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    Late-Breakthrough Submission

    Immunothrombosis

    Late-Breakthrough Session II

    LB 02.4 - Anti-platelet factor 4 induced immunothrombosis independent of heparin or vaccination

    Tuesday, June 27, 2023
    11:30 – 11:45 ET
    Room: 517
    Session Available As: Live-Streamed and On-Demand

      Co-Author(s)

    • Linda Schönborn, Dr. med.

      Medical Resident
      Institut für Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
      Greifswald, Mecklenburg-Vorpommern, Germany

    • OE

      Olga Esteban

      Innovation R&D Senior Investigator
      Werfen, Lliçà d’Amunt, Barcelona, Spain
      Barcelona, Catalonia, Spain

    • JW

      Jan Wesche

      Medical laboratory scientist
      Institut für Transfusionsmedizin, Universitätsmedizin Greifswald.
      Greifswald, Mecklenburg-Vorpommern, Germany

    • PD

      Paulina Dobosz

      Medical Scientist
      Werfen, Lliçà d’Amunt, Barcelona, Spain
      Barcelona, Catalonia, Spain

    • MB

      Marta Broto

      Innovation R&D Scientist
      Werfen, Lliçà d’Amunt, Barcelona, Spain
      Barcelona, Catalonia, Spain

    • SR

      Sara Rovira

      Scientist
      Werfen, Lliçà d’Amunt, Barcelona, Spain
      Barcelona, Catalonia, Spain

    • JF

      Jessica Fuhrmann

      Medical laboratory scientist
      Institut für Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
      Greifswald, Mecklenburg-Vorpommern, Germany

    • RT

      Raquel Torres

      Scientist
      Werfen, Lliçà d’Amunt, Barcelona, Spain
      Barcelona, Catalonia, Spain

    • JS

      Josep Serra

      Scientist
      Werfen, Lliçà d’Amunt, Barcelona, Spain
      Barcelona, Catalonia, Spain

    • RL

      Roser Llevadot

      Principal Scientist, Innovation
      Werfen, Lliçà d’Amunt, Barcelona, Spain
      Barcelona, Catalonia, Spain

    • EL

      Edelgard Lindhoff-Last

      MD, Head of Coagulation Centre and Head of Coagulation Research Centre
      Cardiology Angiology Centre Bethanien Hospital (CCB), Frankfurt Germany
      Frankfurt, Hessen, Germany

    • TH

      Till Hoffmann

      Senior Consultant
      Universitätsklinikum Düsseldorf, Dept.Transfusionsmedizin
      Düsseldorf, Nordrhein-Westfalen, Germany

    • LA

      Lorenzo Alberio, MD (he/him/his)

      Chief Physician, Associated Professor
      Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
      Lausanne, Vaud, Switzerland

    • FL

      Florian Langer

      Medical Specialist in Internal Medicine
      Universitätsklinikum Eppendorf, II. Medizinische Klinik und Poliklinik, Hubertus Wald Tumorzentrum, Universitäres Cancer Center Hamburg (UCCH), Hamburg, Germany
      Hamburg, Hamburg, Germany

    • CB

      Christian Boehme

      Physician
      Neurological Intensive Care Unit, Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria
      Innsbruck, Tirol, Austria

      • Presenting Author(s)

    • Andreas Greinacher, MD

      Professor; Head of Institute
      Institut für Transfusionsmedizin, Universitätsmedizin Greifswald.
      Greifswald, Mecklenburg-Vorpommern, Germany

    Background: We have identified patients with platelet-activating anti-PF4 antibodies causing thrombocytopenia and thrombosis, but without previous heparin exposure or vaccination. Anti-PF4 antibodies are known to cause heparin-induced (HIT) and vaccine-induced (VITT) thrombocytopenia. Both require therapeutic anticoagulation and high-dose intravenous immunoglobulin (IVIG) is indicated in VITT. HIT- and VITT-like antibodies have different characteristics but cannot be differentiated by current antigen assays.

    Aims: 1) To develop an assay prototype able to differentiate HIT and VITT antibodies. 2) To characterize the anti-PF4 antibodies in patients with thrombosis independent of heparin/vaccination.

    Methods: A new assay prototype detecting VITT-like anti-PF4 IgG running on an automated coagulation analyzer ACL AcuStar was developed together with Werfen and we used this new assay and the HemosIL® AcuStar HIT-IgG(PF4-H) to test: HIT-patients (in-house anti-PF4/heparin-IgG-EIA+, heparin-induced platelet-activation assay [HIPA]+; n=131); VITT patients (anti-PF4/heparin-IgG-EIA+, PF4-induced platelet-activation assay [PIPA]+; n=99); patients with thrombosis, thrombocytopenia, and anti-PF4-antibodies without exposure to heparin or vaccination (n=6); and negative controls (n=155).

    Results: The new assay prototype detecting VITT-like anti-PF4 IgG recognized all VITT patients and, in combination with the HemosIL® AcuStar HIT-IgG(PF4-H), clearly differentiates HIT and VITT antibodies (Figure 1). The six patients with anti-PF4 antibodies and thrombosis (Table 1) were all detected by the new antigen assay and showed either exclusively VITT-like (patient 1, 2, 3) or a combination of VITT- and HIT-like antibodies (patients 4, 5, 6). Next, we retested 188 samples with strongly positive in-house anti-PF4/heparin IgG EIA but negative HIPA and found 13 additional patients with PF4-dependent platelet activating VITT-like antibodies.

    Conclusion(s): VITT-like anti-PF4 antibodies are related to severe immunothrombosis independent of heparin or (COVID-19) vaccination. Most of these patients remained previously undiagnosed due to negative results in rapid HIT-tests and heparin-dependent functional tests. The presented assays allow to identify these patients (also within prospective clinical studies), differentiate HIT- and VITT-like antibodies, and enable rapid clinical decision making.