Although commonly regarded as a hemolytic anemia, this hemopoietic stem cell disorder is characterized by formation of defective platelets, granulocytes, and erythrocytes. Paroxysmal nocturnal hemoglobinuria is acquired and arises from one abnormal clone of cells, much like a neoplasm (Luzzatto, 2015). One mutated X-linked gene responsible for this condition is termed PIG-A because it codes for phosphatidylinositol glycan protein A. Resultant abnormal anchor proteins of the erythrocyte and granulocyte membrane make these cells unusually susceptible to lysis by complement (Provan, 2000). The most serious complication is thrombosis, which is heightened in the hypercoagulable state of pregnancy.
Chronic hemolysis has an insidious onset, and its severity ranges from mild to lethal. Hemoglobinuria develops at irregular intervals and is not necessarily nocturnal. Hemolysis may be initiated by transfusions, infections, or surgery. Almost 40 percent of patients sufer venous thromboses and may also experience renal failure, hypertension, and Budd-Chiari syndrome. Because of the thrombotic risk, prophylactic anticoagulation is recommended (Parker, 2005). The treatment of choice is eculizumab, an antibody that inhibits complement activation (Kelly, 2015). Median survival after diagnosis is 10 years, and bone marrow transplantation is the deinitive treatment.
During pregnancy, paroxysmal nocturnal hemoglobinuria can be serious and unpredictable. Complications have been reported in up to three fourths of afected women, and the maternal mortality rate in the past was 10 to 20 percent (De Gramont, 1987; de Guibert, 2011). Complications more often develop postpartum, and half of afected women develop venous thrombosis (Fieni, 2006; Ray, 2000). Kelly and colleagues (2015) described 75 pregnancies in 61 afected women treated with eculizumab. In half of these, the dose was increased during pregnancy. They described no maternal deaths but 4 percent stillbirths.
he most fulminant acquired hemolytic anemia encountered during pregnancy is caused by the exotoxin of Clostridium petingens or by group A J-hemolytic streptococcus (Chap. 47, p. 922). Endotoxin of gram-negative bacteria, that is, lipopolysaccharide, may be accompanied by hemolysis and mild-to-moderate anemia (Cox, 1991). For example, anemia often accompanies acute pyelonephritis. With normal erythropoietin production, red cell mass is restored following infection resolution as pregnancy progresses (Cavenee, 1994; Dotters-Katz, 2013).
he normal erythrocyte is a lexible biconcave disc that allows numerous cycles of reversible deformations. Several genes encode expression of erythrocyte structural membrane proteins or intraerythrocytic enzymes. Various mutations of these genes may result in inherited membrane defects or enzyme deiciencies that destabilize the lipid bilayer. The loss of lipids from the erythrocyte membrane causes a surface area deficiency and poorly deformable cells that undergo hemolysis. Anemia severity depends on the degree of rigidity or decreased distensibility. Erythrocyte morphology similarly is dependent on these factors, and these disorders are usually named after the most dominant red-cell shape characteristic of the disorder. hree examples are hereditary spherocytosis) pyropoikilocytosis, and ovalocytosis.