Gil, Morayma Reyes

ABSTRACT Background Platelet factor 4‐polyanion enzyme‐linked immunosorbent assays (ELISAs) are considered highly sensitive for diagnosing heparin‐induced thrombocytopenia (HIT), such that current practice guidelines recommend use of ELISA‐negative results to exclude HIT. Once HIT is ruled out, alternative, non‐heparin‐based anticoagulant treatments are ceased, and heparin reintroduction frequently occurs. Methods Antigen‐based and PF4‐dependent functional testing were used to study PF4/polyvinylsulfonate ELISA‐negative platelet‐activating antibodies in HIT‐suspected patients. Results Three patients with clinical presentations consistent with HIT tested negative in an ELISA using PF4‐polyvinylsulfonate (PF4/PVS), an antigenic target very commonly used for HIT antibody screening. All three patients demonstrated PF4‐dependent platelet activation in functional testing that was sensitive to blockade of platelet FcγRIIa receptors and inhibited by high concentrations of heparin, consistent with pathogenic HIT antibodies. Functional testing‐based screening of 500 ELISA‐negative patients identified three additional patients whose sera activated platelets in a PF4‐ and FcγRIIa‐dependent manner and had clinical histories consistent with HIT. Five of the six ELISA‐negative HIT patients were re‐exposed to heparin, which precipitated a decrease in platelet counts in all re‐exposed patients, and one patient developed a new thrombus. Conclusions Recognition of ELISA‐negative HIT is critical to avoid harm due to the cessation of alternative anticoagulation therapy and re‐exposure of these patients to heparin.

Abstract Measurement of D-dimer, a fibrin degradation product, is crucial for diagnosing thrombotic and fibrinolytic conditions. Despite its expanding utility, D-dimer testing faces challenges due to varying assay methodologies and nonstandardized reporting. To understand D-dimer reporting practices, the College of American Pathologists Hemostasis and Thrombosis Committee analyzed proficiency testing data from D-dimer surveys conducted between 2020 and 2023 across multiple laboratories. The data demonstrate that laboratories commonly report units that differ from the assay package insert when reporting their proficiency testing results. We sought to assess variability in reporting practices and opportunities for improvement in D-dimer reporting amongst participants. To accomplish this, we harmonized all D-dimer results to ng/mL fibrinogen equivalent units from one distributed sample and assessed distinct populations of entries per instrument/reagent combination. Notable trends emerged from this analysis. Data from laboratories using the same instrument/reagent combinations clustered around different means, suggesting issues with unit reporting and/or conversion. Entries reported in mg/L or ug/mL D-dimer units commonly exhibited significant deviations from the dominant population. For one instrument/reagent combination, most reported values differed by approximately twice the certificate of analysis value. This analysis highlights potential issues with D-dimer reporting in proficiency testing. Whether these issues translate into issues with clinical D-dimer reporting requires further study.