk grade of thrombus extension to the deep veins.

There is no universally accepted classification for SVT. However, when formulating the diagnosis, the most important features of the pathological process that are significant for determining treatment tactics should be reflected:

• localization;

• whether varicose-altered or non-varicose veins are affected;

• involvement of main superficial veins (great and small saphenous vein trunks, AASV) in the pathological process;

• proximal border of the lesion;

• whether there is extension into the deep venous system;

• duration of thrombophlebitis existence (it is appropriate to indicate the approximate date or time period of the onset of thrombophlebitis);

• stage of SVT and dynamics of inflammation manifestations.

If relevant information is available, it is advisable to indicate the state of the vein lumen in the affected area: complete, incomplete recanalization, or absence of recanalization. Prolonged absence of recanalization can be described in the diagnosis as chronic post-thrombotic occlusion of a superficial vein.

Examples of diagnosis formulation for a patient with SVT and post-thrombotic changes in superficial veins:

⁻ Acute varicotrombophlebitis of tributaries and the trunk of the great saphenous vein (GSV) up to the saphenofemoral junction, without extension to the femoral vein, dated 01.01.2019, high risk of thrombus extension to the deep veins;

⁻ Subsided thrombophlebitis of non-varicose tributaries and the trunk of the GSV up to 2 cm from the saphenofemoral junction; incomplete recanalization; high risk of thrombus extension to the deep veins;

⁻ Subsiding thrombophlebitis of non-varicose tributaries of the GSV in the middle and upper thirds of the leg without extension to the trunk, low risk of thrombus extension to the deep veins;

⁻ Acute varicotrombophlebitis of tributaries and the trunk of the small saphenous vein (SSV) up to the saphenopopliteal junction, without extension to the popliteal vein, high risk of thrombus extension to the deep veins;

⁻ Subsiding varicotrombophlebitis of tributaries and the trunk of the SSV up to 5 cm from the saphenopopliteal junction, moderate risk of thrombus extension to the deep veins;

⁻ History of SVT. Chronic post-thrombotic occlusion of GSV tributaries of the left lower leg.

⁻ History of SVT. Post-thrombotic changes in superficial veins, incomplete recanalization of varicose tributaries of the right lower extremity GSV.

In the event of thrombus extension to the deep veins or detected simultaneous deep vein thrombosis (DVT), the diagnosis should be formulated and coded as "deep vein thrombosis" (DVT), based on the clinically more significant disease.

1.6 Clinical presentation of the disease or condition

The clinical picture in phlebitis and superficial thrombophlebitis is determined by the presence of local inflammation in a restricted segment of a superficial vessel with characteristic subjective symptoms of inflammation (pain, general malaise, low-grade fever) and its objective manifestations (local skin hyperemia, edema, painful induration along the inflamed vascular segment).

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for Establishing the Diagnosis/Condition

The criterion for diagnosing superficial thrombophlebitis is a combination of soft tissue inflammation signs during patient interview and physical examination and signs of superficial vein thrombotic occlusion in the inflammation zone on ultrasound examination. If ultrasound examination is not available, the criterion for diagnosis is the detection of signs of inflammation in the projection of major subcutaneous veins and their tributaries. In the stage of subsided thrombophlebitis, the criterion for diagnosis is the detection of signs of prior thrombophlebitis during physical examination and/or the detection of signs of superficial vein thrombotic occlusion on ultrasound examination.

2.1 Complaints and Anamnesis

Depending on the localization of the thrombotic process, its extent, the duration of the disease, and the degree of involvement of the tissues surrounding the affected vein in the inflammatory process, various clinical manifestations of the disease can be observed — from pronounced inflammation along the thrombosed vein accompanied by disorders of the patient's general condition to minor local and systemic manifestations.

• If superficial vein thrombosis (SVT) is suspected, it is recommended to assess the presence and severity of the following subjective and objective symptoms: pain along the thrombosed veins; hyperemia along the thrombosed veins; general hyperthermia; malaise, chills [5,25,39–42].

LNC 4 LeC C

Comment. The described symptoms have not been studied for sensitivity and specificity.

2.2 Physical Examination

• If SVT is suspected, it is recommended to assess the presence and severity of the following objective signs by palpation of the lower extremities: cord-like, dense, sharply painful string or indurated varicose veins along the thrombosed veins; local hyperthermia [5,25,39–42].

LNC 4 LeC C

• When examining a patient with SVT, a targeted search for symptoms of DVT and PE and inspection of both lower extremities are recommended [25,33,35,36,39].

LE 4 GSR C

2.3 Laboratory Diagnostics

LNC 5 LeC C

Comment. The negative recommendation applies to screening tests (aPTT, prothrombin (thromboplastin) time in blood or plasma, thrombin time in blood) or integrated laboratory tests (thromboelastography / thromboelastometry, thrombodynamics, and thrombin generation assay (TGA)). Thrombosis markers (blood D-dimer concentration, blood soluble fibrin monomer complexes, thrombin-antithrombin complex, fibrinopeptides A and B) do not fully determine the activity of the process and assess the likelihood of PE development.

LNC 5 LeC C

Comment. The results of testing for hereditary thrombophilia do not affect patient management tactics. The advisability of testing for hereditary thrombophilia may be considered in case of thrombosis progression during full-dose anticoagulant therapy.

2.4 Instrumental Diagnostics

• If superficial vein thrombosis of the upper or lower extremities is suspected, duplex scanning of the veins of the upper or lower extremities is recommended, evaluating the state of the superficial and deep veins of both extremities to clarify the diagnosis and determine treatment tactics [5,25,39–42,48–50].

Level of Reliability of Evidence 5, Level of Recommendation C

Comment. The main instrumental diagnostic method for SVT is lower extremity venous duplex ultrasound (LEVDUS). The method allows for assessing the state of the venous walls and lumen, the presence of thrombotic masses, the character of the thrombus (occlusive, non-occlusive, floating), its distal and proximal boundaries, and the patency of deep and perforating veins. B-mode imaging with compression of various venous segments has the highest diagnostic value. Ultrasound examination must accurately indicate the proximal boundary of the lesion and note the presence/absence of varicose transformation of superficial veins. Duplex scanning of upper or lower extremity veins to confirm the diagnosis and clarify treatment tactics can be performed by any specialist engaged in the diagnosis and treatment of venous diseases who has practical experience in performing ultrasound examinations.

2.5 Other Procedures

• If extension of the thrombus to the deep veins is suspected and visualization of the deep veins using lower extremity venous duplex scanning is difficult, additional instrumental examination methods are recommended (direct or retrograde lower extremity phlebography, magnetic resonance venography of the lower extremity with or without intravenous contrast, or computed tomography venography of the lower extremity with intravenous bolus contrast) [51–55].

LNC 5 LeC C

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.0. General provisions and treatment tactics for superficial vein thrombophlebitis

The main objectives of SVT treatment are:

- prevention of the extension of the thrombotic process to the deep veins and the development of pulmonary embolism;

- prevention of the involvement of new segments of superficial veins in the process.

- relief of the acute inflammatory reaction of the vein and paravascular tissues;

- relief of symptoms and manifestations of SVT;

- prevention of SVT recurrence.

To achieve these goals, various drugs used locally or systemically, compression therapy, surgical intervention, and combinations of these methods can be used.

Treatment tactics are determined primarily by the stage of SVT and the degree of risk of thrombus extension to the deep veins. When deciding on the need for anticoagulant therapy, its intensity and duration, in addition to the degree of risk of extension to the deep veins and the stage of SVT, the specialist may take into account additional individual risk factors for DVT/PE and bleeding complications. Valid tools for assessing such additional individual risk factors are absent. The combination of additional individual risk factors for DVT/PE and bleeding complications is a situation that precludes the standardization of optimal treatment in the form of recommendations. The decision is made by the physician taking into account the specifics of the particular clinical case. In case of a high risk of bleeding complications, to reduce it, at the discretion of the treating specialist, anticoagulant therapy may not be prescribed, its duration may be shortened, or alternative antithrombotic drugs or, in individual cases, surgical intervention may be preferred. In individuals with an individually increased risk of VTE (presence of additional individual risk factors), ACT may be considered even in SVT with a low risk of thrombus extension to the deep veins, and its duration may be extended beyond the standard 45 days. Reducing the risk of bleeding complications does not guarantee that they will not develop. The absence of additional risk factors for DVT/PE and bleeding complications does not mean that VTE or bleeding complications cannot develop during ongoing therapy.

It is advisable to perform a dynamic assessment of the disease course (examination and/or duplex ultrasound scanning of the veins of the upper or lower extremities) at least once every 5-10 days to rule out the progression of the thrombotic process. During adequate anticoagulant therapy, the risk of thrombophlebitis progression and/or the development of DVT and PE is low. The need for a re-examination of the patient may arise if clinical signs of disease progression or complications develop. Nevertheless, the final decision on the timing of the follow-up examination after prescribing therapy remains with the attending specialist, who must assess the clinical situation and take into account the individual characteristics of the patient.

3.0.1. Indications for hospitalization

LNC 5 LeC C

Comment. In all cases, the decision on hospitalization should be made individually, taking into account the risk of thrombosis progression and the development of pulmonary embolism, the stage of the disease, the feasibility of adequate outpatient therapy, patient compliance with prescriptions, and the possibility of dynamic clinical and ultrasound monitoring of the disease course. The assessment of these and other factors that can influence the outcome of the disease is carried out by the attending specialist individually, including in cases of simultaneous deep vein thrombosis or thrombus extension to the deep veins. If the development of purulent thrombophlebitis is suspected, the patient must be hospitalized and further diagnostic and therapeutic measures must be carried out in a hospital setting.

LNC 5 LeC C

3.0.2. Treatment tactics depending on the degree of risk of thrombus extension to the deep veins and the stage of SVT

3.0.2.1. Low risk of thrombus extension to the deep veins

• In patients with a low risk of thrombus extension to the deep veins in the acute and subsiding stages of SVT, systemically active nonsteroidal anti-inflammatory drugs (NSAIDs) (ATC: M01A, Anti-inflammatory and antirheumatic products, non-steroids) are recommended for the purpose of preventing thrombosis progression [58–63].

Level of Evidence 2, Grade of Recommendation B

Comment. At a low risk of thrombus extension to the deep veins, anticoagulant therapy may be advisable to prevent the progression of thrombosis in superficial veins. The decision on the advisability of anticoagulant therapy is made by the attending specialist, taking into account the specifics of the specific clinical case.

• In case of a low risk of thrombus extension into the deep veins at the resolving superficial thrombophlebitis (STP) stage, it is recommended to limit management to symptomatic therapy or observation [57].

LE 5 GOR C

3.0.2.2. Moderate risk of thrombus extension to the deep veins

• In case of a moderate risk of thrombus extension into the deep veins at any stage of STP, it is recommended to consider anticoagulant therapy as the preferred treatment method [57,60,64,65].

LE 2 GOR A

Comment. If anticoagulant therapy (ACT) is unfeasible during the acute period of the disease or during the resolving phase, the advisability of saphenofemoral junction ligation (high ligation) or crossectomy should be considered.

