Diagnosis, Treatment, and Prevention of Venous Thromboembolic Complications in Traumatology and Orthopedics: Clinical Guidelines

List of Abbreviations

** – the drug is included in the 2024 VED list

# – off-label drug prescription

VKA – vitamin K antagonists (syn: indirect anticoagulants)

ASA – acetylsalicylic acid**

BP – blood pressure

aPTT – activated partial thromboplastin time

VTE – venous thromboembolism

Knee – knee joint

INR – international normalized ratio

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

NSAIDs – non-steroidal anti-inflammatory and antirheumatic drugs

UFH – unfractionated heparin (syn.: sodium heparin**)

MSK – musculoskeletal system

DOAC – direct oral anticoagulants (ATC B01AE Direct thrombin inhibitors, B01AF Direct factor Xa inhibitors)

ISPC – intermittent sequential pneumatic compression

RCTs – Randomized Controlled Trials

Hip – hip joint

TT – thrombin time

DVT – deep vein thrombosis

TP – VTE prophylaxis

SVT – superficial vein thrombosis

PE – pulmonary embolism

CUS – color duplex ultrasound (duplex scanning of lower extremity blood vessels (arteries and veins); duplex scanning of lower extremity veins; pelvic vessel duplex scanning; duplex scanning of the inferior vena cava and portal system veins)

JR – joint replacement

Terms and Definitions

Antiplatelet agents – a collective term, in the context of these guidelines encompassing acetylsalicylic acid**, clopidogrel**, prasugrel, and ticagrelor** (ATC B01AC Platelet aggregation inhibitors excluding heparin).

Anticoagulants – a collective term encompassing parenteral drugs (heparin sodium**, bemiparin sodium, dalteparin sodium, nadroparin calcium, parnaparin sodium**, enoxaparin sodium**) and oral drugs (indirect anticoagulants, apixaban**, dabigatran etexilate**, rivaroxaban**) (ATC B01A Antithrombotic agents).

Venous thromboembolism (VTE) – a collective term encompassing superficial and deep vein thrombosis, as well as pulmonary embolism.

Low-molecular-weight heparins – a collective term encompassing parenteral drugs registered in the Russian Federation: bemiparin sodium, dalteparin sodium, nadroparin calcium, parnaparin sodium**, enoxaparin sodium** (ATC B01AB Heparin group).

Direct oral anticoagulants (DOACs) – a collective term encompassing oral drugs: apixaban**, dabigatran etexilate**, rivaroxaban** (ATC B01AE Direct thrombin inhibitors, B01AF Direct factor Xa inhibitors).

Deep vein thrombosis (DVT) – the presence of a thrombus in a deep vein, which may cause its occlusion.

Superficial vein thrombosis (SVT, thrombophlebitis) – the presence of a thrombus in a superficial vein, usually accompanied by clinically apparent inflammation.

Pulmonary embolism (PE, pulmonary thromboembolism, pulmonary embolism, pulmonary artery thromboembolism) – lodging of thrombi-emboli in the pulmonary circulation arteries that have migrated from systemic veins.

Post-thrombotic syndrome (PTS) – a chronic condition resulting from organic damage to deep veins following thrombosis. It manifests as impaired venous outflow from the affected limb.

1. Brief information on the disease or condition

Keywords

• deep vein thrombosis

• venous thromboembolic complications

• pulmonary embolism

• risk of venous thromboembolic events

• venous thromboembolism prophylaxis

• joint replacement complications

• post-orthopedic surgery complications

1.1 Definition of the disease or condition

Venous thromboembolism (VTE) – a collective term encompassing superficial and deep vein thrombosis, as well as pulmonary embolism.

VTE prophylaxis – a system of measures aimed at preventing life-threatening and limb-threatening complications (PE and DVT).

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

Venous thromboembolism is a complex (multifactorial) disease involving an interaction between acquired or hereditary predisposition to thrombosis and environmental exposure. The etiopathogenesis of VTE in surgical interventions involves two main components: direct surgical trauma and endothelial dysfunction.

Currently, surgical invasiveness is understood not merely as tissue damage at the surgical site, but as a broad range of pathological processes. Surgical stress manifests as multifunctional alterations occurring in the patient's body under the influence of aggressive surgical factors: psychoemotional arousal, pain, soft tissue and blood vessel damage, pathological reflexes, and massive blood loss.

Changes in the body during surgery represent a programmed stress resulting in significant alterations in blood rheology. The combination of hemostatic regulatory disorders leading to hypercoagulability, slowed blood flow in the limb, and vascular wall damage constitutes Virchow's triad, which underlies the pathogenesis of thromboembolic complications. In the pathogenesis of thromboembolic events following major joint replacement, the triggering mechanism is massive tissue trauma, blood vessel damage, and exposure of vascular collagen [1].

The release of catecholamines in response to surgical aggression also increases platelet aggregation properties. At the same time, both platelet-vascular (due to the release of thromboplastic factors from platelets into the bloodstream) and coagulation (due to the release of thromboplastic substances from vessel walls) arms of hemostasis are activated [2, 3]. The extrinsic pathway of coagulation leads to the formation of a primary clot and occurs within 15 seconds in cases of massive tissue damage [4]. Vascular endothelial injury triggers the intrinsic pathway of blood clotting. Normally, the endothelium secretes anticoagulant factors that prevent blood cell adhesion to the vessel wall. During vascular trauma, this ability is lost, and a platelet plug followed by a fibrin clot forms at the injury site. Other causes of increased thrombotic risk include forced limb positioning—for example, during knee replacement, where marked flexion of the operated joint leads to vascular compression in the popliteal fossa—as well as the use of a flexible tourniquet, which causes blood stasis, overstretching, and microtears of the vessel wall. In addition, bone marrow cavity manipulation during endoprosthesis placement and the use of bone cement activate the extrinsic coagulation pathway through the generation of large amounts of thrombin, further increasing the risk of thrombosis.

Thus, the pathogenesis of thrombosis during surgery is represented by sequential processes: surgical aggression triggers the classic Virchow's triad—intraoperative vascular trauma, blood flow stasis due to forced limb positioning and flexible tourniquet application during knee replacement, and activation of coagulation hemostasis. Subsequently, a cascade of cytokines and humoral mediators provokes vascular tone disruption and leukocyte migration to the vascular injury site. As a result, conglomerates consisting of fibrin strands and blood cells form along the vessels. Detaching from the vessel wall, these conglomerates can cause thromboembolism. These factors continue to operate in the postoperative period, with postoperative pain and forced patient immobilization playing a major role.

A separate group consists of patients with fractures of the lower extremities, pelvic bones, and polytrauma victims. Their specific feature is that the activation of the blood coagulation system occurs in several stages. Primary trauma is accompanied by significant tissue damage, including vascular endothelium, and the release of a large amount of tissue factor, which promotes the activation of the blood coagulation system. Then, within a short period of time, these patients undergo fracture osteosynthesis surgery, which is an additional trauma and re-activates the coagulation system. In addition, polytrauma victims often require staged surgeries, performed two, three, or more times at intervals of one to two weeks. At the same time, each surgical intervention leads to the activation of the hemostatic cascade. As a result, the risk of developing post-traumatic venous thrombosis in this group of patients significantly exceeds the risk of such complications in orthopedic patients who usually undergo a single surgery. Furthermore, while an orthopedic patient can be prepared for elective surgery by compensating for cardiovascular diseases, lower limb venous insufficiency, and other comorbid conditions capable of increasing the risks of venous thrombosis, a trauma patient is admitted to the hospital and operated on an emergency or urgent basis. Accordingly, surgeons generally lack the opportunity to adequately address concurrent somatic pathology due to time constraints.

1.3 Epidemiology of the Disease or Condition

Major orthopedic surgeries are associated with a high risk of venous thromboembolism (VTE)—both symptomatic and asymptomatic deep vein thrombosis and pulmonary embolism, which are potentially life-threatening for patients [5]. The main orthopedic operations of greatest concern include total knee arthroplasty, total hip arthroplasty, and hip fractures.

The incidence of various thromboembolic complications varies. Asymptomatic deep vein thrombosis (diagnosed only by screening duplex ultrasound) occurs in 12.6–31.1% of cases after primary arthroplasty [6, 7]. Clinically significant DVT develops much less frequently—in 0.75–2.1% of cases [8, 9]. The most severe complication, pulmonary embolism (PE), is registered in 0.41–1.93% of cases. Moreover, obstruction of the pulmonary artery or its branches is not only potentially life-threatening but can also lead to chronic complications with a poor prognosis, such as chronic thromboembolic pulmonary hypertension [10, 11]. Deep vein thrombosis is the main intermediate process necessary for the development of surgery-related PE and increases the risk of its development. In addition, approximately 5–10% of patients with symptomatic DVT develop severe post-thrombotic syndrome over the subsequent 10 years or more, manifested by the formation of venous ulcers, peripheral edema, and chronic pain [12].

Currently, the universally accepted practice in assessing the effectiveness of thromboprophylaxis is to account only for symptomatic thromboembolisms, due to the lack of differences in clinical outcomes (cardiovascular mortality) 2 years after surgery between patients who experienced asymptomatic VTE and those without these complications [13].

1.4 Features of Coding the Disease or Condition

I80.1 Phlebitis and thrombophlebitis of femoral vein

I80.2 Phlebitis and thrombophlebitis of other deep vessels of lower extremities. Deep vein thrombosis, NOS

I80.3 Phlebitis and thrombophlebitis of lower extremities, unspecified. Embolism or thrombosis of lower extremities, NOS

1.5 Classification of the disease or condition

Venous thrombosis can be classified by localization, direction of the thrombotic process, degree of thrombus fixation, degree of hemodynamic disorders, and presence of complications [14, 15].

By localization, venous thrombosis can be divided depending on:

– the vascular bed: superior or inferior vena cava (most dangerous regarding the development of PE);

– the venous system: superficial, deep;

– the veins affected by the thrombotic process: proximal and distal levels of involvement.

By the extent of thrombotic involvement: segmental or extensive, bilateral, multifocal.

By the direction of spread, ascending or descending thrombotic processes are distinguished.

By the degree of thrombus fixation to the venous wall:

– occlusive;

– non-occlusive: mural, floating (emboligenic).

Three degrees of hemodynamic disorders are distinguished:

– mild;

– moderate;

– severe.

By the presence of complications, venous thrombosis is subdivided into:

– uncomplicated;

– ascending superficial thrombophlebitis (upper border of the thrombus at the level of the upper third of the thigh) ‒ an emboligenic form;

– complicated: PE, venous gangrene, post-thrombotic disease (chronic venous insufficiency), lower limb vein thrombosis extending into the inferior vena cava.

1.6 Clinical presentation of the disease or condition

Clinical manifestations depend on the localization of thrombosis, extent and nature of venous bed involvement, as well as disease duration. In the initial period of non-occlusive forms, clinical symptoms are mild or entirely absent. Sometimes the first sign of DVT may be symptoms of PE. A typical spectrum of symptoms includes edema of the entire limb or part of it; skin cyanosis and increased prominence of subcutaneous veins; bursting pain in the limb; pain along the neurovascular bundle [16].

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnostic criterion is a combination of symptoms of deep vein thrombotic occlusion (lower leg edema, lower leg and thigh edema with or without pain in the lower extremity, a feeling of heaviness in it) occurring suddenly, and instrumental (ultrasound, X-ray) data on the presence of thrombotic masses in the lumen of deep veins. In asymptomatic DVT, the diagnostic criterion is the instrumentally confirmed presence of thrombotic masses in the deep vein lumen in a patient from the VTE risk group referred for screening examination [345]. The main goals of diagnosing acute venous thrombosis upon confirmation are determining its localization, extent, and emboligenic potential. Emboligenic DVTs include floating thrombi with a single point of fixation in the distal segment. Superficial vein thrombosis poses a threat of PE when spreading to the deep venous system.

It is advisable to perform all diagnostic tests for suspected VTE within 24 hours to ensure prompt treatment if the diagnosis is confirmed and to avoid unnecessary repeated doses of anticoagulants if the diagnosis is excluded.

