Detection of Anti-Platelet Factor 4 Antibodies in Acute and Chronic Thromboembolic Disease—A Pilot Study

Heterogeneous antibodies directed against platelet factor 4 (PF4-Abs) are associated with heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT). Emerging evidence suggests that these antibodies may also occur in other thromboembolic diseases. In this pilot study, we assessed the prevalence of PF4-Abs in patients with acute thromboembolism and in patients with thromboembolic antiphospholipid syndrome (APS), a chronic autoimmune thrombophilia. Forty patients with acute thromboembolism and 43 patients with APS were included. Both heparin-dependent and heparin-independent PF4-Abs were evaluated using multiple assay platforms, including a prototype chemiluminescence assay for heparin-independent PF4-Abs, an anti-PF4/polyanion IgG chemiluminescence assay, a latex agglutination assay detecting anti-PF4/polyanion IgG/IgM/IgA antibodies, an anti-PF4/heparin IgG ELISA, and functional platelet activation tests. Across the different assays, positivity in at least one assay was observed in 27.5% (11/40) of patients with acute thromboembolism and 27.9% (12/43) of patients with APS. In most antibody-positive patients, no recent heparin exposure was documented. Functional platelet activation was predominantly absent, arguing against a classical HIT- or VITT-like mechanism. Overall, these results demonstrate assay-dependent PF4-Ab positivity in a substantial proportion of patients with acute and chronic thromboembolic conditions. Their clinical and pathogenic relevance remains unclear and warrants further investigation.