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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

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

5 affiliations
  1. 1Coagulation Centre, Cardiology Angiology Centre Bethanien Hospital (CCB), 60389 Frankfurt, Germany
  2. 2Coagulation Research Centre Bethanien Hospital, 60389 Frankfurt, Germany
  3. 3Institute for Transfusion Medicine, University Hospital Greifswald, 17475 Greifswald, Germany
  4. 4Werfen, 08186 Lliçà d’Amunt, Barcelona, Spain
  5. 5Goethe University Frankfurt, Institute of Biostatistics and Mathemical Modelling, 60590 Frankfurt, Germany

Abstract

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.

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BibTeX
@article{trunk2026detection,
  title = {{Detection of Anti-Platelet Factor 4 Antibodies in Acute and Chronic Thromboembolic Disease—A Pilot Study}},
  author = {Annabell Trunk and Jan Wesche and Stella Jacobi and Marina Bruch-Oms and Donata Metzler and Eva Herrmann and Thomas Thiele and Edelgard Lindhoff-Last},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219899},
  url = {https://www.mdpi.com/1422-0067/27/21/9899},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Detection of Anti-Platelet Factor 4 Antibodies in Acute and Chronic Thromboembolic Disease—A Pilot Study
AU  - Annabell Trunk
AU  - Jan Wesche
AU  - Stella Jacobi
AU  - Marina Bruch-Oms
AU  - Donata Metzler
AU  - Eva Herrmann
AU  - Thomas Thiele
AU  - Edelgard Lindhoff-Last
PY  - 2026
DA  - 2026/11/05
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219899
UR  - https://www.mdpi.com/1422-0067/27/21/9899
AB  - 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.
SN  - 1422-0067
ER  -