How is Aplastic Anemia Treated?

Treatment of congenital forms of aplastic anemia

Fanconi Anemia

• Bone marrow transplantation.

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

Bone marrow transplantation from HLA-identical sibling using softened conditioning - thoracoabdominal irradiation at a dose of 6 Gy and cyclophosphamide at a dose of 20 mg / kg is performed. This approach allows to cure 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	The route of administration	Frequency of administration
Methandoostenolone (nerobol, dianabol)	0.2-0.4	Enteral	Daily
Retabolil (deca-durabolin; nandrolone)	1-1.5	Intramuscularly	1 time in 7-14 days
Fenobolin (durabolin; nerobolil)	0.25-0.4	Intramuscularly	1 time in 7-10 days
Oxymetholone (dihydrotestosterone)	0.5-2	Enteral	Daily
Testosterone enanthate	4	Intramuscularly	1 time in 7 days
Testosterone propionate (orethon)	1-2	Sublingually	Daily

Treatment with androgens is carried out for 3-6 months, during the first 1.5-2 months give a full dose of drugs, and then switch to a support, which is 1/2 of the total therapeutic dose. Improvement of hematological parameters occurs 6-8 weeks after the initiation of therapy - the number of reticulocytes and hemoglobin increases, and then the number of leukocytes increases. The number of platelets does not increase for a long time.

Therapy is usually started with oxymetholone in a dose of 0.5-2 mg / kg / day enterally daily. The response to therapy is noted 4-8 weeks after the start of treatment. Approximately 50% of patients have a significant improvement in hematological indicators. The response to androgen therapy has a prognostic value: the average survival rate of patients responding to androgens is about 9 years, not responding - 2.5 g.

• Replacement blood transfusion therapy.

Indications for substitution therapy are determined by hematological parameters:

• hemoglobin level <80 g / l;
• absolute number of neutrophils <1, 0 x 10 ⁹ / l;
• the number of platelets is <20 x 10 ⁹ / l.

Transfusion of erythrocyte mass and thrombin suspension begins to be carried out only when the indicators reach the indicated level. To diagnose a possible hemosiderosis every 6 months, it is necessary to determine the level of ferritin in order to schedule desferal therapy in time.

• Hematopoietic growth factors.

Can be prescribed as a trial therapy for ineffectiveness of conventional treatment and the absence of a compatible donor. The use of such growth factors as G-CSF, 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, reports of attempts to gene therapy patients with Fanconi anemia have been reported .

Treatment of aplastic anemia with congenital dyskeratosis

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

Treatment of aplastic anemia with Schwamman syndrome

Treatment of aplastic anemia in the syndrome of Shvakhman has not been developed. For the treatment of malabsorption syndrome, substitution therapy with enzymes is prescribed. If infectious complications arise, antibacterial therapy is necessary. In some patients, the administration of small doses of prednisolone increases the number of neutrophils.

Blackempine-Diamond anemia (ABD)

• Corticosteroid therapy - is the main method of treatment of ABD, it is with corticosteroids begin therapy at the onset of the disease. Prescribe prednisolone at a dose of 2 mg / kg / day in 3 divided doses for 4 weeks; then the daily dose in patients with a positive response (increasing Hb to 100 g / l) should be gradually reduced to a minimum maintenance daily dose (daily or every other day to maintain a sustained response).

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

Indicators characterizing the response to the treatment of children with Blackhamen-Diamond anemia

Response to therapy	Increase in the number of reticulocytes	Independence from transfusions	Reduced need for hemotransfusion	The regular need for hemotransfusion (1 every 3-6 weeks)
Full	+	+	-	-
Partial	+	-	+	-
Bad partial	+	-	-	+
No answer	-	-	-	+

• Hemotripsyphoid therapy is a substitution therapy, it is a common alternative in steroid-resistant patients or patients with a high threshold of response to prednisolone therapy.

Transfusions of erythrocytes are carried out every 4-5 weeks, in infants every 2-3 weeks, to maintain the level of hemoglobin, which ensures optimal growth of the child. The most serious complications of blood transfusion therapy are the development of hemosiderosis and the attachment of viral diseases.

