How is aplastic anemia treated?

Treatment of congenital forms of aplastic anemia

Fanconi anemia

• Bone marrow transplant.

It is the method of choice in the treatment of Fanconi anemia.

Bone marrow transplantation from an HLA-identical sibling is performed using mitigated conditioning - thoracoabdominal irradiation at a dose of 6 Gy and cyclophosphamide at a dose of 20 mg/kg. This approach allows curing about 70-75% of patients with Fanconi anemia.

• In the absence of a donor for bone marrow transplantation, conservative treatment is prescribed - androgens (steroid anabolics).

Steroid anabolics used in patients with Fanconi anemia

Name of the drug	Dose mg/kg/day	Route of administration	Frequency of administration
Methandrostenolone (nerobol, dianabol)	0.2-0.4	Enterally	Daily
Retabolil (deca-durabolin; nandrolone)	1-1.5	Intramuscularly	1 time in 7-14 days
Phenobolin (Durabolin; Nerobolil)	0.25-0.4	Intramuscularly	1 time in 7-10 days
Oxymetholone (dihydrotestosterone)	0.5-2	Enterally	Daily
Testosterone Enanthate	4	Intramuscularly	1 time in 7 days
Testosterone propionate (Oreton)	1-2	Sublingually	Daily

Androgen treatment is carried out for 3-6 months, during the first 1.5-2 months the full dose of drugs is given, and then they switch to a maintenance dose, which is 1/2 of the full therapeutic dose. Improvement of hematological parameters occurs 6-8 weeks after the start of therapy - the number of reticulocytes and hemoglobin increases, and then leukocytes. The number of platelets does not increase for a long time.

Therapy is usually initiated with oxymetholone at a dose of 0.5-2 mg/kg/day orally daily. The response to therapy is noted 4-8 weeks after the start of treatment. Approximately 50% of patients show significant improvement in hematological parameters. The response to androgen therapy has prognostic significance: the average survival of patients who responded to androgens is about 9 years, and of those who did not respond - 2.5 years.

• Replacement hemotransfusion therapy.

Indications for replacement therapy are determined by hematological parameters:

• hemoglobin level < 80 g/l;
• absolute neutrophil count < 1.0 x 10 ⁹ /l;
• platelet count < 20 x 10 ⁹ /l.

Transfusions of red blood cells and thrombus suspensions are started only when the indicators reach the specified level. To diagnose possible hemosiderosis, it is necessary to determine the ferritin level once every 6 months in order to prescribe desferal therapy in time.

• Hematopoietic growth factors.

They can be prescribed as a trial therapy when conventional treatment is ineffective and a compatible donor is not available. The use of growth factors such as G-CSF and GM-CSF is discussed. It has been established that the use of erythropoietin and G-CSF in patients with Fanconi anemia increases the absolute number of neutrophils, platelets, erythrocytes, and CD 34+ cells.

• In recent years, attempts at gene therapy for patients with Fanconi anemia have been reported.

Treatment of aplastic anemia in dyskeratosis congenita

Bone marrow transplantation is used (the conditioning regimen is the same as for acquired aplastic anemia), but late mortality after BMT in this group is about 90%. Androgen therapy is effective in some patients.

Treatment of aplastic anemia in Shwachman syndrome

Treatment of aplastic anemia in Shwachman syndrome has not been developed. Enzyme replacement therapy is prescribed to treat malabsorption syndrome. Antibacterial therapy is mandatory if infectious complications occur. In some patients, the administration of small doses of prednisolone helps to increase the number of neutrophils.

Blackfan-Diamond Anemia (BDA)

• Corticosteroid therapy is the main method of treating ABD; it is with corticosteroids that therapy begins at the onset of the disease. Prednisolone is prescribed at a dose of 2 mg/kg/day in 3 doses for 4 weeks; then the daily dose in patients with a positive response (increase in Hb to 100 g/l) should be gradually reduced until the minimum maintenance daily dose is reached (daily or every other day to maintain a stable response).

