Hematology in the post-COVID era: spotlight on vaccine-induced immune thrombotic thrombocytopenia and a conceptual framework (the 4P's) for anti-PF4 diseases

IntroductionVaccine-induced immune thrombotic thrombocytopenia (VITT) is a life-threatening prothrombotic disorder first identified following the introduction of adenoviral vector vaccines for COVID-19. The condition is characterized by anti-PF4 antibodies and clinically presents with thrombocytopenia and thrombosis often in unusual anatomical sites.Areas coveredIn this review, we discuss the clinical presentation, diagnostic testing, and treatment of VITT. We also review VITT-like syndromes that have been described in patients without previous vaccination. We propose a conceptual framework for the mechanism of anti-PF4 diseases that includes sufficiently high levels of PF4, the presence of a Polyanion that can form immune complexes with PF4, a Pro-inflammatory milieu, and an immunological Predisposition - the 4Ps.Expert opinionSignificant progress has been made in understanding the characteristics of the VITT antibody and in testing methods that can confirm that diagnosis. Future work should be directed at understanding long-term outcomes, mechanisms of thrombosis, and individual risk factors for this rare but dangerous immune-thrombotic disease.