COVID-19 Vaccine-Associated Immune Thrombosis and Thrombocytopenia (VITT): Diagnostic Discrepancies and Global Implications

Abstract

Vaccine-induced immune thrombotic thrombocytopenia (VITT) has been reported in association with the coronavirus disease 2019 preventative adenovirus vector-based vaccines ChAdOx1 nCoV-19 (Oxford/AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) in hundreds of recipients across the globe. VITT is characterized by thrombosis, typically at unusual sites, low fibrinogen, and elevated plasma D-dimer, generally manifesting between 4 and 28 days following vaccination. Detection of anti-platelet factor antibodies using an enzyme-linked immunosorbent assay (ELISA) is often confirmatory. Although several similar principles subside in most diagnostic criteria for VITT, the presentation of a positive ELISA assay, use of expert hematology and neurology opinion, and exclusion of possible VITT cases outside the “standard” 4 to 28-day timeframe have contributed a lack of global standardization for defining VITT. Accordingly, the global and regional incidence of VITT differs according to the diagnostic pathway and case definition used. This has influenced the public perception of VITT's severity and the decision to use adenovirus vector-based vaccines for limiting severe acute respiratory syndrome coronavirus 2 infection. We hereby delineate the recognized pathogenic mechanisms, global incidence, discrepancies in diagnostic criteria, recommended treatments, and global implications to vaccine hesitancy from this coagulopathy.

Reverse Engineering of a Pathogenic Antibody Reveals the Molecular Mechanism of Vaccine-Induced Immune Thrombotic Thrombocytopenia

“…VITT typically occurs within 4–28 days of vaccination and has a distinct clinical profile (thromboses at unusual sites, such as cerebral venous sinus thrombosis , in combination with thrombocytopenia) and a high mortality rate . Despite the low incidence rate (ranging from 3 to 36 cases per million doses for ChAdOx1-S and three- to four-fold lower for human Ad-vectored vaccines , ), VITT became one of the major factors contributing to the vaccine hesitancy phenomenon and undermining the global vaccination effort during the pandemic. − Although all VITT cases reported so far had been linked to COVID-19 vaccines, the close association of this thrombopathy with a specific delivery vector raises a specter of other Ad-vectored vaccines being able to trigger VITT, an alarming prospect given the popularity of this platform …”

2024 Eberhard F. Mammen Award Announcements: Part I—Most Popular Articles

“…Consequently, the most popular papers from each category are identified separately. Tables 3 and 4 respectively list the top 25 downloaded articles from STH in 2023 (from 2022 and 2023 inclusive), as eligible for either the “free access” ( Table 3 ) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 or “general category” ( Table 4 ) 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 awards.…”

“…As 2023 is no longer considered a pandemic, and as journals transition back to “business as usual,” COVID-19 papers, while remaining popular, do not seem to entirely dominate as in the recent past. Nevertheless, 16/25 papers in the top 25 list have some connection to COVID-19, with 4 of these actually related to vaccine-induced immune thrombotic thrombocytopenia (VITT), 2 7 12 15 a rare but serious condition arising from vaccination against COVID-19.…”

“…1 The second most popular paper, from Zidan et al, was related to VITT. 2 Thus, the winners of the 2024 most popular awards for the “free access” category are:…”

Evolution of Hemostasis Testing: A Personal Reflection Covering over 40 Years of History*

“…Whereas HIT can occur in some 1 to 3% of exposures to unfractionated heparin, VITT only occurs in around 1/50,000 to 1/100,000 doses of vaccine, with only adenovirus-based vaccines consistently confirmed as being associated with VITT. 122 123 Although relatively rare, VITT became a major preoccupation of many of us active in the hemostasis field, especially given its connection to COVID-19 vaccine use and thrombosis associated with thrombocytopenia. As part of the THANZ (Thrombosis and Haemostasis Society of Australia and New Zealand) group charged to diagnose and manage the unfolding VITT crisis in Australia, we held regular out of normal work hours Thursday evening meetings for almost a year devising diagnostic and management strategies and discussing our cases.…”