Cerebral Venous Sinus Thrombosis Due To Vaccine-induced Immune Thrombotic Thrombocytopenia In Middle-Income Countries

Introduction: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). In India alone, 1.67 billion ChAdOx1 nCoV-19 vaccines have been administered by August 23, 2022. Surprisingly however, there are only few reports of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) from LMICs. We aimed to gain insight into the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared characteristics of CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: By August 15, 2022, 228 CVST cases after vaccination were reported, of which 63 cases from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, and Turkiye). Of these, 32/63 (51%) met the criteria for definite, probable or possible VITT. Only 5/32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-PF4 antibodies were not tested in 21/32 (66%) cases. Patients from MICs were diagnosed in a later time period than patients from HICs (1/32 [3%] vs 65/103 [63%] cases diagnosed before May 2021, respectively). Median age was 26 (IQR 20-37) vs 47 (IQR 32-58) years, and proportion of women was 25/32 (78%) vs 77/103 (75%) in MICs vs HICs, respectively. Clinical manifestations, such as focal neurologic deficits, coma, seizures, and intracranial hemorrhages, were similar. Concomitant venous thromboembolism was less frequent in MICs (3/31 [10%] vs 26/97 [27%]). Median platelet count nadir was higher in the MICs than the HICs group (65 x10 9 /L [IQR 36-115] vs 33 x10 9 /L [IQR 18-55], p =0.001). Intravenous immunoglobulin use was similar (19/30 [63%] vs 63/99 [64%]). In-hospital mortality was lower in the MICs than the HICs group (7/32 [22%, 95%CI 11-39] vs 44/102 [43%, 95%CI 34-53], p =0.031). Conclusions: The absolute number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines in these countries. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.