Management of Cerebral Venous Thrombosis Due to Adenoviral COVID‐19 Vaccination

Abstract

Objective Cerebral venous thrombosis (CVT) caused by vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus‐based severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non‐heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods We used data from an international prospective registry of patients with CVT after the adenovirus‐based SARS‐CoV‐2 vaccination. We analyzed possible, probable, or definite VITT‐CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results Ninety‐nine patients with VITT‐CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in‐line with VITT recommendations ( p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16–1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06–0.58). Treatment with non‐heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24–2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74–6.54). Conclusions In patients with VITT‐CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT‐CVT. ANN NEUROL 2022

Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure

“…Of clinical relevance, the thrombotic episodes in these patients with VITT-like features are similarly life-threatening as in VITT. In VITT, early recognition of patients and treatment with therapeutic-dose anticoagulation and high-dose IVIG 12 , 31 reduced mortality by up to 90%. 32 As in the entity known as pre-VITT, 33 4 of our patients initially presented with severe headache in the emergency room (with initially negative imaging studies) and only later developed overt radiologically-evident CVST (patient 2, 5, 8, and 9), progression of which might have been prevented by early treatment with IVIG.…”

Cerebral venous sinus thrombosis following ChAdOx1 nCoV-19 AstraZeneca COVID-19 vaccine

“…24 Although there is research showing that immunomodulation is linked to a lower mortality, it is unclear as to the efficacy of platelet transfusion and use of non-heparin anticoagulants, with some research showing lower mortality and others showing no significant difference. 9 , 28 …”

COVID and Vaccine-related Cerebral Venous Thrombosis

“…An increase in platelet count with a decrease in d-dimer levels is also reported in these patients after IVIG administration 80 The role of IVIG in non-VITT cohorts is not clear; however, a large multicentric registry revealed the mortality benefit of immunomodulation in patients diagnosed with VITT in COVID-vaccine CVT. 82 Plasma exchange and corticosteroids have also been tried, usually in combination with the above treatments. 78,83 Large studies are not available to document their effects in the management of VITT and vaccine-induced CVT.…”