COVID-19 vaccine–induced immune thrombotic thrombocytopenia: pathophysiology and diagnosis

Coronavirus disease-19 (COVID-19) vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but serious clinical condition with high mortality rate in apparently healthy individuals without noticeable risk factors. VITT typically arises due to the administration of vaccines that possess recombinant adenoviral vectors, including ChAdOx1 nCov-19 (AstraZeneca) and Ad26 COV2.S (Johnson & Johnson/Janssen). Thrombosis frequently occurs at atypical sites, such as the cerebral or splanchnic circulations, in this particular pathological state. Similar to heparin-induced thrombotic thrombocytopenia (HITT), it seems that the cause of VITT is the misdirection of anti-platelet factor 4 antibodies (anti-PF4 Abs), an ancient antimicrobial mechanism. Anti-PF4 Abs in patients with VITT activates the coagulation system, leading to thrombosis. This process occurs through the stimulation of platelets (Plts) and neutrophils and subsequently release of neutrophil extracellular traps (NETs). Due to the potentially fatal consequences of VITT, early diagnosis is mandatory. In addition to thrombocytopenia, thrombosis, and the presence of anti-PF4 Abs, the day of symptoms onset and the elevation of D-dimer are also required for definitive diagnosis of VITT. The absence of one or more criteria can result in the exclusion of definitive VITT and lead to the diagnosis of probable, possible, or unlikely VITT.