• Bone marrow transplantation. It is an important therapeutic alternative for steroid-resistant patients with ABD who need blood transfusions in the presence of an HLA-compatible donor. There have been reports of successful transplantation of umbilical cord blood cells from HLA-compatible sibling, which probably indicates the expediency of umbilical cord freezing from siblings of DBA patients.
• Therapy with high doses of methylprednisolone (VDMP) - is another alternative for patients with ABD.

It is recommended to prescribe methylprednisolone in a dose of 100 mg / kg / day intravenously or according to the scheme:

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

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

1. Sternal punctate - before the course and on the 30th day.
2. Clinical analysis of blood with reticulocytes 1 time in 5 days.
3. Fetal hemoglobin - before the course and on the 30th day.
4. Biochemistry - (ALT, ACT, FMFA, sugar, electrolytes) 1 time in 7 days.
5. Urinalysis 2 times a week (glucose control).
6. ECG - before the course, then 1 time in 14 days.
7. Blood pressure is daily for 45 days.

• With steroid-resistance is possible the appointment of androgens, 6-mercaptopurine, cyclophosphamide, cyclosporine A, ATG / ALG.

Treatment of acquired aplastic anemia

• Bone marrow transplantation (TCM)

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

The frequency of long-term survival in children who underwent bone marrow transplantation in the early stages of the disease from a fully HLA-compatible donor, according to the literature, is 65-90%. The most widespread was allogeneic bone marrow transplantation, which uses bone marrow from siblings, that is, from siblings with the greatest antigenic affinity for the recipient. If it is impossible to obtain bone marrow from snbling try to use bone marrow from other relatives or HLA-compatible unrelated donors. Unfortunately, only for 20-30% of patients you can find a suitable donor. Transplantation of incompletely compatible stem cells of donor cord blood is possible.

Carrying out bone marrow transplantation requires careful preparation for effective immunosuppression. Preparation ("conditioning") before carrying out bone marrow transplantation involves the administration of high doses of cyclophosphamide (200 mg / kg) with anti-thymocyte globulin (ATG) or without it, fractional total body irradiation. A possible complication of allogeneic bone marrow transplantation is the onset of the "graft versus host" reaction, whose frequency is 25% when the bone marrow of relatives is used and 50% for bone marrow transplantation from unrelated donors.

• Alternative therapies

Include the appointment of immunosuppressive therapy (antilnphocytic / antitnmotsitarnogo globulin, cyclosporine A, high doses of methylprednisolone) and hematopoietic growth factors.

• Immunosuppressive therapy

1. Antilymphocytic (antitimotsertpy) globulin (ALG).

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

ALG is administered intravenously via a central infusion catheter for 12 hours, 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. To reduce allergic reactions together with ALG prescribed average doses of corticosteroids.

Those who responded to treatment receive granulocyte counts 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 larger dose.

2. Ciclosporin A (sandimmun).

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

The mechanism of action and the main side effects of drugs used in patients with aplastic anemia

Drug Group	Mechanism of action	Major side effects
Antilymphocytic globulin	Lymphocytotoxic effect on activated T-suppressors. Immunostimulating effect on granulocytopoiesis (increase in production of GM-CSF and IL-3) Effect on stem cells	Chemical phlebitis when injected into the peripheral vein. Allergic reactions: anaphylaxis (in the first 1-3 days), serum sickness (on the 7-10th day after the first dose) CNS: fever, seizures CCC: hypertension, heart failure, pulmonary edema Infectious (bacterial) complications Hematologic complications: hemolysis, DIC-syndrome, aggravation of neutropenia, thrombocytopenia
Corticosteroids (prednisolone, methylprednisolone)	Immunosuppressive effect (decrease in the content of T- and B-lymphocytes, a decrease in the titer of serum immunoglobulins and the titer of specific antibodies). Reduction in the number of stem cells commited for erythropoiesis and granulocytopoiesis. Stimulation of migration of stem cells from the bone marrow to the bloodstream. Hemostatic effect	Endocrine system: Itzenko-Cushing syndrome Metabolism: violation of carbohydrate metabolism, weight gain, osteoporosis. Gastrointestinal: ulcers of the stomach and intestines CNS: mental disorders, increased intraocular pressure CCC: hypertension Immune Deficiency Syndrome
Anabolic steroids (androgens)	Enhance the production of erythropoietin by the kidneys. The effect on stem cells in the phase of G o -G 1 and stimulation of their release into the mitotic, erythropoietin-sensitive phase. Stimulation of granulocytopoiesis due to enhancement of bone marrow macrophages with colony-stimulating factor	Endocrine system: virilization, premature closure of bone growth zones, weight gain. GI: hepatotoxicity with possible development of liver tumors, cholestasis
Cyclosporin A (sandimmun)	Suppress the development of cell-type reactions and T-lymphocyte-dependent formation of antibodies. At the cellular level, it blocks G 0 and G 1 cell lymphocytes , inhibits secretion and production of lymphokines (interleukins 1, 2, beta and γ-interferon) by activated T lymphocytes	Impaired renal function (increased urea concentration and serum creatinine). Gastrointestinal tract: 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. Hypertrophy of the gums. Infectious complications

