Two days after receiving the antimalarial drug primaquine, a 27-yearold black man develops sudden intravascular hemolysis resulting in a decreased hematocrit, hemoglobinemia, and hemoglobinuria. Examination of the peripheral blood film is given. The most likely diagnosis is
Examination of the peripheral blood reveals erythrocytes with a membrane defect forming "bite" cells; when crystal violet stain is applied, many Heinz bodies are seen. Glucose-6- phosphate dehydrogenase (G6PD) is an enzyme of the hexose monophosphate shunt pathway that maintains glutathione in a reduced (active) form. Glutathione normally protects hemoglobin from oxidative injury. If the erythrocytes are deficient in G6PD, as occurs in G6PD deficiency, exposure to oxidant drugs, such as the antimalarial drug primaquine, denatures hemoglobin, which then precipitates with erythrocytes as Heinz bodies. Macrophages within the spleen remove these bodies, producing characteristic "bite" cells. These red cells then become less deformable and are trapped and destroyed within the spleen (extravascular hemolysis). The gene for G6PD is located on the X chromosome and has considerable pleomorphism at this site. Two variants are the A type, which is found in 10% of African Americans and is characterized by milder hemolysis of younger red cells, and the Mediterranean type, which is characterized by a more severe hemolysis of red cells of all ages. Hereditary spherocytosis (HS), an autosomal dominant disorder, is characterized by an abnormality of the skeleton of the red cell membrane that makes the erythrocyte spherical, less deformable, and vulnerable to splenic sequestration and destruction (extravascular hemolysis). In HS, there is a defect in the spectrin molecule, which then is less binding to protein 4.1. This disorder can be diagnosed in the laboratory by the osmotic fragility test. Paroxysmal nocturnal hemoglobinuria (PNH), an acquired clonal stem cell disorder, is characterized by abnormal red cells, granulocytes, and platelets. The red cells are abnormally sensitive to the lytic activity of complement due to a deficiency of glycosyl phosphatidyl inositol (GPI) linked proteins, namely decay-accelerating factor (DAF, or CD55), membrane inhibitor of reactive lysis (CD59), or CD59 (a C8 binding protein). omplement is activated by acidosis, such as with exercise or sleep, which can produce red morning urine. Complications of PNH include the development of frequent thromboses and possibly acute leukemia. Microangiopathic hemolytic anemia refers to hemolysis of red cells caused by narrowing within the microvasculature and is seen in patients with prosthetic hea valves or those with disseminated intravascular coagulopathy, thrombotic thrombocytopenic purpura, or hemolytic-uremic syndrome Reference: Robbins & Cotran Pathologic Basis of Disease, 9edition.
Hereditary spherocytosis
Glucose-6-phosphate dehydrogenase deficiency
Paroxysmal nocturnal hemoglobinuria
Microangiopathic hemolytic anemia
Haematology