2.1 Complaints and Anamnesis

• When examining patients with suspected acute venous thrombosis and/or PE, it is recommended to actively clarify complaints that may indicate thrombotic venous involvement and pulmonary embolism, and to conduct a thorough history taking to identify, among other things, mildly symptomatic forms of venous thrombosis and distal pulmonary artery branch embolism [17–20].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. When taking the medical history, it is necessary to clarify the date of injury or performed orthopedic surgery, whether VTE prophylaxis was administered, and if so, by what methods, history of DVT and PE episodes, and family history (likelihood of hereditary thrombophilia).

In non-occlusive forms of venous thrombosis in patients with musculoskeletal injuries, complaints indicative of venous thrombotic involvement are often minimal or absent, as venous blood flow through the vessel is partially preserved. The occlusive variant of thrombosis is characterized by the development of acute (within several hours) bursting leg pain, edema, and cyanosis of the corresponding segment. The development of a collapse-like state, chest pain, and hemoptysis in a patient requires urgent examination to rule out PE.

2.2 Physical Examination

Clinical signs of superficial (subcutaneous) and deep vein thrombosis of the extremities differ significantly. Superficial vein thrombosis (SVT) is traditionally designated in clinical practice by the term "thrombophlebitis" due to the presence of easily detectable signs of inflammation (usually aseptic) of the vein wall and paravascular tissue.

Clinical signs of superficial vein thrombosis:

• pain along the thrombosed subcutaneous veins;

• strip of hyperthermia and erythema in the projection of the affected vein;

• upon palpation ‒ a cord-like, dense, sharply painful string;

• local temperature rise, skin hyperesthesia.

Clinical manifestations of DVT are less specific and depend on the localization of thrombosis, extent and nature of venous bed involvement, and disease duration. Against the background of post-traumatic (postoperative) edema, clinical detection of DVT is a complex task. In the initial period of non-occlusive forms of thrombosis, clinical symptoms are mild or entirely absent. Frequently, the first signs indicating DVT in a hospitalized patient may be symptoms of PE.

The typical spectrum of DVT symptoms includes:

•  swelling of the entire limb or lower leg;

•  skin cyanosis and enhanced subcutaneous venous pattern;

•  bursting pain in the limb;

•  pain along the neurovascular bundle.

• All patients with suspected VTE are recommended to undergo a physical examination to rule out other causes of clinical symptoms [21–24].

GCR BLEL 3Grade of Recommendations B (Level of Evidence – 3)

Comments. When examining a patient with suspected venous thrombosis, both lower limbs must be examined. Thrombosis frequently develops in the injured and contralateral limbs simultaneously. Bilateral involvement of both superficial and deep veins is possible. Against the background of trauma (surgery), post-traumatic (postoperative) edema, and pain syndrome, DVT lacks pronounced clinical manifestations, and its early diagnosis based solely on clinical signs is significantly hindered. It is necessary to purposefully identify symptoms indicating PE. The development of pulmonary embolism unequivocally indicates deep vein thrombosis.

The embolic risk of a thrombus does not correlate with the severity of clinical symptoms. A free-floating thrombus threatening fatal PE may have minimal clinical manifestations, as it does not completely occlude the lumen of the main vein.

The value of physical examination for accurately determining the extent of superficial vein thrombosis is low due to the fact that the true prevalence of superficial venous thrombosis significantly exceeds the clinically detected signs of thrombophlebitis.

In a significant proportion of patients, the spread of the thrombotic process from superficial to deep venous trunks is asymptomatic.

• For clinical assessment of DVT probability during patient examination, the use of the Wells score (Appendix G1) is recommended. Based on the total score, patients are divided into groups with low, moderate, and high probability of venous thrombosis [25–29].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments. The scope and tactics of further examination and treatment are determined after consultation with a cardiovascular surgeon. Since clinical data do not allow for the reliable exclusion of DVT, the diagnostic workup must include subsequent laboratory and instrumental examinations.

• For clinical assessment of PE probability during patient examination, the use of the Wells score or the revised Geneva score (Appendix G2 and G3) is recommended [26, 28, 30–32].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

Comment. Clinical signs of PE are diverse and non-specific. The presence and severity of symptoms are determined by the size and localization of thromboemboli and the patient's baseline cardiorespiratory status. Clinical data cannot definitively confirm or rule out the presence of PE. However, such a preliminary assessment is necessary to properly interpret the results of instrumental and laboratory diagnostics thereafter. PE can be conditionally subdivided into three groups: massive (embolic involvement of the pulmonary trunk and/or main pulmonary arteries), submassive (occlusion of 30 to 50% of the pulmonary arterial bed), and microvascular pulmonary embolism (total involvement of less than 30% of the pulmonary arterial bed). The scope and tactics of further examination are determined after consultation with a cardiovascular surgeon. The choice of further management tactics for a patient with PE in a specialized department is determined based on the assessment of 30-day mortality risk (high, intermediate, low).

2.3 Laboratory Diagnostics

• Patients without clinical signs suggesting DVT and/or PE are not recommended to undergo blood D-dimer concentration testing for screening purposes [33–36].

GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)

Comments. An elevated plasma D-dimer level indicates active fibrin formation and degradation processes. Along with high sensitivity, the test has low specificity. Elevated D-dimer levels are detected in many conditions, including trauma, recent surgical interventions, inflammation, infection, tumors, as well as in elderly individuals and patients with prolonged hospital stays.

In patients with musculoskeletal injuries, an isolated increase in D-dimer levels cannot be considered a pathognomonic sign of VTE.

• Patients with clinical symptoms and history that leave no doubt about the presence of DVT and/or PE are not recommended to undergo blood D-dimer concentration testing for primary diagnosis [11, 37].

GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)

• Patients with clinical signs suggesting DVT and/or PE, when it is not possible to perform within the next few hours (A04.12.006) Duplex scanning of lower extremity vessels (arteries and veins) or (A04.12.002.001) Ultrasonic Dopplerography of lower extremity vessels (arteries and veins), are recommended to undergo blood D-dimer concentration testing [38, 39, 154-160].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments. An elevated blood D-dimer level in patients after trauma or orthopedic surgery is not a reliable sign of venous thrombosis, as its increase is a compensatory reaction of the hemostatic system to musculoskeletal trauma. However, a normal D-dimer level makes it possible to exclude the presence of VTE with high probability.

2.4 Instrumental Diagnostics

• All patients with suspected superficial or deep lower extremity venous thrombosis and/or PE are recommended to undergo (A04.12.006) Duplex scanning of lower extremity vessels (arteries and veins), or (A04.12.002.001) Ultrasonic Dopplerography of lower extremity vessels (arteries and veins), and (A04.12.022) Duplex scanning of pelvic vessels to clarify the diagnosis and determine further treatment tactics [34, 40–45].

GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)

Comments. The standard scope of (A04.12.006) Duplex scanning of lower extremity vessels (arteries and veins), (A04.12.002.001) Ultrasonic Dopplerography of lower extremity vessels (arteries and veins), (A04.12.022) Duplex scanning of pelvic vessels must necessarily include the examination of superficial and deep veins not only of the injured limb, but also of the contralateral limb to rule out their simultaneous involvement, which is frequently asymptomatic. The deep venous system of both lower limbs is examined throughout its entire length, starting from the distal lower leg to the inguinal ligament level, and, if bowel gas does not obstruct, the vessels of the iliocaval segment as well. When performing (A04.12.006) Duplex scanning of lower extremity vessels (arteries and veins), (A04.12.002.001) Ultrasonic Dopplerography of lower extremity vessels (arteries and veins), (A04.12.022) Duplex scanning of pelvic vessels, (A04.12.015.001) Triplex scanning of the inferior vena cava, iliac veins, and lower extremity veins (complex) in patients with superficial vein thrombosis, the saphenofemoral and saphenopopliteal junctions and typical groups of perforating veins should be visualized to rule out the extension of thrombosis into the deep venous system. If possible, (A04.12.006) Duplex scanning of lower extremity vessels (arteries and veins), (A04.12.002.001) Ultrasonic Dopplerography of lower extremity vessels (arteries and veins), (A04.12.022) Duplex scanning of pelvic vessels should be performed within the next 4 hours.

• If thrombosis extends to the iliocaval segment and it is impossible to determine its proximal border and embolic risk using vascular ultrasound, it is recommended to perform (A06.12.021) Inferior vena cavography or computed tomography angiography to determine the proximal border of the thrombus and its embolic risk [46–49].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments. If an embolic thrombus is detected, therapeutic interventions may be performed as a second stage: vena cava filter implantation***, (A16.12.003.001) Endovascular aspiration thrombectomy, (A16.23.034.012) local endovascular transarterial thrombolysis.

• Patients scheduled for delayed surgical treatment several days after trauma are recommended to undergo lower extremity vascular ultrasound with the examination timed as close as possible to the date of surgery to detect asymptomatic venous thromboses, especially if adequate pharmacological prophylaxis was not administered [50–54].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments. If an embolic thrombus is detected, therapeutic interventions may be performed as a second stage: vena cava filter implantation***, A16.12.003.001 Endovascular aspiration thrombectomy, (A16.23.034.012) local endovascular transarterial thrombolysis.

• For patients who have not undergone full prophylactic measures or who have a particularly high risk of VTE, it is recommended to perform duplex ultrasound scanning before starting mobilization to detect asymptomatic deep vein thrombosis [52, 55–57].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

• In patients hospitalized in trauma or orthopedic departments with suspected pulmonary embolism, it is necessary to urgently perform an electrocardiogram and chest radiography to rule out other cardiovascular and respiratory pathologies [16, 58–60].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. Electrocardiogram and chest radiography allow ruling out other cardiac and pulmonary pathologies presenting with clinical symptoms similar to those of pulmonary embolism. When transferring a patient to a specialized vascular surgery department with suspected pulmonary embolism, additional procedures are performed: contrast-enhanced spiral computed tomography of the lungs to detect perfusion disorders of the pulmonary arterial bed, echocardiography, radionuclide lung perfusion scanning (scintigraphy) (A07.09.003 Perfusion lung scintigraphy), right heart catheterization, and pulmonary angiography with branching.

2.5 Other Procedures

None provided.

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

The objectives of DVT treatment, regardless of its location, are as follows:

– to stop the spread of the thrombotic process;

– to prevent pulmonary embolism;

– to prevent the progression of edema and potential venous gangrene;

– to restore (fully or partially) deep vein patency;

– to prevent thrombosis recurrence.

Surgical and therapeutic methods for DVT treatment are used in combination, depending on the priority of the goals addressed in patient management. Currently, the scope of surgical interventions has a clear tendency to narrow due to the emergence of new generations of effective anticoagulants and highly informative non-invasive diagnostic methods that can be used for dynamic monitoring of treatment efficacy. In the vast majority of cases, their goal is to prevent massive pulmonary embolism. In the postoperative period, prolonged anticoagulant therapy is mandatory (in the absence of contraindications to anticoagulants).

The detection of signs of acute superficial, deep vein thrombosis and/or pulmonary embolism, as well as a well-founded suspicion thereof, is an indication for consultation with a cardiovascular surgeon. Subsequent treatment of patients with VTE is managed jointly by a cardiovascular surgeon and a trauma and orthopedic surgeon.

Surgeries on the musculoskeletal system should be postponed until the risk of potential pulmonary embolism is eliminated. If a plaster cast is present, it should be transected and the edges spread apart. Prior to instrumental examination, patients with DVT and/or pulmonary embolism must be prescribed strict bed rest to reduce the risk of pulmonary embolism. Following the examination, patients with non-embolus-hazardous forms of venous thrombosis may be mobilized.

3.1 Conservative Treatment

Issues regarding the conservative treatment of superficial vein thrombosis are addressed in the clinical guidelines "Phlebitis and Thrombophlebitis of Superficial Vessels" 2024, approved by the Scientific Committee of the Russian Ministry of Health.

