Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel

Abstract

Glanzmann thrombasthenia is a rare, inherited disorder of the platelet glycoprotein IIb/IIIa (GP IIb/IIIa) complex. We previously identified two distinct populations with this disorder in Israel, Iraqi-Jews and Arabs. The groups are indistinguishable in hemorrhagic symptoms and platelet GP IIb/IIIa receptor deficiency, but they differ in their platelet immunodetectable GP lila (β3), with the Iraqi-Jewish population expressing no detectable GP Ilia and the Arab population expressing small amounts. We have now examined the platelets of these two populations as well as normal platelets for the αvβ3 vitronectin receptor. Normal platelets contained between ∼50 to 100 αvβ3 vitronectin receptors as judged by the binding of antibodies to both αv (LM142) and the intact αvβ3 vitronectin receptor complex (LM609). In addition, normal platelets bound to immobilized vitronectin in the presence of 1 mmol/L MnCl2; the adhesion was mediated predominantly through GP IIb/IIIa, but with a distinct contribution by the αvβ3 vitronectin receptor, as determined by monoclonal antibody inhibition studies. Iraqi-Jewish patients' platelets had a profound decrease in immunodetectable αvβ3 vitronectin receptors, and their platelets did not adhere well to vitronectin. In contrast, Arab patients' platelets had normal or increased numbers of platelet αvβ3 vitronectin receptors, and these receptors functioned well in the vitronectin adhesion assay, taking over much of the adhesion mediated by GP IIb/IIIa in normal platelets. These studies define further the heterogeneity of the molecular basis of Glanzmann thrombasthenia; they also have more widespread implications for understanding the synthesis and function of the β3 family of integrin receptors. © 1991 by The American Society of Hematology.