ABSTRACT
Background: Acquired Haemophilia A (AHA) is a rare but devastating acquired bleeding disorder, caused by autoantibodies against Factor VIII (FVIII). Up to 50% are associated with an underlying disorder including autoimmune disease, malignancy or pregnancy with the remainder considered idiopathic. There have been case reports of AHA occurring post vaccination, including following influenza and mRNA-based COVID-19 vaccination. Here we report on five cases of AHA following adenovirus-vector COVID-19 (ChAdOx1 nCoV-19) vaccination in Australia. Aim(s): Report on the clinical characteristics of five patients diagnosed with AHA following ChAdOx1 COVID-19 vaccination Methods: We collected clinical details of cases of AHA reported after COVID-19 vaccination in Australia. Result(s): Five patients were identified. All were aged >70 years and presented between 19-and 35-days following ChAdOx-1 vaccination. Table 1 outlines baseline and disease characteristics and outcomes. All presented with bleeding requiring hospitalisation;two subcutaneous, one oropharyngeal, one intramuscular and one presented with subcutaneous bleeding initially and subsequently had a large retroperitoneal haemorrhage. Three required bypassing agents (BPA) to control bleeding. No underlying aetiology was found despite investigation for malignancy and autoimmune disease. Four received first-line dual immunosuppressive therapy (prednisolone with either cyclophosphamide or rituximab) and one received triple therapy (prednisolone, cyclophosphamide and rituximab). One also received intravenous immunoglobulin (IVIg). All achieved complete remission. Conclusion(s): We report on five cases of AHA occurring following ChAdOx-1 COVID-19 vaccination. Autoimmune disorders are known to occur post vaccination, with postulated mechanisms including antigenic mimicry and non-specific activation of quiescent autoreactive T and B cells. While there was a clear temporal relationship between all five cases of AHA and the ChAdOx-1 COVID-19 vaccination, all were aged >70 years, the age group more likely to be affected by AHA. Causation cannot be definitively proven, however these cases may highlight the risk of a rare adverse event following immunisation (AEFI). (Table Presented).
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).
ABSTRACT
Background: Immune thrombocytopenia (ITP) has been reported following COVID-19 vaccination. From a population of over 20 million eligible vaccine recipients in Australia, over 32 million doses have been administered: 19,600,000 Pfizer BNT162b2 (BNT), 12,600,000 AstraZeneca ChAdOx1 nCoV-19 (ChAd), and 397,000 Moderna mRNA-1273. Aim(s): Describe a comprehensive series of ITP after vaccination with clinical outcomes. Method(s): After obtaining IRB approval (2021/ETH00723), we collected data on all ITP cases diagnosed by haematologists in Australia within six weeks of any COVID-19 vaccination. We analysed their outcomes using international consensus definitions of responses and WHO bleeding. Result(s): Demographics (n = 50), treatments, and platelet outcomes (Figures A and B). Bleeding was mostly minor: 35/50 (70%) WHO score <2. Compared to relapses of prior ITP, new presentations of ITP were significantly associated with ChAd over BNT (OR 7.1: 95% CI 1.7 to 25.7, p = 0.0124*). Most patients responded quickly and deeply: Median TTR 4 days (IQR 2-7), median TTCR 7 days (IQR 4-19), overall RR 45/47 (96%), and CR 40/45 (89%). Gender, age, antecedent influenza vaccination and severity of thrombocytopenia had no significant impact on: Bleeding at presentation, response rates, relapse rates, time to response, or the need for ongoing treatments at day 90. No patients presented with thrombosis. PF4 ELISA was positive in one of 18 cases after ChAd (functional testing was negative). Conclusion(s): We diagnosed ITP more frequently after ChAd than BNT vaccination, occurring de novo after 1st doses. Ascertainment bias cannot be excluded due to greater scrutiny for platelet related complications, but almost all patients in this cohort needed treatment. Standard first-line treatments for ITP are highly effective for both de novo and prior ITP (96%), but second-line therapies are often required (34%). Our data reaffirms the safety of vaccinating patients with pre-existing ITP, as bleeding is mild (92% WHO < 2) and platelets respond quickly (TTCR 5 days).