Similar to FcγRI, FcγRII is divided into FcγRIIA, B and C. 13, 14 FcγRII are low affinity receptors (Ka <10 7 M −1) with molecular weights of 40–43 kDa and specificity for IgG1 and IgG3. 9 – 12 The family of FcγRI receptors is further divided into FcγRIA, B and C each with different affinities for binding Fc (FcγRIA with the highest and FcγRIC with the lowest) and encoded by unique genes.įcγRII is an inhibitory receptor and acts as a negative regulator of B-cell and mast cell activation. Expression of FcγRI can be induced by interferon (IFN)-γ, tumor necrosis factor (TNF)-α or granulocyte colony-stimulating factor G-CSF. 3, 4 FcγRI is expressed on monocytes, macrophages, neutrophils and dendritic cells and is required for antibody-dependent cell-mediated cytotoxicity (ADCC), endocytosis and phagocytosis, 5 – 8 the latter being an important mechanism of RBC destruction in IgG-mediated hemolytic anemia. 2 It is a 72 kDa high affinity receptor (Ka = 10 8 − 10 9 M −1) capable of binding monomeric and multimeric IgG, preferentially IgG1 and IgG3 IgG3 is the most efficient IgG subclass in causing extravascular hemolysis in vivo. FcγRI mediates cytotoxic activity in vitro. There are two extracellular immunoglobulin-like domains for FcγRII and FcγRIII, while FcγRI has three immunoglobulin-like domains. Fcγ receptors are divided into three types depending on their structure, binding affinity and signalling ability: FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16). These phagocytic cells express Fcγ receptors (FcγR) on their surface which bind to the Fc portion of IgG antibodies causing IgG-coated RBCs to be internalized and destroyed. Immunoglobulins and C3b on the RBC surface target these cells for destruction by macrophages in the spleen and less frequently by Kupffer cells in the liver. Spherocytes, bite cells, blister cells, dense fragments, elliptocytes, ovalocytes, normal Table 10.1 Laboratory features of intravascular and extravascular hemolysisĪbsent (may be present with severe extravascular hemolysis) Hemolysis caused by malaria, major ABO blood group incompatibility, mechanical trauma to RBCs, thrombotic thrombocytopenic purpura (TTP) and paroxysmal nocturnal hemoglobinuria (PNH) is intravascular because RBC destruction occurs within the blood vessel. IgG-mediated autoimmune hemolysis is generally extravascular because the RBCs are destroyed by tissue macrophages in the spleen and liver. Laboratory tests can help determine whether the hemolytic anemia is occurring predominantly in the intravascular or extravascular space ( Table 10.1). The determination of RBC life span with radioactive isotope-labeled RBCs is rarely indicated. Bone marrow examination may be useful to uncover an underlying cause. The laboratory tests useful for the diagnosis of acquired hemolytic anemia include peripheral blood film examination, reticulocyte count, direct antiglobulin test (Coombs’ test), lactate dehydrogenase (LDH), bilirubin, aspartate aminotransferase (AST), haptoglobin, hemoglobinemia, methemalbumin and hemopexin, hemoglobinuria and hemosiderinuria. Signs of anemia include dyspnea, pallor, jaundice and brown-discolored urine and in massive acute hemolysis, shock and renal failure can occur. Rapid destruction of RBCs can be associated with fever, abdominal pain, back pain or limb pain, whereas patients with hemolytic anemia that develops gradually are often asymptomatic. Anemia may lead to cardiovascular symptoms such as dyspnea, angina and tachycardia or nonspecific complaints of generalized malaise and dizziness. The symptoms of acquired hemolytic anemia relate to the severity of the anemia and the rate of RBC destruction. Clinical and laboratory features of hemolytic anemia
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