The response to prednisolone therapy most often appears within 2 weeks, but may be delayed. Sometimes it is necessary to increase the starting dose. Treatment should be discontinued in both non-responders and patients with a high response threshold, when a dose of more than 0.5 mg / kg / day is required for a long time to maintain a stable response. In responding children with ABD, the duration of prednisolone use is limited by the development of severe complications of steroid therapy. In all patients, physical development (growth) should be monitored and, if there is a delay, steroid therapy should be temporarily discontinued and regular blood transfusions should be performed. This can restore the child's growth. It should be remembered that the most vulnerable periods in this regard are the first year of life and puberty. According to literary data, the proportion of patients with a good primary response is about 70%, but some patients become refractory during the course of the disease or stop treatment due to a high response threshold and / or severe side effects.

Indicators characterizing the response to treatment in children with Blackfan-Diamond anemia

Response to therapy	Increased reticulocyte count	Transfusion independence	Reduced need for blood transfusions	Regular need for blood transfusions (once every 3-6 weeks)
Full	+	+	-	-
Partial	+	-	+	-
Bad partial	+	-	-	+
No answer	-	-	-	+

• Hemotransfusion therapy is a replacement therapy and is a common alternative in steroid-resistant patients or patients with a high threshold for response to prednisolone therapy.

Red blood cell transfusions are performed every 4-5 weeks, in infants every 2-3 weeks, to maintain hemoglobin levels that ensure optimal growth of the child. The most serious complications of blood transfusion therapy are the development of hemosiderosis and the addition of viral diseases.

• Bone marrow transplantation. It is an important therapeutic alternative for steroid-resistant patients with ABD who require blood transfusions if an HLA-compatible donor is available. There are reports of successful transplantation of cord blood cells from an HLA-compatible sibling, which probably indicates the advisability of freezing cord blood from siblings of patients with ABD.
• High-dose methylprednisolone (HDMP) therapy is another alternative for patients with ABD.

It is recommended to prescribe methylprednisolone at a dose of 100 mg/kg/day intravenously or according to the following regimen:

Days 1-3 - 30 mg/kg/day; Days 4-7 - 20 mg/kg/day; Days 8-14 - 10 mg/kg/day; Days 15-21 - 5 mg/kg/day; Days 22-28 - 2 mg/kg/day. Administered intravenously, slowly, in 20 ml of 0.9% NaCl solution.

From the 29th day at a dose of 1 mg/kg/day in 3 doses enterally for 3-6 months until hemoglobin increases to more than 100 g/l. Monitoring of therapy is mandatory:

1. Sternal puncture - before the course and on the 30th day.
2. Clinical blood test with reticulocytes once every 5 days.
3. Fetal hemoglobin - before the course and on the 30th day.
4. Biochemistry - (ALT, AST, FMPA, sugar, electrolytes) once every 7 days.
5. Urine analysis 2 times a week (control of glucosuria).
6. ECG - before the course, then once every 14 days.
7. Blood pressure - daily for 45 days.

• In case of steroid resistance, androgens, 6-mercaptopurine, cyclophosphamide, cyclosporine A, ATG/ALG may be prescribed.

Treatment of acquired aplastic anemia

• Bone marrow transplantation (BMT)

Bone marrow transplantation from a fully histocompatible donor is considered the treatment of choice for newly diagnosed severe aplastic anemia and should be performed immediately, since this type of treatment is most effective in children.

The long-term survival rate in children who have undergone bone marrow transplantation at early stages of the disease from a fully HLA-compatible donor is 65-90%, according to the literature. The most common type of bone marrow transplant is allogeneic, which uses bone marrow from siblings, i.e. from full brothers or sisters who have the greatest antigenic proximity to the recipient. If it is impossible to obtain bone marrow from siblings, they try to use bone marrow from other relatives or HLA-compatible unrelated donors. Unfortunately, a suitable donor can be found for only 20-30% of patients. Transplantation of incompletely compatible stem cells from donor umbilical cord blood is possible.

