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Thromb Haemost 2017; 117(01): 127-138
DOI: 10.1160/TH16-06-0482
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Identifying patients at high risk of heparin-induced thrombocytopenia-associated thrombosis with a platelet activation assay using flow cytometry

Takuma Maeda
1   Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Katsura Nakagawa
2   Department of Anesthesiology, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Kuniko Murata
2   Department of Anesthesiology, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Yoshiaki Kanaumi
1   Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Shu Seguchi
1   Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Shiori Kawamura
1   Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Mayumi Kodama
1   Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Takeshi Kawai
1   Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Isami Kakutani
1   Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Yoshihiko Ohnishi
2   Department of Anesthesiology, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Koichi Kokame
3   Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka, Japan
,
Hitoshi Okazaki
4   Department of Transfusion Medicine, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan
,
Shigeki Miyata
1   Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
› Author Affiliations Financial support: This research was supported in part by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare of Japan; the Intramural Research Fund (27–1–2) for Cardiovascular Disease of the National Cerebral and Cardiovascular Center; and a grant-in-aid from the Takeda Science Foundation.
Further Information

Publication History

Received: 29 June 2016

Accepted after major revision: 17 September 2016

Publication Date:
01 December 2017 (online)

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Summary

To diagnose heparin-induced thrombocytopenia (HIT), detection of platelet-activating antibodies (HIT antibodies) is crucial. However, serum platelet activation profiles vary across patients and depend on test conditions. We evaluated the association between clinical outcomes and platelet-activating profiles assessed by a platelet microparticle assay (PMA), which detects activation of washed platelets induced by HIT antibodies, in 401 consecutive patients clinically suspected of having HIT. We made modifications to the assay, such as donor selection for washed platelets that increased sensitivity. Serum that activated platelets at a therapeutic (but not high) heparin concentration was defined as positive. Of these, serum that activated platelets within 30 minutes or in the absence of heparin was defined as strongly positive. The remaining samples were considered weakly positive. As a result, 97 % and 93 % of patients who tested strongly and weakly positive had clinical profiles consistent with HIT, respectively. The incidence of thromboembolic events (TEEs) after heparin exposure in patients who tested strongly positive, weakly positive, and negative was 61 %, 40 %, and 29 %, respectively. Among patients who did not experience a TEE on the day HIT was suspected, there was no significant difference in the cumulative incidence of subsequent TEEs between patients who tested strongly and weakly positive when argatroban was initiated on the same day (19.0 % vs 7.1 %, p=0.313), but there was a significant difference when argatroban therapy was delayed by one or more days (61.1 % vs 17.6 %, p=0.007). The modified PMA is effective in diagnosing HIT and identifying patients at high risk for HIT-associated TEEs.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Platelet-activating antibodies - heparin - platelet activation - thrombocytopenia - thromboembolism

 

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