The drug is available in two forms: ampouled for intravenous administration and for oral administration. Preparations for per os:

• 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 in the 1- 14 days of treatment, then dose is increased to 15 mg / kg / day (in 2 divided doses) children and 12 mg / kg / day (in 2 admission) in adults. The level of therapeutic dose in the blood is 200-400 ng / ml. It is necessary to monitor therapy: blood pressure daily, biochemistry (ALT, ACT, FMFA, bilirubin, sugar, urea, creatinine, cholesterol, electrolytes) every 7 days. The level of cyclosporine in the blood serum is determined by the radioimmune method once a week in the first two weeks of treatment, then once in 2 weeks.

It is important to monitor plasma creatinine: increasing creatinine levels by more than 30% of the norm requires reducing the dose of cyclosporine by 2 mg / kg / day every week until the creatinine level is normalized. If the level of cyclosporine> 500 ng / ml - the therapy is stopped. After lowering the level to 200 ng / ml or lower, the therapy is resumed at a dose 20% less than the original.

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

3. Corticosteroids are high doses of methylprednisolone (DMDP).

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

Interaction of cyclosporine with drugs

Pharmacokinetics

Reduce the level of cyclosporine in serum	Increase the level of cyclosporine in serum
Carbomazepine	Erythromycin
Phenobarbital	Fluconazole
Rifampin	Ketoconazole
Trimetonim (intravenously)	Nifedipine
Metoclopramide (raglan)	Imipenem-Celastin
Phenytoin	Methylprednisolone
	Prednisolone

Pharmacological interaction

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

It is possible to administer methylprednisolone enterally or intravenously according to the following schedule: 1-9 days: 1 μg / kg / day 10-11 days: 0.66 mg / kg / day 12-13 days: 0.5 mg / kg / day 14-16 days: 0.33 mg / kg / day 17-18 days: 0.16 mg / kg / day Day 19: 0.04 mg / kg / day Day 20 : 0.33 mg / kg / day 21 day: not administered 22nd day: 0.16 mg / kg / day 23rd day: not administered 24th day: 0.08 mg / kg / day 25 Day: Cancel (the course is over).

In addition to methylprednisolone, especially on days of administration of ATG, transfusion of thromboconcentrate is prescribed so that the number of platelets is more than 20 x 10 ⁹ / L. 4.

High doses of cyclophosphamide.

Assign patients with severe A A, not having a histocompatible donor. The most common is the following scheme:

1-3 days - 45 mg / kg / day intravenously; 4-9 days - 5 mg / kg / day intravenously; 10-20 days - 3.75 mg / kg / day intravenously; 21-27 days - 2.5 mg / kg / day intravenously; 28-31 days - 1, 5 mg / kg / day intravenously; 32nd day - 5 mg / kg / day inside; 33-56 days - 10 mg / kg / day inside; 57-100 days - 7.5 mg / kg / day inside.

• Hematopoietic growth factors

Recombinant human hematopoietic growth factors are used only in the complex treatment of patients with aplastic anemia, as 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, and eosinophils increases and the cellularity of the bone marrow increases. A significant effect of treatment appears after 2 weeks, usually a longer treatment. The effect is better in patients with initially high levels of neutrophils. It is prescribed in a dose of 5 mcg / kg / day from the first day of immunosuppressive therapy.

