Iron-deficiency anemia: clinical guidelines

List of Abbreviations

IDA – iron deficiency anemia

CPA – chronic posthemorrhagic anemia

TIBC – total iron-binding capacity

TS – transferrin saturation

SI – serum iron

SF – serum ferritin

ACD – anemia of chronic disease

CKD – chronic kidney disease

CHF – chronic heart failure

GI – gastrointestinal tract

US – ultrasound examination

PPA – postpartum anemia

MCV – mean corpuscular volume

MCH – mean corpuscular hemoglobin

MCHC – mean corpuscular hemoglobin concentration

IRIDA – iron-refractory iron deficiency anemia

Terms and Definitions

Iron deficiency anemia (IDA) is an acquired disease characterized by a decrease in iron content in blood serum, bone marrow, and tissue stores, resulting in impaired hemoglobin and erythrocyte formation, hypochromic anemia, and trophic tissue disorders.

Latent iron deficiency is a condition characterized by the depletion of iron stores in the body with a normal hemoglobin concentration.

Ferrotherapy is treatment with medicinal iron preparations.

Reticulocytic crisis or reticulocytic response is an increase in the reticulocyte count by more than 20–25% from baseline.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

IDA is a multi-etiological disease whose development is associated with iron deficiency in the body due to impaired intake, absorption, or increased losses of this trace element, characterized by erythrocyte microcytosis and hypochromic anemia.

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

The main causes of IDA in women of reproductive age are heavy menstrual bleeding, pregnancy, childbirth (especially repeated), and lactation. In postmenopausal women and men, the main cause of iron deficiency is gastrointestinal blood loss. Iron deficiency can also develop without blood loss, for example, during periods of rapid growth in children, on a plant-based diet, due to gastric or intestinal resection, and as a result of impaired iron absorption in individuals with inflammatory bowel disease. IDA can develop in blood donors who donate blood continuously for many years, as well as in patients with chronic kidney disease undergoing maintenance hemodialysis (weekly losses of 30–40 ml of blood in the dialyzer circuit) [1–3].

The main causes of IDA in pediatric practice are:

• iron deficiency at birth;

• dietary iron deficiency due to an unbalanced diet;

• increased bodily demands for iron due to rapid growth in children;

• losses of iron from the body exceeding physiological levels.

Diet-related factors in the development of iron deficiency in children include:

• insufficient dietary iron intake;

• reduced iron absorption;

• increased iron losses due to intestinal microhemorrhages (caused by early introduction of kefir and whole cow's/goat's milk into the diet of infants and young children; helminthic infestations, infectious and inflammatory bowel diseases) [4].

1.3 Epidemiology of the Disease or Condition

Iron deficiency anemia (IDA) is one of the most common diseases in the world, as well as one of the leading causes of disability [3,5]. The prevalence of anemia, including IDA, depends on many factors: socio-economic living conditions, food quality, bleeding of various localizations, infectious and parasitic diseases, etc. WHO experts have shown that anemia is more common in developing countries and the two most vulnerable population groups are young children and pregnant women [6] (Table 1). According to Rosstat data from 2021, anemia (without specification of etiology) is diagnosed in 35.5% of pregnant women, without a significant decrease in disease frequency in recent years, while the prevalence of anemia in young children in Russia is lower than the general population average and amounts to about 0.8% [7].

In elderly and senile individuals, anemia is reported with a frequency of 23–46% according to various estimates, and is most characteristic of patients older than 80 years [8]. Deficiency states predominate in the etiological structure of anemia in elderly patients [8].

A high frequency of anemia is characteristic of perioperative patients: in the preoperative period, anemia is reported with a frequency ranging from 12 to 70% according to various studies, while in the postoperative period the incidence reaches 90%. IDA accounts for up to 60–75% of preoperative anemia cases [9,10].

Table 1. Global prevalence of anemia by age, sex, and socio-economic conditions (adapted from [11])

According to WHO experts, the prevalence of IDA in a population can be mild (5 to 19.9%), moderate (20 to 39.9%), and high (40% and over) [11].

1.4 Features of Coding the Disease or Condition

Categories assigned to various iron deficiency states in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), are presented in Table 2 [12].

Table 2. ICD-10 categories assigned to iron deficiency states [6].

1.5 Classification of the disease or condition

According to the predominant mechanism of iron deficiency development, anemias are classified into those associated with blood loss, malabsorption, increased iron demand, and dietary features (Table 3) [3,13–15].

Table 3. Classification of IDA

1.6 Clinical presentation of the disease or condition

The main clinical manifestations of iron deficiency anemia (IDA) are hypoxic and sideropenic syndromes. Hypoxic syndrome includes symptoms common to all anemias: pallor, palpitations, tinnitus, headache, and weakness. Manifestations of sideropenic syndrome include pica (perverted appetite), dry skin, nail changes, hair loss, angular stomatitis, burning tongue, and dyspeptic syndrome. The variety of clinical symptoms of iron deficiency is explained by the wide range of metabolic disorders caused by the dysfunction of iron-containing and iron-dependent enzymes [13–16].

Less well-known clinical manifestations of iron deficiency include neurotic reactions and neurasthenia, decreased muscle performance and overall exercise tolerance, metabolic disorders in the myocardium, impaired peripheral circulation (decreased peripheral resistance and venous tone, reduced functional reserves of arterioles), and microcirculatory disorders. With a prolonged course of IDA, patients progressively develop myocardial dystrophy and sympathicotonia in the autonomic regulation of cardiac activity [3, 14].

IDA is accompanied by gastrointestinal lesions manifesting as chronic gastritis and intestinal malabsorption syndromes. At the same time, the decrease in secretion and acid production in chronic gastritis is viewed as a consequence rather than a cause of iron deficiency and is explained by dysregulator processes in the gastric mucosa. It is hypothesized that iron deficiency in the intestinal wall may cause increased absorption and accumulation in the body of toxic concentrations of iron-antagonist metals, such as cadmium [14, 15].

