Vaccine-Induced Immune Thrombotic Thrombocytopenia: Where does The PF4 Fit?

Abstract

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe and usually fatal syndrome with an aggressive thrombotic process in unusual sites (notably, sinus veins of the brain and/or splanchnic veins) that accompanies profound thrombocytopenia. If not well managed, VITT may progress to a more severe systemic disease such as disseminated intravascular coagulation. VITT was associated with two adenoviral vector vaccines, mainly ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen/ Johnson & Johnson) was first reported in late February 2021 and mid-April 2021, respectively. This thrombotic phenomenon closely resembled that of autoimmune heparin-induced thrombocytopenia. Yet, in 2021, the MHRA (Medicines & Healthcare products Regulatory Agency) and the European Medicines Agency (EMA) claim no association between thrombosis and vaccines. Not long after, three scientific societies from Norway, Germany, and the UK reported in the press and social media the detection of thrombocytopenia with cerebral venous sinus thrombosis (CVST) and anti-platelet factor 4 (anti-PF4) antibodies in patients succeeding adenovirus-based vaccination. The immune response against PF4; (also known as CXCL4) in VITT is probably triggered by the proinflammatory milieu; compounds such as human cell-line proteins, non-assembled adenoviral proteins, and potentially EDTA (edetic acid) could be contributing to the prothrombotic state. This review will address functional aspects of PF4 in the thromboinflammatory phenomena, its role in the current anti-SARS-CoV-2 adenoviral-based vaccines, and evidence for its role in triggering VITT. Physicians as well as the public need to be aware of this new disease to quickly provide accurate diagnosis and timely treatment.