OBJECTIVES:Vaccine-induced immune thrombotic thrombocytopenia is an unexpected consequence of the coronavirus disease 2019 pandemic era. We reviewed the pathogenesis, clinical presentation, diagnosis, and treatment of this rare side effect.DATA SOURCES:Online search of published medical literature through PubMed, Scopus, Web of Science, and Google Scholar using the terms “COVID-19,” “vaccine,” “thrombosis” was performed.STUDY SELECTION:Articles were chosen for inclusion based on their relevance to coronavirus disease 2019, vaccine, and thrombosis.DATA SYNTHESIS:Vaccine-induced immune thrombotic thrombocytopenia manifests most often as unusual thromboses (cerebral venous sinus thrombosis, splanchnic vein thrombosis) but sometimes also “usual” thromboses (arterial stroke, pulmonary embolism, deep-vein thrombosis), with oftentimes severe thrombocytopenia, that becomes clinically evident 5–30 days after adenovirus-vectored coronavirus disease 2019 vaccine administration. Most patients have disseminated intravascular coagulation. These features are the result of vaccine-triggered formation of anti-platelet factor 4 immunoglobulin G that activate platelets, clinically mimicking autoimmune heparin-induced thrombocytopenia. Early recognition based on thrombosis (sometimes, hemorrhage), thrombocytopenia, and d-dimer elevation within the day 5–30 postvaccine “window” is important given treatment with high-dose IV immunoglobulin plus nonheparin anticoagulation.CONCLUSIONS:Vaccine-induced immune thrombotic thrombocytopenia is a serious complication of vaccination that is not feasible to anticipate or prevent. When the patient presents with sustained headache, neurologic symptoms/signs, abdominal pain, dyspnea, or limb pain/swelling beginning 5–30 days post vaccination, platelet count and d-dimer must be measured, and imaging for thrombosis performed. Confirmation of vaccine-induced immune thrombotic thrombocytopenia diagnosis should be ordered (platelet factor 4/polyanion enzyme-linked immunosorbent assay; platelet factor 4–enhanced platelet activation testing) as treatment is initiated (nonheparin anticoagulation, IV immunoglobulin).
