Immunologic and biochemical characterization of homozygous and heterozygous Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations of Israel: comparison of techniques for carrier detection

Abstract

To define biochemically and immunologically the platelet defect in Iraqi-Jews and Arabs with Glanzmann thrombasthenia in Israel, we tested the platelets of 32 thrombasthenics and 37 obligate carriers from 19 families with affected members. Thrombasthenic platelets were devoid of glycoprotein IIb (GPIIb) as judged by polyacrylamide gel electrophoresis and devoid of the GPIIb/IIIa complex as judged by radio-electroimmunoassay. Binding of a murine monoclonal antibody directed at GPIIb and/or GPIIIa to intact thrombasthenic platelets averaged less than 2% of the control value. Evaluation of the number of molecules of antibody bound per platelet permitted discrimination between controls and obligate carriers with a high degree of accuracy (sensitivity = 91.9%, specificity = 92.3%). Obligate carriers could also be discriminated from controls by determining the ratio of GPIIb to GPIb by polyacrylamide gel electrophoresis and by quantifying the GPIIb/IIIa complex by radio-electroimmunoassay. These studies indicate that the thrombasthenics in Israel have the severe form of the disease (type I) and that the platelets of heterozygotes have significantly reduced amounts of both total and surface-exposed GPIIb and/or GPIIIa.