Carrying out bone marrow transplantation requires careful preparation for effective immunosuppression. Preparation ("conditioning") before bone marrow transplantation includes administration of high doses of cyclophosphamide (200 mg/kg) with or without antithymocyte globulin (ATG), fractional total body irradiation. A possible complication of allogeneic bone marrow transplantation is the occurrence of "graft versus host" reaction, the frequency of which is 25% when using bone marrow from relatives and 50% when transplanting bone marrow from unrelated donors.

• Alternative treatments

They include the administration of immunosuppressive therapy (anti-IgG/anti-IgG, cyclosporine A, high doses of methylprednisolone) and hematopoietic growth factors.

• Immunosuppressive therapy

1. Antilymphocyte (antithymocyte) globulin (ALG).

It is used in the treatment of patients with aplastic anemia in the absence of an HLA-compatible donor. ALG isolated from thoracic duct lymphocytes and ATG isolated from human thymus cells are used. In our country, the most common drug is "Antilimpholin", obtained by immunizing rabbits or goats with human lymphocytes.

ALG is administered intravenously through a central catheter as an infusion over 12 hours, and is used at a dose of 15 mg/kg/day for 10 days or 40 mg/kg/day for 4 days. The latter regimen is easier to use and causes less severe serum sickness. Moderate doses of corticosteroids are given with ALG to reduce allergic reactions.

In those who responded to treatment, the number of granulocytes increases within 1-2 months, and transfusion dependence disappears after 2-3 months. Insufficient effectiveness of one course of ALG therapy is an indication for repeated courses, but the drug is prescribed in a higher dose.

2. Cyclosporine A (sandimmune).

A cyclic polypeptide consisting of 11 amino acids; synthesized by two strains of fungi.

Mechanism of action and main side effects of drugs used in patients with aplastic anemia

Group of drugs	Mechanism of action	Main side effects
Antilymphocyte globulin	Lymphocytotoxic effect on activated T-suppressors. Immunostimulating effect on granulocytopoiesis (increased production of GM-CSF and IL-3) Effect on stem cells	Chemical phlebitis when administered into a peripheral vein. Allergic reactions: anaphylaxis (in the first 1-3 days), serum sickness (on the 7-10th day after the first dose) CNS: fever, convulsions CVS: hypertension, heart failure, pulmonary edema Infectious (bacterial) complications Hematological complications: hemolysis, DIC syndrome, worsening neutropenia, thrombocytopenia
Corticosteroids (prednisolone, methylprednisolone)	Immunosuppressive effect (reduction in the content of T- and B-lymphocytes, reduction in the titer of serum immunoglobulins and the titer of specific antibodies). Decreased number of stem cells committed to erythropoiesis and granulocytopoiesis. Inhibition of migration of stem cells from the bone marrow into the bloodstream. Hemostatic effect	Endocrine system: Itsenko-Cushing syndrome Metabolism: carbohydrate metabolism disorder, weight gain, osteoporosis. Gastrointestinal tract: stomach and intestinal ulcers CNS: mental disorders, increased intraocular pressure CCC: hypertension Immune deficiency syndrome
Anabolic steroids (androgens)	Increased production of erythropoietin by the kidneys. Effect on stem cells in the G o - G 1 phase and stimulation of their entry into the mitotic phase, sensitive to erythropoietin. Stimulation of granulocytopoiesis by enhancing the production of colony-stimulating factor by bone marrow macrophages	Endocrine system: virilization, premature closure of bone growth plates, weight gain. Gastrointestinal tract: hepatotoxicity with possible development of liver tumors, cholestasis
Cyclosporine A (sandimmune)	Suppresses the development of cellular reactions and T-lymphocyte-dependent antibody formation. At the cellular level, it blocks G o and G 1 lymphocytes of the cell cycle, suppresses the secretion and production of lymphokines (interleukins 1, 2, beta and y-interferon) by activated T-lymphocytes.	Impaired renal function (increased serum urea and creatinine concentrations). Gastrointestinal: hepatotoxicity, loss of appetite, nausea, vomiting, diarrhea, pancreatitis. CCC: hypertension. CNS: headache, paresthesia, convulsions. Endocrine system: reversible dysmenorrhea and amenorrhea, hirsutism. Allergic reactions: anaphylactic and anaphylactoid reactions, rashes, itching. Gingival hypertrophy. Infectious complications

