PNH due to defect in -
Ans. is 'a' i.e., CD 59 Paroxysmal Nocturnal hemoglobinuria (PNHI.o PNH is a hemolytic anemia caused by an acquired intrinsic defect in the cell membrane,o PNH results from acquired mutation that inhibits the synthesis of Glycosylphospatidyiinositol (CPI),o Several protective proteins called complement regulating proteins are anchored to cell membrane by GPLo These protective proteins prevent activation of complement and there by complement mediated lysis of blood cells.o Deficiency of GP1 results in absence of these proteins and blood cells become unusually sensitive to complement mediated lysis.o The GPI - linked proteins that are missing in paroxysmal nocturnal hemoglobinuria are: -# Urokinase plasminogen activator receptor - Its absence promotes thrombosis.# Leukocyte alkaline phosphotase (LAP) - Decreased LAP score.o Because the causative somatic mutations occur in pluripotent stem cells, all its clonal progeny ie., red cells, white cells, and platelets are deficient in GPI linked protein. So, all these cells are sensitive to complement mediated lysis that results in : - - Anemia, Leucopenia, Granulocytopenia, ThrombocytopeniaClinical features of PNHIntravascular hemolysiso The main feature of PNH is increased intravascular hemolysis that results in -# Hemoglobinemia# Increased urine urobilinogen# Hemoglobinuria# Decreased serum haptoglobin# Hemosiderinuria# Increased serum LDH# Increased serum bilirubin o The hemolysis is paroxysmal and usually occurs in the night because during sleep the pH of blood gets slightly reduced and acidic medium leads to activation of the complement.Thrombosiso In PNH there is epsodic thrombosis due to absence of CD-59 on platelets, this results in extemilization of phosphotidylserine, a site for prothrombinase complexes and thus increase the propensity for thrombosis,o Intrabdominal veins are the most common sites of thrombosis that may result in Budd chiary syndrome due to hepatic vein thrombosis.Other featureso Thrombocytopeniao Granulocytopeniao Decreased LAP scoreo Normoblastic hyperplasia of bone marrowo PNH patients are also at increased risk for developing acute myelogenous leukemia and aplastic anemia.Diagnosis of paroxysmal nocturnal hemoglobinuriao Until recently the diagnosis of P.N.H was based on special tests that were based on the principle that P.N.H red cells are susceptible to complement mediated lysis. These tests are :HAM TestHam's acidified serum test is one of the screening tests for P.N.H. Patients red cells get lysed in an acidic pH in the presence of complement.Sucrose TestRed cells lyse on the addition of sucrose and complement in the medium.Addition of sucrose decreases the ionic strength.o But now the diagnosis of P.N.H depends upon analyzing the expression GP.I.-AP on the hematopoietic stem cells using monochonal antibodies and flow cytometry. The simplest method is to analyze the expression of CD59 on erythrocytes.o PNH is diagnosed by flow cytometry, which provides a sensitive means for detecting red cells that are deficient in GPI-linked protein such as CD59.
CD 59
CD 15
CDIOO
CD20
Hemolytic anemia