ABSTRACT
Background: Vaccine-induced immune thrombocytopenia (VITT) is a rare but serious complication of SARS-COV- 2 vaccination and its diagnosis is based on both clinical and biological criteria. Aim(s): To evaluate the performance of these criteria in a prospective cohort of patients with suspected VITT. Method(s): Among 105 consecutive patients (Table 1), 79 had received one (n = 71) or two (n = 8) injections of adenoviral vector vaccine, and 26 one (n = 18) or two (n = 8) doses of an mRNA vaccine. Most patients presented thrombosis either isolated (n = 40), or associated with thrombocytopenia (T+T = 45). Other patients had isolated thrombocytopenia (n = 15), or variable clinical manifestations. ELISA (PVS/PF4 HAT45G) detected anti-PF4 antibodies, and when present VITT diagnosis was confirmed using PF4 serotonin release assay. Result(s): VITT was confirmed in 26 patients (both PVS/PF4 ELISA and PF4/SRA were positive) and probable in one case (PVS/PF4 ELISA OD = 2.4 but PF4/SRA negative). VITT was excluded in all patients who had received an mRNA vaccine, or in those with isolated thrombocytopenia or thrombosis or with other symptoms. In contrast, the presence of both thrombocytopenia and thrombosis 5 to 30 days after injection was highly suggestive of VITT with a specificity and PPV of 85% and 69%, respectively, these values increasing to 93.6% and 85% if patients had received adenoviral vector vaccine. Importantly, the PPV reached in these cases 100% when OD > 1 in ELISA. (Table) Conclusion(s): The occurrence of thrombocytopenia and thromboses, 5 to 30 days after vaccination with an adenoviral vector is highly predictive of VITT. PF4/PVS ELISA allows to rule out VITT when OD is < 0.4 (NPV 100%) and to confirm the diagnosis when OD is > 1 without necessitating a platelet activation test. Moreover, the follow-up of patients with ELISA is mandatory since anti-PF4 antibodies may remain several weeks after VITT. (Table Presented).
ABSTRACT
Background: Acquired hemophilia A (AHA) is a rare bleeding condition defined by the development of autoantibodies directed against clotting factor VIII (FVIII). It occurs primarily in elderly patients. AHA is associated with comorbidities such as cancer, autoimmune disease and infections. There is growing literature on AHA during or following SARS-CoV- 2 infection or vaccination. Six previous cases of AHA post Covid-19 vaccination have been described;all patients were older than 65 years old (yo). Aim(s): We report on a 45 yo woman presenting with AHA after COVID-19 vaccination. She had no personal or family history of bleeding disorders. Eighteen days after her 2nd dose of Pfizer-BioNTech COVID-19 vaccine, she presented with recurring hematomas. Bleeding events were both spontaneous and provoked by minor traumas but with a disproportionate size. The aim of this report is to bring to light the association between AHA and COVID-19 vaccine in a younger patient with no ongoing or recent pregnancy. Method(s): Case report Results: Biological explorations showed a prolonged activated partial thromboplastin time (aPTT) at 75 seconds (ratio 2.42). FVIII was undetectable and von Willebrand factor explorations were normal. Anti-FVIII antibodies were positive at 373 Bethesda units (BU/ml) confirming the diagnosis of AHA. There was no evidence of pregnancy, cancer, auto-immune disorder or infectious disease. Immunosuppression was initiated with prednisone (1mg/kg), then intensified with rituximab. Bleeding was controlled with repeated infusions of activated prothrombin complex concentrate (aPCC, Feiba) at a dose of 60 IU/kg/injection. A 3rd dose of Covid-19 mRNA vaccine was contraindicated. Conclusion(s): To our knowledge this is the first case of AHA post Covid-19 vaccination in a patient under 50 yo. The exact mechanisms responsible for autoimmune disorders following vaccination are still unclear. However this report might suggest that AHA diagnosis in this context may not be a simple statistical coincidence. Physicians should remain wary of this possible complication. (Figure Presented).
ABSTRACT
Background: COVID-19 convalescent plasma (CCP) contains neutralizing anti-SARS- CoV- 2 antibodies that may be useful as COVID-19 passive immunotherapy in patients at risk of developing severe disease. Aim(s): Such plasma from convalescent patients may also have additional immune-modulatory properties when transfused to COVID-19 patients. Method(s): CCP (n = 766) were compared to control non-convalescent plasma (n = 166) for soluble inflammatory markers, ex-vivo inflammatory bioactivity on endothelial cells, neutralizing auto-Ab to type I IFNs, and reported adverse events in the recipients. Result(s): CCP exhibited significantly higher IL-6 and TNF-alpha (0.531+/-0.04 vs 0.271+/-0.04;p = 0.0061 and 0.900+/-0.07 vs 0.283+/-0.07 pg/ml;p < 0.0001), respectively) and lower IL-10 (0.731+/-0.07 vs 1.22+/-0.19 pg/ ml, p = 0.0034) levels than control plasma. Other inflammatory markers as well as ex-vivo bioactivity did not differ significantly between CCP and control plasma. Neutralizing auto-Abs against type I IFNs were detected in 14/766 (1.8 %) CCP. They were not associated with reported adverse events when transfused (n = 14). Inflammatory markers and bioactivity in CCP with or without auto-Ab, or in CCP associated or not with adverse events in transfused patients, did not differ significantly. Overall, CCP exhibited moderately increased inflammatory markers compared to control plasma with no discernable differences in ex-vivo bioactivity. Auto-Ab to type I IFNs, detected in a small fraction of CCP, were not associated with reported adverse events or differences in inflammatory markers. Conclusion(s): Further defining the clinical relevance of these findings will require further studies including careful clinical evaluation of patients treated with CCP.