• All patients with DVT and/or pulmonary embolism are recommended to receive anticoagulant therapy (in the absence of contraindications) at therapeutic doses (Table 3.1):

unfractionated heparin (UFH; syn.: heparin sodium**) [61-63, 161, 165, 167],

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

LMWH [61-63, 161, 165, 167],

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

fondaparinux sodium [61-63, 162, 164, 166],

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

apixaban** [61-64, 161],

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

dabigatran etexilate** [61-63, 161],

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

rivaroxaban** [61-63, 161, 163, 164],

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

indirect anticoagulant (vitamin K antagonist) [61-63, 161, 163].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comment. The basis of treatment for patients with VTE (including asymptomatic ones) is anticoagulant therapy, as it is the only treatment capable of stopping the progression of thrombosis. The administration of therapeutic doses of anticoagulants in cases of suspected DVT and/or pulmonary embolism and in the absence of contraindications should be initiated even before instrumental verification of the diagnosis. In situations where the further management strategy for the patient has not yet been determined, it is advisable to use intravenous infusion of UFH (heparin sodium**).

Table 3.1. Regimes of use and dosing of anticoagulants for DVT treatment

• In case of a well-founded suspicion of VTE, it is recommended to start anticoagulant therapy prior to instrumental verification of the diagnosis [61].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. Emergency instrumental diagnostics of venous thrombosis are generally possible only in a specialized vascular department. Consequently, the time interval from clinical diagnosis to duplex ultrasound scanning for a patient in the trauma and orthopedics department can be significant. It is known that early initiation of anticoagulant therapy reduces the incidence of pulmonary embolism by 3–4 times. If DVT is ruled out, anticoagulants are discontinued.

• In patients with non-embolus-hazardous forms of DVT, anticoagulant therapy is recommended as the primary treatment method. In cases where surgical or endovascular intervention, or systemic or regional thrombolysis is performed according to indications, subsequent anticoagulant therapy is recommended [61, 62, 169, 170].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• All patients with lower extremity DVT are recommended (in the absence of contraindications) elastic compression of both lower extremities using class 2–3 compression hosiery [71, 72].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments. Elastic compression must not be interrupted during lower extremity surgeries: the stocking (or bandage, which is less effective) should be worn on the unoperated limb during surgery, and on the operated limb, the stocking (bandage) should be put on the operating table immediately upon completion of the surgery. Elastic compression of the lower extremities should be continued until the patient's normal activity routine is restored, and maintained in an outpatient setting.

• Treatment of patients with DVT who are scheduled for surgical, endovascular intervention, or thrombolysis, as well as those undergoing mechanical ventilation, is recommended to begin with parenteral administration of anticoagulants: UFH (heparin sodium**), dalteparin sodium, nadroparin calcium, parnaparin sodium**, enoxaparin sodium**, or fondaparinux sodium [61, 73].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. If DVT develops in a patient with a high risk of bleeding, or if urgent surgical or endovascular intervention is planned, it is advisable to initiate anticoagulant therapy with agents for which an antidote exists. For UFH (heparin sodium**) and LMWH, protamine sulfate** serves as such an antidote, while for dabigatran etexilate**, it is idarucizumab. When using other DOACs, the interval between the last drug intake and surgical intervention should range from 24 to 48 hours depending on creatinine clearance. In most cases, LMWH or fondaparinux sodium should be preferred. For LMWH, both twice-daily and once-daily administration are possible (Table 3.1).

• Anticoagulant therapy in stable patients who are not scheduled for surgery or thrombolysis is recommended to be carried out using apixaban**, dabigatran etexilate**, or rivaroxaban** [61, 62, 73, 168, 173, 174].

GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)

Comments. In a stable patient, therapy with apixaban** or rivaroxaban** should be initiated immediately after confirming the DVT diagnosis or transitioned to these drugs within the first 2 days after starting parenteral anticoagulant administration. Switching to dabigatran etexilate** is possible starting from day 5 of parenteral anticoagulant therapy.

• The majority of patients with DVT are recommended to receive anticoagulant therapy for at least 3 months [61, 62, 175, 176].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

• In patients with proximal DVT who have suffered pulmonary embolism, in the presence of thrombophilia associated with a high risk of VTE recurrence (antiphospholipid syndrome, protein C or S deficiency, factor V Leiden or prothrombin G20210A mutations), with a low bleeding risk and the ability to maintain a stable level of anticoagulation, it is recommended to continue anticoagulant therapy for 6 months or longer [61, 62, 177–183].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

• In patients with DVT associated with malignant neoplasms who have a high bleeding risk, as well as in pregnant women for whom oral anticoagulants are contraindicated, it is recommended to prefer prolonged use of LMWH (subcutaneous administration of a therapeutic dose in the first month with the option of subsequent reduction to 75% of the therapeutic dose) [74–76].

Level of Evidence CGrade of Recommendation 5Level of Clinical Effectiveness C (level of evidence – 5)

• If a non-emboligenic form of DVT is detected in a hospital setting in a patient with musculoskeletal injuries or diseases who does not require emergency or urgent surgery for this condition, it is recommended to administer anticoagulant therapy with parenteral drugs (therapeutic doses of LMWH are preferred) along with serial ultrasound monitoring of the thrombus and venous bed status. After stabilization of the thrombotic process, confirmed by duplex ultrasound data, and subsidence of the acute clinical manifestations of thrombosis (after 3–5 days), surgery on the musculoskeletal system may be performed [77].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments. 12 hours before surgery, the therapeutic dosage of anticoagulants is replaced with a prophylactic dose of LMWH. After surgery (24 hours after the previous injection), provided hemostasis is stable, LMWH is re-administered in a prophylactic dose. From the 2nd day of the postoperative period, therapeutic doses of anticoagulants are used. Serial ultrasound monitoring of the thrombus and venous bed status is performed in the postoperative period (every 3–5 days).

• In patients with PE of up to 14 days duration leading to shock or persistent arterial hypotension, it is recommended to perform thrombolytic therapy (A11.12.003.002 Intravenous administration of medicinal products for thrombolytic therapy) in the absence of contraindications [73, 78, 313–339].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

Comments. PE with severe hemodynamic disturbances (shock, persistent arterial hypotension) is an absolute indication for thrombolytic therapy (A11.12.003.002 Intravenous administration of medicinal products for thrombolytic therapy). The earlier thrombolytic therapy is initiated, the better the outcomes. The best results are achieved when the disease duration is up to 48 hours from the moment of embolization. At the same time, a therapeutic effect can be expected with a disease duration of up to 14 days [73, 78, 313–318].

Massive PE is a life-threatening condition. One of the absolute contraindications is surgery within the preceding 10–14 days, since thrombolysis in massive PE in patients in the early postoperative period is always associated with the risk of fatal bleeding. If unstable hemodynamics and severe respiratory disorders persist on the 10th–12th day of the postoperative period, thrombolytic therapy (A11.12.003.002 Intravenous administration of medicinal products for thrombolytic therapy) should be administered in a standard regimen. In patients in extremely grave condition with verified massive PE, thrombolytic therapy can be administered as a bolus ("lifesaving regimen") [319–326]. The multicenter open-label randomized comparative clinical trial FORPE (n = 310) demonstrated non-inferior efficacy of the recombinant protein containing the amino acid sequence of staphylokinase** (B01AD) compared to alteplase** (B01AD02) in the treatment of patients with massive pulmonary embolism and hemodynamic instability, and it has a more favorable safety profile. The non-immunogenic recombinant protein containing the amino acid sequence of staphylokinase** (B01AD) is used as a single bolus regardless of body weight in all patients with massive PE, which simplifies their management [327]. Thrombolytic therapy (A11.12.003.002 Intravenous administration of medicinal products for thrombolytic therapy) for massive PE in pregnant women helps normalize central hemodynamics, reduce manifestations of right ventricular failure, eliminate hypoxemia in the mother and fetus, and allow full-term delivery; furthermore, the thrombolytic drug alteplase** (B01AD02) has no teratogenic effect in late pregnancy. Preclinical studies have shown that the non-immunogenic recombinant protein containing the amino acid sequence of staphylokinase** (B01AD) lacks embryotoxic, teratogenic, and reprotoxic properties. Management of patients with PE during pregnancy is discussed in detail in the relevant guidelines [328–339].

3.2. Surgical Treatment

The issues of surgical treatment of superficial vein thrombosis are addressed in the clinical guidelines "Phlebitis and Thrombophlebitis of Superficial Vessels" (2024), approved by the Scientific Committee of the Russian Ministry of Health.

• Endovascular (inferior vena cava filter implantation***, catheter thrombectomy) and open surgical interventions (thrombectomy, ligation of the deep vein proximal to the thrombus, IVC plication) as a method to prevent massive PE are recommended for patients with DVT according to the following indications [82, 83, 184–190]:

– inability to administer appropriate anticoagulant therapy;

– ineffectiveness of adequate anticoagulant therapy, against the background of which thrombosis progresses with the formation of an emboligenic thrombus (a free-floating thrombus of significant diameter longer than 5–7 cm);

– presence of an emboligenic thrombus in the iliocaval segment at the time of initial diagnosis of thrombosis;

– recurrent PE with high pulmonary hypertension (systolic pulmonary artery pressure > 50 mm Hg);

– incorrect position of a previously placed permanent vena cava filter model (e.g., its migration into the renal vein), precluding re-implantation (plication is performed after phlebotomy and removal of the vena cava filter***).

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments. Implantation of retrievable vena cava filter models (vena cava filter, temporary/permanent***) is a priority; these filters must be removed after the risk of PE has resolved, specifically when the free-floating thrombus transitions into a non-emboligenic form due to fixation of its mobile part to the venous wall. For most retrievable vena cava filter models (vena cava filter, temporary/permanent***), the optimal removal period is 3–4 weeks.

• If an emboligenic (free-floating) thrombus is detected in a hospital setting in a patient with musculoskeletal injuries or diseases who does not require emergency or urgent surgery for this condition, recommendations include the implantation of a retrievable vena cava filter model (vena cava filter, temporary/permanent***), after which musculoskeletal surgery can be performed at a time determined by the orthopedic traumatologist. The anticoagulant therapy regimen should be similar to that used for the non-emboligenic form of DVT [84, 85].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

• If iliocaval thrombosis is detected in a hospital setting in a patient with musculoskeletal injuries or diseases who requires any form of emergency or urgent surgery for this condition, due to the high probability of progression of the thrombotic process, it is recommended to implant a retrievable vena cava filter model (vena cava filter, temporary/permanent***) followed by the planned musculoskeletal surgery [84, 85].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments. After surgery (6–12 hours later), provided hemostasis is stable, anticoagulants are administered in a prophylactic dose. From the 2nd day of the postoperative period, therapeutic doses of anticoagulants are used. Serial ultrasound monitoring of the thrombus and venous bed status is performed in the postoperative period.

• If an emboligenic thrombus of the femoropopliteal segment is detected in a hospital setting in a patient with musculoskeletal injuries or diseases who requires emergency or urgent surgery for this condition, it is recommended to implant a retrievable vena cava filter model (vena cava filter, temporary/permanent***) or, alternatively, to perform ligation (or plication) of the superficial femoral vein using an absorbable surgical suture (e.g., poly(L-lactide-co-caprolactone) surgical suture***), followed by the planned musculoskeletal surgery [84, 85].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments. Patients with a free-floating thrombus of the common femoral vein first undergo thrombectomy from the common femoral vein. Then, the superficial femoral vein is ligated (plicated) immediately distal to the confluence of the deep femoral vein, the patency of which is a prerequisite for this surgery. Intervention on the deep venous system can be performed as the first stage in the same operative session as the musculoskeletal surgery.

• If isolated calf vein thrombosis is detected in a hospital setting in a patient requiring emergency or urgent orthopedic surgery, it is recommended to perform the necessary intervention and prescribe postoperative anticoagulant therapy combined with serial duplex ultrasound monitoring of the thrombus and venous bed status [84, 85].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

4. Medical Rehabilitation and Sanatorium-Resort Treatment

The rehabilitation program is determined by the underlying disease or its complication and/or the nature of the surgery, in particular, the use of high-tech or minimally invasive interventions.

5. Prevention and Dispensary Observation

Currently, the optimal approach is considered to be one in which VTE prophylaxis is administered to absolutely all patients admitted to the hospital. The nature of preventive measures is determined by the degree of risk.