Impairments of anti-infective immunity in patients with IDA are complex in nature. On the one hand, iron deficiency hinders the growth of pathogenic microorganisms that require iron for their own growth and reproduction. On the other hand, iron deficiency indirectly leads to impaired cellular mechanisms of resistance to infections (decreased microbicidal activity of granulocytes, impaired lymphocyte proliferation). Overall, the susceptibility of patients with IDA to infectious diseases is not as high as previously assumed. Conversely, the treatment of iron deficiency states with parenteral iron preparations significantly increases the risk of infection development, likely due to the availability of the administered iron for utilization by microorganisms and their rapid proliferation [14].

In elderly and senile patients, IDA may be accompanied by the appearance or progression of geriatric syndromes—frailty, sarcopenia, falls, cognitive disorders, depression, etc.

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of IDA is based on the characteristic clinical and hematological picture of the disease and the presence of laboratory evidence of absolute iron deficiency.

2.1 Complaints and Anamnesis

See the "Clinical Presentation" section

2.2 Physical Examination

Comments: the main manifestations of sideropenic syndrome are [13–17]:

• skin changes (café-au-lait pigmentation) and mucous membrane changes (angular cheilitis / cracks at the corners of the mouth);

• nail changes (brittleness, softness, transverse striation, koilonychia);

• hair changes (brittleness, dullness, split ends, alopecia);

• hypotension (muscular, arterial);

• olfactory changes (cravings for the smells of varnish, paints, acetone, car exhaust fumes);

• taste changes (cravings for chalk, clay, raw products).

The main manifestations of anemic syndrome caused by anemic hypoxia include [13, 14]:

• weakness, headache, dizziness;

• poor exercise tolerance;

• decreased appetite;

• decreased performance, attention, and learning ability;

• pallor of the skin and visible mucous membranes;

• tachycardia, systolic murmur.

Despite the clearly outlined clinical picture of IDA, the symptoms of anemia and sideropenia have low diagnostic value and do not allow for a confident diagnosis of IDA [3, 13, 15]. Laboratory tests are of decisive importance in the diagnosis of IDA.

2.3 Laboratory Diagnostics

Comments: in iron deficiency anemia (IDA), there is a decrease in hemoglobin level, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (MCH and MCHC, respectively), and mean corpuscular volume (MCV). The erythrocyte count is usually within the normal range. Reticulocytosis is not characteristic, but may be present in patients with bleeding. The morphological sign of IDA is erythrocyte hypochromia and anisocytosis with a tendency toward microcytosis [13,14,16,19,20]. The listed morphological characteristics do not allow to distinguish iron deficiency anemia from the so-called "anemia of chronic disease", which is based on redistribution iron deficiency associated with the presence of a focus of inflammation, infection, or tumor in the body.

Modern hematological analyzers are capable of determining additional parameters that serve as indicators of iron-deficient erythropoiesis; these include Ret-He (reticulocyte hemoglobin content) and HYPO-He (percentage of hypochromic red blood cells). A decrease in Ret-He below 30.6 pg and an increase in HYPO-He above 5% indicate the presence of iron deficiency [21, 22]. Inflammatory processes, uremia, and pregnancy do not affect the values of these parameters, which is an important advantage over biochemical markers of iron metabolism. An increase in Ret-He against the background of iron therapy is an early marker of the effectiveness of IDA treatment and precedes the development of a reticulocyte crisis and an increase in hemoglobin concentration [21].

Comments: distinguishing features of IDA are a low serum ferritin level, reflecting the depletion of tissue iron stores, and elevated TIBC and transferrin values (Table 2). Serum iron and TSAT values are typically reduced, but normal or even elevated values do not exclude an IDA diagnosis, since the patient's intake of iron supplements on the eve of the test, a meat diet, or a preceding (10–14 days prior) transfusion of red blood cell components can strongly distort the serum iron value and, accordingly, the TSAT coefficient, which must be taken into account when evaluating test results. The development of IDA is preceded by a period of latent iron deficiency, the laboratory criteria for which are low serum iron and ferritin levels against the background of a normal hemoglobin level.

In clinical practice, the need most frequently arises to perform differential diagnostics between IDA and anemia of chronic disease (ACD). These conditions can be distinguished by examining a complete panel of iron metabolism parameters in combination with an assessment of the patient's clinical status and basic laboratory indicators reflecting the functional capacity of the liver and kidneys. Additional information can be provided by determining laboratory indicators—the concentration of C-reactive protein (CRP)—and the calculated parameter — Delta-He (the difference between reticulocyte hemoglobin content and mean corpuscular hemoglobin; the calculation is performed automatically in modern hematological analyzers). ACD is characterized by negative Delta-He values and an elevated CRP level.

Microcytic hypochromic anemia is a characteristic morphological feature of β-thalassemia, severe forms of which are associated with profound anemia and prominent signs of iron overload (elevated serum ferritin and TSAT, reduced transferrin and TIBC). However, mild subclinical forms of thalassemia presenting with mild microcytic hypochromic anemia are frequently misdiagnosed as iron deficiency anemia without evaluating serum iron metabolism parameters, leading to inappropriate iron therapy that can accelerate the development of tissue iron overload.

Table 2. Iron metabolism parameters in patients with IDA, ACD, and congenital anemias presenting with iron overload [26]

*Normal values represent reference ranges from the centralized clinical diagnostic laboratory of the National Research Center for Hematology of the Russian Ministry of Health, which may vary across clinical diagnostic laboratories depending on the commercial test systems used. In children, normal serum ferritin values differ from those specified in the table.

N – normal value; ↓ – decreased value; ↑ – increased value.

