ABSTRACT
Background and aims: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome of unclear aetiology occurring after vaccinations against COVID-19. The aim of this study was to investigate the DNA vaccine-encoded Sars-cov-2 soluble spike protein (SP) as a potential trigger of platelet activation in VITT. Methods: We studied three VITT patients and seven healthy controls (HCs) within 3 weeks from the first dose of ChAdOx1 nCoV-19. Serum levels of SP, soluble angiotensin-converting enzyme 2 (sACE2), and platelet response to VITT serum stimulation were studied. A thrombus retrieved from middle cerebral artery during mechanical thrombectomy of one VITT patient, was analysed by immunohistochemistry for SP and ACE2. Neutrophil extracellular traps (NETs) markers and coagulation parameters were also measured. Results: We detected SP and sACE2 in all VITT patients, and in two and three out of 7 HCs, respectively. VITT sera markedly activated platelets and this activation was inhibited by both anti-SP and anti-FcγRIIA blocking antibodies. The retrieved thrombus showed positive immunohistochemical labelling of platelets using an anti-SP antibody with reduced ACE2 expression, compared to a thrombus from a pre-pandemic stroke patient. Markers of endothelial dysfunction, NETs and hypercoagulability state were present in VITT sera. Conclusions: The present data provide first evidence that DNA vaccineencoded Sars-cov-2 SP is detectable in VITT sera (up to several weeks post-vaccination) and in a platelet-rich thrombus, and suggest that SP may contribute to the initial platelet stimulation in VITT patients. Anti-PF4/ polyanion antibodies development could represent an epiphenomenon, which amplifies platelet aggregation, NETosis, and coagulation cascade.
ABSTRACT
Background and aims: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but catastrophic syndrome characterized by venous and arterial thrombosis, with thrombocytopenia and antibodies against platelet factor-4 (PF4)/polyanion, typically 5-30 days from the first dose of a DNA viral vector vaccine. Very rarely, acute ischemic stroke (AIS) can be the result of VITT. The aim of this study was to define the clinical and radiological characteristics, outcome and therapeutic options of VITT patients with AIS. Methods: We carried out a systematic review of the literature till October 27, 2021 using MEDLINE, PUBMED and Google Scholar databases in order to collect all the published articles related to the development of AIS after vaccination against SARS-CoV-2. Results: We identified 16 patients from case reports or case series published in peer-reviewed journals affected by AIS and confirmed VITT. All patients had received the first dose of ChAdOx1 ncov19 vaccine within 10 days (median). 81% (n=13/16) of the patients had occlusion of the middle cerebral artery (MCA) or its branches, 43.7% (n=7/16) also had thrombotic occlusion of the intracranial internal carotid artery. 45.4% (n=5/16) of the patients with proximal MCA occlusion developed a malignant MCA infarct. Only one patient received intravenous thrombolysis, while three patients underwent mechanical thrombectomy. Conclusions: The management of AIS due to large vessel occlusion in VITT is challenging. Based on the available literature, we propose a therapeutic protocol for acute stroke patients presenting to the Emergency Department within the time window for reperfusion strategies.
ABSTRACT
Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine. Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination. The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes. None of the patients had ever received heparin in the past before stroke onset. Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.