Paroxysmal nocturnal hemoglobinuria (Marciafawa-Mikeli syndrome): causes, symptoms, diagnosis, treatment

Paroxysmal nocturnal hemoglobinuria (Markiafawa-Mikeli syndrome) is a rare disease characterized by intravascular hemolysis and hemoglobinuria and worsening during sleep. It is characterized by leukopenia, thrombocytopenia and episodic crises. Diagnosis requires a study using flowcytometry, an acid hemolysis test may be useful. Treatment is maintenance therapy.

Epidemiology

Paroxysmal nocturnal hemoglobinuria (APG) is more common in men from 20 to 30 years, but in general it occurs in both men and women of all ages.

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Risk factors

A crisis can be triggered by infection, iron intake, vaccination or menstruation.

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Pathogenesis

The disease is caused by a genetic mutation leading to abnormal membrane of stem hemopoietic cells and their descendants, including erythrocytes, leukocytes and platelets. As a result of the mutation, there is an increased sensitivity to the normal SZ component of blood plasma complement, which leads to intravascular hemolysis of erythrocytes and a decrease in production in the bone marrow of leukocytes and platelets. The defect is the absence of glycosyl-phosphatidyl-inositol fixative for membrane proteins, which is due to a mutation of the PIG-A gene located on the X chromosome. A prolonged loss of hemoglobin can lead to iron deficiency. Patients have a pronounced predisposition to the development of venous and arterial thrombosis, including Badda-Chiari syndrome. Thrombosis, as a rule, fatal. A number of patients with paroxysmal nocturnal hemoglobinuria develop aplastic anemia, and in some patients with aplastic anemia - paroxysmal nocturnal hemoglobinuria.

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Symptoms of the paroxysmal nocturnal hemoglobinuria

The disease manifests itself as symptoms of severe anemia, pain in the abdomen and spine, macroscopic hemoglobinuria, splenomegaly.

Diagnostics of the paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria is expected in patients with manifestations of typical symptoms of anemia or unexplained normocytic anemia with intravascular hemolysis, especially if there is leukopenia and thrombocytopenia. If suspicion of paroxysmal nocturnal hemoglobinuria is one of the first tests, a test is performed on glucose based on the enhancement of hemolysis from the SZ complement component in isotonic solutions of low ionic strength, the sample is easily feasible and sensitive enough. However, the test is non-specific, a positive result requires confirmation by subsequent studies. The most sensitive and specific method is the floccytometry method, which determines the deficiency of specific proteins on the erythrocyte or leukocyte membrane. An alternative is the acid hemolysis test (Hema test). Hemolysis usually occurs after the addition of hydrochloric acid to the blood, incubation for 1 hour and subsequent centrifugation. The bone marrow examination is performed to exclude other diseases in which hypoplasia may occur. Expressed hemoglobinuria is a typical phenomenon in the period of crises. Urine may contain hemosiderin.

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Treatment of the paroxysmal nocturnal hemoglobinuria

Treatment is symptomatic. Empirical use of glucocorticoids (prednisolone 20-40 mg per day inside) allows you to control symptoms and stabilize the number of red blood cells in more than 50% of patients. Usually for the crisis period it is necessary to have blood preparations in stock. Transfusion of plasma (SZ) should be avoided. In the washing of red blood cells before transfusions is not necessary. Heparin is necessary for the treatment of thrombosis, but it can enhance hemolysis and should be used with caution. It is often necessary to add drugs to the inside of the iron. In most patients, these measures are sufficient for a long period (from one year or more) for a period of one to many years. Transplantation of allogeneic stem cells is successful in a small number of cases.