- blood total protein test, blood albumin test to assess the protein-synthesizing function of the liver and ensure accurate interpretation of iron metabolism parameters [28–30];

- blood total bilirubin test, unconjugated and conjugated bilirubin test, blood lactate dehydrogenase activity determination for the differential diagnosis of IDA and hemolytic anemias [31];

- blood aspartate aminotransferase activity determination, blood alanine aminotransferase activity determination to rule out cytolytic syndrome for accurate interpretation of iron metabolism parameters [30];

- blood creatinine test, blood urea test to rule out kidney disease-associated anemia [27];

- complete urinalysis to rule out hematuria as a cause of iron deficiency [32,33]

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

Comments: the results of the listed baseline tests can guide further diagnostic workup. Assessment of biochemical liver function tests is necessary for the correct interpretation of iron metabolism parameters, as impaired protein-synthesizing function of the liver leads to reduced hepatocyte production of transferrin and, consequently, decreased serum transferrin and TIBC levels, distorting the calculated TSAT coefficient [26]. Renal impairment can lead to the development of both relative and absolute iron deficiency [27]. Assessment of other biochemical parameters is used in the differential diagnosis with anemias of other etiologies.

Comments: the need for bone marrow aspiration (obtaining a bone marrow cytological preparation by puncture) and trephine biopsy (obtaining a bone marrow histological preparation) may arise in cases of refractory, treatment-resistant anemia and/or in the presence of other cytopenias (leukopenia or thrombocytopenia). In IDA, the bone marrow shows no specific pathological features; cellularity is generally normal, and moderate erythroid hyperplasia may be present. A characteristic feature of the bone marrow in IDA is a decrease in the number of sideroblasts—erythroblasts containing iron granules (normally 20–40%).

IDA must be differentiated from anemias complicating chronic inflammatory and neoplastic diseases ("anemia of chronic disease"), as well as hypochromic anemias presenting with iron overload: α- and β-thalassemias, porphyrias, lead poisoning.

Comments: anemia is associated with a number of geriatric syndromes: frailty [38,39], sarcopenia [40], falls and fractures [41,42], dementia [43].

Comments: IDA – a frequent condition in patients scheduled for surgical interventions [9,10]. The presence of preoperative anemia negatively affects surgical outcomes [46], which necessitates timely diagnosis (optimally – immediately after establishing indications for elective surgery) and correction of anemia at the primary health care stage.

Comments: anemia – is the most common complication of pregnancy, which can negatively affect its outcomes [49]. The diagnosis of anemia in pregnancy is based on determining the blood hemoglobin concentration: Hb less than 110 g/L in the first and third trimesters of pregnancy and Hb less than 105 g/L in the second trimester of pregnancy; in the postpartum period, Hb less than 100 g/L at 24–48 hours after delivery [50]. Postpartum anemia (PPA) is also defined as an Hb concentration of less than 110 g/L at 1 week postpartum and an Hb concentration of less than 120 g/L at 8 weeks postpartum [51]. Depending on the Hb concentration, the following severity grades of anemia are distinguished [52,53]:

• 90–110 g/L – mild;

• 70–90 g/L – moderate;

• less than 70 g/L – severe.

The criteria for IDA in pregnancy do not differ from those in all other patients.

Comments: interpretation of parameters is presented in section 2.3

Comments: screening for postpartum anemia (PPA) should be performed to ensure early and appropriate treatment. Due to the combination of intrapartum hemorrhage and hemodynamic shifts, postpartum Hb concentration should stabilize at least 48 h after delivery before an accurate diagnosis of PPA can be made. In case of massive blood loss (more than 1500 ml), a hemorrhage management protocol (including serial Hb measurements) should be applied [56]. Postpartum anemia (PPA) is diagnosed when Hb concentration is <100 g/L within 48 hours after delivery and Hb <120 g/L at 8 weeks postpartum [48,51].

2.4 Instrumental Diagnostics

Identification of iron deficiency anemia (IDA) requires a standard set of instrumental diagnostic tests to determine the underlying cause of the anemia.

- Chest X-ray or chest CT;

- Ultrasound examination of the abdominal cavity (comprehensive), retroperitoneal space, and pelvic organs (comprehensive);

- Ultrasound examination of the thyroid gland and parathyroid glands;

- Electrocardiography.

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

Comments: examination of the upper (EGD) and lower (colonoscopy or CT colonography) gastrointestinal tract is performed in all adult male patients with newly diagnosed IDA and in postmenopausal women or women of reproductive age in whom IDA does not correlate with monthly menstrual blood loss or childbirth. The detection of esophagitis, erosions, or ulcers on EGD should not be considered the primary cause of IDA until the lower GI tract has been evaluated. If colonoscopy is unavailable, contraindicated, or incomplete, CT colonography or video capsule colonoscopy (medical service code A03.18.001.006) may be performed. The superiority of video capsule colonoscopy over CT colonography was described in a study by C. Spada et al., 2015 [62].

In cases where a source of bleeding in the upper and lower gastrointestinal tract cannot be identified, small bowel endoscopy (enteroscopy) must be performed. This procedure is advisable using video capsule enteroscopy (medical service code A03.17.002.002). Subsequently, if video capsule enteroscopy reveals pathology requiring morphological verification of the diagnosis and/or elimination of the bleeding source, double-balloon enteroscopy (A03.17.002.001) may be used.

The most difficult to diagnose are bleedings into closed cavities, most commonly associated with endometriosis – ectopic proliferation of the endometrium, typically in the muscular and submucosal layers of the uterus, and less frequently – extragenitally. In this process, the iron released from extravasated blood is not reused for erythropoiesis, leading to iron deficiency. A similar situation of bleeding into closed cavities is observed in isolated pulmonary hemosiderosis, as well as glomus tumors originating in anastomotic arteries and found in certain arteriovenous anastomoses, such as in the lungs and pleura. These tumors, especially when ulcerated, can lead to blood loss and the development of IDA.

Other sources of blood loss may include epistaxis, mainly in patients with hemorrhagic diathesis (hereditary hemorrhagic telangiectasia, immune thrombocytopenia, etc.), hematuria of various origins (chronic hematuric nephritis, IgA nephropathy, urolithiasis, permanent intravascular hemolysis), iatrogenic blood loss (frequent repeated blood sampling for laboratory tests), and therapeutic phlebotomy (in polycythemia vera).

Comments: performing Doppler ultrasound of uteroplacental blood flow with evaluation of fetal cerebral circulation in pregnant women makes it possible to assess the condition of the fetus and its hemodynamic parameters. Severe anemia in a pregnant woman is associated with pronounced fetal hemodynamic maladaptation and requires prompt optimal treatment of the anemia [49,64] or addressing the issue of labor induction/delivery via cesarean section [47,63].