• In case of a moderate risk of thrombus extension into the deep veins at any stage of STP, with the aim of preventing thrombosis progression and the development of DVT and PE, it is recommended to administer subcutaneous intermediate doses of low-molecular-weight heparins (LMWHs, ATC: B01AB Heparin group) (50–75% of the therapeutic dose), or subcutaneous fondaparinux sodium at a dose of 2.5 mg once daily [31,56,59–61,66–69].

Level of Evidence 1, Grade of Recommendation B

• In case of a moderate risk of thrombus extension into the deep veins at any stage of STP and in the presence of contraindications to parenteral anticoagulants (ATC: antithrombotic agents), with the aim of preventing thrombosis progression and the development of DVT and PE, it is recommended to use #rivaroxaban** at a dose of 10 mg daily [70].

LE 2 GSR A

3.0.2.3. High risk of thrombus extension to the deep veins

• In case of a high risk of thrombus extension into the deep veins at any stage of STP, with the aim of preventing thrombosis progression and the development of DVT and PE, it is recommended to use therapeutic doses of anticoagulants (ATC: antithrombotic agents) used for the treatment of DVT (Appendix A3.8. Therapeutic doses of anticoagulants (ATC: Antithrombotic agents)) [56,59,60,66–68].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. For STP with a high risk of thrombus extension into the deep veins, recent guidelines suggest administering anticoagulant therapy at therapeutic doses using the entire spectrum of drugs effective in the treatment of DVT and PE; thus, tactically, high-risk STP is equated to DVT [56,71]. At the same time, prescribing many of the anticoagulants used in DVT and PE treatment to a patient with STP is an off-label prescription.

The need for initial therapy with increased doses of DOACs should be determined based on an individual benefit-risk assessment. Initial therapy may be advisable if the patient has additional risk factors for STP progression with DVT/PE development (see Section "7. Additional Information (including factors influencing the outcome of the disease or condition)") and a low risk of bleeding complications. In the absence of such factors or in the presence of a high risk of bleeding complications, it is advisable to use DOACs without an increased dose at the start of therapy.

• In case of a high risk of thrombus extension into the deep veins and when ACT is unfeasible during the acute and resolving stages of STP, with the aim of preventing thrombus extension into the deep veins and the development of DVT and PE, it is recommended to perform saphenofemoral junction ligation (high ligation) or crossectomy [31,65,72,73].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

3.0.2.4. Management tactics in case of superficial vein thrombus floatation

LE 5 GOR C

Comment. To date, there is no evidence indicating the possibility of clinically significant pulmonary embolism in isolated STP without involvement of the deep venous system. Therefore, the detection of such thrombotic masses in superficial veins should not serve as a reason for choosing a more aggressive management strategy for the patient.

3.0.2.5. Adjunctive therapy in the acute and subsiding stages of superficial vein thrombophlebitis

• During the acute and resolving stages of STP, regardless of the risk of thrombus extension into the deep veins, with the aim of accelerating recanalization of thrombosed superficial veins, it is recommended to use elastic compression (A15.12.002 Lower extremity elastic compression) with a pressure level of 23–32 mmHg [75].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

• During the acute and resolving stages of STP, regardless of the risk of thrombus extension into the deep veins, with the aim of relieving inflammatory response and pain, it is recommended to consider the use of systemic NSAIDs (ATC: M01A, Anti-inflammatory and antirheumatic products, non-steroids), topical NSAIDs (ATC: M02AA Topical products for joint and muscular pain, non-steroids), heparin-containing topical preparations, and elastic compression [43,56,60,62,63,75–86].

LE 2 GOR C

Comment. Systemic NSAIDs in addition to ACT should be used only in patients without additional risk factors for bleeding complications.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.0.3. Duration of anticoagulant therapy

3.0.3.1. Duration of anticoagulant therapy at moderate risk of thrombus extension to deep veins

• In case of a moderate risk of thrombus extension into the deep veins, it is recommended to administer anticoagulant therapy for 45 days from the onset of STP [31,56,59,61,66,88].

Level of Evidence 2, Grade of Recommendation B

Comment. At any stage of STP, if the onset date cannot be established, anticoagulation may be administered for 45 days from the start of therapy.

The optimal duration of anticoagulant therapy (ATC: antithrombotic agents) in the management of STP has not yet been established. The recommendations on the duration of ACT are primarily based on data from the large-scale CALISTO RCT, which included 3,002 participants [66]. The STEFLUX study demonstrated that prolonged administration (30 days) of intermediate doses of parnaparin sodium** is superior to a short-term course of administration (10 days) [67]. A systematic review and meta-analysis of 21 studies showed that short-term anticoagulant therapy (B01 Antithrombotic agents) of less than 14 days is associated with the highest risk of subsequent DVT and PE, exceeding that even in the absence of anticoagulant treatment (B01 Antithrombotic agents) [89].

LE 2 GOR A

Comment. In most studies evaluating the efficacy of STP anticoagulant therapy in patients with additional VTE risk factors, including the randomized SURPRISE trial, the incidence of thrombotic events increased significantly after the completion of treatment [59,67,70]. Therefore, when these risk factors are identified in a patient, the duration of anticoagulant therapy may be extended (beyond 45 days).

3.0.3.2. Duration of anticoagulant therapy at high risk of thrombus extension to deep veins

• In case of a high risk of thrombus extension into the deep veins, it is recommended to administer anticoagulant therapy for 3 months from the onset of STP [43,56].

LNC 5 LeC C

Comment. Patients with a proximal thrombus border within 3 cm of the junction were not included in randomized controlled trials investigating the efficacy and safety of anticoagulant therapy in STP. Therefore, this recommendation is extrapolated, equating high-risk STP to established DVT.

3.0.4. Management tactics and duration of therapy: summary data

Table 1. Level of evidence for various treatments of lower extremity STP.

*Risk of thrombus extension into deep veins

**Only in patients with a low risk of bleeding complications

***When ACT is unfeasible, detailed in the "Surgical Treatment" section

**** (B01 Antithrombotic agents)

Table 2. Tactics and duration of lower extremity STP therapy to prevent thrombosis progression and the development of DVT and PE.

*(B01 Antithrombotic agents)

3.0.5. Progression of superficial vein thrombophlebitis

• In the absence of positive dynamics in clinical manifestations of STP during ongoing treatment, to detect thrombosis progression (spread of thrombus to previously non-thrombosed segments of superficial veins), a repeat lower extremity venous duplex scan is recommended [24,43,90].

LNC 4 LeC C

Comment. The necessity and frequency of repeat ultrasound examinations are determined by the attending physician.

• If there is instrumental confirmation or clinical signs of superficial vein thrombosis (SVT) progression, and antithrombotic agents were not used in the treatment of SVT , at any stage of SVT, in order to prevent further thrombosis progression, thrombus extension into the deep veins, and the development of DVT and PE, anticoagulant therapy is recommended in accordance with the risk of thrombus extension into the deep veins [65,72].

LE 3 GSR C

• If there is instrumental confirmation or clinical signs of SVT progression, and antithrombotic agents were used in the treatment of SVT , at any stage of SVT, in order to prevent further thrombosis progression, thrombus extension into the deep veins, and the development of DVT and PE, it is recommended to assess patient adherence to prescriptions and increase the anticoagulant dose (ATC: antithrombotic agents) and/or switch the antithrombotic drug [56,91].

Level of Evidence 2, Grade of Recommendation B

In case of instrumental confirmation or clinical signs of SVT progression at any stage of SVT, the feasibility of hospitalization must be considered [57].

3.1. Special situations affecting examination and treatment tactics

3.1.1. Simultaneous deep vein thrombosis or thrombus extension to deep veins

• In simultaneous DVT or thrombus extension into the deep veins, treatment is recommended in accordance with DVT treatment guidelines, prescribing a therapeutic dose of an anticoagulant (ATC: antithrombotic agents) for at least 3 months [56,92].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.1.2. Thrombophlebitis of non-varicose superficial veins

• Treatment of non-varicose superficial vein thrombosis (NVSVT) is recommended to be carried out in accordance with SVT treatment guidelines [57,93].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Compared to varicose superficial vein thrombosis, non-varicose superficial vein thrombosis is associated with a 1.8-fold increased risk of deep vein thrombosis and pulmonary embolism at initial diagnosis and a 2–2.5-fold increased risk of VTE over the next 3 months of follow-up [33,37,94].

• In cases of NVSVT, when symptoms, laboratory, or instrumental signs indicate a possible malignancy, to assess the need for and perform cancer screening, it is recommended to refer the patient to a general practitioner, physician, or oncologist [10,95].

LE 4 GSR C

Comment. Malignant pathology is detected in 10–20% of patients with NVSVT [8,10].

• For the treatment of post-injection SVT in the acute and subsiding stages of thrombophlebitis, in order to achieve faster symptom relief, it is recommended to use systemic and/or topical non-steroidal anti-inflammatory drugs (M01A Anti-inflammatory and antirheumatic products, non-steroids, M02AA Topical products for joint and muscular pain, non-steroidal anti-inflammatory drugs) and/or topical heparin-containing agents (C05BA Heparins or heparinoids for topical use) [96].

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

3.1.3. Recurrent thrombophlebitis

• Treatment of recurrent SVT is recommended in accordance with the guidelines for treating the first episode of SVT [57].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.1.4. Suppurative thrombophlebitis

• If purulent thrombophlebitis is suspected, hospital admission and early empiric antibiotic therapy are recommended [97–99].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. In baseline superficial vein thrombosis, suppurative thrombophlebitis (ST) should be suspected in the presence of excessively pronounced local inflammatory signs and two or more signs of systemic inflammatory response syndrome (body temperature >38℃ or <36℃, heart rate >90/min, respiratory rate >20/min, leukocytosis >12*10⁹/L (or leukopenia <4*10⁹/L, or a left shift with >10% band forms). An absolute sign of ST is purulent discharge from the venipuncture site. Basic therapy for ST does not differ from that for SVT. Conservative treatment should start with empiric therapy, followed by adjustment based on the isolated pathogen and its sensitivities [97–99]. Treatment must include drainage of the primary infection source [97,100,101].

3.1.5. Superficial vein thrombophlebitis of the upper extremities

Management tactics for upper extremity SVT in cancer patients differ and are presented separately (see section 3.2.7).

• If the development of upper extremity superficial thrombophlebitis is associated with a peripheral intravenous catheter, discontinuation of intravenous drug administration through this catheter and its removal are recommended [43,102].

LE 4 GSR C

• For upper extremity superficial vein thrombosis in the acute and subsiding stages, in order to achieve faster symptom relief, it is recommended to use systemic NSAIDs (ATC: M01A, Anti-inflammatory and antirheumatic products, non-steroids), topical NSAIDs (ATC: M02AA Topical products for joint and muscular pain, non-steroidal anti-inflammatory drugs), topical heparin-containing preparations, and local hypothermia [43,58,103–106].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.1.6. Superficial vein thrombophlebitis during pregnancy and in the postpartum period

SVT during pregnancy is characterized by a low incidence but a high risk of thromboembolic complications. The most informative data on the epidemiology of SVT in pregnant women come from the Danish nationwide cohort study, which collected data on all pregnant women who gave birth in Denmark between 1997 and 2017 [107]. The incidence of SVT from conception to 12 weeks postpartum was 710 cases per 1,276,046 deliveries: 0.6 per 1000 person-years, 95% CI 0.5–0.6. The incidence rate of SVT (number of SVT cases per 1000 person-years) by period was: 1st trimester 0.1 (95% CI 0.1–0.2), 2nd trimester 0.2 (95% CI 0.2–0.3), 3rd trimester 0.5 (0.5–0.6), postpartum period 1.6 (95% CI 1.4–1.7). PE developed in 10.4% of women with postpartum SVT and in 0.1% without SVT; the relative risk of PE was 83.3, 95% CI 46.3–149.7.