The drug is available in two forms: ampoules for intravenous administration and for oral administration. Drugs for oral administration:

• Neoral oral solution - solution, 100 mg/ml
• Neoral capsule or Sandimmun capsule no 10, 25, 50 and 100 mg in capsule

The solution can be mixed with milk or orange juice at room temperature.

Cyclosporine is prescribed at a dose of 5 mg/kg/day daily throughout the course of treatment or at a dose of 8 mg/kg/day on days 1-14 of treatment, then the dose is increased to 15 mg/kg/day (in 2 doses) in children and 12 mg/kg/day (in 2 doses) in adults. The level of therapeutic dose in the blood is 200-400 ng/ml. Monitoring of therapy is mandatory: blood pressure daily, biochemistry (ALT, AST, FMPA, bilirubin, sugar, urea, creatinine, cholesterol, electrolytes) once every 7 days. The level of cyclosporine in the blood serum is determined by a radioimmune method once a week in the first two weeks of treatment, then once every 2 weeks.

It is important to monitor plasma creatinine: an increase in creatinine by more than 30% of the norm requires a reduction in the cyclosporine dose by 2 mg/kg/day every week until the creatinine level is normalized. If the cyclosporine level is > 500 ng/ml, therapy is stopped. After the level has decreased to 200 ng/ml or less, therapy is resumed at a dose 20% less than the initial one.

The maximum effect of cyclosporine is observed 3-6 months after the start of treatment.

3. Corticosteroid therapy - high doses of methylprednisolone (HDMP).

Methylprednisolone is administered intravenously at a dose of 20 mg/kg/day for 3 days, followed by a gradual reduction in dose over 1 month.

Cyclosporine drug interactions

Pharmacokinetics

Reduces serum cyclosporine levels	Increases serum cyclosporine levels
Carbamazepine	Erythromycin
Phenobarbital	Fluconazole
Rifampin	Ketoconazole
Trimethotriene (intravenous)	Nifedipine
Metoclopramide (Raglan)	Imipenem-celastine
Phenytoin	Methylprednisolone
	Prednisolone

Pharmacological interactions

• Aminoglycosides, amphotericin B, NSAIDs, trimethoprim - increase nephrotoxicity
• Methylprednisolone - seizures
• Azathioprine, corticosteroids, cyclophosphamide - increase immunosuppression, increase the risk of infection and the risk of malignancy.

Methylprednisolone may be administered enterally or intravenously according to the following regimen: Days 1-9: 1 mcg/kg/day Days 10-11: 0.66 mg/kg/day Days 12-13: 0.5 mg/kg/day Days 14-16: 0.33 mg/kg/day Days 17-18: 0.16 mg/kg/day Day 19: 0.04 mg/kg/day Day 20: 0.33 mg/kg/day Day 21: not administered Day 22: 0.16 mg/kg/day Day 23: not administered Day 24: 0.08 mg/kg/day Day 25: discontinue (course completed).

In addition to methylprednisolone, especially on the days of ATG administration, platelet concentrate transfusions are prescribed to ensure that the platelet count is greater than 20 x 10 ⁹ /L. 4.

High doses of cyclophosphamide.

Prescribed to patients with severe A A who do not have a histocompatible donor. The most common scheme is as follows:

Days 1-3 - 45 mg/kg/day intravenously; Days 4-9 - 5 mg/kg/day intravenously; Days 10-20 - 3.75 mg/kg/day intravenously; Days 21-27 - 2.5 mg/kg/day intravenously; Days 28-31 - 1.5 mg/kg/day intravenously; Day 32 - 5 mg/kg/day orally; Days 33-56 - 10 mg/kg/day orally; Days 57-100 - 7.5 mg/kg/day orally.

