Chronic hemolysis

Folic acid supplementation with 1 mg daily generally is recommended in adult SCD patients, women considering pregnancy, and any SCD patient with chronic hemolysis.6 Because of accelerated erythropoiesis, these patients have an increased need for folic acid. There are conflicting studies in the SCD population, especially among infants and children, but if the child has chronic hemolysis, supplementation is recommended.21... 

F12. Fujii, H., Kanno, H., Hirono, A., Shiomura, T., and Miwa, S., A single amino acid substitution (157 Gly - Val) in a phosphoglycerate kinase variant (PGK Shizuoka) associated with chronic hemolysis and myoglobinuria. Bloodl% 1582-1585 (1992). 

Folic acid, 1 mg daily, is recommended in adult patients, pregnant women, and patients of all ages with chronic hemolysis. 

Chronic hemolysis, CGD-like symptoms (very rare)... 

J2. Jorgensen, C. R., Zimmerman, T. S., and Wang, Y., Serum lactate dehydrogenase elevation in ambulatory cardiac patients Evidence for chronic hemolysis. Circulation 35, 79-89 (1967). 

Hereditary spherocytosis (HS) comprises a group of inherited hemolytic anemias characterized by chronic hemolysis with a broad spectrum of severity (Hassoun et al, 1997). The principal cellular defect is the loss of erythrocyte surface area relative to the intracellular volume, although increased osmotic frailty is also a factor. A distinctive spherical red blood cell (RBC) morphology is observed in sufferers of HS and splenic destruction of these abnormal erythrocytes is the primary cause of the hemolysis experienced (Delaunay, 1995 Palek and Jarolim, 1993). 

The accumulation of hydrogen peroxidase affects many intracellular processes and results in hemolysis. These include the cross-linking of membrane proteins hemoglobin denaturation (manifest as Heinz body formation), which in turn affects the physical properties of the erythrocyte and lipid peroxidation, which may affect the cell membrane to cause direct hemolysis (Fig. 11-8). The resultant damage leads to a mixture of intravascular hemolysis and extravascu-lar hemolysis (by which hemolysis occurs in the reticuloendothelial system). In acute hemolytic episodes, the clinical picture is of predominantly intravascular hemolysis, while predominantly extravascular hemolysis is seen in patients with chronic hemolysis. 

Generally, these individuals only have mild anemia as increased erythropoiesis compensates for the chronic hemolysis. The anemia may worsen if there is reduced erythropoietic capacity for any reason, such as hematin deficiency, infection, or parvovirus-induced aplastic crises. 

Both vitamin E supplements and splenectomy have been suggested as potential therapeutic options, but neither has proven to be beneficial. Gene therapy is a potential future treatment under development but would only be clinically justified in the most severe cases affected by chronic hemolysis. 

R19. Rieder, R. F., and Bradley, T. B., Jr., Hemoglobin Gun Hill an unstable protein associated with chronic hemolysis. Blood 32, 355-369 (1968). 

There are two distinct types of GSH-S deficiency, both associated with mild chronic hemolysis in one type, hemolysis is the only clinical manifestation. In the other, the major clinical features are mental retardation, severe generalized muscle weakness, tremors, incoordination, hemolytic anemia, and metabolic acidosis. This second and much more severe type of GSH-S deficiency is also known as 5-oxopro-linurta or pyroglutamic aciduria. The difference in severity of these disorders reflects the fact that in the mild form, GSH-S deficiency is confined to the RBCs because in this disorder the GSH-S is unstable. GSH-S activity is present in adequate quantity in young RBCs, but it rapidly declines as the cells age, because the cells are unable to synthesize new molecules of GHS-S. Other cells of the body that have nuclei and ribosomes can compensate for accelerated denaturation of GSH-S by synthesizing more. On the other hand, in the severe systemic form of GSH-S deficiency, aE cells of the body have low activities of GSH-S because they cannot form this enzyme in adequate amounts. In both types of GSH-S deficiency, RBCs exhibit notable reduction in GSH concentration. 

Intravascular destruction of sickle cells may occur at an accelerated rate. The stresses of circulation, and repetitive sickle-unsickle cycles are likely to lead to cell fragmentation. Damage to the cell membrane promotes cell recognition by macrophages. Rigid ISCs are easily trapped, resulting in short circulatory survival and chronic hemolysis. The typical sickled cell survives for about 10 to 20 days, while life spans of normal RBCs are 100 to 120 days. 

Cholelithiasis is a common occurrence in the SCD patient. It is the result of the chronic hemolysis that results in increased bilirubin production, leading to biliary sludge and/or stone formation. Cholecystitis, exemplified by pain in the right iliac fossa, can be confused with abdominal pain crisis. ... 

Improved erythrocyte survival with combined vitamin E and selenium therapy in children with glucose-6-phosphate dehydrogenase deficiency and mild chronic hemolysis. 

Reduced chronic hemolysis in Mediterranean glucose-6-phosphate dehydrogenase deficiency after vitamin E therapy. 

High-dose vitamin E does not decrease the rate of chronic hemolysis in glucose-6-phosphate dehydrogenase deficiency. 

Reduced chronic hemolysis during high-dose vitamin E administration in Mediterranean-type glucose-6-phosphate dehydrogenase deficiency. 

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