Platelet aggregating IgG antibody to platelet surface glycoproteins associated with thrombosis and thrombocytopenia

Abstract

Previously described platelet-aggregating antibodies associated with thrombosis and thrombocytopenia required heparin for their in vivo and in vitro expression. We have observed a patient with thrombosis who became thrombocytopenic during heparin treatment, but who suffered further thrombotic events and continued thrombocytopenia for 3 months after heparin withdrawal. The patient's plasma contained a potent platelet aggregating factor reactive with both his own and normal platelets in the absence of heparin. It also caused [14C]serotonin secretion from labelled platelets from normal donors and patients with either Glanzmann's thrombasthenia or Bernard-Soulier syndrome. This factor was an IgG and was neutralized by antibody specific for IgG lambda light chains. While the patient was thrombocytopenic an IgG paraprotein with lambda light chains was detected by isoelectrofocussing. After corticosteroid treatment it disappeared and the patient recovered. The active, but not the recovery serum contained IgG which immunoprecipitated a glycoprotein with characteristics of Glycoprotein IV from platelets labelled with Na[3H]BH4/periodate. Thus platelet-aggregating IgG antibodies with direct specificity for platelet surface glycoproteins may be associated with thrombosis/thrombocytopenia.

Evidence that thrombocytopenia observed in humans treated with orally bioavailable glycoprotein IIb/IIIa antagonists is immune mediated

“…Numerous methods have been developed for the retrospective detection of platelet-associated DDABs in patients with druginduced thrombocytopenia. 24,25,[29][30][31][32][33][34][35][36][37] However, the clinical utility appears to be limited due to requirements for specialized equipment, testing centers, and insufficient sensitivity and specificity of these methods. Importantly, the positive and negative predictive value of these assays is unknown in most settings.…”

Idiopathic thrombocytopenic purpura: Pathophysiology and management

“…Platelet dysfunction in ITP has been well described in the literature, indicating that antiplatelet antibodies can and do influence platelet function [18][19][20][21][22]. Antibodies may bind to adhesion molecules or other receptors on platelets to alter platelet function.…”

“…These patients bleed even with normal platelet counts. In contrast, some antibodies may activate platelets, promoting thrombotic complications in ITP [22].…”

Location of the Quinine-Dependent Epitope on Platelet Glycoprotein IlIa

“…0.3 pg 125I-GPII la treated with buffer or soluble trypsin as described above was incubated with 50 pi whole serum MS containing Q.Ab in the presence or absence of 2 mM quinine hydrochloride for 16 h at 4°C . Antigen-antibody complexes were immunoprecipitated using immunobeads coated with rabbit anti-human IgG (BioRad, Richmond, Calif.) as described [10] and analysed by SDS-PAGE on 5-20% gels [4],…”