How is thalassemia treated?

Transfusion therapy

Indications for initiation of transfusion therapy:

• major form of β-thalassemia, hemoglobinopathy H with a hemoglobin level below 70 g/l;
• intermediate and major forms of β-thalassemia, hemoglobinopathy H with a hemoglobin level of 70-90 g/l with a pronounced delay in physical development, the presence of bone changes, and a significant increase in the spleen.

Transfusion of red blood cells in thalassemia is necessary to maintain the hemoglobin level of about 120 g/l, which prevents the development of secondary hypersplenism, skeletal bone deformation and hypervolemia due to the suppression of ineffective erythropoiesis. The interval between transfusions is on average 2-6 weeks and depends on the patient's ability to visit the clinic with a certain frequency, as well as on the volume of available red blood cells.

In the absence of intercurrent diseases, the rate of decrease in hemoglobin concentration after transfusion is approximately 10 g/l per week. The volume of transfused red blood cells is determined depending on the interval between transfusions and the concentration of the available red blood cells.

On average, to increase the patient's hemoglobin level by 10 g/L, 3 ml of red blood cells per kilogram of the patient's body weight is required with an Ht of red blood cells of 70%. Iron accumulates in the body most slowly with a pre-transfusion hemoglobin level of 90-100 g/L and with intervals between transfusions exceeding 2 weeks.

Chelation therapy for secondary (post-transfusion) iron overload

Iron overload can be estimated from the amount of red blood cell transfused, transferrin saturation with iron, or the level of SF. These parameters correlate with both total body iron stores and the iron content of the liver (direct measurement of the amount of iron in the dry matter of a liver biopsy by atomic absorption spectrometry). Patients with the large form of β-thal receive on average 165 (140) mg of red blood cell mass/kg per year, which corresponds to 180 (160) mg Fe/kg per year or 0.49 (0.44) mg Fe/kg per day (values u200bu200bfor splenectomized patients are given in brackets). Excess iron accumulates in the cells of the phagocytic macrophage system, their capacity is about 10-15 g of iron; then, iron is deposited in all parenchymatous organs and the skin, leading to the development of life-threatening complications:

• cirrhosis of the liver;
• cardiomyopathy;
• diabetes mellitus;
• hypothyroidism;
• hypoparathyroidism;
• hypogonadism.

The only way to prevent organ and tissue damage is long-term administration of chelating agents. To achieve a negative iron balance in transfusion-dependent patients, excretion of 0.4-0.5 mg/kg iron daily is necessary.

Standard chelation therapy is carried out with the drug deferoxamine (Desferal - DF) subcutaneously at a dose of 20-40 mg/kg per day in children and 40-50 mg/kg per day in adults 8-12 hours 5-7 days per week constantly or intravenously continuously for 24 hours for 7 days, followed by a transition to subcutaneous administration.

Administration of desferal begins when the serum ferritin (SF) level is more than 100 ng/ml or liver iron is more than 3.2 mg/g dry matter. The starting dose of desferal for children is 25-30 mg/kg 5 nights a week. Therapy is carried out under the control of the therapeutic index, which should be maintained at least 0.025. In children under 5 years of age, it is undesirable to use desferal in a dose of more than 35 mg/kg, before the end of the growth period - more than 50 mg/kg. If chelation therapy begins before the age of 3, careful monitoring of bone growth and development processes is necessary.

Therapeutic index = average daily dose (mg/kg) / SF (ng/ml)

Indications for intravenous administration of deferoxamine:

Absolute:

• heavy iron overload:
  • SF is constantly more than 2500 mcg/l;
  • iron in the liver is more than 15 mg/g dry matter;
• significant heart damage:
  • arrhythmia;
  • heart failure;

Additional:

• difficulties with regular subcutaneous infusions;
• pregnancy period;
• planned BMT;
• active viral hepatitis.

Deferasirox is another oral chelator that is currently used as first-line monotherapy for transfusion-induced iron overload in patients with thalassemia. The recommended starting dose in patients with thalassemia major is 20 mg/kg once daily, with possible increases to 40 mg/kg.

Splenectomy

Indications for splenectomy in thalassemic syndromes:

• an increase in the need for red blood cell transfusions over 200-220 ml/kg per year (with its Ht 75%);
• splenomegaly, accompanied by pain in the left hypochondrium and/or the threat of rupture of the spleen;
• phenomena of hypersplenism.

Splenectomy in thalassemic syndromes should be performed according to very strict indications at the age of no earlier than 5 years after completion of prophylactic vaccination, including meningococcal, pneumococcal, Haemophilus influenzae type B and hepatitis B vaccines (no earlier than 2 weeks after vaccination).

Given the tendency of patients with thalassemia to hypercoagulation, immediately before surgery it is necessary to study hemostasis, prescribe prophylactic doses of acetylsalicylic acid (80 mg/kg per day) or direct-acting anticoagulants in the early postoperative period.

Outpatient observation

Once a month - general clinical blood test.

Once a quarter - iron metabolism test, biochemical blood test (glucose concentration, uric acid, urea, creatinine, alkaline phosphatase activity, γ-GTP, ALT, AST, LDH).

Once every 6 months - ECG, echocardiography (measurement of ventricular volumes, myocardial contractility, ejection fraction, systolic and diastolic indices).

Once a year - virological examination:

• markers of hepatitis B and C, HIV;
• liver biopsy with determination of dry matter iron content;
• assessment of endocrine gland function: determination of concentration of free T4 _, TSH, parathyroid hormone, follicle-stimulating hormone, luteinizing hormone, testosterone, estradiol, cortisol; glucose tolerance test, densitometry, determination of level of total and ionized calcium in blood.

If deviations from the norm are detected, appropriate treatment should be carried out.

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