5.1 Assessment of VTE Risk in Traumatology and Orthopedics

Despite the impossibility of precisely predicting the development of venous thromboembolic complications, it is necessary to assess the probability of their occurrence. The presence of risk factors predisposing the patient to VTE (Table 5.1) serves as the basis for assigning them to a specific risk group. One of the most convenient tools for determining VTE risk in surgery is the Caprini scale (Appendix G5). Depending on the presence of risk factors and the planned surgery, the patient is assigned a VTE risk level (Appendix G6) [86]. In the absence of prophylaxis, the probability of VTE in patients with very low (0 points), low (1–2 points), moderate (3–4 points), and high (≥ 5 points) risk is less than 0.5, 1.5, 3, and 6%, respectively. Due to the lack of fundamental differences in VTE incidence and the management and prophylaxis tactics for low- and very-low-risk patients, it is practical in clinical practice to combine them into a single low VTE probability group.

Table 5.1. Probability of VTE associated with various predisposing factors

5.2 VTE Prophylaxis Modalities

To prevent VTE in a patient with trauma or musculoskeletal surgery, the primary step is to minimize or eliminate factors contributing to thrombus formation: restore circulating blood volume, normalize hemodynamics, apply adequate analgesia, and prevent infectious complications. Early mobilization of the patient and restoration of the range of motion in the limb joints should be pursued as early as possible. Whenever possible, bone fragments should be stably fixed in the early post-fracture period. The use of stable functional osteosynthesis and minimization of surgical trauma through modern closed osteosynthesis technologies help reduce the duration of immobilization in patients with musculoskeletal injuries and disorders.

VTE prevention includes the following methods:

• non-pharmacological – used in all patients with limited mobility:

— maximum and earliest possible mobilization of patients after surgery, including passive load methods: verticalization, mechanotherapy, kinesiotherapy, etc.;

— ensuring the maximum possible activity of the lower extremity muscles in patients on prolonged bed rest, local procedures that increase blood flow volume through the deep veins of the lower extremities (elastic compression of the lower extremities, intermittent pneumatic compression of the lower extremities, calf muscle myostimulation, etc.);

— active and passive loads on the upper extremities, improving overall blood circulation and stimulating endothelial antithrombotic activity;

• medical — pharmacological thromboprophylaxis in patients with moderate and high risk of VTE.

5.2.1 Non-pharmacological VTE Prophylaxis Modalities

Non-pharmacological methods include mechanical prophylaxis, namely static elastic compression of the lower extremities, sequential intermittent pneumatic compression (IPC), foot venous pump, calf muscle myostimulation, and therapeutic exercise. The main purpose of non-pharmacological methods is to accelerate venous blood flow, while their use does not increase the risk of hemorrhagic complications. Mechanical prophylaxis should be initiated before surgery and continued during and after it until motor activity is restored.

Sequential intermittent pneumatic compression (SIPC) of the lower extremities of 40–50 mm Hg using special cuffs and a device is the most effective mechanical prophylaxis method. It should be applied in accordance with the device manual in patients on bed rest.

Static elastic compression of the lower extremities using medical compression hosiery (stockings ensuring optimal pressure distribution on the lower extremities) or medical elastic bandages should be started upon admission, as hospital stay is always associated with limited motor activity and slowed venous blood flow. The medical elastic bandage must be applied by trained personnel (the rules for applying elastic bandages are described in Appendix G7). The condition of the bandage should be checked daily in the morning and evening and adjusted if necessary. Special prophylactic medical compression hosiery (graduated compression stockings) is more effective and easier to use, independently maintaining the required pressure gradient. However, it requires prior sizing and, due to developing edema, does not always provide an adequate degree of compression in the early postoperative period. The use of compression hosiery is advisable for elective surgeries. Elastic compression is continued during lower extremity surgeries: the stocking (bandage) must be on the unoperated limb during surgery, and put on (applied) the operated limb on the operating table immediately after surgery completion [55].

• A17.02.001 Calf muscle electrical stimulation (CMES) – the procedure is recommended for all bedridden patients, both in the inpatient setting and at the outpatient stage of treatment. It is performed using various electroneurostimulators (stationary devices or individual portable ones) according to the attached instructions. A necessary element is the presence of electrodes applied to the patient's calf muscles. The method can be combined with static elastic compression and exercise therapy. It can be considered as an alternative to the SIPC method [88].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Therapeutic physical training is used in all patients. Movements in the ankle joint and toe joints are of particular importance. Therapeutic exercise cannot replace pharmacological and mechanical methods of VTE prophylaxis.

5.2.2. Medications, doses, and administration regimens

The anticoagulant group includes UFH (sodium heparin**), LMWH, DOACs (Table 5.3), and vitamin K antagonists (VKAs). However, currently, VKA drugs (warfarin**) are practically not used independently for VTE prophylaxis in traumatology and orthopedics. The only group of patients who need to take them remains patients receiving VKAs due to somatic pathology or having intolerance to all other anticoagulants.

Special attention during medical VTE prophylaxis should be paid to reducing perioperative blood loss. Careful intraoperative hemostasis must be achieved, modern hemostatic agents applied, blood-saving technologies and antifibrinolytic agents (tranexamic acid**, etc.) used.

Table 5.3. Recommended doses and administration regimens of anticoagulants for VTE prophylaxis in surgical patients¹

^{1 –} _{drugs are grouped according to their pharmacological properties; LMWHs and oral anticoagulants are listed in alphabetical order;}

^{2 –} _{in underweight patients (less than 50 kg), it is reasonable to reduce the prophylactic dose of LMWH by half, while in severely obese patients (body weight over 120 kg, body mass index over 50 kg/m²), to increase it by 25%; dose adjustment of LMWH based on blood anti-Xa activity is justified in such patients;}

^{3 –} _{the timing of UFH (heparin sodium**) administration prior to surgery reflects expert consensus, taking into account the extensive nature of orthopedic procedures associated with an increased risk of blood loss;}

^{4 –} _{these recommendations reflect expert consensus and are based on the dosages and administration regimens of heparin group drugs in general surgery.}

When using any anticoagulants, it is necessary to actively monitor for signs of potential hemorrhagic complications, baseline determination and regular monitoring of hemoglobin levels, hematocrit, and creatinine clearance (see section 5.4). When administering heparin group drugs, it is also necessary to regularly monitor platelet counts in the blood.

According to the instructions for use, when prescribing and selecting a dose of direct-acting oral anticoagulants (DOACs), renal function must be taken into account. For this purpose, blood creatinine levels should be determined (A09.05.020 Blood creatinine test) and creatinine clearance calculated using the Cockcroft–Gault formula:

If serum creatinine is expressed in μmol/L, the result must be multiplied by 88. The degree of renal impairment is determined based on the calculated creatinine clearance:

Mild – creatinine clearance 51–80 ml/min.

Moderate – creatinine clearance 30–50 ml/min.

Severe – creatinine clearance less than 30.

Depending on the severity of renal impairment, the prescription and dose adjustment of DOACs and LMWHs are performed (Table 5.4).

Table 5.4. Dosing of DOACs and LMWHs for VTE prophylaxis in patients with impaired renal function

^{1 –} _{drugs are grouped according to their pharmacological properties; LMWHs and oral anticoagulants are listed in alphabetical order}

Antiplatelet agents, excluding heparin, represent a group of drugs with a fundamentally different mechanism of action in preventing thrombosis. Unlike anticoagulants, they act at the initial stage of blood coagulation, during which platelet aggregation occurs, by blocking platelet adhesion to the vascular endothelium.

Currently, ASA** is the only drug included in a number of national guidelines for VTE prophylaxis after elective total hip or knee arthroplasty (see sec. 5.4.1) in patients without additional risk factors for thrombosis [89–92]. Randomized clinical trials and published meta-analyses demonstrate that ASA** exhibits efficacy comparable to anticoagulants in preventing VTE after knee or hip arthroplasty, both in stepped pharmacological prophylaxis when prescribed after several days of LMWH regardless of additional VTE risk factors in patients [93], and when administered from the first postoperative day in patients without additional risk factors [94].

Other drugs in this group (clopidogrel**, prasugrel, ticagrelor**) are used in the treatment of cardiac conditions. Patients permanently taking antiplatelet agents (other than heparin) or anticoagulants for therapeutic indications have a high risk of hemorrhagic complications. Guidelines for the management of this category of patients are outlined in Section 5.4.10.

Table 5.5 presents drugs that can, to varying degrees, neutralize the effect of anticoagulants or antiplatelet agents (other than heparin) in cases of severe bleeding or the need for emergency surgery in a patient receiving antithrombotic therapy or prophylaxis [95, 96].

Table 5.5. Drugs for reversing the effects of antithrombotic agents

5.3 General approaches to VTE prophylaxis

• Every patient with trauma or scheduled for elective orthopedic surgery is recommended to assess and document the risk of VTE development [16, 86].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: to assess the risk of VTE in a patient prior to surgery, it is advisable to use the Caprini risk assessment scale (Table 5.2), though other scales or calculators may also be used.

• All patients with restricted mobility, regardless of the determined VTE risk level, are recommended to receive mechanical VTE prophylaxis [92].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• All patients with musculoskeletal system injuries and/or trauma at moderate or high risk of VTE are recommended to receive pharmacological VTE prophylaxis, typically until normal or expected mobility is restored (Table 5.6) [89, 90, 92].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Table 5.6. Medications recommended for VTE prophylaxis

^{1 –} _{drugs are numbered in order of prescription priority (according to the accumulated evidence base and expert judgment);}

^{2 –} _{these medicinal products have been studied in hip and knee arthroplasty, however, according to their registration in the Russian Federation, they can also be used for the specified orthopedic surgeries;}

^{3 –} _{only in the form of enteric-coated film-tablets;}

^{4 –} _{except for acute spinal cord injury and severe traumatic brain injury (see clause 5.4.8).}

Comments. When choosing an anticoagulant, it is necessary to consider the contraindications to the drug specified in the manufacturer's instructions. Preference should be given to drugs that have dedicated clinical studies evaluating their efficacy and safety performed in this patient population. Low-molecular-weight heparin analogues (biological analogues) (ATC B01AB Heparin group) can only be used when appropriate prospective comparative clinical trials in the prevention and treatment of VTE have proven that the efficacy and safety of this medicinal product do not significantly differ from the original drug.

• In patients with moderate/high risk of VTE requiring pharmacological prophylaxis after injury or musculoskeletal system surgery, if anticoagulants are contraindicated, refused, or if adverse events develop during their administration, it is recommended to consider prescribing ASA** in combination with mechanical methods of prophylaxis [93, 94, 104, 152, 153].

GRC ALEL 1Grade of Recommendation A (Level of Evidence – 1)

Comment: it has been shown that ASA** in doses from 30 mg to 150 mg is sufficient to inhibit COX-1 platelet function [5]. A recent crossover trial showed that low doses of acetylsalicylic acid** are associated with a lower incidence of gastrointestinal complications while maintaining the antithrombotic effect [343]. The most commonly used dosage in Russia is 100 mg [94, 344].

• In patients with a moderate or high risk of VTE for whom any pharmacological prophylaxis is contraindicated or who refuse drug therapy, it is recommended to prescribe mechanical methods of prophylaxis [16, 55, 90, 92, 97].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

5.4 Specific features of anticoagulant prophylaxis in various clinical scenarios

5.4.1. Elective total hip or knee replacement

• All patients after elective total hip or knee arthroplasty are recommended pharmacological prophylaxis of VTE [16, 167, 191-198].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

Comments. Major orthopedic surgeries, which include knee and hip arthroplasty, are associated with a high risk of VTE [5, 89, 195, 196].