• Hematopoietic growth factors

Recombinant human hematopoietic growth factors are used only in the complex treatment of patients with aplastic anemia, since they cause only a transient increase in the number of leukocytes and do not affect the natural course of the disease, but reduce the risk of infectious complications.

1. Granulocyte-macrophage colony-stimulating factor (GM-CSF).

When using GM-CSF, the level of neutrophils, monocytes, eosinophils increases and the cellularity of the bone marrow increases. A significant effect from treatment appears after 2 weeks, usually the treatment is longer. The effect is better in patients with an initially high level of neutrophils. It is prescribed at a dose of 5 mcg / kg / day from the first day of immunosuppressive therapy.

2. Granulocyte colony-stimulating factor (G-CSF).

When used, the number of neutrophils increases, the effect of treatment is noticeable after 2 weeks. Children with initially low levels of neutrophils respond worse to treatment. The dose is 5 mcg/kg/day.

3. Interleukin 3 (IL-3).

Since 1990, there have been reports of the effectiveness of IL-3 in patients with aplastic anemia. Given that IL-3 affects pluripotent cells, a bi- or trilinear effect of its use was expected when prescribing the drug. However, the hematological effect was limited to the myeloid component and IL-3 was less effective in correcting neutropenia than GM-CSF and G-CSF. The drug has pronounced toxicity, the most common side effects are fever, bleeding and headache. At present, a conclusion has been made about the low therapeutic value of IL-3.

4. Other hematopoietic growth factors.

There are reports in the literature on the use of interleukin 1 (IL-1), but high toxicity of the drug and insufficient hematological effect have been demonstrated. Erythropoietin is usually administered in combination with G-CSF, the response to treatment is noted after 10 days or more. Clinical trials of thrombopoietin (megakaryocyte growth factor) are in the very early stages and do not include patients with aplastic anemia.

The combined use of immunosuppressive therapy and growth factors prevents early mortality from infections in agranulocytosis. Increasing the level of neutrophils already at the beginning of the course of therapy with growth factors allows to prolong the survival of patients long enough until the restoration of bone marrow with the help of immunosuppressive drugs (or until BMT).

Currently, the best results have been obtained with the combined use of ATG, cyclosporine A, and G-CSF. The immediate results of combined immunosuppressive therapy do not differ from the results of bone marrow transplantation, but it has been noted that after successful immunosuppression, both the risk of aplasia recurrence and the risk of developing (up to 32%) late clonal abnormalities - myelodysplastic syndrome and acute myeloid leukemia - are high.

Hematopoietic growth factors

Name of the factor	Mechanism of action	Release form	Manufacturer	Main side effects
Granocyte (lenograstim)	G-CSF	Vial of 33.6 million IU (263 mcg)	Rhone-Poulenc Rorer, France	Gastrointestinal anaphylaxis: anorexia, nausea, vomiting, diarrhea.
Neupogen (filgrastim)	G-CSF	Vial or syringe-tube of 30 million IU (300 mcg) and 48 million VD (480 mcg)	Hoffman LaRoche, Switzerland	CCC: arterial hypotension, cardiac arrhythmia, heart failure, pericarditis. CNS: fever, cerebrovascular accident, confusion, seizures, increased intracranial pressure.
Leukomax (molgramosgym)	G-CSF	Vial of 150, 300, 400 mcg of active substance	Schering-Plough, USA	Reactions at the injection site (with subcutaneous administration). Enlargement of parenchymatous organs, edema (when using GM-CSF in high doses)

• Androgens

They are not used independently, but are partially effective when used together with ALG.

• Symptomatic therapy

Includes the prescription of hemocomponent (replacement) therapy, antibacterial therapy, symptomatic hemostatic therapy, and desferal to patients with aplastic anemia.