3.1.6.1. General provisions

• It is recommended to assess the risk of developing and recurrence of VTEC during pregnancy and the postpartum period, in order to determine VTEC prevention tactics, taking into account the grading of risk factor significance (Appendix G1) [87,108,109].

LNC 5 LeC C

• When determining treatment tactics after a history of SVT, it is recommended to account for previous SVT as 1 moderate risk factor. [87,105,108–114].

LE 4 GSR C

• Risk factors for hemorrhagic complications to determine the appropriateness of hospitalization for a pregnant woman with SVT are recommended to be considered in accordance with the RCOG/ROAG guidelines (Appendix A3.1) [87,108,109].

LNC 5 LeC C

• Doses of low molecular weight heparins (LMWHs) (ATC: B01AB Heparin group) for the prophylaxis and treatment of SVT during pregnancy and the postpartum period are recommended to be determined in accordance with Appendices A3.2 and A3.3, taking into account pre-pregnancy weight. [87,108–110,113,115].

LNC 5 LeC C

• After delivery, it is recommended to re-evaluate VTE risk factors to determine the anticoagulant dosage (ATC: antithrombotic agents) and the duration of postpartum anticoagulation [105,112,116].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.1.6.2. Indications for hospitalization

General indications for hospitalization applicable to patients with SVT remain valid during pregnancy and the postpartum period. However, any additional risk factors for VTE recurrence or hemorrhagic complications should be considered as an argument in favor of hospitalization.

3.1.6.3. Management of acute and subsiding thrombophlebitis during pregnancy

This section presents treatment tactics for SVT depending on the risk level of thrombus extension into the deep veins, the stage of SVT, gestational age, and the presence of additional risk factors for VTE recurrence. Treatment tactics for SVT during pregnancy are presented in a tabular format: "Appendix A3.4. Treatment tactics for SVT during pregnancy".

The goal of anticoagulation in the acute and subsiding stages of SVT during pregnancy and the postpartum period is to prevent SVT progression and the development of DVT and/or PE. The goal of anticoagulation in the subsided stage of SVT during pregnancy and the postpartum period is to prevent VTE recurrence.

The rationale for prolonged anticoagulant therapy throughout pregnancy and the postpartum period is based on data regarding the increased risk of VTE in pregnant and postpartum women compared to non-pregnant women of childbearing age, the increased likelihood of a new VTE episode in patients with reproductive risk factors and a history of SVT, the persistence of VTE recurrence risk for up to 6 months after the acute period of SVT (in non-pregnant patients), as well as data on the reduction of VTE recurrence risk and mortality in pregnant patients with acute VTE receiving anticoagulant therapy while maintaining a low risk of complications such as bleeding, osteopenia, and heparin-induced thrombocytopenia [114,117–131].

Low risk of thrombus extension into the deep veins in the acute and subsiding stages of thrombophlebitis

• In patients with a low risk of thrombus extension into the deep veins during the acute and subsiding stages of SVT, it is recommended to administer anticoagulant therapy using intermediate doses of LMWH (ATC: B01AB Heparin group) (50–75% of the therapeutic dose) (Appendix A3.3. Therapeutic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for up to 45 days from the onset of SVT (until transition to the subsided period) [114,115,120,121].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• Following the completion of a 45-day course of anticoagulant therapy, it is recommended to assess the risk of recurrent VTE to decide whether to discontinue or prolong treatment [112,113].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• If at least 1 additional high-risk factor is identified, or 3 or more additional medium- and/or low-risk factors, regardless of the gestational age at the onset of superficial vein thrombosis (SVT), it is recommended to extend anticoagulation with prophylactic doses of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for the remainder of the pregnancy and for 6 weeks of the postpartum period [108,109,114,120,121].

LNC 5 LeC C

• If 2 additional medium- and/or low-risk factors are identified and SVT develops from 20 weeks of gestation onwards, it is recommended to extend anticoagulation with prophylactic doses of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for the remainder of the pregnancy and for at least 10 days of the postpartum period [108,109,114,120,121].

LNC 5 LeC C

• If 2 additional medium- and/or low-risk factors are identified and SVT develops before 20 weeks of gestation, it is recommended to temporarily discontinue anticoagulant therapy after the 45-day course and resume it using prophylactic doses of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) from 28 weeks of gestation until delivery and for at least 10 days of the postpartum period [108,109,114,120,121].

LNC 5 LeC C

Comment. A gestational age of 20 weeks is chosen as a reference point for selecting antenatal anticoagulation management, taking into account the RCOG/ROAG recommendations on initiating VTE thromboprophylaxis from 28 weeks of gestation in the presence of a combination of 3 medium- or low-risk VTE factors. In cases where the gestational age at the time of SVT confirmation is less than 20 weeks, the time interval from the completion of the standard 45-day treatment course until 28 weeks of gestation is considered sufficient and appropriate for a temporary withdrawal of anticoagulants (ATC: antithrombotic agents).

• If 1 additional medium- or low-risk factor is identified, as well as in the absence of additional risk factors, continuation of anticoagulant therapy after the 45-day course is not recommended [108,109,114,120,121].

LNC 5 LeC C

• If 1 additional medium- or low-risk factor is identified, as well as in the absence of additional risk factors, after delivery it is recommended to carry out anticoagulant thromboprophylaxis for recurrent VTE using prophylactic doses of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for at least 10 days [108,109,114,120,121].

LNC 5 LeC C

Moderate risk of thrombus extension into the deep veins, progressing to acute and subsiding thrombophlebitis

• In case of a moderate risk of thrombus extension into the deep veins to the stage of acute and subsiding SVT, it is recommended to administer anticoagulant therapy using intermediate doses of LMWH (ATC: B01AB Heparin group) (50–75% of the therapeutic dose) up to 45 days from the onset of SVT [114,120,121,132].

LNC 5 LeC C

• Upon completion of the standard 45-day course, it is recommended to prolong anticoagulation for the remainder of the pregnancy and for 6 weeks of the postpartum period with a prophylactic dose of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) [108,109,114,120,121].

LNC 5 LeC C

High risk of thrombus extension into the deep veins to the stage of acute and subsiding thrombophlebitis

• In case of a high risk of thrombus extension into the deep veins to the stage of acute and subsiding SVT, it is recommended to administer anticoagulant therapy using therapeutic doses of LMWH (ATC: B01AB Heparin group) (Appendix A3.3. Therapeutic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for up to 3 months from the onset of SVT [56].

LNC 5 LeC C

• Following the completion of a 3-month course of anticoagulant therapy, it is recommended to prolong anticoagulation for the remainder of the pregnancy and for 6 weeks of the postpartum period with a prophylactic dose of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) [56].

LNC 5 LeC C

3.1.6.4. Management of subsiding SVT developing during pregnancy

Low risk of thrombus extension into the deep veins to the stage of subsiding thrombophlebitis

• When subsiding SVT developing during pregnancy is identified, it is recommended to assess the risk of a recurrent VTE episode to determine the management strategy [108,109,114,120,121].

LNC 5 LeC C

• In the presence of at least 1 additional high-risk factor or 3 or more medium- and/or low-risk factors, it is recommended to initiate and administer anticoagulation for the remainder of the pregnancy and for 6 weeks of the postpartum period using a prophylactic dose of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) [108,109,114,120,121].

LNC 5 LeC C

• In the presence of 2 additional medium- and/or low-risk factors, it is recommended to initiate and administer anticoagulation from 28 weeks of gestation until delivery and for at least 10 days of the postpartum period using a prophylactic dose of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) [108,109,114,120,121].

LNC 5 LeC C

• In the presence of only 1 additional medium- or low-risk factor, as well as in the absence of additional risk factors, the administration of anticoagulant therapy for the remainder of the pregnancy is not recommended [108,109,114,120,121].

LNC 5 LeC C

• In the presence of only 1 additional medium- or low-risk factor, as well as in the absence of additional risk factors, it is recommended to perform anticoagulant thromboprophylaxis for recurrent VTE after delivery using a prophylactic dose of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for at least 10 days [108,109,114,120,121].

LNC 5 LeC C

Moderate risk of thrombus extension into the deep veins to the stage of subsiding thrombophlebitis

• In case of a moderate risk of thrombus extension into the deep veins to the stage of subsiding SVT, it is recommended to administer anticoagulant therapy using intermediate doses of LMWH (ATC: B01AB Heparin group) (50–75% of the therapeutic dose) (Appendix A3.3. Therapeutic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for up to 45 days from the onset of SVT (until transition to the subsiding stage) [114,120,121,132].

LNC 5 LeC C

• Upon completion of the standard 45-day course, it is recommended to prolong anticoagulation for the remainder of the pregnancy and for 6 weeks of the postpartum period with a prophylactic dose of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) [108,109,114,120,121].

LNC 5 LeC C

High risk of thrombus extension into the deep veins to the stage of subsiding thrombophlebitis

• In case of a high risk of thrombus extension into the deep veins to the stage of subsiding SVT, it is recommended to administer anticoagulant therapy using therapeutic doses of LMWH (ATC: B01AB Heparin group) (Appendix A3.3. Therapeutic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for up to 3 months from the onset of SVT [56].

LNC 5 LeC C

• Following the completion of a 3-month course of anticoagulant therapy, it is recommended to prolong anticoagulation for the remainder of the pregnancy and for 6 weeks of the postpartum period with a prophylactic dose of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) [56].

LNC 5 LeC C

3.1.6.5. Management of acute and subsiding thrombophlebitis in the postpartum period

This section presents the management of SVT in the postpartum period depending on the risk level of thrombus extension into the deep veins, the stage of SVT, and the presence of additional risk factors for VTE recurrence. The postpartum period in this context refers to the 6-week period following delivery during which the risk of VTE is elevated. The management of SVT in the postpartum period is presented in tabular form: "Appendix A3.5. Management of SVT in the postpartum period". The aim of anticoagulation in the stage of acute and subsiding SVT in the postpartum period is to prevent SVT progression and the development of deep vein thrombosis (DVT) and/or pulmonary embolism (PE). The aim of anticoagulation in the stage of subsiding SVT in the postpartum period is to prevent VTE recurrence.

• In low or moderate risk of thrombus extension into the deep veins to the stage of acute and subsiding SVT in the postpartum period, it is recommended to administer anticoagulant therapy using intermediate doses of LMWH (ATC: B01AB Heparin group) (50–75% of the therapeutic dose) (Appendix A3.3. Therapeutic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for 45 days from the onset of SVT, regardless of the presence of additional risk factors [108,109,114,120,121].

