MLAB 1415: H EMATOLOGY K ERI B ROPHY -M ARTINEZ Hemolytic Anemias: Membrane Defects Part Two

D ISORDERS  Membrane lipid disorders  RBCs can acquire lipids when plasma lipid increase  Results in expansion of membrane and formation of abnormal shapes  Acanthocytosis  Spur cell anemia  Abetalipoproteinemia

D ISORDERS Paroxysmal nocturnal hemoglobinuria (PNH) Acquired intravascular hemolytic anemia characterized by intermittent (paroxysmal) sleep- associated (nocturnal) blood in the urine (hemoglobinurea). Onset is gradual occurring mostly in young adulthood of either gender. Strongly associated with aplastic anemia

E TIOLOGY Stem cell mutation leading to abnormal clones of differentiated hematopoietic cells. These clones bind complement At least 9 cell surface proteins that regulate complement are missing. As a result, the red cell membrane is markedly sensitive to complement. PNH RBC Lacks a complement inhibitor Complement attack PNH cells susceptible to complement attack RBC Lysis Cells are lysed, releasing contents into the plasma

PNH C LINICAL FEATURES Hemoglobinurea in first morning specimen Hemosidinurea Chronic anemia Infections Thrombosis 5-10% of cases will convert to acute myelogenous leukemia; 25% will convert to aplastic anemia. Illustration Source: PNHSource.com

L AB F EATURES : PNH Haptoglobin: decreased Hgb: 8-10 g/dL Leukopenia Thrombocytopenia PB Normocytic or macrocytic If IDA develops: Hypochromic, microcytic nRBCS

D IAGNOSTIC LABORATORY TESTS Screening test : Sugar water test Blood is incubated in a solution of sugar water. The low ionic strength of the solution activates complement and PNH cells are lysed. Confirmation test : Ham’s Test (Acidified Serum Lysis Test) PNH cells incubated in acidified serum will lyse whereas normal cells will not lyse. In order to be called positive, two conditions must be met: 1) Hemolysis occurs with the patient’s cells and not with normal cells, 2) Hemolysis is enhanced by acidified serum and does not occur with heat activated serum in which complement has been destroyed. Flow cytometry More sensitive and specific than above tests Immunophenotype of RBC

T HERAPY Therapy is directed at the complications that arise from infections, anemia and thromboses. Anemia - iron therapy or transfusion if severe enough Hemolytic episodes - corticosteroid therapy to stimulate erythropoiesis Thromboses - anticoagulant therapy Bone marrow transplant if Aplasia exists Patient younger than 50

R EFERENCES Harmening, D. M. (2009). Clinical Hematology and Fundamentals of Hemostasis (5th ed.). Philadelphia, PA: F.A. Davis Company. McKenzie, S. B. (2010). Clinical Laboratory Hematology (2nd ed.). Upper Saddle River, NJ: Pearson Education, Inc.