• Hemocomponent therapy

It is used to treat anemic and hemorrhagic syndromes. Washed (EMOLT) or defrosted erythrocytes, thromboconcentrate, and fresh frozen plasma are used.

Currently, hemotherapy for patients with aplastic anemia is based on the following principles:

• refusal to use banked blood;
• strictly differentiated indications for the use of blood components;
• use of effective doses of blood components;
• maximum observance of immunological compatibility of donor and recipient blood;
• the use of components obtained primarily from donors who are relatives of the patient;
• compliance with the “one donor – one recipient” provision.

Washed or defrosted red blood cells are used to treat anemic syndrome. They are characterized by a low content of leukocytes, plasma protein antigens, antibodies, sodium citrate, and platelets, which significantly reduces the risk of post-transfusion complications. The frequency of their administration depends on the patient's condition and the severity of anemia. To relieve severe anemic syndrome (hemoglobin below 60 g/l, red blood cells less than 2.0 x 10 ¹² /l), washed or defrosted red blood cells are transfused at a rate of 10 ml/kg of body weight daily. Subsequently, with improvement in red blood cell count, transfusions are performed twice a week to maintain the blood hemoglobin level at least 90 g/l, which is sufficient to eliminate tissue hypoxia.

Platelet concentrate transfusions are indicated for:

• platelet count < 5.0 x 10 ⁹ /l, regardless of the presence or absence of hemorrhage;
• platelet count 5-10 x 10 ⁹ /l even with minimal hemorrhages and/or hyperthermia of 38 ^o C or more;
• platelet count 20 x 10 ⁹, l with spontaneous bleeding;
• platelet count < 30 x 10 ⁹ /l with pronounced signs of bleeding (bleeding from the mucous membranes of the mouth, nose, genitals; local visceral - gastrointestinal tract, genitourinary system and cerebral hemorrhages);
• platelet count 20-50 x 10 ⁹ /l or less in children before punctures (sternal, lumbar and others), catheterization of large venous trunks and other traumatic procedures;
• a sharp decrease in the platelet count by more than 50 x 10 ⁹ /l in 24 hours or 2.5 x 10 ⁹ /l in 1 hour, regardless of the presence or absence of bleeding.

For transfusions, 1 dose of platelet concentrate 0.5-0.7 x 10 ⁹ cells obtained from 500 ml of preserved blood is used for every 10 kg of body weight or 4 doses per 1 m ² of the child’s body surface.

When transfusing platelet concentrates, it is important to monitor the therapeutic effectiveness: relief of hemorrhagic syndrome, determination of the number of platelets in the peripheral blood.

The main indications for transfusion of fresh frozen plasma in patients with aplastic anemia are hemorrhagic complications caused by a deficiency of blood clotting factors observed in cases of DIC syndrome and liver dysfunction.

• Antibacterial therapy

It is prescribed to relieve emerging infectious complications. The risk of infection increases significantly at a neutrophil count below 0.5 x 10 ⁹ /l and directly depends on the duration of neutropenia. With severe neutropenia, signs of infection may be vague, so prophylactic antibiotics may be prescribed to such patients. Absolute indications for antibacterial therapy in a patient with aplastic anemia and neutropenia of 0.5 x 10 ⁹ /l are the development of fever up to 38 ^o C, which should be regarded as a manifestation of infection. During a physical examination, it is necessary to try to establish the source of infection, paying special attention to the site of insertion of the venous catheter, paranasal sinuses, oral cavity, and anorectal area. Before starting treatment, blood cultures from a peripheral vein (from two different sites), urine, feces, sputum, a swab from the throat and nose, as well as cultures of material from possible foci of infection are mandatory; chest X-ray is performed. Empirical antibiotic treatment begins immediately after collecting the material for culture. If the source of infection cannot be identified, broad-spectrum antibiotics are prescribed that are effective against gram-negative rods and gram-positive cocci. Combined therapy is prescribed with third-generation aminoglycosides: amikacin, tobramycin, sisomicin, netilmicin and third-generation cephalosporins cefotaxime (claforan), ceftriaxone (rocephin), ceftazidime (fortaz, tazidime, tazicef), ceftizoxime (cefisox, epocillin), etc. or ureidopenicillinamine: azlocillin, mezlocillin, piperacillin, monotherapy with third-generation cephalosporins or carbapenems is possible: tienam, imipenem, meropinem. After receiving the culture results or if the treatment is ineffective, it may be necessary to change the antibiotic therapy regimen. If the fever lasts more than 72 hours, antifungal drugs are prescribed (amphotrecin B 0.5-1 mg/kg/day). After the infection has stopped, antibiotic treatment is continued until the neutrophil count exceeds 0.5x10 ⁹ /l.

