Anti-Platelet Glycoprotein Antibodies in Thrombocytosis Are Frequently Detected and Are Associated with Platelet Activation and Thrombosis.

Abstract

Introduction: Thrombosis is the major cause of morbidity and mortality in patients with thrombocytosis (TS) associated with myeloproliferative disorders (MPD), but predicting which patients are at risk has been challenging. We recently reported that antiphospholipid antibodies (APLA) and platelet activation are risk factors in TS [C Bidot et al; Hematology, 10:451, 2005]. To shed further light on the cause of platelet activation in TS, we here report on measuring anti-platelet antibodies in a group of these patients.Material and Methods: Thirty-three TS patients, 15 with clinical thrombosis and 18 without, were evaluated using PAICA method of L. Macchi et al [Thromb Haemost 76:1020, 1996]. We assayed anti-platelet antibodies against 3 target antigens, GPIIb/IIIa (CD41b), GP Ib/IX (CD42b) and GP IV (Cd36) for IgG and IgM. We also measured platelet activation marker CD62P, and microparticles from platelets (PMP, defined by CD31+/CD42+) and endothelial cells (EMP, defined by CD31+/CD42−) by flow cytometry.Results: At least one anti-platelet antibody was detected in 19/33 (57.5%) of TS patients. Considering first IgG in the19 who were anti-platelet antibodies positive, 14/19 (73.6%) were positive for CD36, 12/19 (63%) for CD41b and 8/19 (42.1%) for CD42b. For IgM in these 19 patients, incidences were 58.8% for CD41b, 38.8% for CD36 and 35% for CD42b. When we compared the anti-platelet antibody positive group with the negative group, we observed that activation marker CD62P was significantly higher in the former (p= 0.04), as were EMP levels (p= 0.02), but PMP levels were not different. Next, we compared results with incidence of thrombosis. None of the IgG results discriminated thrombosis from non-thrombosis. However, all three IgM results were significant in this regard: CD36 (p< 0.05), CD42b (p< 0.02), and most notably, CD41b (p< 0.0003).Conclusions: These results show that anti-platelet antibodies of IgM class, especially anti-CD41b, are associated with platelet activation, endothelial activation, and clinical thrombosis in TS. These findings parallel our previous report on APLA in TS. We suggest that IgM-CD41b may activate platelets, predisposing to hypercoagulable state in this disorder.