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

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

3. Interleukin 3 (IL-3).

Since 1990, there have been reports of the effectiveness of IL-3 in patients with aplastic anemia. Considering that IL-3 affects polypotent cells, a bi-or trilinear effect of its use was expected when the drug was prescribed. However, the haematological 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 a pronounced toxicity, the most frequent side effects are fever, bleeding and headache. Currently, a conclusion is drawn about the low therapeutic value of IL-3.

4. Other hematopoietic growth factors.

In the literature there are reports of the use of interleukin 1 (IL-1), but demonstrated high toxicity of the drug and an insufficient hematologic effect. Erythropoietin is usually prescribed in combination with G-CSF, the response to treatment is noted 10 days later. Clinical studies of thrombopoietin (megakaryocytic growth factor) are at very early stages and do not include patients with aplastic anemia.

Joint 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 prolonging the survival of patients long enough before the restoration of bone marrow with the help of immunosuppressive drugs (or before TCM).

At present, the best results are obtained with the joint use of ATG, cyclosporin A, G-CSF. Immediate results of combined immunosuppressive therapy do not differ from the results of bone marrow transplantation, but it is noted that after successful immunosuppression, both the risk of recurrence of aplasia and the risk of developing (up to 32%) late clonal anomalies, myelodysplastic syndrome and acute myeloid leukemias, is high.

Hematopoietic growth factors

Name of factor	Mechanism of action	Form of issue	Company manufacturer	Major side effects
Granocyte (lenograstim)	G-CSF	The bottle was 33.6 million IU (263 μg)	Ron-Poulenc Rohrer, France	Anaphylaxis of the digestive tract: anorexia, nausea, vomiting, diarrhea.
Neupogen (filgrastim)	G-CSF	A vial or syringe tube of 300 MU ED (300 μg) and 48 million VD (480 μg)	Hoffman LaRouche, Switzerland	SSS: arterial hypotension, heart rhythm disturbance, heart failure, pericarditis. CNS: fever, cerebral circulation, confusion, convulsions, increased intracranial pressure.
Leucomax (molegrass)	G-CSF	The vial is 150,300, 400 μg of the active substance	Schering-Plow, USA	Reactions at the injection site (with subcutaneous injection). Increased parenchymal organs, edema (when using GM-CSF in high doses)

• Androgens

Independently are not used, partially effective when used in conjunction with ALG.

• Symptomatic therapy

Includes the appointment of patients with aplastic anemia of hemocomponent (replacement) therapy, antibiotic therapy, symptomatic hemostatic therapy, desferal.

• Hemocomponent therapy

Used to treat anemic and hemorrhagic syndromes. Apply washed (EMOLT) or defrosted erythrocytes, thromboconcentrate, freshly frozen plasma.

At present, the hemotherapy of patients with aplastic anemia is based on the following principles:

• refusal to use canned blood;
• strictly differentiated indications for the use of the components of blood;
• the use of effective doses of blood components;
• maximum compliance with the immunological compatibility of donor and recipient blood;
• use of components derived primarily from donor-relatives of the patient;
• compliance with the provision "one donor - one recipient".

For the treatment of anemic syndrome, washed or thawed red blood cells are used which are characterized by a low content of leukocytes, plasma protein antigens, antibodies, sodium citrate and platelets, which significantly reduces the risk of posttransfusion complications. The frequency of their administration depends on the patient's condition and severity of anemia. To relieve severe anemic syndrome (hemoglobin below 60 g / l, erythrocytes less than 2.0 x 10 ¹² / L), transfuse washed or thawed red blood cells at a rate of 10 ml / kg body weight daily. Further, with improvement of red blood transfusion parameters, 2 times a week are carried out to maintain blood hemoglobin level not lower than 90 g / l, which is sufficient to eliminate tissue hypoxia.

Transfusions of platelet concentrates are shown when:

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

For transfusion use 1 dose of platelet concentrate 0,5-0,7 x 10 ⁹ cells, obtained from 500 ml of canned blood, for every 10 kg of body weight or 4 doses per 1 m ² of the child's body surface.

When carrying out transfusions of platelet concentrates, it is important to monitor the therapeutic effectiveness of: stopping hemorrhagic syndrome, determining the number of platelets in the peripheral blood.

The main indications for transfusion of freshly frozen plasma in patients with aplastic anemia are hemorrhagic complications due to a deficiency of clotting factors observed in cases of DIC syndrome, violations of liver function.