To prevent infection in patients with aplastic anemia with neutropenia, it is necessary to place the patient in a separate room, quartz the room, change linen daily, rinse the throat, and perform selective decontamination of the intestine.

• Symptomatic hemostatic therapy

Includes the administration of adroxone, dicinnon, epsilon-aminocaproic acid in age-appropriate doses; the use of local hemostatic agents (hemostatic sponge, thrombin).

• Chelation therapy

It is prescribed to reduce the manifestations of hemosiderosis developing in patients with aplastic anemia. Desferal (deferoxamine) binds and removes trivalent iron from tissues with urine. The drug splits off iron from ferritin, hemosiderin, transferrin and does not extract it from heme compounds. Indications for the prescription of desferal are increased ferritin levels > 1000 ng/ml and positive results of the desferal test (increased iron excretion with urine). Desferal is prescribed at a dose of 20 mg/kg/day intravenously by drip daily for 30 days. After a four-week break, the treatment courses are repeated.

• Splenectomy

Previously, it was often performed as a "desperation therapy", currently it has no independent value, it is an auxiliary method of treatment. It is practically not used in hereditary aplastic anemia. Indications for splenectomy in patients with acquired aplastic anemia may be deep refractory thrombocytopenia, severe hemorrhagic syndrome and the need for frequent platelet transfusions, hypersplenism.

To evaluate the results of treatment of patients with aplastic anemia, the following criteria are used to characterize the presence of remission.

1. Complete clinical and hematological remission.
   • Absence of clinical symptoms of the disease and manifestations of hemorrhagic syndrome.
   • The hemoglobin content in the blood is more than 110 g/l.
   • Granulocyte content is more than 2 x 10 ⁹ /l.
   • Platelet count is more than 100 x 10 ⁹ /l.
   • Hematocrit is above 0.35.
   • No risk of infectious complications.
2. Partial clinical and hematological remission.
   • Absence of clinical symptoms of the disease and manifestations of hemorrhagic syndrome.
   • The hemoglobin content in the blood is more than 80 g/l.
   • Granulocyte content is more than 0.5 x 10 ⁹ /l.
   • Platelet count is more than 20 x 10 ⁹ /l.
   • Absence of infectious complications.
   • Patients do not depend on transfusions of blood components.
3. Clinical and hematological improvement.
   • Peripheral blood parameters allow for outpatient treatment of patients.
   • Absence of pronounced hemorrhagic manifestations.
   • Granulocyte content is more than 0.5 x 10 ⁹ /l.
   • Platelet count is more than 20 x 10 ⁹ /l.
   • The need for hemocomponent therapy remains.
4. No effect.

Progression of clinical and hematological symptoms, increase in hemorrhagic manifestations, occurrence of infectious complications.

Outpatient observation

Outpatient monitoring of patients with aplastic anemia in the remission stage is carried out by a hematologist.

• Clinical blood test once every 10 days.
• Permanent medical exemption from vaccinations.
• Exemption from physical education classes.
• School classes are allowed, but, depending on the condition, individual classes and home classes are possible.
• The following medications are contraindicated: chloramphenicol, salicylates and other non-steroidal anti-inflammatory drugs, antiplatelet agents (curantil, etc.); FTL is contraindicated.

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