LNC 5 LeC C

• In case of a high risk of thrombus extension into the deep veins progressing to acute or subsiding superficial vein thrombosis (SVT) in the postpartum period, it is recommended to administer anticoagulant therapy using therapeutic doses of LMWH (ATC: B01AB Heparin group) (Appendix A3.3. Therapeutic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) for 3 months from the onset of SVT [56,108,109,114,116,120,121].

LNC 5 LeC C

3.1.6.6. Management of subsiding thrombophlebitis developed during pregnancy, detected in the postpartum period

• When subsiding SVT developed during pregnancy is detected in the postpartum period, it is recommended to assess the risk of recurrent VTE to determine further management [108,109,114,120,121].

LNC 5 LeC C

• In the presence of at least 1 additional high-risk factor or 3 or more moderate- and/or low-risk factors, it is recommended to initiate and administer anticoagulation until 6 weeks postpartum using prophylactic doses of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) [114,120,121,132].

LNC 5 LeC C

• In the presence of 2 or fewer additional moderate- and/or low-risk factors, or in the absence of additional risk factors, it is recommended to initiate and administer anticoagulation up to 10 days postpartum with a prophylactic dose of LMWH (ATC: B01AB Heparin group) (Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight) or to limit management to clinical observation [114,120,121,132].

LNC 5 LeC C

3.1.6.7. Features of anticoagulant therapy during pregnancy and the postpartum period

• For anticoagulant therapy/prophylaxis in the antenatal and postnatal periods, including during lactation and breastfeeding, it is recommended to use LMWH (ATC: B01AB Heparin group) [87,108–113,120,133,134].

LNC 5 LeC C

Comment. The applicability of LMWH in the treatment of SVT is discussed separately (see section 3.3.3.2. Low-molecular-weight heparins) (ATC: B01AB Heparin group).

• In cases of extremely low or high body weight, it is recommended to assess the adequacy of the daily dose of LMWH (ATC: B01AB Heparin group) by determining anti-Xa activity [114,120,121,134].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. The daily dose of LMWH, with the exception of parnaparin sodium**, depends on pre-pregnancy body weight. The daily dose of parnaparin sodium**—whether therapeutic, intermediate, or prophylactic—is fixed and does not depend on pre-pregnancy body weight.

• Fondaparinux sodium (ATC: B01AX05 Fondaparinux), used in the treatment of superficial vein thrombosis in non-pregnant patients, is not recommended for routine use in pregnant and lactating women [114,120,121,134].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Fondaparinux sodium crosses the placental barrier, and currently there is insufficient data regarding its safety for the embryo/fetus.

• Rivaroxaban**, used in the treatment of superficial vein thrombosis in non-pregnant patients, is not recommended for use in pregnant and lactating women [114,120,121,134].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Rivaroxaban** crosses the placental barrier; currently, its embryo- and fetotoxicity cannot be ruled out [135,136]. There are currently no data on whether Rivaroxaban** passes into human breast milk.

3.1.6.8. Delivery in women receiving LMWH (ATC: B01AB Heparin group) due to SVT.

Recommendations for anticoagulation management during anticipated delivery are based on standard clinical guidelines for the treatment and prevention of perinatal VTE by RCOG, ROAG, and ASH [108–110,112]. Currently, there is no evidence that SVT requires separate management approaches during this period.

• It is recommended that the mode of delivery be determined primarily by the obstetric situation [108–110,112].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• At the onset of labor, it is recommended to discontinue LMWH (ATC: B01AB Heparin group) [108–110,112].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• If discontinuation of LMWH (ATC: B01AB Heparin group) is not feasible during labor (e.g., in women with spontaneous labor occurring within 12 hours after the last therapeutic dose of LMWH), regional anesthesia/analgesia techniques are not recommended [108–110,112].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• When planned delivery is anticipated (scheduled cesarean section, induced labor), the last prophylactic dose of LMWH (ATC: B01AB Heparin group) is recommended 12 hours before the onset of labor, while intermediate and therapeutic doses of LMWH (ATC: B01AB Heparin group) are recommended 24 hours before the onset of labor [108–110,112].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• Application of regional anesthesia/analgesia techniques is recommended no earlier than 12 hours after administration of the last prophylactic dose of LMWH (ATC: B01AB Heparin group) and no earlier than 24 hours after administration of an intermediate or therapeutic dose of LMWH (ATC: B01AB Heparin group) [108–110,112].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• Resumption of prophylactic LMWH (ATC: B01AB Heparin group) is recommended 6–12 hours after delivery, but no earlier than 4–6 hours after spinal anesthesia or removal of the epidural catheter [108–110,112].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Resumption of LMWH within the specified timeframes is possible in the absence of hemorrhagic complications in the early postpartum period and in the absence of a traumatic epidural puncture.

• Resumption of intermediate and therapeutic doses of LMWH (ATC: B01AB Heparin group) is recommended 24 hours after delivery and no earlier than 24 hours after spinal anesthesia or removal of the epidural catheter [108–110,112].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Resumption of LMWH within the specified timeframes is possible in the absence of hemorrhagic complications in the early postpartum period and in the absence of a traumatic epidural puncture.

3.1.6.9. Other drug therapy for SVT during pregnancy and the postpartum period, including lactation

• The use of NSAIDs (ATC: M01A Anti-inflammatory and antirheumatic products, non-steroids), topical NSAIDs (ATC: M02AA Topical products for joint and muscular pain, NSAIDs), and paracetamol** (ATC: N02BE01) during pregnancy and breastfeeding is not recommended [137–147].

Level of Evidence (LoE) 3, Grade of Recommendation (GoR) B.

Comment. NSAIDs such as ibuprofen**, diclofenac**, naproxen, celecoxib, ketoprofen**, and indomethacin cross the placental barrier when administered orally and parenterally. The use of NSAIDs in the 3rd trimester increases the risk of premature closure of the ductus arteriosus and the development of persistent pulmonary hypertension in the newborn, and is associated with oligohydramnios, fetal nephrotoxicity, and the risk of periventricular hemorrhage [137–141]. Currently in the US, according to the Pregnancy and Lactation Labeling Rule (PLLR) adopted by the FDA in 2015, it is recommended to [142–145]:

- avoid the use of NSAIDs during the last trimester of pregnancy;

- use NSAIDs (ibuprofen**, diclofenac**, naproxen, celecoxib, ketoprofen**, indomethacin) up to 30 weeks of gestation only if the potential benefit justifies the potential risk to the fetus.

Paracetamol** has weak anti-inflammatory activity, but can potentially be considered as an analgesic for severe pain caused by soft tissue inflammatory changes. Paracetamol**, like other NSAIDs, crosses the placental barrier. FDA recommendations allow its use "with caution" and suggest avoiding routine use [146,147].

NSAIDs pass into breast milk in low concentrations. NSAIDs with a short half-life (#ibuprofen**, #diclofenac**) are considered acceptable for use in nursing women by most researchers. #Ibuprofen** at a dose of up to 1200 mg/day is preferred because, in addition to having a short half-life, there is evidence of its safety in infants, and its concentrations detected in breast milk are significantly lower than those used directly in infants, including newborns [115,143,148–153]. #Paracetamol** at a dose of 500 mg 3–4 times daily is considered an acceptable analgesic for use in nursing women [146,154–158]. In a systematic review of studies addressing the side effects of short-term NSAID use, short-term use is defined as a course of up to 10 days [115,159].

• The use of acetylsalicylic acid** (ASA**) as an antithrombotic agent for the treatment of SVT during pregnancy and the postpartum period is not recommended [112,113,160–163].

LoE 5, GoR C

Comment. ASA** is not recommended for non-pregnant patients with SVT due to lower efficacy compared to standard anticoagulant therapy; accordingly, there are currently no grounds for expanding the indications for ASA** in the treatment of SVT in pregnant and lactating women. Currently, the use of low doses (50–150 mg/day) of #ASA** during pregnancy is primarily permitted as part of preeclampsia prevention [112,113,160,161].

ASA** passes into breast milk, and the salicylate level in breast milk depends on the daily dose taken by the mother. Currently, low doses of ASA** (no more than 162 mg/day) are considered by experts to be compatible with breastfeeding, but the infant should be closely monitored (risk of hemolysis, thrombocytopenia with hemorrhagic syndrome, metabolic acidosis) [162,163].

• To relieve local inflammatory symptoms during the acute or subsiding stage of superficial superficial vein thrombosis (SSVT) during pregnancy and breastfeeding, it is recommended to use topical heparin-containing medications (ATC group: C05BA Topical heparin products) (ointments, gels) based on sodium heparin as part of combination therapy [111,164–166].

LE 4 GSR C

Comment. Currently, there are no data on the safety of topical NSAID formulations during the 1st and 2nd trimesters of pregnancy and during breastfeeding. In a systematic review of studies addressing the side effects of short-term NSAID use, short-term use is defined as a course of up to 10 days [159].

3.1.7. Superficial vein thrombophlebitis in cancer patients

3.1.7.1. General provisions

This section is based on the NCCN 1.2024 guidelines regarding superficial vein thrombosis [71]. In the vast majority of cases, the presence of SSVT is not a contraindication to antitumor treatment. On the other hand, isolated superficial vein thrombosis affects the life prognosis of a cancer patient in a manner similar to deep vein thrombosis (DVT) and pulmonary embolism (PE). Specifically, in an observational study, the mortality of cancer patients with SSVT was estimated at 23% of patients per year, which is comparable to that of cancer patients with DVT (sHR 1.0 (95% CI 0.6–1.9)) [167]. This may necessitate more aggressive and prolonged anticoagulant therapy for SSVT in cancer patients compared to non-cancer-related SSVT. The incidence of PE in superficial vein thrombosis in cancer patients was estimated at 4% in one cohort study [168].

• In a patient with a confirmed cancer diagnosis and clinical suspicion of superficial vein thrombosis or a diagnosed SSVT, it is recommended to determine the platelet count to assess the feasibility of anticoagulant therapy (ATC: Antithrombotic agents) [71].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• In patients with a confirmed cancer diagnosis and upper or lower extremity SSVT associated with a peripheral catheter, it is recommended to remove the peripheral catheter [71,169].

LOD 5 LOC C

As antithrombotic agents for venous thromboembolic events (DVT, PE, SSVT) in a patient with a confirmed cancer diagnosis, sodium heparin** (ATC B01AB01), LMWH (B01AB Heparin group), fondaparinux sodium (ATC B01AX), direct factor Xa inhibitors (ATC B01AF), and vitamin K antagonists (ATC B01AA) may be used [71].

For SSVT with a high risk of thrombus extension into the deep veins in a cancer patient, the 2023 NCCN guidelines suggest administering therapeutic-dose anticoagulant therapy using the full spectrum of drugs effective in the treatment of DVT and PE; i.e., tactically, high-risk SSVT for deep vein extension is equated to DVT [73,87]. At the same time, the prescription of many anticoagulants (ATC: Antithrombotic agents) used in the treatment of DVT and PE to a patient with SSVT is an off-label use.

