How is thalassemia treated?

Transfusion therapy

Indications for the beginning of transfusion therapy:

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

Transfusion of erythrocyte mass in thalassemia is necessary to maintain a hemoglobin level of about 120 g / l, which prevents the development of secondary hypersplenism, deformation of the bones of the skeleton and hypervolemia due to the inhibition of its own ineffective erythropoiesis. The interval between transfusions averages 2-6 weeks and depends on the patient's ability to visit the clinic with a certain frequency, as well as the volume of the available erythrocyte mass.

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 the transfused erythrocyte mass is determined depending on the interval between transfusions and the concentration of the available erythrocyte mass.

On average, 3 ml of erythrocyte mass per kilogram of patient's body weight with Ht of erythrocyte mass of 70% is needed to raise the patient's hemoglobin level by 10 g / l. Iron accumulates in the body most slowly at a pre-transfusion level of hemoglobin 90-100 g / l and at intervals between transfusions exceeding 2 weeks.

Cholator therapy in secondary (post-transfusion) iron overload

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

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

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

The standard chelation therapy is performed with deferoxamine (Desferal-DF) subcutaneously at a dose of 20-40 mg / kg daily for children and 40-50 mg / kg daily for adults for 8-12 hours 5-7 days per week continuously or intravenously for 24 hours for 7 days, followed by a transition to a subcutaneous injection.

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

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

Indications for intravenous administration of deferoxamine:

Absolute:

• heavy iron overload:
  • SF is permanently more than 2500 μg / l;
  • iron in the liver more than 15 mg / g dry matter;
• a significant defeat of the heart:
  • arrhythmia;
  • heart failure;

Additional:

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

Deferazirox is another oral chelator, which is currently used as a first-line monotherapy for transfusion overload with iron in patients with thalassemia. The recommended starting dose in patients with a large form of thalassemia is 20 mg / kg once daily, with a possible increase to 40 mg / kg.

Splenectomy

Indications for splenectomy in thalassemia syndromes:

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

Splenectomy in thalassemia syndromes should be performed at very strict indications at the age not earlier than 5 years after the end of the prophylactic vaccination, including meningococcal, pneumococcal vaccine, hemophilic type B vaccine and hepatitis B vaccine (not earlier than 2 weeks after vaccination).

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

Dispensary supervision

Once a month - a general clinical blood test.

Once a quarter - an examination of iron metabolism, a biochemical blood test (concentration of glucose, uric acid, urea, creatinine, activity of alkaline phosphatase, y-GTP, ALT, ACT, LDH).

Every 6 months - ECG, echocardiogram (measurement of ventricular volume, contractility of the myocardium, ejection fraction, systolic and diastolic parameters).

Once a year - virologic examination:

• markers of hepatitis B and C, HIV;
• liver biopsy with determination of iron content in dry matter;
• evaluation function endocrine glands: determining the concentration of free T ₄, TTG, parathyroid hormone, follicle stimulating hormone, luteinizing hormone, testosterone, estradiol, cortisol; a test for glucose tolerance, densitometry, determination of the level of total and ionized calcium in the blood.

If abnormalities are found, appropriate treatment should be provided.

[1], [2], [3], [4], [5]