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

Paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli syndrome) is a rare disorder characterized by intravascular hemolysis and hemoglobinuria, worsening during sleep. It is characterized by leukopenia, thrombocytopenia, and episodic crises. Diagnosis requires flow cytometry, and an acid hemolysis test may be useful. Treatment is supportive care.

Epidemiology

Paroxysmal nocturnal hemoglobinuria (PNH) is more common in men aged 20 to 30 years, but generally occurs in both men and women of all ages.

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Risk factors

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

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Pathogenesis

The disease is caused by a genetic mutation that results in an abnormality of the membrane of hematopoietic stem cells and their progeny, including red blood cells, white blood cells, and platelets. The mutation results in increased sensitivity to the normal C3 component of plasma complement, leading to intravascular hemolysis of red blood cells and decreased production of white blood cells and platelets in the bone marrow. The defect is the absence of the glycosyl-phosphatidyl-inositol fixative for membrane proteins, which is caused by a mutation in the PIG-A gene, which is located on the X chromosome. Prolonged loss of hemoglobin can lead to iron deficiency. Patients have a pronounced predisposition to the development of venous and arterial thromboses, including Budd-Chiari syndrome. Thrombosis is usually fatal. Some patients with paroxysmal nocturnal hemoglobinuria develop aplastic anemia, and some patients with aplastic anemia develop paroxysmal nocturnal hemoglobinuria.

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Symptoms paroxysmal nocturnal hemoglobinuria.

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

Diagnostics paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria is suspected in patients with manifestations of typical symptoms of anemia or unexplained normocytic anemia with intravascular hemolysis, especially if leukopenia and thrombocytopenia are present. If paroxysmal nocturnal hemoglobinuria is suspected, one of the first tests performed is a glucose test based on the enhancement of hemolysis from the C3 component of the complement in isotonic solutions of low ionic strength; the test is easy to perform and quite sensitive. However, the test is nonspecific, a positive result requires confirmation by subsequent studies. The most sensitive and specific method is the flowcytometry method, which determines the deficiency of specific proteins on the membrane of the erythrocyte or leukocyte. An alternative is the acid hemolysis test (Hema test). Hemolysis usually appears after adding hydrochloric acid to the blood, incubation for 1 hour and subsequent centrifugation. Bone marrow examination is performed to exclude other diseases that may cause hypoplasia. Marked hemoglobinuria is typical during crises. Urine may contain hemosiderin.

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Treatment paroxysmal nocturnal hemoglobinuria.

Treatment is symptomatic. Empirical use of glucocorticoids (prednisolone 20-40 mg daily orally) allows control of symptoms and stabilization of the red blood cell count in more than 50% of patients. Blood products should usually be kept in stock for periods of crisis. Plasma transfusions (PTP) should be avoided. There is no need to wash red blood cells before transfusions. Heparin may be necessary to treat thrombosis, but it may increase hemolysis and should be used with caution. Oral iron supplementation is often necessary. In most patients, these measures are sufficient for a long period (from a year or more) for a period of from a year to many years. Allogeneic stem cell transplantation is successful in a small number of cases.