Heparin-induced Thrombocytopenia Diagnosis: A Retrospective Study Comparing Heparin-induced Platelet Activation Test to 14C-serotonin Release Assay

Abstract

Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is of crucial importance and remains challenging and relies on platelet functional assays highlighting the presence of heparin-dependent platelet-activating antibodies in patient serum or plasma. Platelet functional assays using washed platelets include the 14C-serotonin release assay (SRA), usually described as the gold standard, and the heparin-induced platelet activation assay (HIPA). Since its first comparison with SRA there has been no additional published study regarding HIPA diagnostic performances compared to SRA. Aim of our retrospective study was to compare the concordance between HIPA and SRA in HIT suspected-patients with positive anti-PF4/heparin antibodies between October 2010 and October 2015. Fifty-five HIT-suspected patients who beneficiated from both HIPA and SRA were included. Positive and negative percent agreements were 83.8% (95% CI 68.0–93.8%) and 66.7% (95% CI 41.0–86.7%), respectively. Overall percent agreement was 78.2% (95% CI 65.0–92.2%). Agreement was higher in patients who underwent cardiopulmonary bypass with extracorporeal circulation circuit for cardiac surgery. We also confirm that the use of a minimum of 2 platelet donors to establish positive HIT diagnosis and 4 platelet donors to exclude HIT diagnosis allows obtaining a good agreement with SRA. Although HIPA and SRA were performed with different platelet donors and in different laboratories, HIPA had a good positive agreement with SRA for HIT diagnosis, showing that HIPA is a useful functional assay that does not require radioactivity and could be developed worldwide to improve HIT diagnosis.

A machine-learning model for reducing misdiagnosis in heparin-induced thrombocytopenia: a prospective, multicenter, observational study

“… 12 , 34 , 35 , 41 , 48 , 49 , 50 , 51 , 52 , 53 , 54 HIPA and SRA are both regarded as reference standards for the diagnosis of HIT by the American Society of Hematology (ASH) guidelines, 41 the British Committee for Standards in Haematology, 53 and many authors. 12 , 34 , 35 , 48 , 49 , 50 , 51 , 55 We decided against the adjudication of HIT cases by an expert panel to avoid incorporation/verification bias (clinical and laboratory variables of the prediction model are used for reference standard testing). 56 , 57 …”

Challenges in the Monitoring of Therapeutic Plasma Exchange during Acute Heparin-Induced Thrombocytopenia in Adults under ECMO

“…Plasma samples were then heated at 56°C for 30 minutes to inactivate traces of thrombin and were stored at -80°C for functional test. Heparin-induced platelet activation assay (HIPA) was performed as previously reported (12,13). In HIPA+PF4 experiments, 10 µg/mL recombinant human PF4 (Hyphen Biomed) was added with low and high concentrations of UFH.…”

Diagnosis and management of heparin‐induced thrombocytopenia: Third edition

“…69,70 HIPA and SRA have a good correlation for positive HIT cases, reaching 84% concordance in a recent retrospective analysis. 71…”

“…Enhanced sensitivity has been reported by using WP instead of PRP in the assay, considered by some a ‘gold standard’ reference method 69,70 . HIPA and SRA have a good correlation for positive HIT cases, reaching 84% concordance in a recent retrospective analysis 71 …”