key: cord-1023124-2cregz1s authors: Park, Kwan Young; Jeong, Dong Young; Ha, Sang Hee; Kim, Bum Joon title: Arterial Embolic Infarction After COVID-19 Vaccination Associated With Antiplatelet Factor 4 Antibody date: 2022-02-25 journal: J Clin Neurol DOI: 10.3988/jcn.2022.18.2.230 sha: b078d4f74f6c6de64d2d0eba680378b80ca762cc doc_id: 1023124 cord_uid: 2cregz1s nan complex. The complex is internalized in antigen-presenting cells, which then results in the massive production of anti-PF4 antibodies. The venous drainage system, and especially splanchnic and cavernous sinus drainage, provides an environment that facilitates a strong interplay with microbiota due to its vicinity with the gut and respiratory barrier tissue. A physiologically adequate level of immunity toward microbes can be maintained by PF4 immunity within the venous system. 2 In the presence of a high titer of anti-PF4 antibodies, these reactions may result in pathological immunothrombosis, which is mediated by platelet activation and the release of alpha granules including thrombin, leading to thrombosis. 3 However, arterial infarctions including in our case have also been reported despite their rarity. One study suggested that the PF4/Von Willebrand factor complexes bind with HIT antibody, leading to injury of the arterial endothelium, thrombus formation, and propagation that is associated with arterial thrombosis. 1, 4 There have been no comprehensive reports on the lesion pattern or severity of stroke following COVID-19 vaccination. 2 Several cases of malignant infarction with large-vessel occlusion have been reported in patients with high titers of anti-PF4 antibody. It was particularly interesting that our patient showed a lower titer of anti-PF4 antibody with multiple small embolic infarctions. This might reflect a spectrum of VIPIT-related stroke, and so further data are needed to confirm the factors affecting the severity of VIPIT-related stroke. The incidence of VIPIT is unknown. For the ChAdOx1 nCoV-19 vaccine, the highest reported incidence was 5 cases from among approximately 130,000 individuals (Norwegian data). 5 Despite this rarity, screening for VIPIT is important for stroke management. Although the most frequent form of cerebral involvement of VIPIT is venous thrombosis, rare cases of arterial infarctions have been reported. 1 The main stroke mechanism in these cases has been large-artery occlusions. 4 Because of its pathophysiological background, treatments for VIPIT-related strokes are nonheparin anticoagulation and intravenous immunoglobulin. Considering its pathophysiology, the application of heparin and platelet transfusion are contraindicated. 6 Therefore, checking the vaccination history is important in suspected stroke patients. The study design was approved by the local ethics committee (IRB no. 2021-1724), which did not require informed consent to be obtained from the patient. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination Mechanisms of immunothrombosis in vaccine-induced thrombotic thrombocytopenia (VITT) compared to natural SARS-CoV-2 infection Platelet alpha-granules: basic biology and clinical correlates Malignant cerebral infarction after ChAdOx1 nCov-19 vaccination: a catastrophic variant of vaccine-induced immune thrombotic thrombocytopenia Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination Ischaemic stroke can follow COVID-19 vaccination but is much more common with COVID-19 infection itself The authors have no potential conflicts of interest to disclose. The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.