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
Background: TTP is a rare and life-threatening thrombotic microangiop-athy caused by auto-antibody induced severe deficiency of ADAMTS13, the specific von Willebrand-factor-cleaving protease. A few cases of iTTP after exposure to mRNA-based-COVID-19-vaccines have been described. The pathophysiology is unknown, but molecular mimicry and/or aberrant activation of the immune system are considered. Goals: To describe the clinical context of the rare possible adverse effect acute iTTP following BNT162b2 vaccine administration, and its management. Methods: We report the case of a 60-year-old man who suffered an is-chemic stroke one week after the first exposure to BNT162b2. Ten days after his second exposure he was referred to our emergency department with retrosternal pain and confusion. Results: Severe thrombocytopenia, anemia, signs of hemolysis, schisto-cytes on the blood smear, and slightly elevated high-sensitivity troponin were documented in the laboratory workup. ADAMTS13 activity was <5%, the functional ADAMTS13 inhibitor was negative, but non-inhibitory ADAMTS13 IgG-autoantibodies determined by ELISA were weakly positive, confirming the diagnosis of a first episode of iTTP. Antibodies to PF4-complex were negative, ruling out VIPIT/VITT. The patient was treated with three PEX sessions and steroids, achieving clinical and laboratory remission, including normalization of ADAMTS13 activity over the ensuing days. Conclusions: We describe a first acute iTTP episode in the context of vaccination with BNT162b2. The close temporal association suggests a link between the vaccination and TTP, possibly through BNT162b2 induced formation of anti-ADAMTS13 antibodies. The patient is now in regular follow-up like other iTTP-survivors without an apparent trigger of their autoimmune reaction.