**5.1. Hemolytic anemia**

**5.1.1 Mechanism of hemolysis.** In some people, for example, the Mediterranean-type, G6PD deficiency from drug intake occurs, although not a permanent hemolytic condition. In erythrocytes, NADPH cannot form with G6PD deficiency and unformed NADPH creates a deficiency in conversion of the oxidized form of glutathione (GSSG), to its reduced form (GSH) (Lachant*, et al.*, 1984, Beutler, 1994). There is normally plenty of GSH in erythrocytes and it protects the cell from oxidizing agents. If G6PD is deficient, hemoglobin is oxidized by oxidative substances to be eliminated and it returns methemoglobin that cannot function normally. Also, hemoglobin precipitates with denaturation in the cytoplasm forms Heinz bodies. These structures attach to the membrane with disulfide bonds and disrupt its normal structure. The erythrocytes that contain Heinz bodies in their cytoplasm are sequestered by macrophages in the spleen and removed from the circulation. G6PD deficiency hemolysis occurs like that in the extravascular compartment and also occurs again as a result of membrane defects (Alving*, et al.*, 1956). Thus, drug-induced hemolysis is the first and best-known morbid effect of G6PD deficiency. After a 1- or 2-day delay in such drug administration, a fall in the hemoglobin (Hb) concentration occurs.

The red blood cell (RBC) membrane was adhered to by Heinz bodies, which are particles of denatured protein. These appear in the early stages of drug administration and disappear as hemolysis progresses. Hemolysis usually occurs in blood vessels and hemoglobinuria follows. The increase of reticulocytes emerges in response to this situation and the hemoglobin level begins to increase again within 8-10 days (Beutler, 1994). In severe hemolysis, the patient may complain of back and stomach pain and the urine turns dark. The hemolytic anemia is self-limited when G6PD deficiency is relatively mild because only the older RBCs are destroyed and the young RBCs have normal or nearly-normal enzyme activity (Beutler, 1994).

Table 1 lists the drugs and chemicals that cause clinically significant hemolytic anemia.

**5.2. Diabetes mellitus-induced hemolysis.** Hemolysis in G6PD deficiency individuals might initiate diabetic ketoacidosis. This situation is not exactly accepted. However, hemolysis formation has been reported when blood glucose levels are normal in diabetic individuals (Beutler, 1994). It has also has been reported that hypoglycemia might precipitate hemolysis in patients with G6PD deficiency (Beutler, 1994).

**5.3. Infection-induced hemolysis.** Infections are probably the most common cause of hemolysis in people with G6PD deficiency. There are numerous reports about the importance of infection in causing hemolytic anemia. A large number of bacterial, viral and rickettsial infections have been reported as predisposing factors. Infectious hepatitis (hepatitis A), pneumonia and typhoid fever are known to trigger hemolysis. Involving the upper respiratory tract and gastrointestinal system, viral infections have been reported to cause a more severe hemolysis (Luzzatto, 2001). The mechanism of infection-induced hemolysis is not clear, but it is thought to be that during the infection, superoxide anion and H2O2 production by macrophages causes the hemolysis (Glader, 1999, Luzzatto, 2001).