2.5 Other Procedures

Comments: celiac disease can lead to impaired intestinal iron absorption due to autoimmune damage to the intestinal mucosa, as well as chronic occult bleeding.

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

3.1 Conservative Treatment

The goal of IDA treatment is to administer iron in the amount necessary to normalize hemoglobin levels (120-140 g/L in women, 130-160 g/L in men) and replenish tissue iron stores (serum ferritin >40-60 ng/mL). Oral ferrous iron preparations (ATC code B03AA) or oral ferric iron preparations (ATC code B03AB) are used for treatment and prevention. The quantitative and qualitative composition of iron medications varies widely: high- and low-dose, single-ingredient and combination products. According to WHO recommendations, the optimal iron dose for treating IDA is 120 mg daily, and for iron deficiency prevention – 60 mg daily. However, evidence has now been obtained that low-dose iron supplementation in short courses (2 weeks per month) or alternative regimens (every other day for a month) has sufficient efficacy and a lower incidence of side effects compared to previously used high-dose iron preparations, including those administered repeatedly (2-3 times daily) [3].

In children, the dose of iron preparations (B03A) depends on age and is 3 mg/kg per day in children under three years of age, 45-60 mg per day in children over three years old, and up to 120 mg per day in adolescents. Approximately 20% of patients develop diarrhea or constipation during treatment, which is managed with symptomatic therapy. Signs of gastric irritation, such as nausea and epigastric discomfort, can be minimized by taking iron supplements with meals or reducing their dose. The use of high-dose iron preparations (B03A) (more than 120 mg/day) is accompanied by an increased incidence of gastrointestinal side effects. The duration of treatment is determined by the severity of the initial iron deficiency and can range from 1 to 3 months. It is advisable to combine treatment with multivitamins to fully support plastic metabolic processes.

Table 5. Normal Hb concentration in children of various ages (cited from [66–68])

3.1.1 Treatment with oral iron preparations

Comments:

The goal of treating latent iron deficiency is to normalize tissue iron store concentrations (increasing ferritin above 40–60 ng/mL) and achieve regression of sideropenic syndrome manifestations.

The ATC classification divides oral iron medicinal products for the treatment of iron deficiency anemia into oral ferrous iron preparations (B03AA) and oral ferric iron preparations (B03AB). Recent randomized trials have demonstrated that the efficacy of oral ferrous and ferric iron preparations is similar [3,68,73,74].

The treatment of iron deficiency anemia in children has certain specific features that should be taken into account in the treatment protocol [68,74–76].

1) During the treatment of iron deficiency anemia with oral ferrous iron preparations in children, the following issues may arise:

- overdose and even poisoning due to uncontrolled intestinal absorption;

- interactions with other medicinal products and food;

- pronounced metallic taste; staining of tooth enamel and gums;

- frequent patient refusal of treatment (up to 30–35% of those who started treatment), indicating low compliance of children to the treatment of iron deficiency anemia with oral ferrous iron preparations.

Most of the listed problems can be avoided by using oral ferric iron preparations, which have the following properties and advantages:

- high safety, no risk of overdose, intoxication, or poisoning; excellent tolerability;

- absence of gum and tooth pigmentation, pleasant taste;

- no interactions with other medicinal products and food; presence of antioxidant properties.

The aforementioned properties of oral ferric iron preparations ensure high treatment compliance in children with iron deficiency anemia [74,76].

2) Administration of 100% of the dose of an oral ferric iron preparation throughout the entire treatment period in pediatric patients is associated with 100% treatment adherence, a minimal number (6.3%) of adverse events, and high treatment efficacy. Thus, oral ferric iron preparations are the optimal medicinal products for the treatment of iron deficiency anemia in children and adolescents [74]. It is important that iron preparations are available on the market in various oral pharmaceutical formulations (drops, syrup, tablets), making their use feasible in children of various ages and adolescents.

Comments: therapeutic approaches for latent iron deficiency and iron deficiency anemia in pregnant women depend on the gestational age and severity of anemia. For latent iron deficiency (serum ferritin less than 30 ng/mL) in early pregnancy, it is recommended to administer 60 mg of elemental iron per day due to the increased iron demand during pregnancy [78].

Comments: today, there is evidence of sufficiently high efficacy and a lower frequency of adverse reactions when using low-dose iron preparations in short courses (2 weeks per month) or alternating regimens (every other day for a month) compared to previously used high-dose iron preparations, including repeated daily administrations (2–3 times a day).

3.1.2 Treatment with parenteral iron preparations

Comments: the use of parenteral ferric iron preparations is indicated for patients with malabsorption disorders due to prior extensive intestinal resection, patients with inflammatory bowel disease (ulcerative colitis, Crohn's disease) and malabsorption syndrome, patients with chronic kidney disease in the pre-dialysis and dialysis periods, patients with chronic heart failure, as well as when a rapid effect is required to replenish iron stores and enhance erythropoiesis efficacy [3,81].

Possible side effects of intravenous iron preparations include: anaphylactic reactions (less than 1% of patients), development of iron overload (with prolonged and uncontrolled use of parenteral preparations), as well as toxic reactions associated with the activation of free radical reactions of biological oxidation (lipid peroxidation) by iron ions.

Intramuscular administration of iron preparations is not used due to low efficacy, the development of local hemosiderosis, and the risk of infiltrates, abscesses, and even myosarcoma at the injection site.

Comments: the prevalence of anemia in patients scheduled for surgery significantly exceeds that in the general population, ranging from 12% to 70% according to various studies, with iron deficiency anemia (IDA) accounting for up to 60–75% of preoperative anemia cases [9,10]. The presence of preoperative anemia negatively affects surgical outcomes [46], which necessitates timely diagnosis (optimally – immediately after the indication for elective surgery is established) and correction of anemia. The modern approach to correcting IDA in preparation for elective surgery involves preemptive replenishment of tissue iron stores to normalize hemoglobin levels and reduce the need for red blood cell transfusions [32]. If urgent or emergency surgery is required, preoperative correction of IDA is generally not feasible; therefore, blood component replacement therapy is used when indicated.