When treating SSVT in cancer patients with therapeutic doses of LMWH, it is advisable to consider dose reduction after 30 days of anticoagulant therapy (ACT). LMWH doses for prolonging ACT after 30 days are given in Appendix A 3.8, "Therapeutic Doses of Anticoagulants".

3.1.7.2. Treatment tactics for a cancer patient with superficial vein thrombophlebitis

• In patients with a confirmed cancer diagnosis and SSVT of the forearm superficial veins in the acute or subsiding stage, short-term symptomatic therapy and periodic ultrasound monitoring to detect thrombus progression are recommended to relieve the inflammatory response and pain [71].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. The frequency of monitoring is determined by the attending physician, taking into account the specifics of the clinical situation. Nonsteroidal anti-inflammatory and antirheumatic drugs (ATC M01A) for systemic or local use, local heparin-containing preparations, and local hypothermia can be used as symptomatic therapy [31]. The duration of symptomatic therapy is determined by the treating specialist, taking into account the instructions for medical use of the specific medicinal product.

• In patients with a confirmed cancer diagnosis and SSVT of the forearm superficial veins in the acute or subsiding stage, it is recommended to consider the feasibility of anticoagulant therapy with prophylactic doses of anticoagulants (ATC: Antithrombotic agents) for 45 days [71].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. At the discretion of the treating specialist, the doses of anticoagulants (ATC: Antithrombotic agents) may be increased to therapeutic levels.

• In patients with a confirmed cancer diagnosis and upper extremity SSVT extending to the superficial veins of the arm no closer than 3 cm from the axillary vein, anticoagulant therapy for at least 45 days with subsequent assessment of the risk-benefit balance of prolonging anticoagulation is recommended to prevent thrombus progression [71,96,169,170].

LOD 5 LOC C

Comment. Depending on the specifics of the clinical case, the treating specialist may use prophylactic, intermediate, or therapeutic doses of anticoagulants (ATC: Antithrombotic agents).

• In patients with a confirmed cancer diagnosis and upper extremity SSVT extending to the superficial veins of the arm closer than 3 cm from the axillary vein at any stage of SSVT, anticoagulant therapy with therapeutic doses for 3 months is recommended to prevent recurrence, thrombus progression, and the development of PE [71,96,169,170].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. The duration of ACT may be increased or decreased by the treating specialist, depending on the specific clinical case.

The need for initial therapy with increased doses of DOACs should be determined based on an individual benefit-risk assessment. Initial therapy may be advisable if the patient has additional risk factors for STP progression with DVT/PE development (see Section "7. Additional Information (including factors influencing the outcome of the disease or condition)") and a low risk of bleeding complications. In the absence of such factors or in the presence of a high risk of bleeding complications, it is advisable to use DOACs without an increased dose at the start of therapy.

• In patients with a confirmed cancer diagnosis and lower extremity SSVT at any stage with a low and moderate risk of thrombus extension into the deep veins, anticoagulant therapy for at least 45 days with subsequent assessment of the risk-benefit balance of prolonging anticoagulation is recommended to prevent thrombus progression [71].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Depending on the specifics of the clinical case, the treating specialist may use prophylactic, intermediate, or therapeutic doses of anticoagulants (ATC: Antithrombotic agents).

• In patients with a confirmed cancer diagnosis and lower extremity SSVT at any stage with a high risk of thrombus extension into the deep veins, anticoagulant therapy with therapeutic doses for 3 months with subsequent assessment of the risk-benefit balance of prolonging anticoagulation is recommended to prevent recurrence, thrombus progression, and the development of PE [71].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. The duration of ACT may be increased or decreased by the treating specialist, depending on the specific clinical case.

The need for initial therapy with increased doses of DOACs should be determined based on an individual benefit-risk assessment. Initial therapy may be advisable if the patient has additional risk factors for STP progression with DVT/PE development (see Section "7. Additional Information (including factors influencing the outcome of the disease or condition)") and a low risk of bleeding complications. In the absence of such factors or in the presence of a high risk of bleeding complications, it is advisable to use DOACs without an increased dose at the start of therapy.

• In the event of simultaneous DVT or thrombus extension into the deep veins of the upper or lower extremities in patients with a confirmed cancer diagnosis, treatment in accordance with DVT management guidelines with the prescription of a therapeutic dose of an anticoagulant (ATC: Antithrombotic agents) for at least 3 months is recommended [56,92].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.1.7.3. Superficial vein thrombophlebitis in the presence of permanent venous access devices

LNC 4 LeC C

Comment. In a prospective study, the overall incidence of PICC-associated asymptomatic upper extremity venous thrombosis was 48.8%, and the median time to development was 3 days. Furthermore, the incidence of thrombosis per day was determined to be 37%, and at one week – 85.5% [171]. In addition, SSVT in this category of patients is characterized by a high risk of extension from superficial to deep veins. Given the above, it is advisable to initially consider pharmacological thromboprophylaxis when placing a PICC. In SSVT associated with a peripherally inserted central venous catheter (PICC) and its normal functioning, catheter removal is not mandatory [172].

3.1.7.4. Assessment of the risk of progression or recurrence of superficial vein thrombophlebitis

• Additional risk factors for the progression or recurrence of SSVT in patients with malignant neoplasms are recommended to include:

⁻ persistence/worsening of symptoms despite ongoing therapy;

⁻ multiple thrombotic lesions (especially if not related to the presence of catheters);

⁻ thrombus progression despite catheter removal and initiation of treatment;

⁻ advanced stages of malignant neoplasm (metastatic cancer);

⁻ active specific cancer treatment (chemotherapy, radiation therapy, etc.) at the time of thrombophlebitis development [172].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• In the presence of additional risk factors for progression or recurrence of superficial vein thrombosis (SVT), it is recommended to consider extended anticoagulant therapy with periodic evaluation of the appropriateness of its continuation [172].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. The schedule for follow-up examinations and reassessment of the appropriateness of continuing anticoagulation is determined by the attending physician

3.1.8. Migratory thrombophlebitis, Mondor's disease

3.1.8.1. Migratory thrombophlebitis

Migrating thrombophlebitis is a superficial vein disorder in which the thrombotic process subsides in some areas of the venous system while arising in others, often distant from one another. At the same time, there is no actual movement (migration) of thrombi from the primary site of involvement. The disease begins with the appearance of a cord-like induration of varying length along the projection of a subcutaneous vein in one location, after which thrombosis develops in the veins of other anatomical zones, creating the impression of migration. It seems to "jump" to new areas, frequently affecting the veins of the upper extremities. Occasionally, multiple foci of thrombosis occur simultaneously.

• In cases of migrating thrombophlebitis, to assess the need for and conduct cancer screening, it is recommended to refer the patient to a general practitioner, physician, or oncologist [173–175].

LNC 5 LeC C

Comment. Tumor-associated migrating thrombophlebitis (Trousseau syndrome) is considered a variant of a paraneoplastic process. The syndrome manifests as episodes of vascular inflammation with thrombus formation that recur periodically and occur in atypical sites for SVT, such as the trunk and upper extremities. This syndrome is most commonly encountered in pancreatic and lung cancer [173–175]. Therefore, upon detecting migrating thrombophlebitis, an active search for an underlying malignancy should be deemed appropriate. Migrating thrombophlebitis can be a manifestation of Buerger's disease (thromboangiitis obliterans) [176,177].

3.1.8.2. Mondor's syndrome (Mondor's disease)

First described by the author in 1939. It represents superficial vein thrombosis of the anterior chest wall and abdomen [178,179]. Clinically manifested by pain and cord formation in the lower chest wall and/or along the anterolateral abdominal wall. Tenderness on palpation persists for 3–7 days, indurations for up to several months, while skin pigmentation and hyperesthesia may persist for several months; sometimes unusual pain occurs in the area of former involvement [179–182].

• In the case of Mondor's disease, to relieve disease symptoms and prevent thrombosis progression, systemic NSAIDs (ATC: M01A, Anti-inflammatory and antirheumatic products, non-steroids), topical NSAIDs (ATC: M02AA, Topical products for joint and muscular pain, non-steroids) or anticoagulants (ATC: antithrombotic agents) are recommended [43,87,183].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.2. Compression hosiery

• During the acute and subsiding stages of SVT, regardless of the risk level for thrombus extension into the deep veins, elastic compression (A15.12.002 Lower limb elastic compression) with a pressure level of 23–32 mmHg is recommended to accelerate recanalization of thrombosed superficial veins [75].

Level of Evidence 2, Grade of Recommendation B

Comment. In the study, medical compression hosiery with a pressure of 23–32 mmHg for 3 weeks combined with prophylactic doses of LMWH did not affect the rate of pain and hyperemia relief, analgesic demand, or D-dimer levels, but contributed to a more rapid regression of thrombotic masses during the first week of wearing the stocking [75]. Compression therapy cannot be considered an independent treatment method for SVT, but it is acceptable to use it as part of a multimodal therapeutic approach.

3.3. Pharmacotherapy

3.3.1. Antibiotics (Antibacterials for systemic use, ATC J01)

• Routine use of antibacterial drugs for SVT is not recommended [103].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Early empirical antibiotic therapy is required when suppurative thrombophlebitis is suspected (see Section 3.2.4).

3.3.2. Non-steroidal anti-inflammatory and antirheumatic drugs (ATC M01A)

• In the acute and subsiding stages of superficial vein thrombosis (SVT), regardless of the risk of thrombus extension into the deep veins, it is recommended to use systemic NSAIDs (ATC: M01A, Anti-inflammatory and antirheumatic products, non-steroids) and topical NSAIDs (ATC: M02AA Topical products for joint and muscular pain, non-steroidal anti-inflammatory drugs) to relieve the inflammatory response and pain [60,61,76].

LRE 1, GR A

3.3.3. Antithrombotic agents (ATC B01A)

Various drugs can be used as antithrombotic agents for venous thromboembolic complications (DVT, PE, SVT): heparin sodium** (ATC: B01AB Heparin group), LMWH (ATC: B01AB Heparin group), fondaparinux sodium (ATC: B01AX05 Fondaparinux), vitamin K antagonists (ATC: B01AA Vitamin K antagonists), DOACs (ATC: B01AE Direct thrombin inhibitors, ATC: B01AF Direct factor Xa inhibitors).

3.3.3.1. Heparin sodium** (direct-acting anticoagulants, ATC heparin group B01AB)

• When choosing #heparin sodium** (ATC: B01AB Heparin group) as an antithrombotic agent for SVT, depending on the risk of thrombus extension into the deep veins, it is recommended to use therapeutic (333 IU/kg subcutaneously once, then every 12 h at 250 IU/kg subcutaneously twice daily without aPTT monitoring), intermediate (12,500 IU twice daily subcutaneously for one week, then 10,000 IU twice daily subcutaneously), or prophylactic (5,000 IU twice daily subcutaneously) doses [56,60,65,87,91,184].

