Vaccine-induced immune thrombotic thrombocytopenia: what do we know hitherto?

Abstract

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome, is a catastrophic and life-threatening reaction to coronavirus disease 2019 (COVID-19) vaccines, which occurs disproportionately in response to vaccination with non-replicating adenovirus vector (AV) vaccines. The mechanism of VITT is not well defined and it has not been resolved why cases of VITT are predominated by vaccination with AV vaccines. However, virtually all VITT patients have positive platelet-activating anti-platelet factor 4 (PF4) antibody titers. Subsequently, platelets are activated and depleted in an Fcγ-receptor IIa (FcγRIIa or CD32a)-dependent manner, but it is not clear why or how the anti-PF4 response is mounted. This review describes the pathogenesis of VITT and provides insight into possible mechanisms that prompt the formation of a PF4/polyanion complex, which drives VITT pathology, as an amalgam of current experimental data or hypotheses.

Long-Term Clinical Safety of the Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: A Prospective, Multi-Country, Observational Study

“…Furthermore, to date, no cases of VITT have been reported in any non-COVID-19, Ad26-based vaccine development programs, including for the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen, either in clinical studies or post-marketing surveillance activities. The mechanism for VITT following vaccination is currently unknown [ 44 ].…”

Ischemic stroke following COVID-19 vaccination

“…These antibodies trigger a coagulation cascade and cause thrombotic complications. 22,24 HIT is a potentially devastating immune-mediated adverse drug reaction, which is believed to be strongly associated with thromboembolic complications, involving both the arterial and venous systems. In our case, since platelet counts were normal and the patient did not receive heparin, HIT would not be as a differential diagnosis.…”

Temporal changes in biomarkers of neutrophil extracellular traps and NET‐promoting autoantibodies following adenovirus‐vectored, mRNA, and recombinant protein COVID‐19 vaccination

“…Results of in vitro studies indicate that various factors, including lipopolysaccharide, interleukin‐8 (IL‐8), and reactive oxygen species as well as anti‐heparin platelet factor 4 (anti‐HPF4) antibodies, can trigger formation of NETs 9–12 . Anti‐HPF4 antibodies may be induced by the presence of a polyanion–protein complex resulting from the interaction between positively charged platelet factor 4 and negatively charged adenoviral vectors, as observed in vaccine‐induced immune thrombotic thrombocytopenia (VITT) patients 13–17 . Exposure to purified VITT IgG resulted in a significant rise in activated neutrophil counts and prompted neutrophils to undergo NETosis.…”

“…[9][10][11][12] Anti-HPF4 antibodies may be induced by the presence of a polyanion-protein complex resulting from the interaction between positively charged platelet factor 4 and negatively charged adenoviral vectors, as observed in vaccine-induced immune thrombotic thrombocytopenia (VITT) patients. [13][14][15][16][17] Exposure to purified VITT IgG resulted in a significant rise in activated neutrophil counts and prompted neutrophils to undergo NETosis. The in vitro release of NETs was further amplified by the presence of PF4 protein, particularly when triggered by VITT IgG.…”