Postoperative anemia is observed in the majority of patients who have undergone major surgical interventions [83]. In addition to perioperative blood loss, anemia is promoted by a deficiency of hematopoietic factors (folates, vitamin B12) due to undernutrition, frequent blood draws for laboratory tests, and the acute inflammatory response accompanying reparative processes following surgery.

In the early postoperative period, the administration of parenteral ferric iron preparations is associated with the risk of developing acute infectious and inflammatory processes or exacerbating chronic infections, as anemia during this period is predominantly of the anemia of inflammation type and is characterized by redistribution (or functional) iron deficiency.

At the same time, the negative effects of postoperative anemia manifest as a prolonged recovery period, the development of surgical and non-surgical complications, and increased mortality. Assessing serum iron metabolism parameters may be uninformative during the first 7–10 days postoperatively due to the inflammatory response to surgical trauma. In cases of proven absolute iron deficiency and the absence of infectious complications, parenteral iron preparations are the first-line therapy due to the low bioavailability of oral forms in the postoperative period [50–53].

Comments: Switching to a parenteral ferric iron preparation is indicated in the following cases:

1) lack of response to oral iron therapy (an increase in Hb concentration of less than 10 g/L after 4 weeks of therapy);

2) poor compliance or intolerance to oral iron preparations (gastrointestinal adverse events);

3) severe, progressive iron deficiency anemia;

4) the need for rapid treatment of anemia (e.g., gestational age over 34 weeks, refusal of blood component transfusion).

Women should be informed about potential adverse events associated with intravenous iron preparations.

The high efficacy and safety of high-dose parenteral ferric iron preparations have been proven [84,85]. Intravenous iron preparations should not be administered concomitantly with oral iron preparations or in the presence of active infection. Contraindications for parenteral iron therapy include: anemia not related to iron deficiency, a history of anaphylactic reaction to parenteral iron, the 1st trimester of pregnancy, active acute or chronic infection, and chronic liver disease.

Comments: The high efficacy and favorable safety profile of parenteral ferric iron forms have been proven. Currently available data support the administration of high-dose intravenous iron preparations to postpartum women with severe anemia [87].

Comments: senile asthenia is associated with excessive synthesis of pro-inflammatory cytokines (IL-6, TNF-alpha) [60,61], which contributes to the development of functional (redistributive) iron deficiency due to increased hepcidin synthesis, decreased ferroportin activity, and impaired iron absorption in the small intestine. In this case, oral iron preparations prove to be ineffective [90,91]. To normalize hemoglobin levels and improve the functional status of patients with senile asthenia syndrome and confirmed iron deficiency, the administration of parenteral ferric iron preparations is preferred [92–95].

3.1.3 Blood transfusion therapy

Comments: indications for initiating blood transfusion therapy should be determined by the attending physician on an individual basis. When determining indications for transfusion, the patient's comorbidities—such as coronary artery disease—should be taken into account, which may necessitate blood transfusion therapy even with a moderate decrease in hemoglobin.

Comments: hemotransfusion therapy is prescribed according to individual indications in pregnant women with severe anemia and concomitant cardiovascular pathology if there is a risk of condition decompensation against the background of anemia [97]. Transfusion of red blood cell components should be provided for women at risk of ongoing hemorrhage, cardiac dysfunction, or in the presence of symptoms requiring immediate treatment. Severe anemia in pregnant women with an Hb concentration of less than 70 g/L is associated with impaired fetal oxygenation, leading to fetal heart rate abnormalities, decreased amniotic fluid volume, fetal cerebral vasodilation, and fetal death [98]. In such cases, transfusion of red blood cell components to a pregnant woman should be performed based on fetal indications. In the absence of bleeding and the need for hemotransfusion, 1 unit of a red blood cell component should be transfused, followed by an assessment of the clinical status and determination of the Hb concentration to decide on the need for further hemotransfusions [96].

3.1.4 Monitoring the efficacy of iron therapy during treatment

Comments: the effectiveness of treatment in patients with IDA is determined by the dynamics of clinical and laboratory parameters. Patients' well-being begins to improve 5–6 days after the initiation of iron therapy, reticulocyte counts increase after 8–12 days, hemoglobin concentration rises after 2.5–3 weeks, and normalizes in most cases within a month or later. Upon completion of the course of iron therapy, hemoglobin levels should be monitored monthly for a year to determine the need for maintenance iron therapy.

3.2 Surgical Treatment

Not used

3.3 Dietary therapy

Not used

3.4. Other Treatment

Pain management is not applied

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Not required.

5. Prevention and Dispensary Observation

The problem of iron deficiency is primarily a nutritional problem; therefore, primary prevention of IDA and latent iron deficiency consists of an adequate, balanced human diet at any age. The daily requirement for iron in an adult is about 1–2 mg, and in a child, 0.5–1.2 mg. A standard diet provides an intake of 5 to 15 mg of elemental iron per day. Only 10–15% of the iron contained in food is absorbed in the gastrointestinal tract (duodenum and upper jejunum).

- exclusively or mixed-breastfed infants, starting from 4 months of age and until the introduction of complementary foods (1 mg of iron per 1 kg of body weight per day);

- preterm breastfed infants, starting from the 1st month of life until switching to iron-fortified infant formula or until the introduction of complementary foods (2 mg of iron per 1 kg of body weight per day);

- children and adults in whom the cause of the iron deficiency state cannot be eliminated (chronic blood loss from menometrorrhagia, gastrointestinal diseases accompanied by malabsorption [malabsorption syndrome, celiac disease, etc.] or recurrent bleeding [Crohn's disease, ulcerative colitis, hiatal hernia, etc.]; patients on maintenance hemodialysis; patients with inoperable tumors of any localization accompanied by recurrent bleeding);

- adults following a vegetarian or vegan diet;

- regular blood donors.