• In patients before total hip or knee arthroplasty in need of preoperative pharmacological VTE prophylaxis, it is recommended to use LMWH, and if they cannot be administered, UFH (sodium heparin**) [16, 55, 167, 191, 193, 199-201].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

• In patients at risk for hemorrhagic complications after total hip or knee arthroplasty, it is recommended to postpone the first administration of LMWH, dabigatran etexilate**, or rivaroxaban** until hemostasis is achieved (at least 8-12 hours after surgery completion) [13, 98, 202].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments. To prevent postoperative hemorrhagic complications, it is advisable to start LMWH administration no later than 12 hours before or no earlier than 12 hours after arthroplasty, and UFH (sodium heparin**) no later than 4-6 hours before or no earlier than 12 hours after surgery [13, 202]. At the same time, it is known that there are no fundamental differences in the efficacy and safety of pharmacological prophylaxis whether it is initiated before or after arthroplasty [98]. According to the instructions for use, the minimum time after surgery when drug intake can be initiated is 1-4 hours for a half-dose of dabigatran etexilate**, 6-10 hours for rivaroxaban**, and 12-24 hours for apixaban**; however, if hemostasis has not been achieved, anticoagulant administration should be delayed. The efficacy of dabigatran etexilate** is comparable, while that of rivaroxaban** and apixaban** is superior to enoxaparin sodium** [99, 170, 171, 203-205], with all drugs characterized by a rapid C_max in the bloodstream. Thus, by analogy with delaying the first LMWH administration to reduce the risk of hemorrhagic complications, it is advisable to postpone the first DOAC dose by at least 8 hours.

• In patients after elective total hip or knee arthroplasty, provided early mobilization and absence of other VTE risk factors besides surgery, it is recommended to consider ASA** alongside anticoagulants as a method of VTE prophylaxis [89–92, 191, 206-210].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

• In patients after total hip arthroplasty performed as an emergency or urgent procedure for a proximal femur or femoral neck fracture, in the absence of contraindications to anticoagulants, it is not recommended to use ASA** as the sole means of VTE prophylaxis [191, 194, 207, 208, 210].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

Comments. In recent years, due to the reduced invasiveness of elective knee or hip arthroplasty and the possibility of early mobilization of patients, interest has grown in the use of ASA** for the prevention of DVT and PE in this category of patients. Published results from the Danish and Spanish National Arthroplasty Registers demonstrated a DVT incidence of less than 1% and a PE incidence of 0.3% or less in cohorts comprising 37,223 and 58,037 patients receiving ASA**, respectively [100, 101]. In 2012, the drug was included in the guidelines of the American College of Chest Physicians (USA) for use in elective hip or knee arthroplasty when DOACs and LMWHs cannot be prescribed [5]. Subsequent comparative studies and meta-analyses showed a comparable incidence of thrombosis with ASA** versus warfarin** with target INR values of 1.5–1.8 [102], and with extended thromboprophylaxis after 10 days of LMWH followed by ASA** or LMWH [93]. Furthermore, the combination of ASA** with mechanical prophylaxis showed no advantage compared to pharmacological prophylaxis with ASA** alone [103]. A randomized study of thromboprophylaxis in patients without additional risk factors for VTE after elective knee arthroplasty also revealed no differences between comparison groups depending on the administration of ASA**, dabigatran etexilate**, or rivaroxaban** [94]. In 2018, ASA** was included as one of the drugs of choice, alongside DOACs and LMWHs, for elective hip or knee arthroplasty in the British (NICE), Australian, and European national guidelines [90–92]. Despite the variation in ASA** dosages found in publications, in the Russian Federation the doses approved for the prevention of DVT and PE during prolonged immobilization resulting from major surgery are 100–200 mg once daily. Domestic RCTs investigated an ASA** dose of 100 mg once daily [104]; a similar administration regimen for this antiplatelet agent, apart from heparin, is recommended by the Arthroplasty Society of Australia (ASA) [92]. Thus, to date, a large body of evidence has been accumulated to include ASA** in guidelines for VTE prophylaxis in elective procedures in patients without severe cardiac or other somatic pathology leading to a high risk of DVT and PE. It must be remembered that the combined use of antiplatelet agents (other than heparin) with anticoagulants is accompanied by an increased risk of bleeding, and the use of high doses of ASA** increases the risk of gastric ulcers, which can lead to gastrointestinal bleeding.

• In patients after total hip arthroplasty, it is recommended to continue VTE prophylaxis for up to 5 weeks; after total knee arthroplasty, for at least 2 weeks or until the patient's expected motor activity is restored, whichever comes first [16, 90, 92, 167].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. Modern national guidelines define the duration of thromboprophylaxis after knee and hip arthroplasty as at least 10-14 days, extending up to 35 days if the patient has additional risk factors [5, 16, 55, 90, 92, 97, 203, 204, 212-226]. These durations of anticoagulant administration are due to changes in the coagulation system that persist for several weeks after surgery. These include suppression of blood fibrinolytic activity, activation of coagulation, and a decrease in natural anticoagulants such as AT-III. Due to the ongoing trend toward shorter hospital stays, potential VTE events more frequently develop in the outpatient setting after hospital discharge.

• In patients undergoing maintenance or peritoneal hemodialysis with no history of spontaneous bleeding from parenchymal organs, it is recommended to administer medical and mechanical VTE prophylaxis after total hip or knee arthroplasty [92, 105, 106].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments. Chronic kidney disease is accompanied by an increase in pro-inflammatory and prothrombotic agents. The incidence of deep vein thrombosis in patients with stage 3-4 CKD is 43.8% [106]. The incidence of pulmonary embolism in end-stage renal disease patients is 2.1% [105]. Patients on chronic hemodialysis should be stratified as high risk for thromboembolic complications, and anticoagulant administration should be performed daily, including the anticoagulant dose during the hemodialysis session [92]. Mechanical prophylaxis (lower extremity elastic compression) for VTE in the postoperative period exerts a more significant clinical effect compared to the general patient population [92]. It is known that in patients with stage 5D end-stage CKD after total hip or knee arthroplasty, VTE prophylaxis solely during the hemodialysis procedure is insufficient [107, 108]. Hip and knee arthroplasty is an orthopedic surgical intervention carrying a high risk of VTE in patients on chronic hemodialysis. The probability of deep vein thrombosis during major joint arthroplasty in hemodialysis patients is 1.65 (95% CI: 1.13–2.40; p = 0.01) times higher compared to patients without CKD [106]. A single administration of LMWH at a standard dosage at the end of the hemodialysis procedure following hip and knee arthroplasty does not reduce the risk of VTE, while increasing the risk of death by 1.32 times (95% CI: 1.01 – 1.71, p < 0.05) [107].

• In patients undergoing maintenance or peritoneal hemodialysis with a history of spontaneous bleeding from parenchymal organs, it is not recommended to perform medical VTE prophylaxis on interdialytic days after total hip or knee arthroplasty [109, 227-229].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments. Additional administration of LMWH to end-stage CKD patients on interdialytic days following major surgery increases the risk of bleeding and general somatic complications [109].

• In patients with end-stage chronic kidney disease (CKD stage 5D) after "major" orthopedic surgery, pharmacological VTE prophylaxis is recommended using LMWH on interdialytic days (dalteparin sodium 2500 anti-Xa IU s.c. once daily or enoxaparin sodium** at a dose of 20 mg s.c. once daily), or UFH (heparin sodium**) if LMWH is unavailable [63, 109–112, 227, 230-232].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

GCR CLOE 4Grade of Recommendation C (Level of Evidence – 4) – for enoxaparin sodium**

Comments. The most common cause is cardiovascular complications caused by hyperkalemia and dyslipidemia, aggravated by UFH (heparin sodium**) [111, 112]. The incidence of VTE with daily LMWH use is 5.6%, which is significantly lower compared to UFH (heparin sodium**) [110]. UFH (heparin sodium**) leads to elevated potassium levels and lipid metabolism disorders due to the release of lipoprotein lipase from the vascular wall into the bloodstream, manifesting as blood chyle, which in turn worsens existing cardiovascular diseases [109]. When using LMWH after THA and TKA in patients on maintenance hemodialysis, drug bioaccumulation must be taken into account. Dalteparin sodium has the highest molecular weight among LMWHs while having the lowest anti-Xa activity, and its clearance is less dependent on renal function [113].

• In patients with end-stage CKD stage 5D, postoperative VTE prophylaxis with direct oral anticoagulants (ATC B01AE Direct thrombin inhibitors, B01AF Direct factor Xa inhibitors) is not recommended [114].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

5.4.2. Pelvic, femoral neck, and proximal femur fractures

• If surgery cannot be performed within the first 24 hours, it is recommended to start medical prophylaxis with LMWH or UFH (heparin sodium**) immediately after patient admission; in case of high risk or ongoing bleeding, prophylaxis should be performed using non-pharmacological methods [5, 16, 55].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. It is advisable to start anticoagulants once primary hemostasis is achieved, after examination and exclusion of potential contraindications in the victim (usually 6–24 hours after injury). If surgery in a trauma patient is planned on a delayed basis (several days after injury), medical prophylaxis is recommended throughout the entire preoperative period with LMWH, or with UFH (heparin sodium**) if LMWH cannot be administered. The last dose before surgery should be administered no later than 12 hours before surgery for LMWH [90, 92], or 4–6 hours before surgery for UFH (heparin sodium**) [8, 11].

• In cases where the administration of anticoagulants is forcedly delayed for 24 hours or more, duplex ultrasound scanning (DUS) is recommended to rule out DVT [55, 233-235].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

• Depending on the clinical situation, patients after surgery are recommended to: continue parenteral administration of LMWH, UFH (heparin sodium**), or prescribe fondaparinux sodium, or switch the patient to oral medications: dabigatran etexilate**, rivaroxaban**, or VKA (warfarin**) if these cannot be prescribed [8, 11].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments. To date, there are conflicting results comparing the efficacy of ASA** and LMWH regarding VTE prophylaxis in patients after pelvic and proximal femur fractures. Some studies demonstrate comparable efficacy in preventing DVT in patients undergoing lower limb and pelvic fracture surgery who receive ASA** and LMWH [346]. However, a recent meta-analysis showed that LMWH is superior to ASA** in preventing VTE with no difference in bleeding rates, wound infection, and mortality [347].

• During surgical and conservative management of patients with pelvic, femoral neck, and proximal femur fractures, pharmacological prophylaxis is recommended to be continued until the patient's expected mobility is restored, but for at least 5 weeks postoperatively [16, 55, 90, 233, 236-240].

GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)

5.4.3. Knee surgery, excluding arthroplasty

• Patients requiring arthroscopic surgery are not recommended routine VTE prophylaxis in the absence of additional VTE risk factors, and if the duration of the flexible tourniquet use is less than 45 minutes and/or the surgical intervention is less than 90 minutes [55, 90].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. Arthroscopic reconstructions of the knee capsule-ligamentous apparatus structures are classified as low VTE risk procedures. However, it should be borne in mind that the presence of additional aggravating factors increases the risk of VTE [115–118].

• If arthroscopy is performed using a flexible tourniquet for 45 minutes or more, with a surgical duration of more than 90 minutes, or if the patient is at high risk for VTE (e.g., history of VTE and/or PE, obesity with BMI ≥ 40 kg/m², etc.), it is recommended to consider prescribing LMWH 6–12 hours postoperatively, followed by a transition to DOACs (dabigatran etexilate** or rivaroxaban**) with an extended thromboprophylaxis course of up to 10–14 days [55, 90].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• In patients undergoing osteotomy or osteosynthesis for fractures of bones forming the knee joint, in the absence of active bleeding, pharmacological VTE prophylaxis is recommended until the patient's normal or expected physical activity is restored [55, 222, 238-240].

GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)

5.4.4. Lower limb immobilization

• In patients with lower limb immobilization, pharmacological VTE prophylaxis is recommended to be started immediately after active bleeding has been ruled out: the drugs of choice are LMWHs, or UFH (heparin sodium**) if LMWHs are unavailable; subsequently – starting from days 3–4 depending on the patient's condition – switching to VKAs (warfarin**) is possible, provided that the dose is adequately adjusted and INR is regularly monitored [55, 241-257].

GCR BLoE 1Grade of Recommendation B (Level of Evidence – 1)

Comments: the advisability and timing of switching a patient from parenteral drugs to VKAs (warfarin**) are determined by the attending physician, taking into account inpatient/outpatient treatment settings, the feasibility of LMWH/UFH (heparin sodium**) injections, and laboratory INR monitoring when using VKAs. The rules for using VKAs (using warfarin** as an example) are set out in Appendix G8.

