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Thromb Haemost 1996; 76(05): 774-779
DOI: 10.1055/s-0038-1650659
Original Article
Schattauer GmbH Stuttgart

The Mechanism of Platelet Aggregation Induced by HLA-Related Antibodies

John T Brandt
The Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA
,
Carmen J Julius
The Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA
,
Jeanne M Osborne
1   The Department of Pathology, Ohio State University, Columbus, Ohio, USA
,
Clark L Anderson
1   The Department of Pathology, Ohio State University, Columbus, Ohio, USA
› Author Affiliations
Further Information

Publication History

Received 08 February 1996

Accepted after revision 19 August 1996

Publication Date:
11 July 2018 (online)

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Summary

Immune-mediated platelet activation is emerging as an important pathogenic mechanism of thrombosis. In vitro studies have suggested two distinct pathways for immune-mediated platelet activation; one involving clustering of platelet FcyRIIa, the other involving platelet-associated complement activation. HLA-related antibodies have been shown to cause platelet aggregation, but the mechanism has not been clarified. We evaluated the mechanism of platelet aggregation induced by HLA-related antibodies from nine patients. Antibody to platelet FcyRIIa failed to block platelet aggregation with 8/9 samples, indicating that engagement of platelet FcyRIIa is not necessary for the platelet aggregation induced by HLA-related antibodies. In contrast, platelet aggregation was blocked by antibodies to human C8 (5/7) or C9 (7/7). F(ab’)2 fragments of patient IgG failed to induce platelet activation although they bound to HLA antigen on platelets. Intact patient IgG failed to aggregate washed platelets unless aged serum was added. The activating IgG could be adsorbed by incubation with lymphocytes and eluted from the lymphocytes. These results indicate that complement activation is involved in the aggregation response to HLA-related antibodies. This is the first demonstration of complement-mediated platelet aggregation by clinical samples. Five of the patients developed thrombocytopenia in relationship to blood transfusion and two patients developed acute thromboembolic disease, suggesting that these antibodies and the complement-dependent pathway of platelet aggregation may be of clinical significance.