Level of Evidence 2, Grade of Recommendation C

Comment. Within a single RCT, the use of intermediate doses of UFH (ATC: B01AB Heparin group) (12,500 IU twice daily for the first week and 10,000 IU twice daily for the remaining 3 weeks) compared to prophylactic doses (5,000 IU twice daily for 4 weeks) was associated with a non-significant but strong trend toward a reduced risk of DVT and PE (RR, 0.17; 95% CI, 0.02-1.30) [60,91]. Thus, when using UFH, it is advisable to prefer intermediate doses of the drug. In a systematic review with meta-analysis of 17 studies, the use of any doses of UFH compared to other antithrombotic therapy options was associated with a relatively high risk of DVT (15.2; 95% CI, 17.7-38.6 cases per 100 patient-years) and bleeding (1.64; 95% CI, 0.3-8.9 cases per 100 patient-years) [65].

3.3.3.2. Low-molecular-weight heparins (ATC group: B01AB Heparin group)

• When choosing LMWH (ATC: B01AB Heparin group) as an antithrombotic agent for SVT, depending on the risk of thrombus extension into the deep veins, it is recommended to use therapeutic or intermediate (50–75% of the therapeutic) doses of #nadroparin calcium, #dalteparin sodium, #enoxaparin sodium**, or #parnaparin sodium** (Appendix A3.7. Intermediate doses of low-molecular-weight heparins (LMWHs, ATC: B01AB Heparin group), Appendix A3.8 Therapeutic doses of anticoagulants (ATC: Antithrombotic agents)) [56,60,65,68,185].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. Therapeutic and intermediate doses of LMWH are given in Appendix A3.7. Intermediate doses of low-molecular-weight heparins (LMWHs, ATC: B01AB Heparin group) and Appendix A3.8 Therapeutic doses of anticoagulants (ATC: Antithrombotic agents). The efficacy and safety of the following LMWH dosing regimens have been studied in randomized clinical trials: nadroparin calcium at a fixed dose of 0.3 ml or 0.6 ml or weight-adjusted at 31.5 IU/kg or 0.4-0.9 ml once daily [68,69]; dalteparin sodium at a fixed dosage of 10,000 IU once daily [61]; enoxaparin sodium** at a fixed dosage of 4,000 IU once daily or a weight-adjusted dose of 150 IU/kg once daily [59]. A meta-analysis of 17 studies showed that the risk of PE is lower with higher doses of the drug (2.4; 95% CI, 0.8-4.8 cases per 100 patient-years) compared to prophylactic doses (2.9; 95% CI, 1.0-5.8 cases per 100 patient-years). Therefore, intermediate doses of LMWHs should be considered preferable.

• When choosing #parnaparin sodium** (ATC: B01AB07 Parnaparin) as an antithrombotic agent, subcutaneous administration of #parnaparin sodium** at a dose of 8,500 IU once daily for 10 days, followed by 6,400 IU once daily, is recommended [67].

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

Comment. The recommendation specifies the maximum efficacy regimen of #parnaparin sodium** obtained in the STEFLUX study, which differs from the official prescribing information for the drug.

3.3.3.3. Fondaparinux sodium (ATC: B01AX05 Fondaparinux)

• When choosing #fondaparinux sodium (ATC: B01AX05 Fondaparinux) as an antithrombotic agent, its subcutaneous administration at a dose of 2.5 mg once daily is recommended [65,66].

LE 2 GSR A

Comment. In a meta-analysis comparing various treatment methods for SVT, the use of fondaparinux was associated with the lowest risk of PE, DVT, and SVT progression [65].

3.3.3.4. Direct factor Xa inhibitors (ATC B01AF)

• When choosing direct oral anticoagulants (drugs from the ATX groups B01AE Direct thrombin inhibitors and B01AF Direct factor Xa inhibitors) as an antithrombotic agent, it is recommended to use #rivaroxaban** at a dose of 10 mg once daily [70].

LE 2 GSR A

Comment. At the time of publication of these Guidelines, the instructions for direct oral anticoagulants (drugs from the ATX groups B01AE Direct thrombin inhibitors and B01AF Direct factor Xa inhibitors) registered in the Russian Federation do not indicate the treatment of superficial vein thrombosis as an approved indication. Meanwhile, in a randomized open-label comparative clinical trial, the use of #rivaroxaban** at a dose of 10 mg for 45 days proved to be no less effective than subcutaneous administration of #fondaparinux sodium at a dose of 2.5 mg once daily when comparing the incidence of symptomatic progression or recurrence of superficial vein thrombosis (SVT), deep vein thrombosis (DVT), pulmonary embolism (PE), as well as all-cause mortality (OR=1.9; 95% CI 0.6–6.4, p=0.0025 for non-inferiority design) [70]. Regarding major and clinically relevant non-major bleeding, the incidence rates also did not differ between the groups. In a meta-analysis comparing various treatment modalities for SVT, the use of #rivaroxaban** was associated with the minimal risk of PE (0; 95% CI, 0–4 cases per 100 patient-years) [65].

3.3.3.5. Vitamin K antagonists (ATC B01AA)

• The use of vitamin K antagonists as an antithrombotic agent for the treatment of SVT is not recommended if heparin sodium** (ATX: B01AB Heparin group), LMWH (ATX: B01AB Heparin group), fondaparinux sodium (ATX: B01AX05 Fondaparinux), or DOACs (ATX: B01AF Direct factor Xa inhibitors, ATX: B01AE Direct thrombin inhibitors) are available [60,186].

LRE 1, GR A

Comment. VKAs can be used as the primary antithrombotic agent in the treatment of SVT for the purpose of preventing thrombosis progression and the development of DVT and PE, determined by the physician on a case-by-case basis. In patients with a mechanical heart valve, valvular atrial fibrillation, GFR less than 15 mL/min, lactation, or antiphospholipid syndrome, VKAs are the drugs of choice among oral anticoagulants (ATX: Antithrombotic agents).

3.3.3.6. Acetylsalicylic acid (ATC B01AC06)

• The use of acetylsalicylic acid** (ASA**, ATX: B01AC06 Acetylsalicylic acid) as an antithrombotic agent for the treatment of SVT is not recommended [187,188].

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

Comment. It is known that ASA** at a dose of 100 mg has a weak protective effect in the secondary prevention of DVT and PE after completion of a standard course of anticoagulant therapy [187]. This effect is significantly inferior to #rivaroxaban** at doses of 10 mg and 20 mg while having a similar safety profile [188]. ASA** cannot be recommended for the treatment of an acute episode of SVT or for the prevention of SVT recurrence. In the latter case, ASA** may be prescribed at the studied dosage (100 mg once daily) only when other antithrombotic agents cannot be used.

3.3.3.7. Sulodexide (ATC: B01AB11 Sulodexide)

• The use of sulodexide (ATX: B01AB11 Sulodexide) as an antithrombotic agent for the treatment of SVT is not recommended [189].

LNC 5 LeC C

Comment. To date, studies on the use of sulodexide as an antithrombotic agent exist only for extended thromboprophylaxis in lower extremity deep vein thrombosis following a course of anticoagulant therapy (ATX: Antithrombotic agents) [189–191].

3.3.4. HMG-CoA reductase inhibitors (ATC C10AA)

• The use of HMG-CoA reductase inhibitors (statins) as an antithrombotic agent for the treatment and secondary prevention of SVT and VTE is not recommended [192–195].

LNC 5 LeC C

3.3.5. Bioflavonoids (ATC C05CA)

LNC 5 LeC C

Comment. Venoactive drugs (ATX: bioflavonoids) have proven efficacy in reducing pain in acute hemorrhoids [197]. In routine practice, this fact is often extrapolated to cases of SVT [196]. The efficacy of bioflavonoids regarding pain and inflammatory manifestations in SVT has not been studied; however, given the low risk of adverse effects, the expert panel considers their use acceptable in the comprehensive treatment of a patient with SVT, provided the patient is appropriately informed.

3.3.6. Topical medications

• To relieve local inflammatory symptoms in the stage of acute or subsiding SVT, it is recommended to use topical heparin-containing preparations (ATX group: C05BA) (ointments, gels) based on NSAIDs and/or heparin sodium** as part of the complex therapy for SVT [78,80,82,198–200].

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

3.4. Surgical treatment

Goals of surgical treatment for SVT:

⁻ reducing the risk of PE by disconnecting veins at sites where thrombi most frequently extend from superficial to deep veins;

⁻ reducing the likelihood of proximal thrombus propagation along major superficial veins and reducing the risk of thrombosis recurrence in incompetent major superficial veins after discontinuation of anticoagulants (ATX: Antithrombotic agents);

⁻ partial or complete removal of thrombotic masses or thrombosed veins to accelerate symptom regression;

⁻ reducing inflammation severity and accelerating the regression of thrombophlebitis symptoms by eliminating pathological reflux and blood congestion in affected veins;

The use of surgical methods in patients with SVT cannot replace therapeutic agents, primarily anticoagulants (ATX: Antithrombotic agents). According to available data, anticoagulant therapy is more effective in reducing the risk of thrombus propagation into deep veins and preventing PE than any type of surgical intervention [65].

3.4.1. Surgical treatment tactics depending on the stage of superficial vein thrombophlebitis

• In the acute stage of SVT, it is recommended to perform only interventions aimed at reducing the risk of PE (high ligation/crossectomy or saphenofemoral/saphenopopliteal junction ligation), as well as reducing inflammatory manifestations [43,73,87].

LNC 5 LeC C

• In the stage of subsiding or subsided SVT, it is recommended to perform only interventions aimed at reducing the risk of thrombosis propagation along superficial veins or their thrombosis after discontinuation of anticoagulant therapy [43,73,87,201].

LNC 5 LeC C

Comment. Such interventions include thermal ablation of the non-thrombosed incompetent segment of the major superficial vein.

• Interventions aimed at the complete elimination of pathological refluxes and varicose superficial veins are recommended to be performed at the stage of subsided thrombophlebitis or after a prior episode of SVT [39,43,44,87].

LNC 5 LeC C

3.4.2. Junctional ligation (high ligation), crossectomy, deep vein thrombectomy

Crossectomy (Trendelenburg operation) is high ligation (immediately at the deep trunk) of the great (or small) saphenous vein with mandatory ligation of all junctional tributaries and excision of the superficial vein trunk within the surgical wound. To disconnect the superficial and deep veins in the area of the saphenofemoral or saphenopopliteal junctions in order to prevent thrombus propagation into the deep veins, junctional ligation (high ligation) of major superficial veins or crossectomy may be performed.

LNC 4 LeC C

• In patients with a high risk of thrombus extension into deep veins during the acute and subsiding stages of SVT who undergo junctional ligation (high ligation) or crossectomy in addition to anticoagulation, it is recommended to use prophylactic or intermediate doses of LMWH postoperatively for 45 days from the onset of SVT [60,72,186,203].

LRE 1, GR A

• In patients with a moderate risk of thrombus extension into deep veins during the acute and subsiding stages of SVT, it is recommended to perform high ligation or crossectomy only if anticoagulant therapy is contraindicated or impossible [31,60,65,72,203].