5.4.5. Orthopedic surgery on the distal lower extremity (ankles, ankle joint, foot)

• Patients requiring surgery on the distal lower extremity are not recommended routine VTE prophylaxis in the absence of additional VTE risk factors [83, 119–121].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments. The incidence of VTE following arthroscopic and open surgical interventions on the foot and ankle is significantly lower than that in surgical treatment of several other areas of the musculoskeletal system. Moreover, prophylactic administration of LMWH after certain surgical procedures of this profile does not significantly affect this parameter, except for Achilles tendon injury surgery [119, 120, 122]. Upon patient admission, it is advisable to decide on the method of VTE prophylaxis based on the assessment of their development risk (Table 5.1), taking into account the planned management tactics for the disease or injury [83, 119–121]. It is known that the maximum risk of VTE is associated with limb immobilization after surgery on this segment using a fixing bandage or external fixation device, as well as reconstructive surgery on the calcaneal tendon.

5.4.6. Upper extremity orthopedic surgery

• Routine VTE prophylaxis for upper extremity surgery under local or regional anesthesia is not recommended [123, 124].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

• If general anesthesia or flexible tourniquet time exceeds 90 minutes during upper extremity interventions, or if the surgery may significantly impair the patient's mobility, or in the presence of a history of VTE episodes, it is recommended to consider perioperative VTE prophylaxis [125].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments: major and minor shoulder surgeries are characterized by a low risk of VTE [123–125]. However, given the growing population of individuals with genomically determined thrombophilias (antithrombin III, protein C, or protein S deficiency, factor V Leiden mutation, prothrombin G20210A mutation, etc.), the widespread and often uncontrolled use of estrogens, population aging, and the rising incidence of diabetes and other metabolic disorders that increase VTE risk, pharmacological thromboprophylaxis may be advisable when treating patients with additional VTE risk factors for fractures of the humerus and forearm, as well as extensive soft tissue injuries of the upper extremities. The final decision is made by the attending physician, taking into account the extent of injury, the nature of the planned procedure, and additional patient-related VTE risk factors. Perioperative administration of LMWH to this category of patients is possible according to the regimens and dosages given in Table 5.3 for 7–10 days (until hospital discharge) or for several days until normal/expected motor activity is restored.

5.4.7. Elective spine surgery

• In patients with a high risk of bleeding, it is recommended to use mechanical thromboprophylaxis before surgery, and to postpone the first administration of LMWH until hemostasis is achieved (12–24 hours postoperatively) [92, 126–128].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

• If a patient is admitted with restricted motor activity, including due to hemi- and tetraparesis/-paralysis, it is recommended to initiate pharmacological VTE prophylaxis in the preoperative period [16, 55].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. The final dose of LMWH should preferably be administered no later than 12–24 hours before elective spinal surgery, depending on the clinical evaluation of the patient's condition and the nature of the planned procedure.

5.4.8. Severe trauma (multiple and polytrauma, including traumatic brain injury, spinal cord injury, spinal and pelvic/lower extremity trauma)

All patients with severe trauma are classified as being at high risk for VTE.

• Upon admission of a patient with severe trauma, it is recommended to consider prescribing mechanical VTE prophylaxis [92, 129].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments. Depending on the type of injuries sustained, mechanical prophylaxis may be contraindicated in patients with lower extremity trauma. However, in the absence of other contraindications, mechanical prophylaxis should be applied to the uninjured leg. In cases of high bleeding risk or active bleeding, only mechanical methods of prophylaxis should be used, primarily IPC. Electrical muscle stimulation and medical compression stockings may also be used [16].

In patients with severe trauma, it is recommended to reassess and document the risk of VTE and bleeding daily or more frequently if their clinical condition changes [233, 258–260].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

• In patients with severe trauma, it is recommended to prescribe pharmacological VTE prophylaxis as soon as possible, once the VTE risk outweighs the bleeding risk [90, 92].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• If a patient with severe trauma has an incomplete spinal cord injury, spinal hematoma, or intracranial hemorrhage, it is recommended to postpone pharmacological prophylaxis until satisfactory hemostasis is achieved (usually 1–3 days) [90, 92].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: LMWHs are the drugs of choice for preoperative pharmacoprophylaxis in the treatment of severe trauma; when LMWH use is not feasible, UFH (sodium heparin**) is used. Due to the slow onset and offset of action and insufficient data, the use of VKAs (warfarin**) for preoperative VTE prophylaxis is impractical. In traumatic brain injury, the timing for initiating pharmacological prophylaxis should be discussed with the neurosurgical team. Typically, in patients without intracranial hemorrhage, pharmacological prophylaxis can be initiated immediately [92].

• In patients with severe trauma, it is recommended to continue pharmacological thromboprophylaxis until motor activity is restored, but for at least 10–14 days in the absence of additional risk factors [92].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• In patients with acute spinal cord injury or traumatic brain injury, it is recommended to continue pharmacological VTE prophylaxis for 3 months after trauma and/or surgery or until the completion of inpatient rehabilitation [55, 92, 130, 131].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. The risk of VTE persists for a long time as long as risk factors are present. Studies have shown that at least half of VTE events develop after hospital discharge while patients' motor activity remains limited. For extended postoperative thromboprophylaxis, patients may be switched to oral agents: dabigatran etexilate**, rivaroxaban**, or VKAs (provided adequate INR monitoring is ensured). If elderly patients undergo inpatient rehabilitation, it is advisable to consider extending the duration of prophylaxis beyond the minimum recommended duration: until activity returns to expected or clinically acceptable levels, or until hospital discharge.

5.4.9. Onco-orthopedics

Comments. The risk of thromboembolic complications is three times lower in patients who underwent surgery for benign bone tumors than in patients with malignant neoplasms. Compared to malignant tumors, benign tumors and tumor-like bone lesions also show a statistically significant reduction in the rate of hemorrhagic complications. Operations for benign bone tumors and planar, marginal, intralesional, segmental, and juxta-articular resections on long and short bones of segments, excluding the femur and pelvic bones, are associated with a moderate and low risk of VTE (Table 5.7) [86, 134–136].

Table 5.7. VTE risk levels in surgeries for bone tumors and tumor-like lesions depending on the type of surgical intervention

• In all patients with malignant neoplasms undergoing surgical treatment, it is recommended to perform VTE prophylaxis, the format of which is determined by the VTE risk level and includes medical and mechanical methods of TP, while early patient mobilization is advisable in all cases [132, 133, 231, 261–284].

GCR ALEL 1Grade of Recommendations A (Level of Evidence – 1)

Comments. Deep vein thrombosis frequently accompanies surgeries for bone neoplasms, especially involving the pelvic bones, major joints, and segments [132, 133, 137–139, 261–284]. One-fifth of patients diagnosed with DVT are cancer patients after surgery, and the risk of postoperative DVT in these clinical settings is twice as high compared to patients with other pathologies. The risk of fatal pulmonary embolism is three times higher in patients with malignancies compared to patients who underwent surgery for benign neoplasms [10]. The choice of prevention method and duration of preventive measures depend on the severity of the oncologic process, presence of a pathological fracture, anatomical location, nosological entity, age and comorbidities, scope of surgery, adjuvant chemotherapy, and presence of metastases [16, 73, 133].

• For cancer patients scheduled for surgical treatment, it is recommended to perform lower extremity duplex ultrasound with the examination scheduled as close as possible to the surgery date [16, 140].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments. When planning VTE prophylaxis measures, the possibility of asymptomatic DVT in a significant proportion of cancer surgery patients should be taken into account [16, 133, 140].

• If it is not possible for the patient to undergo surgery for a pathological femoral fracture on the first day, it is recommended to start medical prophylaxis using LMWHs or UFH (sodium heparin**) immediately after diagnosis; in case of a high risk of development or ongoing bleeding, prophylaxis should be performed using non-pharmacological means [16, 133].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. Medical prophylaxis of VTE at moderate risk should continue until discharge, but for at least 10–14 days after surgery. In patients with a high risk of VTE, it is advisable to extend medical prophylaxis up to 28–35 days, regardless of the hospital discharge date. Following major onco-orthopedic/orthopedic surgeries, prophylaxis for up to 35 days is justified. Patients undergoing surgical treatment for skeletal neoplasms often have a high risk of thromboembolic complications, which depends on the patient's performance status, medical history, comorbid conditions, and prior treatment. It is known that the risk of deep vein thrombosis in cancer patients doubles in the presence of metastases, and chemotherapy increases the risk of venous thromboembolism by approximately six to seven times in patients with bone tumors compared to patients without this pathology [134, 142–145, 285-296].

• In onco-orthopedic patients, it is recommended to consider reducing the duration of use or avoiding manipulations that increase the risk of blood clot formation (use of a flexible tourniquet or hemostatic tourniquet, general anesthesia, prolonged immobilization, etc.) [134, 135, 146, 297-309].

GGR BLOE 1Grade of Recommendation B (Level of Evidence – 1)

Comments. The negative impact of individual risk factors can be reduced by avoiding certain manipulations that provoke blood clot formation or by modifying them to be less thrombogenic/emboligenic. This goal can be achieved by eliminating the flexible tourniquet or hemostatic tourniquet in lower limb surgeries or reducing the time of their application. Significant positive results are provided by preferring regional anesthesia over general anesthesia, which allows for early postoperative mobilization of the patient, as well as avoiding permanent immobilization whenever possible and using functional treatment methods, and reducing surgical time through the introduction of high technologies.

• Cancer patients with a benign bone neoplasm and a low risk of VTE are recommended to undergo thromboprophylaxis using mechanical methods only (lower limb elastic compression, intermittent pneumatic compression, calf muscle electrical stimulation, etc.), unless otherwise required by the nature of the surgical intervention and concomitant risk factors [133].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. Mechanical prophylaxis in cancer patients, as well as medical or combined prophylaxis, is strictly individual and is carried out throughout the entire period of risk for thromboembolic complications, since in addition to the nature of the neoplasm, it depends on the surgery performed, the duration and type of immobilization, the timing of motor activity recovery, and the rehabilitation of limb or segment function. At the same time, in patients with malignancy, which is in itself a major risk factor, pharmacoprophylaxis during hospitalization is essential [15, 33].

5.4.10. Patients receiving long-term antithropic agents

Patients with diseases and injuries of the musculoskeletal system who are receiving long-term anticoagulants and antiplatelet agents (other than heparin) for therapeutic indications have a high risk of VTE development and, at the same time, a high risk of hemorrhagic complications at the time of hospitalization.

• For patients constantly receiving antithrombotic agents, in cases where the VTE risk of the planned musculoskeletal intervention exceeds the bleeding risk, it is recommended to perform pharmacological prophylaxis (LMWHs, direct oral anticoagulants, etc.) [147].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• Patients continuously taking acetylsalicylic acid** (ASA) who are admitted for elective musculoskeletal system surgery with low (minor orthopedic interventions, where transfusions are usually not required) and moderate (major orthopedic interventions, including joint arthroplasty, with possible transfusions) bleeding risk are recommended not to interrupt antiplatelet therapy other than heparin [95, 147, 148].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• For patients permanently receiving ASA** and admitted for elective musculoskeletal surgery with a high bleeding risk (neurosurgical interventions), it is recommended to discontinue the drug 3 days before surgery [95, 147].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• For patients admitted for elective musculoskeletal surgery and receiving clopidogrel**, ticagrelor**, or prasugrel, it is recommended to discontinue the antiplatelet agent (except heparin) 5, 5, and 7 days before surgery, respectively [95, 147, 148].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• After surgery, the intake of ASA** is recommended to be resumed as soon as hemostasis is achieved, and clopidogrel**, ticagrelor**, or prasugrel after 24–48 hours [147].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• For patients chronically receiving clopidogrel**, ticagrelor**, or prasugrel, if emergency musculoskeletal surgery is required, to urgently reverse the effects of antiplatelet agents (other than heparin), it is recommended to transfuse platelet concentrate — 2 doses per 7 kg of the patient's body weight (may be ineffective within 12 hours after ticagrelor** administration) [95, 211, 310-312].

LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)

• For patients admitted for elective surgery and receiving VKAs (warfarin**), it is recommended to determine the INR [16]:

- if the INR is < 1.5, prompt performance of surgery is possible with the initiation of pharmacological thromboprophylaxis (LMWH, UFH) in the postoperative period,

- if the INR is > 2, it is necessary to discontinue VKAs at least 5 days before surgery and monitor the INR daily; when the INR value becomes < 2, it is recommended to administer LMWHs (in the absence of UFH [sodium heparin**] as a continuous IV infusion in therapeutic doses); LMWH administration should be interrupted 24 hours before surgery, and UFH (sodium heparin**) 4–6 hours before.

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments. After the intervention, it is necessary to resume the administration of LMWH or UFH (sodium heparin**) and, from the moment full hemostasis is achieved (postoperative days 1–3), begin titrating the dose of warfarin** (Appendix G8). LMWH or UFH (sodium heparin**) can be discontinued no earlier than stable therapeutic INR values are reached.

• For patients chronically receiving DOACs, it is recommended to postpone elective surgery with a moderate and high bleeding risk for a period depending on the drug used and renal function (Table 5.8); in most cases, DOAC intake is resumed after surgery once stable hemostasis is achieved, but in certain categories of patients in whom VTE risks significantly exceed the bleeding risk, "bridging therapy" with perioperative parenteral anticoagulants may be considered [96, 149, 150].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Table 5.8. DOAC half-lives and time intervals after the last dose recommended for performing surgical interventions with moderate and high bleeding risks [96]

_{where, * - calculated by the Cockcroft-Gault formula}

• For patients chronically receiving DOACs, if emergency musculoskeletal surgery is required on an urgent basis, it is recommended to follow the algorithm presented in Table 5.9 [96, 149, 151].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Table 5.9. Management of emergency and urgent surgical interventions/procedures in patients receiving DOACs [96]

^{Notes: 1-} _{for dabigatran etexilate** – activated partial thromboplastin time, ecarin clotting time, thrombin time, diluted thrombin time; for rivaroxaban** and apixaban**) – prothrombin time, plasma anti-Xa activity,}

^{2 –} _{if the last dose of the drug was taken 2-4 hours ago,}

^{3 –} _{in patients receiving dabigatran etexilate** – administration of idarucizumab or #coagulation factors II, VII, IX, and X in combination [Prothrombin complex]**, #anti-inhibitor coagulant complex**, recombinant activated #coagulation factor VII** (if idarucizumab is unavailable); in patients receiving rivaroxaban** or apixaban** – #coagulation factors II, VII, IX, and X in combination [Prothrombin complex]**, #anti-inhibitor coagulant complex**, recombinant activated #coagulation factor VII**. #Coagulation factors II, VII, IX, and X in combination [Prothrombin complex]**, #anti-inhibitor coagulant complex**, and recombinant activated #coagulation factor VII** should be used with caution, especially in patients at high risk of thrombosis; data on efficacy and safety in patients receiving DOACs are limited.}

5.5 Laboratory monitoring during pharmacological prophylaxis

These recommendations do not imply mandatory laboratory monitoring of hemostasis, except for determining the INR when taking vitamin K antagonists. However, renal function is important for dose selection, determining safety, and identifying contraindications to the use of LMWHs, fondaparinux sodium, and DOACs, and should be evaluated in all patients by creatinine clearance or glomerular filtration rate.

In some cases, during pharmacological prophylaxis, laboratory assessment of hemostasis using methods available to the specific medical institution is advisable. Laboratory monitoring is indicated: for emergency interventions during the period of effective action of antithrombotic agents; in cases of non-standard response to antithrombotic therapy according to history (increased or decreased drug sensitivity); in severe and combined hemostatic disorders (prior massive blood loss, established thrombosis, high risk of thrombotic complications, thrombosis against the background of thrombocytopenia, etc.); in the presence of clinical manifestations of hemostatic disorders such as progressive thrombosis or bleeding.

During the administration of UFH (heparin sodium**) or LMWH preparations, a decrease in blood platelet count is possible. Immune thrombocytopenia usually occurs 4–14 days after the start of heparin sodium** administration (more often with UFH), but can develop earlier in patients who have recently received heparin group drugs. To timely detect immune thrombocytopenia, it is necessary to monitor the blood platelet count (platelet count test):

– with the administration of prophylactic or therapeutic doses of heparin sodium** – at least every other day from the 3rd to the 14th day of treatment or until earlier drug discontinuation;

– if the patient received heparin sodium** in the preceding 3.5 months, the first blood platelet count test should be performed within the first 24 hours after starting heparin sodium**, and in case of any deterioration within half an hour after intravenous administration of UFH (heparin sodium**) – immediately.

If the blood platelet count decreases by 2 times or more from the baseline level and/or is less than 100 × 10⁹/L, all administration of heparin sodium** should be discontinued and duplex ultrasound of the lower extremity veins should be performed to check for DVT. During the period of low blood platelet count, dabigatran etexilate**, fondaparinux sodium, or rivaroxaban can be used. After recovery of the blood platelet count, one can switch to VKAs, starting them at low doses (for warfarin** not exceeding 5 mg/day).

The use of UFH (heparin sodium**), LMWHs, fondaparinux sodium, dabigatran etexilate**, apixaban**, and rivaroxaban** in prophylactic doses does not require routine coagulation monitoring of the hemostatic system.

Laboratory tests reflecting the effect of the administered drug:

• UFH (heparin sodium**) — heparinase-modified thromboelastography, APTT, thromboelastometry/thrombodynamics, blood platelet count.

• LMWH — heparinase-modified thromboelastography, anti-Xa activity, thromboelastodynamics, blood platelet count.

• Fondaparinux sodium — heparinase-modified thromboelastography, anti-Xa activity.

• Rivaroxaban** — prothrombin time by Quick, INR.

• Dabigatran etexilate** — APTT, TT.

• Vitamin K antagonists — INR, prothrombin time by Quick.

• Antiplatelet agents other than heparin — platelet aggregation test.

6. Organization of Medical Care

Despite the planning of diagnostic and therapeutic measures for patients when DVT develops, care is of an emergency nature. Delaying the start of treatment leads to a decrease in treatment efficacy in this category of patients and worsens the prognosis for thrombus recanalization in a particular patient, and in some cases, with the development of PE, it can be fatal.

Diagnostic procedures at the staging of diagnosis and between treatment stages can be performed on an outpatient basis. Surgical treatment stages, including anesthesia and other supportive therapy, require hospitalization.

7. Additional Information

After the first episode of DVT, post-thrombotic syndrome develops within 2 years in 60% of patients. Every fourth patient with PE develops recurrent thromboembolism within the next 5 years, especially in the presence of oncological diseases or hemostatic disorders. About 20% of untreated proximal DVTs lead to the development of PE, the mortality of which is 10-20%. Prescribing rational anticoagulant therapy reduces mortality by 5-10 times.

Given the large number of drug interactions of VKAs (warfarin**) with drugs and food, patients receiving this anticoagulant should be informed about the need to follow a diet and regular INR monitoring to maintain its therapeutic range. In women taking systemic hormonal contraceptives, the risk of DVT increases 3-5 times, with the risk being maximum in the first 4 months after starting this category of drugs and decreasing to the population baseline 3 months after their discontinuation.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Svetlana A. Bozhkova (Saint Petersburg) – Doctor of Medical Sciences, Professor, Head of the Scientific Department of Prevention and Treatment of Wound Infection and the Department of Clinical Pharmacology, Vreden National Medical Research Center of Traumatology and Orthopedics of the Russian Ministry of Health; RF delegate to the European Bone and Joint Infection Society (EBJIS), member of the scientific committee of the World Association against Infection in Orthopedics and Trauma (WAIOT), member of MACMAH; no conflict of interest.

2. Rashid M. Tikhilov (Saint Petersburg) – Corresponding Member of the RAS, Doctor of Medical Sciences, Professor, Director of the Vreden National Medical Research Center of Traumatology and Orthopedics of the Russian Ministry of Health, Chief Trauma Surgeon-Orthopedist of the Healthcare Committee of Saint Petersburg, Vice-President of the ATOR, member of the European Hip Society, member of the International Hip Society; no conflict of interest.

3. Vyacheslav V. Andriyashkin (Moscow) – Doctor of Medical Sciences, Professor at the Department of Faculty Surgery, Institute of Surgery, Pirogov Russian National Research Medical University; no conflict of interest.

4. Ildar F. Akhtyamov (Kazan) – Doctor of Medical Sciences, Professor, Head of the Department of Traumatology, Orthopedics, and Emergency Surgery, Kazan State Medical University of the Russian Ministry of Health, member of the International Society of Orthopaedic Surgery and Traumatology (SICOT) and ATOR; no conflict of interest.

5. Mikhail V. Belov (Yaroslavl) – Candidate of Medical Sciences, Associate Professor at the Department of Traumatology and Orthopedics, Yaroslavl State Medical University of the Russian Ministry of Health, Head of the Department of Traumatology and Orthopedics, Solovyov Clinical Emergency Hospital, member of ATOR; no conflict of interest.

6. Sergey V. Dianov (Astrakhan) – Honored Doctor of the RF, Doctor of Medical Sciences, Professor, Head of the Department of Traumatology and Orthopedics, Astrakhan State Medical University of the Russian Ministry of Health, member of the International Society of Orthopaedic Surgery and Traumatology (SICOT) and ATOR; no conflict of interest.

7. Oleg A. Kaplunov (Volgograd) – Doctor of Medical Sciences, Professor at the Department of Traumatology, Orthopedics, and Military Field Surgery, Volgograd State Medical University of the Russian Ministry of Health, Head of the Traumatology and Orthopedics Service of the Sova Medical Clinic Network; no conflict of interest.

8. Alina R. Kasimova (Saint Petersburg) – Candidate of Medical Sciences, Associate Professor, Clinical Pharmacologist at the Department of Clinical Pharmacology, Vreden National Medical Research Center of Traumatology and Orthopedics of the Russian Ministry of Health; Associate Professor at the Department of Clinical Pharmacology and Evidence-Based Medicine, Pavlov First Saint Petersburg State Medical University of the Russian Ministry of Health, no conflict of interest.

9. Sergey S. Kopenkin (Moscow) – Candidate of Medical Sciences, Associate Professor at the Department of Traumatology, Orthopedics, and Military Field Surgery, Pirogov Russian National Research Medical University of the Russian Ministry of Health, member of ATOR, no conflict of interest.

10. Dmitry A. Malanin (Volgograd) – Doctor of Medical Sciences, Professor, Head of the Department of Traumatology, Orthopedics, and Disaster Surgery, Volgograd State Medical University of the Russian Ministry of Health, member of ATOR, RAO, European Society of Sports Traumatology, Knee surgery and Arthroscopy (ESSKA), no conflict of interest.

11. Nikita E. Mushtin (Saint Petersburg) – Candidate of Medical Sciences, Associate Professor at the Department of Traumatology and Orthopedics, Pavlov First Saint Petersburg State Medical University, trauma surgeon-orthopedist at Traumatology and Orthopedics Department No. 2, Pavlov First Saint Petersburg State Medical University, member of ATOR; no conflict of interest.

12. Sergey N. Tereshchenko (Moscow) – Doctor of Medical Sciences, Professor, Head of the Department of Myocardial Diseases and Heart Failure, Head of the Expert Center for Cardiac Amyloidosis, Chazov National Medical Research Center of Cardiology, Chairman of the Board of the Society of Specialists in Emergency Cardiology, member of the Board of the Russian Society of Cardiology, member of the European Working Group on Emergency Cardiology; no conflict of interest.

13. Aleksandr N. Tsed (Saint Petersburg) – Doctor of Medical Sciences, Associate Professor, Head of Traumatology and Orthopedics Department No. 2, Pavlov First Saint Petersburg State Medical University, member of ATOR and AO Trauma Russia; no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Trauma and orthopedic surgeons

2. Surgeons

3. Anesthesiologists-intensivists

4. Clinical pharmacologists

5. Medical students, residents, postgraduate students

Methods used for collection/selection of evidence: search in electronic databases.