• Antibiotic therapy

It is prescribed for relief of emerging infectious complications. The risk of infection increases significantly when the level of neutrophils is below 0.5 x 10 ⁹ / L and directly depends on the duration of neutropenia. With severe neutropenia, signs of infection can be erased, so in such patients, a prophylactic appointment of antibiotics is possible. Absolute indications for antibacterial therapy in a patient with aplastic anemia and neutropenia 0.5 x 10 ⁹ / L is the appearance of fever to 38 ^o C, which should be regarded as a manifestation of infection. In case of physical examination, it is necessary to try to establish a focus of infection, paying special attention to the venous catheter insertion site, paranasal sinuses, oral cavity, anorectal area. Prior to the start of treatment, blood cultures from the peripheral vein (from two different sites), urine, feces, sputum, a smear from the pharynx and nose, and also the sowing of the material from possible foci of infection are necessarily conducted; perform a chest x-ray. Empirical treatment with antibiotics begins immediately after taking the material for seeding. If the source of infection could not be identified, antibiotics of a wide spectrum, acting on gram-negative rods and Gram-positive cocci, are prescribed. Assign a combination therapy with aminoglycosides III generation: amikacin, tobramycin, sizomycin, netilmitsin and cephalosporins of the third generation cefotaxime (claforan), ceftriaxone (rocephin), ceftazidime (fortaz, tazidim, tazitsef), ceftizoxime (cefizox, epocillin), and ureidopenicillinamine: azlocillin , mezlocillin, piperotsillin, monotherapy with cephalosporins of the third generation or carbapenems: tienam, imipenem, meropinem. After receiving the results of inoculation or if the treatment is ineffective, it may be necessary to change the regimen of antibiotic therapy. If the fever lasts more than 72 hours, antimycotic drugs are prescribed (amphotorecin B 0.5-1 mg / kg / day). After cessation of infection, treatment with antibiotics continues until the amount of neutrophils does not exceed 0.5 × ^{10 9} / L.

For the prevention of infection in patients with aplastic anemia with neutropenia necessarily placing the patient in a separate room, quartz chamber, daily change of clothes, rinsing throat, selective decontamination of the intestine.

• Symptomatic haemostatic therapy

Includes the appointment of adroxone, dicnon, epsilon-aminocaproic acid in age doses; use of local hemostatics (hemostatic sponge, thrombin).

• Cholator therapy

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

• Splenectomy

Previously, quite often performed as a "therapy of despair", now has no independent value, is an auxiliary method of treatment. With hereditary aplastic anemia is practically not used. Indications for splenectomy in patients with acquired aplastic anemia can be deep refractory thrombocytopenia, severe hemorrhagic syndrome and the need for frequent transfusions of platelets, hypersplenism.

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

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.
   • The granulocyte content is more than 2 x 10 ⁹ / l.
   • The number of platelets is more than 100 x 10 ⁹ / l.
   • The hematocrit is higher than 0.35.
   • Absence of risk of infectious complications.
2. Partial clinico-hematologic 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.
   • The granulocyte content is more than 0.5 x 10 ⁹ / l.
   • The number of platelets is more than 20 x 10 ⁹ / l.
   • Absence of infectious complications.
   • Patients do not depend on transfusions of blood components.
3. Clinico-hematologic improvement.
   • Parameters of peripheral blood allow to treat patients outpatient.
   • Ovosence of expressed hemorrhagic manifestations.
   • The granulocyte content is more than 0.5 x 10 ⁹ / l.
   • The number of platelets is more than 20 x 10 ⁹ / l.
   • There is a need for hemocomponent therapy.
4. Lack of effect.

Progress clinical-hematological symptoms, the increase of hemorrhagic manifestations, the emergence of infectious complications.

Dispensary supervision

Clinical follow-up of patients with aplastic anemia in remission is performed by a hematologist.

• Clinical blood test once every 10 days.
• Permanent medical advice from vaccinations.
• Exemption from physical education lessons.
• School classes are allowed, but, depending on the state, classes are possible on an individual plan and at home.
• Contraindicated taking the following medicines: levomitsetina, salicylates and other non-steroidal anti-inflammatory drugs, disaggregants (kurantil, etc.); contraindicated by FTL.

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