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

Comments: Term-born healthy infants have sufficient iron stores in the first 4 months of life. Due to the low iron content in breast milk, exclusively breastfed and mixed-fed infants are indicated for supplemental iron from 4 months of age until the introduction of complementary foods. Formula-fed infants receive adequate iron from infant formulas or complementary foods. Infants aged 6–12 months should receive 11 mg of iron daily. Complementary foods should include red meat and vegetables with a high iron content. If iron intake from formula or complementary foods is insufficient, supplemental iron in the form of drops or syrup should be prescribed. Children aged 1–3 years should receive 7 mg of iron daily, preferably through foods containing sufficient red meat, high-iron vegetables, and fruits rich in vitamin C, which enhances iron absorption. Additional supplementation with liquid iron preparations or multivitamins is also possible.

Adult patients at risk for iron deficiency states are indicated for oral iron therapy at a dose of 30–60 mg/day administered daily or every other day, monitored by serum iron metabolism parameters.

Comments: in children aged 2–5 years without risk factors, screening for IDA is performed annually. Among school-age children and adolescent males, screening for anemia is indicated for those with a history of IDA or special needs due to health status or low dietary iron intake.

Starting from adolescence, screening for anemia should be performed in all non-pregnant women every 5–10 years throughout their reproductive age. Annual screening is indicated for women with risk factors for IDA (heavy menstrual bleeding or bleeding of other etiologies, inadequate iron intake, and a prior diagnosis of IDA).

Clinical follow-up (dispensary observation) for children and adolescents with IDA is conducted in our country for one year from the date of diagnosis. The patient's well-being and general condition are monitored. Prior to discharging the patient from follow-up, a complete blood count (CBC) is performed, and all parameters must be within normal limits.

6. Organization of Medical Care

Indications for emergency hospitalization to a medical organization:

1. development of symptoms of IDA decompensation.

Indications for planned hospitalization in a medical organization:

1. dispensary examination, including upon initial diagnosis of moderate or severe IDA.

Indications for patient discharge from a medical organization:

1. regression of symptoms of IDA decompensation, completion of the workup to identify the cause of IDA.

7. Additional Information

Criteria for the efficacy of oral iron therapy for IDA include:

• an increase in Ret-He by 2–3 days of iron therapy, reflecting erythropoiesis activation and cellular hemoglobin synthesis;

• reticulocyte response: on days 7–10 of iron therapy, the reticulocyte count increases (typically by 2–3% or 20–30 ‰) compared to baseline pre-treatment values;

• an increase in Hb concentration by the end of the 4th week of iron therapy by 10 g/L and Ht by 3% relative to pre-treatment baseline values [101];

• resolution of clinical manifestations of the disease 1–1.5 months after initiating iron therapy;

• resolution of tissue sideropenia and replenishment of iron stores within 3–6 months of treatment initiation (depending on anemia severity), monitored by normalization of serum ferritin (SF) concentration (>30 ng/mL).

Refractory IDA to iron therapy is most commonly due to inadequate prescribed therapy or anemia unrelated to iron deficiency. A lack of positive response to adequate iron therapy may indicate so-called "iron-refractory iron deficiency anemia" (IRIDA) [102–104].

IRIDA is an autosomal recessive disorder with familial cases described. Treatment of this variant of IDA with oral iron preparations is known to be ineffective; a partial effect can be achieved using parenteral iron preparations. The cause of IRIDA is a congenital genetic defect—a mutation in the gene encoding transmembrane serine protease 6 (TMPRSS6). The consequence of this genetic defect is the overproduction of hepcidin, which suppresses intestinal iron absorption, recycling, and the release of iron from tissue stores [103, 104].

With timely diagnosis, identification of underlying causes, and proper treatment, IDA is curable in 100% of cases. So-called "relapses" of IDA most frequently indicate an unidentified (unresolved) cause of the disease or improper diagnosis and treatment.

To ensure that parenteral trivalent iron therapy is effective and safe for the patient, strict adherence to the following treatment principles is required:

• use of modern parenteral trivalent iron preparations with lower toxicity and without life-threatening anaphylactoid reactions;

• cessation of therapy after replenishment of iron stores to avoid iron overload. For the same reasons, it is advisable to administer parenteral trivalent iron therapy under the monitoring of serum iron metabolism parameters;

• compliance with the intravenous infusion technique for parenteral trivalent iron preparations;

• mandatory compliance with the instructions for use of the parenteral trivalent iron preparation, if a test dose is required before initiating treatment;

• treatment should be administered within the range of safe doses, as adverse events of parenteral trivalent iron preparations are dose-dependent.

Routine vaccinations in children with IDA are not contraindicated, do not require normalization of Hb concentration, and should be administered to patients with mild anemia on the standard schedule, as patients have an adequate number of immunocompetent cells. In our country, the official document "Vaccine Prophylaxis. Medical Contraindications to Preventive Vaccinations with National Immunization Schedule Preparations. Methodological Guidelines" has been published [105]. According to this document, anemias, including IDA, should not be a contraindication to vaccination. Section 13.4 of this document states: "Mild nutritional anemia should not be a reason for deferral of vaccination, following which the child is prescribed appropriate treatment. Severe anemia requires identification of the cause followed by a decision on the timing of vaccination."

