Original ArticlesThe role of platelet factor 4 in platelet aggregation induced by the antibodies implicated in heparin-induced thrombocytopeniaGerotziafas, G. T.; Elalamy, I.; Lecrubier, C.; Lebrazi, J.; Mirshahi, M.; Potevin, F.; Lecompte, T.; Samama, M. M.Author Information G. T. Gerotziafas, I. Elalamy, C. Lecrubier, J. Lebrazi, F. Potevin and M. M. Samama are with the Service d'Hématologie Biologique, Hôpital Hôtel-Dieu de Paris, Paris, France; G. T. Gerotziafas is also with the Department of Hematology, Theagenio Cancer Hospital, Thessaloniki, Greece; M. Mirshahi is with the Unité INSERM 37, Hôpital Hôtel-Dieu de Paris, Paris, France; and T. Lecompte is with the Laboratoire d'Hématologie, Exploration de l'Hémostase et de la Thrombose, CHU de Nancy, France. (Received 25 September 2000; revised 28 May 2001; accepted 30 May 2001) Address correspondence to Grigoris T. Gerotziafas, Department of Hematology, Theagenion Cancer Hospital, 2, A. Simeonidi St. 54161 Thessaloniki, Greece. Tel: + 30 31 898612; fax: + 30 31 898614; e-mail: email@example.com Blood Coagulation & Fibrinolysis: October 2001 - Volume 12 - Issue 7 - p 511-520 Buy Abstract Heparin-induced thrombocytopenia (HIT) is a severe side effect of heparin treatment. Recent studies using immunological methods demonstrated that antibodies contained in plasma, or in purified total immunoglobulin (Ig)G from patients suffering HIT, recognize as target antigen the complex heparin/platelet factor (PF4). In the present study, the role of PF4 in in-vitro platelet aggregation induced by purified total IgG or platelet-poor plasma from patients suffering HIT was investigated. In order to demonstrate the functional role of PF4, an anti-PF4 antibody that specifically blocked PF4 was used. In an experimental system composed of washed platelet suspension, incubation of F(ab′)2 fragments (0.125 μg/ml) of the polyclonal anti-PF4 antibody resulted in complete inhibition of platelet aggregation triggered by purified total IgG from patients suffering HIT and heparin. In platelet-rich plasma, a significantly higher concentration (4.25 μg/ml) of the anti-PF4 F(ab′)2 was required to inhibit platelet aggregation induced by HIT-PPP and heparin. Intermediate concentrations of the anti-PF4 antibody partially inhibited platelet aggregation. In plasma milieu, the concentration of PF4 was about five-fold higher in comparison with that measured in the purified system. The intensity of platelet aggregation depended on the concentration of HIT-IgG. Platelet aggregation was abolished in the presence of high concentrations of heparin (superior or equal to 10 IU/ml). The present study shows that PF4 is essential for platelet aggregation triggered by the antibodies related to HIT in the presence of heparin. The concentration of PF4 that is available to bind with heparin or with the HIT-related antibodies is critical for platelet aggregation induced by HIT antibodies. © 2001 Lippincott Williams & Wilkins, Inc.