hematology and oncology
Overview of Hemolytic Anemia
Pathophysiology of Hemolytic Anemia
Hemolysis may be Acute Chronic Episodic Hemolysis may also be Extravascular Intravascular Both Senescent RBCs lose membrane and are cleared from the circulation by the phagocytic cells of the spleen, liver, bone marrow, and reticuloendothelial system. Hemoglobin is broken down in these cells primarily by the heme oxygenase system. The iron is conserved and reutilized, and heme is degraded to bilirubin, which is conjugated in the liver to bilirubin glucuronide and excreted in the bile. Most pathologic hemolysis is extravascular and occurs when damaged or abnormal RBCs are cleared from the circulation by the spleen and liver. The spleen contributes to hemolysis by destroying mildly abnormal RBCs or cells coated with warm antibodies. An enlarged spleen may sequester even normal RBCs. Severely abnormal RBCs or RBCs coated with cold antibodies or complement (C3) are destroyed within the spleen and liver, which (because of its large blood flow) can remove damaged cells efficiently. In extravascular hemolysis, the peripheral smear will show spherocytes or with cold agglutinins, erythrocyte agglutination if the blood is not warmed upon collection. Intravascular hemolysis is an important reason for premature RBC destruction and occurs when the cell membrane has been severely damaged by any of a number of different mechanisms, including Autoimmune phenomena Direct trauma (eg, march hemoglobinuria) Shear stress (eg, defective mechanical heart valves) Disseminated Intravascular Coagulation (DIC) (DIC) Toxins (eg, clostridial toxins, venomous snake bite) Intravascular hemolysis results in hemoglobinemia when the amount of hemoglobin released into plasma exceeds the hemoglobin-binding capacity of the plasma-binding protein haptoglobin, a protein normally present in concentrations of about 100 mg/dL (1.0 g/L) in plasma. Thus, intravascular hemolysis reduces unbound plasma haptoglobin. With hemoglobinemia, unbound hemoglobin dimers are filtered into the urine and reabsorbed by renal tubular cells; hemoglobinuria results when reabsorptive capacity is exceeded. Iron is released from catabolized hemoglobin and embedded in hemosiderin within the tubular cells; some of the iron is assimilated for reutilization and some reaches the urine when the tubular cells slough. Unconjugated (indirect) hyperbilirubinemia and Jaundice occur when the conversion of hemoglobin to bilirubin exceeds the liver’s capacity to Increased production oferythropoietinby the kidneys in response to the ensuing anemia causes the bone marrow to accelerate production and release of RBCs, resulting in a reticulocytosis. 