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Members of the Association for the Promotion of Hematology and Bone Marrow Transplantation "National Hematological Society"

1. Parovichnikova E.N., MD, General Director, National Medical Research Center for Hematology of the Russian Ministry of Health

2. Lukina E.A., MD, Professor, Head of the Department of Orphan Diseases, National Medical Research Center for Hematology of the Russian Ministry of Health

3. Ponomarev R.V., PhD, Head of the Sector for the Study of Non-Neoplastic Blood System Diseases, National Research Center for Hematology of the Russian Ministry of Health

4. Latyshev V.D., Head of the Hematology Day Hospital for Patients with Inherited Metabolic Diseases, National Medical Research Center for Hematology of the Russian Ministry of Health

5. Tsvetayeva N.V., PhD, Senior Researcher, Sector of Non-Neoplastic Blood System Diseases, National Medical Research Center for Hematology of the Russian Ministry of Health

6. Dvirnyk V.N., PhD, Head of the Centralized Clinical Diagnostic Laboratory, National Medical Research Center for Hematology of the Russian Ministry of Health

7. Ptushkin V.V., MD, Chief freelance specialist hematologist of the Moscow Healthcare Department, Deputy Chief Physician for Hematology, City Clinical Hospital named after S.P. Botkin of the Moscow Healthcare Department, Professor of the Department of Oncology, Hematology and Radiation Therapy, Pirogov Russian National Research Medical University of the Russian Ministry of Health

Members of the Russian Society of Pediatric Hematologists and Oncologists:

8. Rumyantsev A.G., Academician of the RAS, MD, Professor, President, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Russian Ministry of Health

9. Maschan A.A., MD, Professor, Director of the Institute of Hematology, Immunology and Cell Technologies, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Russian Ministry of Health

10. Chernov V.M., MD, Professor, Chief Researcher, Department of Pediatrics, Institute of Molecular and Experimental Medicine, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Russian Ministry of Health

11. Tarasova I.S., MD, Chief Researcher, Department of Pediatrics, Institute of Molecular and Experimental Medicine, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Russian Ministry of Health

12. Smetanina N.S., MD, Professor, Deputy Director of the Institute of Hematology, Immunology and Cell Technologies, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of the Russian Ministry of Health

Members of the Federation of Laboratory Medicine:

13. Lugovskaya S.A., MD, Professor of the Department of Clinical Laboratory Diagnostics, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health

Members of the Russian Endoscopic Society RENDO:

14. Ivanova E.V., MD, Chief Researcher, Research Laboratory of Surgical Gastroenterology and Endoscopy, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Head of the Endoscopy Department, Pokrovskie Vorota Medical Center

15. Fyodorov E.D., MD, Prof., Chief Researcher and Head of the Endoscopy Department, Department of Hospital Surgery No. 2 with the Research Laboratory of Surgical Gastroenterology and Endoscopy, Pirogov Russian National Research Medical University of the Russian Ministry of Health

Members of the Russian Scientific Medical Society of Internal Medicine (RSMSIM)

16. Martynov A.I., Academician of the RAS, MD, Professor of the Department of Hospital Therapy, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health

17. Malyavin A.G., MD, Professor of the Department of Phthisiology and Pulmonology, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health

Members of the Russian Association of Gerontologists and Geriatricians

18. Tkacheva O.N., MD, Professor, Corresponding Member of the RAS, Chief Geriatrician of the Russian Ministry of Health, Director of the structural unit "Russian Gerontological Research and Clinical Center" under Pirogov Russian National Research Medical University of the Russian Ministry of Health

19. Kotovskaya Yu.V., MD, Professor, Deputy Director for Research, structural unit "Russian Gerontological Research and Clinical Center" under Pirogov Russian National Research Medical University of the Russian Ministry of Health

20. Khovasova N.O., MD, Senior Researcher, Laboratory of Musculoskeletal Diseases, Associate Professor, Head of Academic Affairs, structural unit "Russian Gerontological Research and Clinical Center" under Pirogov Russian National Research Medical University of the Russian Ministry of Health

Members of the Russian Society for Prevention of Noncommunicable Diseases

21. Drapkina O.M., MD, Prof., Academician of the RAS, Director, National Medical Research Center for Therapy and Preventive Medicine of the Russian Ministry of Health, Chief freelance specialist in therapy and general medical practice of the Russian Ministry of Health

Members of the Russian Society of Obstetricians and Gynecologists

22. Serov V.N., Academician of the RAS, Doctor of Medical Sciences, Professor, Honored Scientist of the Russian Federation, President of the Russian Society of Obstetricians and Gynecologists, Chief Researcher, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation (Moscow).

23. Pavlovich S.V., Candidate of Medical Sciences, Associate Professor, Academic Secretary, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation (Moscow).

24. Fedorova T.A., Doctor of Medical Sciences, Head of the Department of Transfusiology and Hemocorrection, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation (Moscow).

25. Shmakov R.G., Doctor of Medical Sciences, Professor of the RAS, Director of the Institute of Obstetrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation (Moscow). Chief freelance specialist of the Ministry of Health of the Russian Federation (Moscow).

26. Dolgopolova E.L., obstetrician-gynecologist of the obstetric department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation (Moscow).

Conflict of interest: the authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Hematologists

2. Internists

3. Pediatricians

4. Surgeons

5. Obstetricians-gynecologists

6. Oncologists

7. Gastroenterologists

8. Geriatricians

Methodology for evidence collection

Methods used for evidence collection/selection:

• Search for publications in specialized periodical print media

• Search in electronic databases.

Methods used for assessing the quality and strength of evidence:

• Expert consensus;

• The significance of the evidence was evaluated in accordance with the levels of evidence (LE) grading scale for diagnostic methods (Table A1) and for preventive, therapeutic, and rehabilitation methods (Table A2).

Table A1. Levels of evidence (LE) grading scale for diagnostic methods (diagnostic interventions)

Table A2. Scale for evaluating the levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Description of the methodology for evidence analysis and recommendation development:

When selecting publications as potential sources of evidence, the methodology used in each study was examined to ensure its compliance with evidence-based medicine principles. The result of this examination influenced the level of evidence assigned to the publication, which in turn affects the strength of the resulting recommendations.

Methodological analysis focused on the study design features that had a significant impact on the quality of results and conclusions.

To eliminate the influence of subjective factors, each study was evaluated independently by at least two independent members of the authoring team. Discrepancies in evaluation were discussed at meetings of the working group of the authoring team for these guidelines.

Based on the evidence analysis, the sections of the clinical guidelines were consistently developed with strength assessment in accordance with the recommendation grading scheme (Table 3).

Methods used to formulate the recommendations:

• Expert consensus;

• Evaluation of the strength of recommendations in accordance with the rating scheme (Table A3).

Table A3. Grades of recommendation (GR) scale for preventive, diagnostic, therapeutic, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Final version

For the final version and quality control, the guidelines were re-analyzed by the members of the authoring team, who concluded that all significant comments and feedback from experts had been taken into account, and the risk of bias during development was minimized.

