title: Identifying patients at high risk of heparin-induced thrombocytopenia-associated thrombosis with a platelet activation assay using flow cytometry.
abstract: 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.
authors.forename: Takuma
authors.initials: T
authors.lastname: Maeda
authors.forename: Katsura
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Kuniko
authors.initials: K
authors.lastname: Murata
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kanaumi
authors.forename: Shu
authors.initials: S
authors.lastname: Seguchi
authors.forename: Shiori
authors.initials: S
authors.lastname: Kawamura
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kodama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawai
authors.forename: Isami
authors.initials: I
authors.lastname: Kakutani
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazaki
authors.affiliation: Shigeki Miyata MD, PhD, Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita-city, Osaka 565-8565, Japan, Tel.: +81 6 6833 5012 ext. 2294, Fax: +81 6 6872 8175, E-mail: smiyata@ncvc.go.jp.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood*; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010979:Platelet Function Tests / Q000379:methods*; D011237:Predictive Value of Tests; D012042:Registries; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D013923:Thromboembolism / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D015415:Biomarkers; D006493:Heparin
keywords: Platelet-activating antibodies; heparin; platelet activation; thrombocytopenia; thromboembolism