Level of Evidence 2, Grade of Recommendation C

Comment. Surgery compared to anticoagulant therapy is associated with an increased incidence of complications (surgical site infection, bleeding, DVT, and PE) with a similar probability of SVT progression [72]. A prospective comparative non-randomized study by domestic authors concluded that the risk of DVT and PE when using anticoagulants (ATC: antithrombotic agents) as the primary method does not exceed that of the standard surgical approach, while the complication rate in patients undergoing surgery is significantly higher [203]. In a meta-analysis comparing various approaches to SVT treatment, surgery was associated with the maximum risk of PE (4.7; 95% CI, 0.5–12.7 cases per 100 patient-years) [65]. Thus, there is no convincing scientific evidence of the benefits of saphenofemoral junction ligation in preventing DVT and PE.

• At low risk of thrombus extension into the deep veins, regardless of the SVT stage, high ligation or saphenofemoral junction ligation is not recommended [43, 87].

LNC 5 LeC C

• Thrombectomy from major deep veins is recommended if the thrombus extends beyond the saphenofemoral or saphenopopliteal junction in cases where a decision has been made to perform saphenofemoral junction ligation / high ligation [202].

LNC 4 LeC C

Comment. The choice of access and thrombectomy method is determined by the level of the proximal part of the thrombus. After freeing the junction, saphenofemoral junction ligation is performed.

3.4.3. Catheter-directed thrombectomy

LNC 5 LeC C

3.4.4. Endovenous thermal ablation

• In the resolving or resolved stage of thrombophlebitis, or after a history of SVT, it is recommended to consider the feasibility of endovenous thermal ablation of incompetent saphenous vein segments to prevent the spread of thrombosis through the superficial veins or prevent their thrombosis after discontinuation of anticoagulant therapy [201, 205].

LNC 4 LeC C

Comment. Data on the efficacy and safety of thermal ablation of the proximal great saphenous vein and small saphenous vein trunk at the acute SVT stage are very limited [201, 205]. To date, there is insufficient data to conclude whether thermal ablation is appropriate for preventing the spread of the thrombotic process into the deep venous system. Therefore, there is no reason to consider SVT an indication for endovenous thermal ablation.

3.5. Medical nutrition therapy for patients with phlebitis and superficial thrombophlebitis

The organization of therapeutic nutrition for patients with phlebitis and superficial thrombophlebitis during inpatient treatment in medical organizations is carried out in accordance with the orders of the Russian Ministry of Health No. 330 dated August 5, 2003, "On measures to improve therapeutic nutrition in medical and preventive institutions of the Russian Federation," No. 395n dated June 21, 2013 (registered by the Ministry of Justice of the Russian Federation on July 5, 2013, No. 28995) "On approval of therapeutic nutrition standards," and No. 1008n dated September 23, 2020, "On approval of the procedure for providing patients with therapeutic nutrition" [206–208].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Specific rehabilitation is not required after superficial vein thrombophlebitis. Indurations in the areas of thrombosed superficial veins and symptoms may persist for several months (6 months or more).

5. Prevention and Dispensary Observation

5.0. Follow-up monitoring.

A history of SVT does not require follow-up monitoring. In the case of varicose thrombophlebitis, the possibility of treatment to eliminate varicose veins should be considered.

5.1. Prevention of the first episode of superficial vein thrombophlebitis

• To prevent the first episode of varicose thrombophlebitis, it is recommended to eliminate pathological refluxes and varicose-altered superficial veins electively, taking into account the balance of risks associated with the intervention and the risk of VTE [43, 87, 209, 210].

LNC 4 LeC C

LRE 1, GR A

5.2. Prevention of recurrent superficial vein thrombophlebitis

• To prevent recurrence of varicose thrombophlebitis, it is recommended to eliminate pathological refluxes and varicose-altered superficial veins electively at the stage of resolved thrombophlebitis or after a history of SVT [43, 87, 209, 210].

LNC 5 LeC C

• To prevent VTE recurrence in recurrent SVT (2 or more episodes), it is recommended to consider the feasibility of extended thromboprophylaxis [67, 212].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

• If extended thromboprophylaxis is necessary in recurrent SVT, it is recommended to use #rivaroxaban** 10 mg daily, or #sulodexide 500 LSU (250 LSU × 2) twice daily, or #acetylsalicylic acid** 100 mg daily indefinitely with regular evaluation of the benefits and risks of further extension [188–190, 213–216].

LNC 5 LeC C

Comment. To date, there are no studies on extended thromboprophylaxis in SVT. SVT with a high risk of recurrence is considered a variant of venous thromboembolism that may require extended thromboprophylaxis. This recommendation uses extrapolation of extended thromboprophylaxis methods for lower extremity deep vein thrombosis as a more studied form of VTE [188, 190, 213].

6. Organization of Medical Care

Patients with SVT receive all types of specialized medical care, including high-tech care, provided by surgeons or cardiovascular surgeons in outpatient or inpatient (day hospital) settings.

Indications for hospitalization in superficial vein thrombosis are a high risk of thrombus extension into the deep veins during the acute SVT stage when adequate medical care cannot be provided in an outpatient setting, and purulent thrombophlebitis.

In all other cases, the decision on hospitalization should be made individually, taking into account the risk of thrombosis progression and pulmonary embolism, the stage of the disease, the feasibility of adequate outpatient therapy, patient compliance, and the possibility of dynamic clinical and ultrasound monitoring of the disease course. The assessment of these and other factors capable of influencing the outcome of the disease is carried out by the attending specialist individually, including in cases of simultaneous deep vein thrombosis or thrombus extension into the deep veins. If deep vein thrombosis is suspected, the patient must be hospitalized, and further diagnostic and therapeutic measures should be performed in an inpatient setting.

If lower extremity duplex scanning cannot be performed in patients with acute SVT with clinical signs of acute inflammation reaching the middle third of the thigh in the great saphenous vein system and/or the upper third of the leg in the small saphenous vein system, hospitalization of the patient is recommended.

During pregnancy and the postpartum period, the general indications for hospitalization for patients with SVT apply. The presence of at least one risk factor for hemorrhagic complications according to the RCOG/ROAG criteria (Appendix A3.1) is a strong argument for hospitalization for SVT during pregnancy and the postpartum period.

An indication for discharge from the hospital is the absence of SVT progression and subsiding manifestations of acute inflammation during ongoing anticoagulant or symptomatic therapy.

7. Additional Information

• Additional VTE risk factors associated with an increased probability of detecting DVT/PE at the time of SVT diagnosis should include: male sex, personal or family history of VTE, age over 75 years, presence of untreated cancer, presence of systemic inflammatory disease, patient hospitalization, and thrombosis of non-varicose veins [37].

• Additional risk factors for SVT recurrence or its progression with the development of DVT/PE within 3 months after diagnosis should include: male sex, personal or family history of VTE, history of cancer, inpatient treatment, thrombosis of non-varicose veins, symptom duration less than 7 days, severe venous insufficiency, and overweight [33, 37, 217, 218].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Apkhanova T.V., Cand. of Sci. (Med.), member of the Russian Society of Cardiology (RSC), member of the European Society of Cardiology (ESC), member of the American Vein and Lymphatic Society (USA);

2. Bitsadze V.O., Dr. of Sci. (Med.), Professor, Professor of the RAS, member of the Russian Society of Obstetricians and Gynecologists, member of the National Association of Specialists in Thrombosis, Clinical Hemostaseology and Hemorheology;

3. Bredikhin R.A., Dr. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR), Executive Secretary of the Phlebology Society of the Republic of Tatarstan, member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

4. Bulatov V.L., Cand. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR);

5. Vavilova Tatyana Vladimirovna – Dr. of Sci. (Med.), Professor, member of the Russian Society of Cardiology (RSC), member of ISTH (International Society on Thrombosis and Haemostasis);

6. Golovina V.I., Cand. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR), Engagement working group International Union of Phlebology;

7. Dzhenina O.V., Cand. of Sci. (Med.), member of ISTH (International Society on Thrombosis and Haemostasis), EMLTD (European and Mediterranean League against Thrombotic Diseases), NATG (National Association of Specialists in Thrombosis, Clinical Hemostaseology and Hemorheology), MARS (Interdisciplinary Association of Reproductive Medicine Specialists);

8. Zolotukhin I.A., Dr. of Sci. (Med.), Professor, Professor of the RAS, Executive Secretary of the Association of Phlebologists of Russia (APR);

9. Ilyukhin E.A., Cand. of Sci. (Med.), Vice-President of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS);

10. Kalinin R.E., Dr. of Sci. (Med.), Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS), member of the Board of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), member of the Association of Cardiovascular Surgeons of Russia (ACSR), member of European Society for Vascular Surgery (ESVS);

11. Kamaev A.A., Cand. of Sci. (Med.), member of the Scientific Council of the Association of Phlebologists of Russia (APR), Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

12. Katelnitskiy I.I., Dr. of Sci. (Med.), Associate Professor, member of the Association of Phlebologists of Russia (APR);

13. Katorkin S.E., Dr. of Sci. (Med.), Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS);

14. Konchugova T.V., Dr. of Sci. (Med.), Prof., member of the National Association of Experts in Sanatorium-Resort Treatment;

15. Kudykin M.N., Dr. of Sci. (Med.), Vice-President of the Association of Phlebologists of Russia (APR), Member of the Russian Society of Surgeons (RSS);

16. Lobastov K.V., Dr. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR), European Venous Forum (EVF), International Union of Angiology (IUA); American Venous Forum (AVF); American Venous and Lymphatic Society (AVLS);

17. Makatsariya A.D., Dr. of Sci. (Med.), Professor, Honored Doctor of the RF, Corresponding Member of the RAMS, Corresponding Member of the RAS, Vice-President of the Russian Society of Obstetricians and Gynecologists, Doctor of Medical Sciences, Academician of the RAS, member of the National Association of Specialists in Thrombosis, Clinical Hemostaseology and Hemorheology, laureate of the V.F. Snegirev Prize;

18. Mzhavanadze N.D., Dr. of Sci. (Med.), Associate Professor, member of the Association of Phlebologists of Russia (APR), Russian Society of Angiologists and Vascular Surgeons (RSAVS), European Society for Vascular Surgery (ESVS);

19. Petrikov A.S., Dr. of Sci. (Med.), Associate Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR);

20. Porembskaya O.Ya., Cand. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR), European Venous Forum (EVF);

21. Pryadko S.I., Cand. of Sci. (Med.), member of the Executive Council of the Association of Phlebologists of Russia (APR), Deputy Chairman of the Phlebology and Lymphology Section of the Association of Cardiovascular Surgeons of Russia (ACSR), European Society for Vascular Surgery (ESVS), European Society of CardioVascular Surgery (ESCVS);

22. Roitman E.V., Dr. of Biol. Sci., Professor, President of the National Association of Specialists in Thrombosis, Clinical Hemostaseology and Hemorheology;

23. Sapelkin S.V., Dr. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR), member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), member of the American Venous Forum (AVF), member of the European Society for Vascular Surgery (ESVS);

24. Seliverstov E.I., Dr. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS);

25. Sonkin I.N., member of the Association of Phlebologists of Russia (APR), Association of Cardiovascular Surgeons of Russia (ACSR);

26. Soroka V.V., Dr. of Sci. (Med.), Professor, Honored Doctor of the RF; member of the Board of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

27. Stoyko Yu.M., Dr. of Sci. (Med.), Professor, Honored Doctor of the RF, Honored Scientist of the RF, laureate of the RF Government Prize, Honorary President of клиника Association of Phlebologists of Russia (APR), member of the Board of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Honorary Member of the European Venous Forum (EVF);

28. Suchkov I.A., Dr. of Sci. (Med.), Professor, President of the Association of Phlebologists of Russia (APR), member of the Board ofমাত্র the Russian Society of Surgeons (RSS); member of the Board of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), member of the Association of Cardiovascular Surgeons of Russia (ACSR), member of European Society for Vascular Surgery (ESVS);

29. Schastlivtsev I.V., Cand. of Sci. (Med.), Associate Professor, member of the Association of Phlebologists of Russia (APR), European Venous Forum (EVF), Russian Society of Surgeons (RSS), National Association of Specialists in Thrombosis, Clinical Hemostaseology and Hemorheology (NATG);

30. Cherkashin M.A., member of the Association of Phlebologists of Russia (APR), European Society of Medical Oncology, European Society of Radiology;

31. Shevela A.I., Dr. of Sci. (Med.), Professor, Member of the Association of Phlebologists of Russia (APR), Russian Society of Surgeons (RSS), Russian Society of Endoscopic Surgeons (RSES);

32. Shimanko A.I., Dr. of Sci. (Med.), Professor, Member of the Association of Phlebologists of Russia (APR), Member of the Russian Society of Surgeons (RSS);

All members of the Working Group confirmed the absence of financial support or other conflicts of interest in the preparation of these guidelines.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the developed clinical guidelines:

• Cardiovascular surgeon;

• Surgeon;

• Ultrasound diagnostics physician;

• Medical students, residents, postgraduate students.