Description of methods used to collect evidence: the evidence base for these clinical guidelines includes materials from MedLine, PubMed, the Cochrane database, Elsevier publications, and articles in reputable domestic journals on traumatology and orthopedics. The search depth is 20 years.

In these clinical guidelines, all information is ranked by the level of certainty (evidence) depending on the quantity and quality of studies on the issue. The group used the methodology for assessing the level of persuasive clinical recommendations and the degree of certainty of evidence in accordance with Appendix No. 2 to the "Requirements for the Structure of Clinical Guidelines, Composition and Scientific Validity of Information Included in Clinical Guidelines", approved by the order of the Russian Ministry of Health dated February 28, 2019, No. 1034.

Table P1. Scale for assessing levels of certainty of evidence (LCE) for diagnostic methods (diagnostic interventions)

Table P2. Scale for assessing levels of certainty of evidence (LCE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table P3. Scale for determining the levels of persuasiveness of recommendations

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Federal Healthcare Legislation

(Main legislative acts of the Russian Federation)

These clinical guidelines were developed taking into account the following regulatory legal documents:

1. Constitution of the Russian Federation.

2. Declaration of Human and Civil Rights and Freedoms.

3. Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation" (with amendments and additions).

4. Federal Law No. 326-FZ dated November 29, 2010, "On Compulsory Medical Insurance in the Russian Federation" (with amendments and additions).

5. Federal Law No. 61-FZ dated April 12, 2010 (as amended on December 26, 2024) "On the Circulation of Medicines" (with amendments and additions, effective March 1, 2025).

6. Federal Law No. 152-FZ dated July 27, 2006 (as amended on April 5, 2013) "On Personal Data".

7. Order of the Russian Ministry of Health No. 901n dated November 12, 2012, "On Approval of the Procedure for Providing Medical Care to the Population in the Profile 'Traumatology and Orthopedics'".

8. Order of the Russian Ministry of Health No. 203n dated May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care".

9. Order of the Russian Ministry of Health No. 1029n dated September 28, 2020, "On Approval of Lists of Medical Indications and Contraindications for Sanatorium-Resort Treatment".

10. The list of vital and essential medicines for medical use approved by the Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on April 16, 2024).

11. Order of the Ministry of Health and Social Development of the Russian Federation No. 1024n dated December 17, 2015, "On Classification and Criteria Used in Carrying Out Medical and Social Expertise of Citizens by Federal State Institutions of Medical and Social Expertise".

Appendix B. Physician Action Algorithms

Title of algorithm 1 in the clinical guidelines "Diagnosis, Treatment, and Prevention of Venous Thromboembolic Complications in Traumatology and Orthopedics":

1. Algorithm for diagnostic search in a patient with suspected deep vein thrombosis

2. Algorithm for VTE prevention in patients with musculoskeletal trauma

Appendix C. Patient Information

Information for a patient who has undergone major orthopedic surgery (arthroplasty, hip osteosynthesis, etc.)

If you have undergone hip or knee replacement or another major orthopedic surgery, your attending physician will prescribe anticoagulants.

The purpose of prescribing drugs of this group is to prevent the development of deep vein thrombosis of the lower extremities, which can lead to a life-threatening complication — pulmonary embolism. The risk of thrombosis without anticoagulants after major orthopedic surgeries is very high: after hip replacement — 40–60%, after knee replacement — 60–80%. To reduce the risk of thrombosis, anticoagulant therapy must be continued even after discharge from the hospital. You must strictly follow the recommendations of your attending physician.

Always inform any healthcare worker you consult that you are taking anticoagulants. Most dental procedures (except tooth extractions) can be performed without changing your treatment regimen. When extracting a tooth, it is usually sufficient to use a local tampon with a hemostatic agent (thrombin sponge). If you have blood pressure problems, it needs to be regularly monitored and maintained at a level no higher than 130/80 mm Hg.

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

Appendix G1. Clinical probability assessment of lower extremity DVT: Wells score

Russian title: Assessment of lower extremity DVT probability based on clinical data: Wells score (Wells).

Original title: Wells Criteria for DVT.

Source: Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997 Dec 20-27;350(9094):1795-8. PubMed ID: 9428249.

Purpose: a clinical tool for assessing the probability of lower extremity DVT before imaging studies (duplex ultrasound). Used in emergency departments, medical and surgical inpatient units, especially in cases of unilateral leg swelling, pain, or skin discoloration.

Type: rating scale.

Content:

Key (interpretation): Wells scoring system for assessing the probability of lower extremity DVT: from –2 to 1 — low probability of DVT or DVT unlikely; from 2 to 8 — moderate/high probability of DVT or DVT likely.

Notes: criteria for assessing possible lower extremity DVT were proposed based on the results of a study published in the Lancet in 1997. The use of the scale helps improve the management of patients with suspected DVT. In particular, it helps reduce the number of repeat ultrasound examinations.

Appendix G2. Clinical probability assessment of PE: Wells score

Russian title: Assessment of PE probability based on clinical data: Wells score (Wells).

Original title: Wells' Criteria for Pulmonary Embolism.

Source: Wells PS, Anderson DR, Rodger M. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83(03):416-420.

Purpose: a clinical tool for the preliminary assessment of PE probability in a patient with dyspnea, tachycardia, chest pain, or syncope.

Type: rating scale.

Content:

Key (interpretation):

- clinical probability (3 tiers, original version of the scale) — score sum: low — 0–1, moderate — 2–6, high — ≥ 7;

- clinical probability (2 levels, original version) — score sum: PE unlikely — 0–4, PE likely — > 4;

- clinical probability (2 levels, simplified version) — score sum: PE unlikely 0–1, PE likely — ≥ 2.

Notes: The Wells score for clinical probability of PE helps avoid unnecessary testing in low-risk patients and speeds up diagnosis in patients with a high probability of PE.

Appendix G3. Clinical probability assessment of PE: modified Geneva score

Russian title: Clinical probability of pulmonary embolism: modified Geneva score.

Original title: the Geneva prognostic score.

Source: https://pubmed.ncbi.nlm.nih.gov/16461960/, https://pubmed.ncbi.nlm.nih.gov/26178041/

Purpose: The modified Geneva score is used to assess the clinical probability of PE. The calculation takes into account factors predisposing to deep vein thrombosis and PE, as well as symptoms and signs characteristic of these conditions.

Type: rating scale.

Content:

Key (interpretation):

- clinical probability (3 levels, original version) — score sum: low — 0–3, moderate — 4–10, high — ≥ 11;

- clinical probability (3 levels, simplified version) — score sum: low — 0–1, moderate — 2–4, high — ≥ 5 clinical probability (2 levels, original version) — score sum: PE unlikely — 0–5, PE likely — ≥ 6;

- clinical probability (2 levels, simplified version) — score sum: PE unlikely — 0–2, PE likely — ≥ 3.

Notes: when using the three-level classification by the Geneva score, the diagnosis of PE is confirmed in approximately 10% of patients in the low probability category, 30% in the intermediate probability category, and 65% in the high probability category.

Appendix G4. PESI (Pulmonary Embolism Severity Index)

Russian title: Pulmonary Embolism Severity Index.

Original title: Pulmonary Embolism Severity Index (PESI).

Source: https://pubmed.ncbi.nlm.nih.gov/37575526/

Purpose: The PESI score allows determining the severity of PE and predicting the 30-day mortality risk.

Type: index.

Content:

Notes: the use of the PESI score allows stratifying patients into risk groups, from low to high, which is important for making treatment management decisions.

Appendix G5. Caprini risk score for VTE risk assessment in surgical patients [87]

Russian title: Caprini score for VTE risk assessment in surgical patients.

Original title: Caprini risk score (CRS, Caprini Risk Assessment Model).

Source: https://pubmed.ncbi.nlm.nih.gov/22315263/

Purpose: The Caprini score is used for risk stratification of venous thromboembolic events in surgical patients.

Type: rating scale.

Content:

Key (interpretation): results are presented as the sum of the points obtained. Low risk: 0–2 points; moderate risk: 3–4 points; high risk: 5–8 points; very high risk: 9–10 points; extremely high risk: 11 points or more.

Appendix G6. Risk of VTE depending on trauma, injuries, and surgical interventions in traumatology and orthopedics patients

^{1 -} _{"minor" surgeries: correction of foot deformities, arthroscopic surgeries on lower extremity joints, soft tissue surgeries on the lower extremities with subsequent immobilization}

² - _{see tables 5.1 and 5.2. (pp. 28-29)}

^{3 -} _{"major" surgeries: osteotomy and osteosynthesis of the pelvis, femur, lower leg, hip, knee and ankle arthroplasty, spine surgery, femoral amputation}

Appendix G7. Rules for applying elastic medical bandages

The bandage is stretched at the start of each turn and applied from the level of the metatarsophalangeal joints to the upper third of the thigh with the foot extended and supinated, overlapping half the width of the previous turn and gradually decreasing compression. The pressure exerted by the bandage should ideally be 14–18 mm Hg in the lower middle third of the lower leg, and 8–10 mm Hg at the level of the lower third of the thigh. To help the patient feel the required degree of compression, a blood pressure cuff can be applied in the retro-malleolar region. The end of the bandage is secured with a fastener or pin, strictly avoiding any "constrictions" or "tourniquet effects" during bandaging that impair hemodynamics.

Appendix G8. Guidelines for the use of vitamin K antagonists

VKA dose adjustment using warfarin as an example**

VKA dose adjustment is initiated while parenteral anticoagulant administration is ongoing. The effective VKA dose is adjusted to maintain INR values between 2.0 and 3.0. To maintain a therapeutic level of hypocoagulation during the transition from parenteral anticoagulants to VKAs, two conditions must be strictly met:

1) the duration of concurrent administration of parenteral anticoagulants (UFH, LMWH preparations, or sodium fondaparinux) and VKAs must be at least 5 days;

2) parenteral anticoagulants can be discontinued no earlier than when two consecutive tests, taken approximately 24 hours apart (on two consecutive days), show INR values exceeding the lower limit of the therapeutic range (2.0 and above).

Algorithm for vitamin K antagonist dose adjustment using warfarin as an example**

Subsequently, INR must be determined daily or every few days until stable therapeutic values are achieved, then 2–3 times a week for 1–2 weeks. After achieving stable therapeutic values, INR should be determined at least every 4 weeks (more frequent assessment is advisable in patients with significant fluctuations). Patient sensitivity to VKAs varies, depends on multiple factors, and can change over time. Therefore, the maintenance dose varies within a wide range.

If dose correction (increase or decrease) is required, the cycle of more frequent INR testing should be repeated until stable values are achieved again. With long-term VKA use, dose monitoring can be performed by medical personnel or by the patient themselves (if a portable INR monitoring device is available).

If the INR in patients with a titrated VKA dose goes outside the therapeutic range, potential causes must be identified and eliminated where possible (inaccuracies in INR testing, intercurrent illnesses, marked dietary changes, alcohol consumption, medications affecting warfarin** efficacy, poor treatment adherence). If the INR does not reach the lower limit of the therapeutic range despite regular warfarin** intake, it is usually sufficient to increase the total weekly dose by 10–20% and monitor INR more frequently until it stabilizes. In selected cases, a higher single dose of warfarin** may be given, followed by more frequent INR determinations with or without adjustment of the total weekly dose.

If the INR rises above the therapeutic range in the absence of significant bleeding, it is recommended to reduce or omit the warfarin** dose. Monitor INR more frequently and resume warfarin** at a lower dose once the INR returns to the therapeutic range. If the INR is only slightly above the upper limit of the therapeutic range, a dose reduction is not mandatory.

When clinically significant bleeding develops, the fastest, albeit short-acting, reversal of warfarin** effects is achieved by intravenous administration of phytomenadione solution, fresh frozen plasma, blood coagulation factors II, VII, IX, and X in combination [Prothrombin complex]**, or recombinant activated #blood coagulation factor VII**. Menadione sodium bisulfite**, available in the Russian Federation, is not an analogue of the parenteral form of phytomenadione. Menadione sodium bisulfite** promotes the de novo synthesis of vitamin K-dependent coagulation factors by affecting carboxylation processes, so its effect is slow-acting and it is useless for rapid reversal of VKA effects.