[Antiplatelet factor 4 (PF4)-associated disorders: from drug adverse reactions to thrombotic disease]

Antibodies against platelet-derived factor 4 (anti-PF4) lead to severe acute or chronic thrombosis. Anti-PF4-associated immune thromboses include heparin-induced thrombocytopenia (HIT) and HIT-related diseases, vaccine- or virus-induced immune thrombocytopenia and thrombosis (VITT), and chronic monoclonal gammopathy of thrombotic significance (MGTS). The etiology of anti-PF4-associated diseases varies, but all share the positive detection of platelet-activating antibodies against PF4. Clinically, arterial and venous thrombosis develops, usually accompanied by moderate thrombocytopenia. In acute forms, these symptoms typically occur within a time window of 4-12 days (HIT) or 4-30 days (VITT) after a trigger, e.g., heparin therapy or a viral infection. Laboratory diagnosis is based on the detection of anti-PF4 antibodies and functional evidence of platelet activation in the presence of heparin (HIT) or PF4 (VITT). Acute treatment is based on alternative anticoagulation at therapeutic doses and high-dose intravenous immunoglobulins (IVIG). In chronic immune thrombosis, an underlying monoclonal gammopathy must be treated. Bruton's tyrosine kinase inhibitors (e.g., ibrutinib) can reduce platelet activation and thus control the clinical picture. This review article summarizes the classification, diagnosis, and treatment of anti-PF4-associated diseases.