The guidelines are based on a cumulative analysis of evidence presented in the global literature and obtained from the clinical application of modern principles and methods for the diagnosis and treatment of limb vein thrombophlebitis. The main provisions of the Guidelines are ranked in accordance with Order No. 103n of the Ministry of Health of the Russian Federation dated February 28, 2019 "On approval of the procedure and timelines for the development of clinical guidelines, their revision, the standard form of clinical guidelines, and requirements for their structure, composition, and scientific validity of the information included in clinical guidelines". The guidelines were prepared in accordance with the Methodological Recommendations for Assessing the Scientific Validity of Information Included in Clinical Guidelines, Center for Expertise and Quality Control of Medical Care of the Ministry of Health of the Russian Federation, 2019.

1. Scale for assessing levels of evidence (LoE) for diagnostic methods (diagnostic interventions):

1.1. Systematic reviews of studies with reference method control or systematic review of randomized clinical trials using meta-analysis

1.2. Individual studies with reference method control or individual randomized clinical trials and systematic reviews of studies of any design, excluding randomized clinical trials, using meta-analysis

1.3. Studies without sequential control by a reference method, or studies with a reference method that is not independent of the method under study, or non-randomized comparative studies, including cohort studies

1.4. Non-comparative studies, case report

1.5. Only justification of the mechanism of action or expert opinion is available

2. Scale for assessing levels of evidence (LoE) for prevention, treatment, and rehabilitation methods:

2.1. Systematic review of randomized clinical trials using meta-analysis

2.2. Individual randomized clinical trials and systematic reviews of studies of any design, excluding randomized clinical trials, using meta-analysis

2.3. Non-randomized comparative studies, including cohort studies

2.4. Non-comparative studies, case report or case series study, case-control study

2.5. Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available

3. Scale for assessing grades of recommendation (GoR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitative interventions)

A. Strong recommendation (all considered criteria of efficacy (outcomes) are important, all studies have high or satisfactory methodological quality, and their conclusions regarding the outcomes of interest are consistent)

B. Conditional recommendation (not all considered criteria of efficacy (outcomes) are important, not all studies have high or satisfactory methodological quality, and/or their conclusions regarding the outcomes of interest are inconsistent)

C. Weak recommendation (lack of proper quality evidence (all considered criteria of efficacy (outcomes) are unimportant, all studies have low methodological quality, and their conclusions regarding the outcomes of interest are inconsistent)

Appendix A3. Reference Materials

Appendix A3.1. Risk factors for hemorrhagic complications during pregnancy, childbirth, and the postpartum period

Risk factors for hemorrhagic complications during pregnancy, childbirth, or the postpartum period are given in accordance with the RCOG/ROAG guidelines [109, 108]

• Antepartum or postpartum hemorrhage

• High risk of major hemorrhage (e.g., in placenta previa)

• Hemophilia or other diagnosed bleeding disorders (e.g., von Willebrand disease or acquired coagulopathy)

• Thrombocytopenia (platelet count less than 75 x 10⁹/L)

• Acute stroke within the preceding 4 weeks ( ischemic or hemorrhagic)

• Renal impairment (glomerular filtration rate less than 30 mL/min/1.73 m²)

• Hepatic impairment (prothrombin time above normal or existing esophageal varices)

• Uncontrolled arterial hypertension (systolic blood pressure above 200 mm Hg or diastolic blood pressure above 120 mm Hg).

Appendix A3.2. Prophylactic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight

Based on RCOG/RUOG guidelines [109,108,106,112,219]

Appendix A3.3. Therapeutic doses of LMWH (ATC: B01AB Heparin group) depending on pre-pregnancy body weight.

Based on RCOG/RUOG guidelines [109,108,106,112,219,220]

^∇ The therapeutic dose of parnaparin sodium** for the treatment of superficial vein thrombosis (SVT) during pregnancy is indicated in accordance with the instructions, taking into account that the therapeutic dose is used at high risk of thrombus extension to the deep veins and must correspond to the dose used in the treatment of DVT. The dosage of parnaparin sodium** for the treatment of SVT outside of pregnancy, studied in the STEFLUX study, is given in the relevant section.

Appendix A3.4. Management of superficial vein thrombophlebitis during pregnancy

Based on the recommendations of the Russian Society of Obstetricians and Gynecologists (ROAG) 2014, RCOG 2015 [109,108,112]

∗ in the postpartum period, it is recommended to continue anticoagulation at the same dose that was used before delivery.

Appendix A3.5. Management of superficial vein thrombophlebitis in the postpartum period

Based on the recommendations of the Russian Society of Obstetricians and Gynecologists (ROAG) 2014, RCOG 2015 [109,108,112]

Appendix A3.6. Prophylactic doses of anticoagulants (ATC: Antithrombotic agents) for the treatment of SVT in patients with a confirmed cancer diagnosis

Prophylactic doses of anticoagulants (ATC: Antithrombotic agents) for the treatment of SVT in patients with a confirmed cancer diagnosis are given according to Cancer-Associated Venous Thromboembolic Disease, NCCN Guidelines, Version 2.2024 [71]

Appendix A3.7. Intermediate doses of low molecular weight heparins (LMWH, ATC: B01AB Heparin group)

According to a systematic review and meta-analysis by Eck R.J. et al. [185]

The systematic review by Eck R.J. et al. discusses primary prevention of VTE; the proposed intermediate doses of LMWH (ATC: B01AB Heparin group) serve as a reference guide. When prescribing a specific drug, it is acceptable to define the intermediate dose of LMWH (ATC: B01AB Heparin group) as 50–75% of the dose recommended for the treatment of deep vein thrombosis.

IU – international units, mg – milligrams;

^a The maximum efficacy regimen of #parnaparin sodium** for the treatment of superficial phlebitis, obtained in the STEFLUX study, is indicated, which differs from the official product labeling [67].

Appendix A3.8. Therapeutic doses of anticoagulants (ATC: Antithrombotic agents)

Therapeutic doses of anticoagulants (ATC: Antithrombotic agents) are given in accordance with the instructions for medical use of the respective drugs. Therapeutic doses of anticoagulants (ATC: Antithrombotic agents) for patients with a confirmed cancer diagnosis are provided according to Cancer-Associated Venous Thromboembolic Disease, NCCN Guidelines, Version 2.2024 [71], section "Therapeutic anticoagulation for VTE".

^а dose reduction after 30 days in cancer patients

^б in cancer patients, 100 IU/kg for BMI <40 kg/m² or 80 IU/kg for BMI ≥40 kg/m²;

^вThe therapeutic dose is indicated in accordance with the instructions, taking into account that the therapeutic dose is used at high risk of thrombus extension to deep veins and should correspond to the dose used in the treatment of DVT.

^г5 mg/day for patient weight <50 kg, 7.5 mg/day for patient weight 50–100 kg, 10 mg/day for patient weight >100 kg;

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

1. The main signs of acute superficial phlebitis are painful induration with skin erythema and local hyperthermia in the area of varicose veins or large superficial veins; a cord-like, dense, and painful vein may be present.

2. Superficial phlebitis is associated with the risk of thrombus extension to deep veins and the development of thromboembolic events.

3. The main diagnostic method is duplex ultrasound of veins.

4. Indications for hospitalization include a high risk of thrombus extension to deep veins in the acute stage of phlebitis when adequate outpatient care cannot be provided, or the development of purulent thrombophlebitis.

5. For thrombophlebitis of major vein tributaries, nonsteroidal anti-inflammatory drugs locally or systemically (tablets, capsules), compression therapy (compression hosiery class 1–2), other local and systemic agents (heparins, venoactive drugs), and local hypothermia may be prescribed.

6. In certain situations, when treating superficial phlebitis to prevent thrombus extension to deep veins and the development of thromboembolic complications, anticoagulants (ATC: antithrombotic agents) may be prescribed.

7. If the thrombus extends to major superficial veins, treatment is carried out according to the guidelines for deep vein thrombosis management.

8. Surgical methods of treatment for acute superficial phlebitis are chosen when adequate anticoagulant therapy cannot be administered and there is a high risk of thrombus extension to deep veins and the development of thromboembolic complications.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Grading of risk factor significance for VTE recurrence during pregnancy and the postpartum period

Russian title: Grading of risk factor significance for VTE recurrence during pregnancy and the postpartum period.

Original title: none

Source (official developer website, publication from

validation): https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a/

Type: rating scale

Purpose: assessment of the significance of VTE risk factors during pregnancy and the postpartum period across low, moderate, and high-risk categories.

Assessment tool, content:

* An episode of superficial vein thrombosis (SVT) may be considered a possible manifestation of a thrombophilic condition; therefore, in the event of SVT, it is advisable to combine all forms of hereditary thrombophilia and antiphospholipid syndrome into high-risk factors for VTE recurrence in the current pregnancy.

**Symptomatic varicose veins of the leg, or with a history of thrombophlebitis, or with venous edema, or with trophic changes in soft tissues

Key: risk factor belongs to the low, moderate, or high-risk category in accordance with the table.

Notes: this grading of VTE risk factors during pregnancy and the postpartum period was developed taking into account the 2014 RUPOG and 2015 RCOG clinical guidelines [109,108,112]. The presence of VTE risk factors, depending on their number and significance, is taken into account when determining the management tactics for SVT during pregnancy or in the postpartum period (see Section 3.1.6. "Superficial Vein Thrombophlebitis During Pregnancy and in the Postpartum Period", Appendix A3.4. "Management Tactics for SVT During Pregnancy", Appendix A3.5. "Management Tactics for SVT in the Postpartum Period").