Recognizing Vaccine-Induced Immune Thrombotic Thrombocytopenia

Abstract

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).

Thrombosis and thrombocytopenia in COVID-19 and after COVID-19 vaccination

“…Whereas deep vein thrombosis/pulmonary embolism and arterial thrombus are common in HIT, CVST and splanchnic vein thrombosis are most often seen in VITT/TTS. The anti-PF4 ELISA tests are usually positive for both diseases but HIT rapid screening assays (e.g., latex immunoassay, chemiluminescence immunoassay, particle gel immunoassay) are generally positive only for HIT [51] , indicating differences in target antigens on PF4 between HIT and VITT/TTS. Sangli et al [52] .…”

COVID-19 phase 4 vaccine candidates, effectiveness on SARS-CoV-2 variants, neutralizing antibody, rare side effects, traditional and nano-based vaccine platforms: a review

“…Possible treatment methods are high doses of intravenous immunoglobulins (IVIG), non-heparin-based anticoagulants, corticosteroid administration, and plasma exchange. After clinical stabilization, oral anticoagulants such as apixaban, rivaroxaban can be given (Iba et al 2021 ; Mohseni Afshar et al 2021 ; Siegler et al 2021 ).…”

Upper Limb Ischemia Due to Arterial Thrombosis after COVID-19 Vaccination

“…The great majority of patients were previously healthy and fit [ 11 ]. So when a patient presents with headache, abdominal pain, shortness of breath, and/or limb swelling postvaccination, a platelet count and imaging for thrombosis must be carried out [ 12 ].…”