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Vaccine-induced thrombotic thrombocytopenia following coronavirus vaccine: A narrative review.

ABSTRACT: The novel coronavirus pandemic has taken a toll on the global healthcare systems and economy. Safety precautions, along with vaccination, are the most effective preventive measures. The global vaccination program against COVID-19 has dramatically reduced the number of deaths and cases. However, the incidence of thrombotic events and thrombocytopenia post-COVID-19 vaccination known as vaccine-induced thrombotic thrombocytopenia has raised safety concerns. This has led to an element of vaccine hesitancy. The exact mechanism for vaccine-induced thrombotic thrombocytopenia is unknown. Although the incidence of thrombosis associated with COVID-19 vaccination is low, it still requires attention, especially in older people, smokers, and people with preexisting comorbidities. This study aims to review the pathophysiology, diagnosis, and management of vaccine-induced thrombotic thrombocytopenia, to provide a concise and comprehensive update.

SUBMITTER: Ahmed SH

PROVIDER: S-EPMC8556865 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Vaccine-induced thrombotic thrombocytopenia following coronavirus vaccine: A narrative review.

Ahmed Syed Hassan SH Shaikh Taha Gul TG Waseem Summaiyya S Qadir Nashwa Abdul NA Yousaf Zohaib Z Ullah Irfan I

Annals of medicine and surgery (2012) 20211030

The novel coronavirus pandemic has taken a toll on the global healthcare systems and economy. Safety precautions, along with vaccination, are the most effective preventive measures. The global vaccination program against COVID-19 has dramatically reduced the number of deaths and cases. However, the incidence of thrombotic events and thrombocytopenia post-COVID-19 vaccination known as vaccine-induced thrombotic thrombocytopenia has raised safety concerns. This has led to an element of vaccine hes ...[more]

PMID: 34745596

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Project description:In the spring of 2021, reports of rare and unusual venous thrombosis in association with the ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to a brief suspension of their use by several countries. Thromboses in the cerebral and splanchnic veins among patients vaccinated in the preceding 4 weeks were described in 17 patients out of 7.98 million recipients of the Ad26.COV2.S vaccine (with 3 fatalities related to cerebral vein thrombosis) and 169 cases of cerebral vein thrombosis among 35 million ChAdOx1 recipients. Events were associated with thrombocytopenia and anti-PF4 (antibodies directed against platelet factor 4), leading to the designation vaccine-induced immune thrombotic thrombocytopenia. Unlike the related heparin-induced thrombotic thrombocytopenia, with an estimated incidence of <1:1000 patients treated with heparin, and a mortality rate of 25%, vaccine-induced immune thrombotic thrombocytopenia has been reported in 1:150 000 ChAdOx1 recipients and 1:470 000 Ad26.COV.2 recipients, with a reported mortality rate of 20% to 30%. Early recognition of this complication should prompt testing for anti-PF4 antibodies and acute treatment targeting the autoimmune and prothrombotic processes. Intravenous immunoglobulin (1 g/kg for 2 days), consideration of plasma exchange, and nonheparin anticoagulation (argatroban, fondaparinux) are recommended. In cases of cerebral vein thrombosis, one should monitor for and treat the known complications of venous congestion as they would in patients without vaccine-induced immune thrombotic thrombocytopenia. Now that the Ad26.COV2.S has been reapproved for use in several countries, it remains a critical component of our pharmacological armamentarium in stopping the spread of the human coronavirus and should be strongly recommended to patients. At this time, the patient and community-level benefits of these two adenoviral vaccines vastly outweigh the rare but serious risks of vaccination. Due to the relatively low risk of severe coronavirus disease 2019 (COVID-19) in young women (<50 years), it is reasonable to recommend an alternative vaccine if one is available. Ongoing postmarketing observational studies are important for tracking new vaccine-induced immune thrombotic thrombocytopenia cases and other rare side effects of these emergent interventions.

Project description:Background: In February 2021, a few cases of unusual, severe thrombotic events associated with thrombocytopenia reported after vaccination with ChAdOx1 nCoV-19 (Vaxzevria) or with Johnson & Johnson's Janssen vaccine raise concern about safety. The vaccine-induced thrombotic thrombocytopenia (VITT) has been related to the presence of platelet-activating antibodies directed against platelet Factor 4. Objectives: We investigated VITT subject genetic background by a high-throughput whole exome sequencing (WES) approach in order to investigate VITT genetic predisposition. Methods: Six consecutive patients (females of Caucasian origin with a mean age of 64 years) were referred to the Atherothrombotic Diseases Center (Department of Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi, Florence) with a diagnosis of definite VITT underwent WES analysis. WES analysis was performed on the Illumina NextSeq500 platform. Results:WES analysis revealed a total of 140,563 genetic variants. Due to VITT's rare occurrence, we focused attention on rare variants. The global analysis of all high-quality rare variants did not reveal a significant enrichment of mutated genes in biological/functional pathways common to patients analyzed. Afterwards, we focused on rare variants in genes associated with blood coagulation and fibrinolysis, platelet activation and aggregation, integrin-mediated signaling pathway, and inflammation with particular attention to those involved in vascular damage, as well as autoimmune thrombocytopenia. According to ACMG criteria, 47/194 (24.2%) rare variants were classified as uncertain significance variants (VUS), whereas the remaining were likely benign/benign. Conclusion: WES analysis identifies rare variants possibly favoring the prothrombotic state triggered by the exposure to the vaccine. Functional studies and/or extensions to a larger number of patients might allow a more comprehensive definition of these molecular pathways.

Dataset Information

Vaccine-induced thrombotic thrombocytopenia following coronavirus vaccine: A narrative review.

Publications

Vaccine-induced thrombotic thrombocytopenia following coronavirus vaccine: A narrative review.

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