Paroxysmal nocturnal hemoglobinuria (Marciafava-Micheli disease)

Paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease) is a rare form of acquired hemolytic anemia, occurring with a frequency of 1:50,000 in the population.

In paroxysmal nocturnal hemoglobinuria, the clone of hematopoietic cells loses the ability to synthesize glycanphosphatidylinositol, which is necessary for binding complement regulators to the erythrocyte membrane, which makes erythrocytes extremely sensitive to lysis by complement. Paroxysmal nocturnal hemoglobinuria is characterized by episodes of intravascular hemolysis with the appearance of hemoglobinuria and hemosiderinuria. Venous thromboses are often observed, especially mesenteric, portal, cerebral and deep veins, the cause of which is platelet aggregation caused by uncontrolled activation of complement. Transformation of the disease into aplastic anemia, myelodysplastic syndrome, acute myeloid leukemia is possible.

Laboratory tests reveal normocytic anemia, normochromic (in the early stages of the disease) or hypochromic (as the disease progresses), hyperregenerative, morphologically anisopoikilocytosis, polychromasia are noted, the appearance of normocytes is possible. Thrombocytopenia (usually moderate) and leukogranulocytopenia (can be pronounced) are noted. The level of serum iron is significantly reduced. The activity of alkaline phosphatase in leukocytes is low. The disease is diagnosed based on confirmation of abnormal lysis of erythrocytes in the presence of complement activated with acidified serum (Ham test) or lysis in a hypotonic medium in the presence of sucrose. Currently, a flow cytometry method has been developed that makes it possible to determine the absence of the decay acceleration factor and reactive lysis inhibitor on the erythrocyte membrane. These two proteins are regulators of complement function and are attached to the cell membrane using glycan-phosphatidylinositol. Treatment is symptomatic. Replacement hemotransfusion therapy is performed to suppress the proliferation of the abnormal clone. Sometimes, corticosteroids are effective. In the case of transformation of paroxysmal nocturnal hemoglobinuria into aplastic anemia or development of severe thrombotic complications, bone marrow transplantation is advisable.

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