Prompt diagnostic work-up of suspected heparin-induced thrombocytopenia (HIT) is critical for guiding initial patient management. We assessed the performance of three immunoassays detecting anti-PF4/heparin-antibodies, derived a diagnostic algorithm with a short analytical turnaround-time (TAT) and prospectively validated it. Plasma samples were analysed by Zymutest-HIA-IgG, HemosIL-AcuStar-HIT-IgG and ID-H/PF4-PaGIA in retrospective (n=221) and prospective (n=305) derivation cohorts. We calculated likelihood ratios (LR) of result intervals and cut-off values with 100% negative (NPV) and positive (PPV) predictive value for a positive gold-standard functional assay (HIPA). We established a diagnostic algorithm based on the Bayesian combination of pre-test probability and LR of first- and second-line immunoassays. Cut-offs with 100% PPV for positive HIPA were >3.0 U/ml (HemosIL-AcuStar-HIT-IgG) and titre {greater than or equal to}16 (ID-H/PF4-PaGIA); cut-offs with 100% NPV were <0.13 U/ml and {less than or equal to}1, respectively. During the prospective validation of the derived algorithm (n=687), HemosIL-AcuStar-HIT-IgG was used as unique testing in 566/687 cases (82.4%) (analytical TAT 30 min). In 121/687 unresolved cases (17.6%), ID-H/PF4-PaGIA was used as second-line testing (additional TAT 30 min). The algorithm accurately predicted HIT in 51/687 (7.4%) and excluded it in 604/687 (87.9%) patients, leaving only 20/687 (2.9%) cases unresolved. Additionally, we identified 12/687 (1.7%) positive predictions not confirmed by HIPA: 10 patients with probable HIT despite negative HIPA and two possible false positive algorithm predictions. The combination of pre-test probability with first- and second-line immunoassays for anti-PF4/heparin-antibodies is accurate for ruling in or out HIT in {greater than or equal to}95% of cases within 60 minutes. This diagnostic approach improves initial management of patients with suspected HIT.

Knowledge on heparin-induced thrombocytopenia keeps increasing. Recent progress on diagnosis and management as well as several discoveries concerning its pathogenesis have been made. However, many aspects of heparin-induced thrombocytopenia remain partly unknown, and exact application of these new insights still need to be addressed. This article reviews the main new concepts in pathogenesis, diagnosis, and management of heparin-induced thrombocytopenia.

Platelets are active key players in haemostasis. Qualitative platelet dysfunctions result in thrombocytopathies variously characterized by defects of their adhesive and procoagulant activation endpoints. In this review, we summarize the traditional platelet defects in adhesion, secretion, and aggregation. In addition, we review the current knowledge about procoagulant platelets, focusing on their role in bleeding or thrombotic pathologies and their pharmaceutical modulation. Procoagulant activity is an important feature of platelet activation, which should be specifically evaluated during the investigation of a suspected thrombocytopathy.

Background Early recognition and treatment of heparin‐induced thrombocytopenia (HIT) are key to prevent severe complications. Objective To assess the diagnostic performance of rapid immunoassays (IA) in detecting anti‐PF4/heparin‐antibodies. Methods Diagnostic performances of lateral‐flow IA (LFIA; STic Expert HIT) and latex IA (LIA; HemosIL HIT‐Ab) were analyzed in pilot (n = 74) and derivation cohorts (n = 267). Two novel algorithms based on the combination of HIT clinical probability with sequentially performed LIA and chemiluminescent IA (CLIA; HemosIL AcuStar‐HIT‐IgG) were compared with published rapid diagnostic algorithms: the “Lausanne algorithm” sequentially combining CLIA and particle‐gel IA (PaGIA) and the “Hamilton algorithm” based on simultaneously performed LIA and CLIA. Results LFIA missed 6/30 HIT. The sensitivity and specificity of LIA were 90.9% and 93.5%. The Lausanne algorithm correctly predicted HIT in 19/267 (7.1%), excluded it in 240/267 (89.9%), leaving 8/267 (3%) cases unsolved. The algorithm sequentially combining CLIA and LIA predicted HIT in 19/267 (7.1%) with 1/19 wrong prediction, excluded it in 236/267 (88.4%), leaving 11/267 (4.1%) cases unsolved. The algorithm employing LIA as a first assay predicted HIT in 22/267 (8.2%), excluded it in 235/267 (88%), leaving 9/267 (3.4%) cases unsolved. Finally, the Hamilton algorithm correctly predicted HIT in 10/267 (3.7%), excluded it in 229/267 (85.7%), leaving 28/267 (10.5%) cases unsolved. Conclusion LFIA cannot be used to exclude or predict HIT when using frozen plasma. A Bayesian approach sequentially employing two rapid immunoassays for anti‐PF4/heparin antibodies is most effective for the accurate diagnosis of HIT. Based on retrospective data, the combination LIA/CLIA is a candidate for a prospective validation.

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