Clinico-serological positivity preceding laboratory functional conversion in heparin-induced thrombocytopenia: a case series

Introduction Heparin-induced thrombocytopenia (HIT) is a rare but potentially life-threatening complication of heparin therapy, whose diagnosis is based on clinical and biological characteristics. Functional assays, such as heparin-induced platelet activation (HIPA), PF4-enhanced HIPA (PIPA), and serotonin release assay (SRA) are considered diagnostic gold standards. However, because of their limited availability and delayed turnaround time, the initial work-up is usually performed combining a clinical scoring system, such as the “4T” with rapid quantitative immunoassays (IA), pending confirmation by functional testing. Yet, functional assays are known to have limited sensitivity [ 1 ], and a possible delayed functional conversion has been reported [ 2 ] [ 3 ]. Recently, a flow cytometry–based functional test, the HIT antibody-induced procoagulant platelets (HIT-PCP) assay, has been developed with the aim of improving the sensitivity, rapidity, and accessibility of HIT diagnosis [ 4 ]. Here, we report four cases of delayed functional conversion and evaluate the timing of conversion using the HIT-PCP assay in these cases. Method We report four cases of delayed functional conversion relative to clinico-serological positivity observed in our center between March 2021 and September 2025. Diagnostic work-up was performed using the first version of the Lausanne algorithm [ 5 ] until December 2021, and the adapted algorithm [ 6 ] [ 7 ] from January 2022 onward. Functional conversion was assessed using the HIPA/PIPA assays performed at the reference laboratory in Greifswald [ 8 ] [ 9 ]. We investigated stored plasma samples with the HIT-PCP assay, as described [ 4 ]. Results During the study period, four out of 109 HIT cases (3.7%) showed delayed functional conversion relative to clinico-serological positivity. Details of these cases are presented in [ Fig. 1 ]. The HIT-PCP assay was negative in all cases at the time of clinico- serological work-up and became positive concurrently with HIPA and/or PIPA positivity. Fig. 1 Characteristics of the four cases of delayed functional conversion relative to clinico-serological positivity. F, female; M, male; STEMI, ST-elevation myocardial infarction; CLIA, chemiluminescence immunoassay; PaGIA, particle-gel immunoassay; LIA, latex immune-turbidimetric immunoassay; ELISA, enzyme-linked immunosorbent assay; HIPA, heparin-induced platelet aggregation assay; PIPA, PF4-enhanced HIPA; HIT-PCP, HIT antibody-induced procoagulant platelet assay; NA, not applicable. Conclusion As illustrated by these four cases, and although considered the gold standard, functional HIT assays have limited sensitivity, partly due to delayed in vitro functional conversion. The HIT-PCP assay, a recently developed flow cytometric method, has raised hopes for a functional assay with improved sensitivity. However, in these four cases with delayed functional conversion, HIT-PCP failed to identify HIT at the time of its clinico-serological recognition using the Lausanne Algorithm. Therefore, despite initial negative functional results, in cases of strong clinical and serological suspicion of HIT, alternative anticoagulation should be maintained, and heparin discontinued, until repeat functional testing is performed. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany