Platelet factor 4 (PF4) is a positively charged molecule stored in the alpha granules of blood platelets and secreted during platelet activation, endothelial breach, or in the presence of microorganisms. PF4 binds to glycosaminoglycans on the endothelial surface and neutralizes their anticoagulant properties. Moreover, PF4 can combine with heparin, mainly unfractionated, in heparin-induced thrombocytopenia (HIT), with cartilage components or other negatively charged polyanions (so-called spontaneous HIT), and with some constituents of the SARS-CoV-2 adenovirus vaccine, resulting in post-vaccination thrombocytopenia. The common feature of these molecules is their negative charges which induce their binding to PF4 and a conformational change of the latter. This complex is recognized by anti-PF4 antibodies, which activate platelets and inflammatory cells via the Fc receptor, induce a pro-thrombotic state, and venous, arterial, or microcirculation thrombosis. The diagnosis of HIT is based on the detection of anti-PF4-heparin antibodies by immunoassay in cases of clinical suspicion and intermediate or high pre-test probability, estimated by different scores, the 4T score being the most common. Functional tests may also be performed. HIT management consists in stopping heparin and starting non-heparin anticoagulant therapy.
What is already known about the topic?
Platelet factor 4 (PF4) is stored in platelets and has a pro-coagulant role. Exposure to heparin can induce thrombocytopenia and a pro-thrombotic state (HIT). PF4 may also be responsible for platelet activation in the absence of heparin.
What does this article teach us?
This article describes the functions of PF4 and its implications in heparin-induced thrombocytopenia (HIT), in SARS-CoV-2 adenovirus vaccine-induced thrombocytopenia (VIT), and in other situations gathered under the term autoimmune HIT.
Key Words
Platelet factor 4 (PF4), thrombocytopenia, polyanion, COVID-19, heparin