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

These clinical guidelines have been developed taking into account the following regulatory and legal documents:

1. Federal Law No. 323-FZ "On the Fundamentals of Protecting Citizens' Health in the Russian Federation" dated November 21, 2011.

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

3. Order of the Ministry of Health and Social Development No. 1687n dated December 27, 2011 "On Medical Criteria of Birth, Form of the Birth Document and Procedure for its Issuance" (registered with the Ministry of Justice of the Russian Federation on March 15, 2012, No. 23490).

4. Order of the Russian Ministry of Health No. 1130n dated October 20, 2020, "On Approval of the Procedure for Providing Medical Care in the Field of 'Obstetrics and Gynecology'"

5. Order of the Russian Ministry of Health No. 804n dated October 13, 2017 (as amended on April 16, 2019) "On Approval of the Nomenclature of Medical Services"

6. Decree of the Government of the Russian Federation No. 797 dated June 22, 2019, "On Approval of the Rules for Procurement, Storage, Transportation, and Clinical Use of Donored Blood and Its Components and on Invalidation of Certain Acts of the Government of the Russian Federation"

7. Order of the Russian Ministry of Health No. 1170n dated October 28, 2020, "On Approval of the Rules for Providing Medical Care to the Population in the Field of Transfusiology"

8. Order of the Russian Ministry of Health No. 1148n dated October 26, 2020, "On Approval of Requirements for Organizing the Safety System for Activities of Entities Dealing with Donated Blood and (or) Its Components during Procurement, Storage, Transportation, and Clinical Use of Donated Blood and (or) Its Components."

9. Order of the Russian Ministry of Health No. 138n dated April 4, 2023, "On Approval of the Standard of Medical Care for Adults with Iron Deficiency Anemia (Diagnosis, Treatment, and Dispensary Monitoring)" (Registered with the Ministry of Justice of Russia on May 15, 2023, No. 73300)

Table 1. Main oral drugs used to treat iron deficiency anemia and their elemental iron content

Table 2. Some modern parenteral iron preparations

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Iron deficiency anemia

1. Iron deficiency anemia is a 100% curable condition. The main treatment objectives are to identify the cause of the hemoglobin drop and administer iron replacement therapy. The duration of treatment can range from 1–2 to 6 months, depending on the severity of the anemia.

2. You should obtain dietary recommendations from your attending physician.

3. Poor tolerance of iron preparations (abdominal pain, nausea, vomiting, constipation, diarrhea) is a reason to consult your attending physician. Changing the medication or reducing the dose may be necessary.

4. A cure for iron deficiency anemia is defined not by achieving a normal Hb concentration, but by replenishing the body's iron stores, which can be verified through biochemical testing—specifically, determining serum ferritin concentration.

5. Discontinuing iron supplementation sets the stage for disease relapse.

6. Parents of children with iron deficiency anemia should receive vaccination advice from their pediatrician. In children with mild iron deficiency anemia, routine vaccinations are administered in accordance with the immunization schedule.

Iron deficiency anemia in pregnant women

What is anemia?

Anemia is a decrease in blood hemoglobin concentration

Why is anemia a concern?

Anemia in pregnancy is an important medical and social issue, with a prevalence of 36% among pregnant women. Maternal anemia during pregnancy represents a general and potentially reversible risk factor for complications during the prenatal, intrapartum, and postpartum periods, increasing maternal and perinatal morbidity and mortality.

What leads to anemia

It is well known that during pregnancy, a number of physiological changes occur in a woman's body, including hematological changes. Total plasma volume increases by approximately 30–50% from baseline, whereas red cell mass increases by only 25%. The demand for micronutrients and vitamins—essential both for hemoglobin synthesis and for ensuring normal development of the fetus and placenta—increases. In the absence of adequate supplementation to meet these growing demands, micronutrient deficiency develops, and as a result, pregnancy may be complicated by varying degrees of anemia. This is driven by multiple factors: frequently, pregnancy begins with a baseline low hemoglobin level, and anemia is diagnosed due to more rigorous laboratory monitoring of pregnant women. However, the most frequent cause is insufficient iron stores in the body, often attributable to dietary habits (vegetarianism), chronic gastrointestinal diseases, or prolonged heavy menstrual bleeding, which, combined with the increased iron requirements during pregnancy, leads to the development of anemia. Detecting and correcting anemia at the preconception stage and in early pregnancy plays a crucial role in the subsequent carrying of the pregnancy to term.

What hemoglobin concentrations indicate anemia

• Anemia is defined as a hemoglobin level below 110 g/L (first and third trimesters), below 105 g/L (second trimester), and below 100 g/L (postpartum period). Upon confirmation of pregnancy, laboratory parameters must be monitored at least once per trimester.

• Dietary regimen during pregnancy: a balanced diet containing meat products, especially red meat, and vegetables rich in iron.

What options are available for correcting anemia?

• Dietary modification. A standard diet provides approximately 10.5 mg of iron daily. About 15% of this is absorbed. Dietary iron absorption depends on the amount present in the diet, gastrointestinal function, and physiological needs. The primary dietary source of iron is meat, making a vegetarian diet a high-risk factor for iron deficiency. During pregnancy and the postpartum period, when iron deficiency is identified, dietary modification alone is insufficient—pharmacotherapy is required.

Oral therapy is prescribed by a physician

Upon confirmation of iron deficiency anemia and iron deficiency, the dosage depends on the severity of the anemia and the presence of concurrent abnormalities. As is well known, there are oral and parenteral iron preparations. For mild to moderate anemia (hemoglobin above 90 g/L), oral iron therapy is indicated.

- For more severe anemia, as well as in cases of insufficient response to oral therapy (hemoglobin failing to increase by 10 g/L within 4 weeks) or poor tolerance (gastrointestinal side effects), parenteral iron therapy is required. Currently, the most effective therapeutic approach, allowing for the rapid and safe achievement of the maximum effect, is the use of intravenous iron formulations.

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

No.