ABSTRACT
Background and aims: Since initiation of COVID-19 vaccination, cases of cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) have been reported. Reported in-hospital mortality varies between 20-50%, but data on longterm outcome of surviving patients with CVT-VITT are not available. Methods: We report follow-up data of CVT-VITT cases after COVID- 19 vaccination from an international registry. VITT was classified according to the Pavord criteria. Outcomes were mortality, functional dependency, relapse of VITT, new thrombosis, and new bleeding events. Results: Of 62 patients with CVT-VITT who survived initial hospital admission, follow-up data were available for 48/62 (77%) cases (32 (67%) definite VITT, 7 (15%) probable VITT, 9 (19%) possible VITT). Median time from diagnosis to last follow-up was 110 days (IQR 86-174). There were no new venous or arterial thrombotic events reported in any case. Among 35/44 (80%) cases that achieved clinical remission, 0/29 cases had a relapse of VITT. Major bleeding was reported in 1/45 (2%) cases (intracranial bleed). Mortality at follow-up was 1/48 (2%, 95%CI 0-11%). 44/48 (92%) cases had a modified Rankin Scale score of 0-2 at follow-up, compared to 32/46 (70%) at hospital discharge. 16/34 (47%) of cases had returned to work or school. Conclusions: In patients who survive the acute phase of CVT-VITT, long-term mortality is low and thrombotic and bleeding events are rare. Approximately half of the CVT-VITT patients at follow-up could resume all daily activities.
ABSTRACT
Background and aims: Cerebral venous sinus thrombosis with thrombocytopenia syndrome (CVST-TTS) is a rare adverse effect of adenovirus- based SARS-CoV-2 vaccines. After the autoimmune pathogenesis of TTS was discovered, treatment recommendations were issued. The aim of this study was to evaluate if adherence to treatment recommendations was associated with lower mortality. Methods: TTS was defined according to the Brighton criteria. Cases from a prospective international CVT registry with symptom onset within 28 days of adenovirus-based SARS-CoV-2 vaccination were analysed. Treatment recommendations, following the International Society of Thrombosis and Haemostasis, included use of immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusions, unless needed for surgery. Results: Out of 178 CVT cases from 117 centres in 19 countries reported between March 29 and September 3, 2021, 95 patients fulfilled inclusion criteria. Five of 37 (14%), 13/25 (52%), and 29/33 (88%) of patients diagnosed in March, April, and from May onwards, respectively, were treated according to recommendations. Proportion of patients diagnosed in March, April, and from May onwards who received immunomodulation increased from 19/37 (51%) over 15/25 (60%) to 30/33 (90%), and the percentage of patients who were treated with heparins [26/37 (70%), 4/25 (16%), 1/33 (3%)] and platelet transfusion [15/37 (41%), 4/25 (16%), 7/33 (21%), respectively] decreased accordingly. Mortality of patients treated according to recommendations was 14/47 (30%, 95%CI 19-44%) compared to 28/48 (58%, 95%CI 44-71%) in patients not treated according to recommendations (OR 3.30, 95%CI 1.41-7.71). Conclusions: Over time, adherence to treatment recommendations improved, and mortality rate of patients with CVST-TTS decreased.
ABSTRACT
Background and aims: Cerebral venous sinus thrombosis with thrombosis with thrombocytopenia syndrome (CVST-TTS) is a serious adverse drug reaction after adenoviral SARS-CoV-2 vaccinations. CVST-TTS patients may need decompressive surgery to avoid fatal brain herniation, but despite this intervention, many CVST-TTS patients die during the initial hospital admission. Here, we describe the characteristics and outcomes of CVST-TTS patients who underwent decompressive surgery and explore predictors of mortality in CVST-TTS patients. Methods: We used data from an ongoing international registry collecting data from patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March and 9 December 2021. TTS was defined in accordance with the Brighton Collaboration case definition. Results: Out of 97 CVST-TTS patients, 29 (30%) underwent decompressive surgery. All operated patients had an intracerebral haemorrhage before the surgery. In-hospital mortality was 19/29 (66%) in the operated and 23/68 (34%) in the non-operated group. In the operated group, the highest mortality rate was among patients who were in coma before the surgery (14/15, 93% vs 4/12, 33% in those not in coma), had bilateral absence of the pupillary response (7/7, 100% vs 8/16, 50% in patients with uni/bilateral pupillary response) and platelet count <50 x103/μL (11/14, 79% vs 6/12, 50% in cases with a platelet count ≥50 x103/μL). Conclusion: Mortality rate of CVST-TTS patients who underwent decompressive surgery is extremely high. Among the operated patients, coma before the surgery, bilateral absence of the pupillary response, and platelet count <50 x103/μL were the predictors of mortality.
ABSTRACT
Introduction: Cerebral Venous Sinus Thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of SARS-CoV-2 vaccination. The estimated background rate of CVST in adults is around 1 case per million per month, and CVST with thrombocytopenia accounts for 8% of all CVST. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination. Methods: We estimated the absolute risk of any CVST, CVST with thrombocytopenia, and CVST without thrombocytopenia, within 28 days of first dose SARS-CoV-2 vaccination, using data from the European Medicines Agency's EudraVigilance database (until 13 June 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category. Results: The absolute risk of CVST within 28 days of first dose vaccination was 7.5 (95%CI 6.9- 8.3), 0.7 (95%CI 0.2-2.4), 0.6 (95%CI 0.5-0.7) and 0.6 (95%CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95%CI 3.9-4.9), 0.7 (95%CI 0.2-2.4), 0.0 (95%CI 0.0-0.1) and 0.0 (95%CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the risk of CVST, both with and without thrombocytopenia, was the highest in the 18-24 years age group (7.3 per million, 95%CI 2.8-18.8 and 3.7, 95%CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia was the lowest in ChAdOx1 nCov-19 recipients ≥70 years (0.2, 95%CI 0.0- 1.3). Age <60 compared to ≥60 was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79;95%CI 2.98-11.24, p<0.001). Discussion: The risk of CVST with thrombocytopenia within 28 days of first dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S, comparing with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of mRNA vaccines for SARS-CoV-2.