Vaccine induced thrombotic thrombocytopenia post dose 2 ChAdOx1 nCoV19 vaccination: Less severe but not void of catastrophic outcomes

ABSTRACT

Background: Clinical and pathological features of vaccine induced immune thrombotic thrombocytopenia (VITT) following first dose ChAdOx1 nCoV19 vaccination (AZD1222) are well described. VITT post 2nd dose AZD1222 is not widely recognised however its plausible undiagnosed platelet activating antibodies formed after dose 1 may be boosted upon subsequent exposure. (Greinacher et al). Aim(s) We describe the clinicopathological features of suspected VITT post 2nd dose AZD1222 in Australia. Method(s) We conducted a prospective cohort study capturing sequential requests for confirmatory testing for suspected VITT after 2nd dose AZD1222. Testing was based upon key clinicopathological features Thrombosis within timeframe (4-42 days), thrombocytopenia, D-Dimer >5xULN. High probability VITT (all criteria) underwent immunoassay Asserachrom HPIA IgG (Diagnostica Stago) and functional assay (serotonin release assay or procoagulant flow cytometry). Confirmed VITT cases were compared with those presenting after first dose AZD1222. Descriptive and comparative statistics were performed using SAS studio version 9.4. Result(s) 35 high probability VITT cases presented at a median of 14 days (IQR 9,18) post 2nd dose with platelet count 116 x 109/L (IQR 92, 139) and 14.5 fold increase in D-dimer (IQR 9.4,28.8) were tested. Median dose interval was 84 days (range 25-100), age 70 years (IQR 62, 78) with a male predominance of 66%. Platelet count and D-dimer fold change were less severe compared to cases post 1st dose (Table 1). PF4 antibodies by ELISA were detected in 4 (11%) and antibody mediated platelet activation demonstrable in 19 (54%). These cases were classified as confirmed VITT. Three catastrophic cases including 2 fatalities occurred (Graph 2). Concomitant factors were present in all and influenced outcome severity. Conclusion(s) We describe the largest cohort of suspected VITT post 2nd dose AZD1222. Confirmed cases are similar to those post D1 but platelet count and D-Dimer changes were milder. Similarly, catastrophic cases occurred however concomitant factors were present in all including shorter dosing intervals. (Table Presented).