Ischemic Stroke and Vaccine-Induced Immune Thrombotic Thrombocytopenia following COVID-19 Vaccine: A Case Report with Systematic Review of the Literature

Abstract

<b><i>Introduction:</i></b> Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic syndrome observed after adenoviral vector-based vaccines for severe acute respiratory syndrome coronavirus 2. It is characterized by thrombocytopenia, systemic activation of coagulation, extensive venous thrombosis, and anti-platelet factor 4 antibodies. Arterial thrombosis is less common and mainly affects the aorta, peripheral arteries, heart, and brain. Several cases of ischemic stroke have been reported in VITT, often associated with large vessel occlusion (LVO). Here, we describe a case of ischemic stroke with LVO after Ad26.COV2.S vaccine, then we systematically reviewed the published cases of ischemic stroke and VITT following COVID-19 vaccination. <b><i>Methods:</i></b> We describe a 58-year-old woman who developed a thrombotic thrombocytopenia syndrome with extensive splanchnic vein thrombosis and ischemic stroke due to right middle cerebral artery (MCA) occlusion, 13 days after receiving Ad26.COV2.S vaccination. Then, we performed a systematic review of the literature until December 3, 2021 using PubMed and EMBASE databases. The following keywords were used: (“COVID-19 vaccine”) AND (“stroke”), (“COVID-19 vaccine”) AND (“thrombotic thrombocytopenia”). We have selected all cases of ischemic stroke in VITT. <b><i>Results:</i></b> Our study included 24 patients. The majority of the patients were females (79.2%) and younger than 60 years of age (median age 45.5 years). Almost all patients (96%) received the first dose of an adenoviral vector-based vaccine. Ischemic stroke was the presenting symptom in 18 patients (75%). Splanchnic venous thrombosis was found in 10 patients, and cerebral venous thrombosis in 5 patients (21%). Most patients (87.5%) had an anterior circulation stroke, mainly involving MCA. Seventeen patients (71%) had an intracranial LVO. We found a high prevalence of large intraluminal thrombi (7 patients) and free-floating thrombus (3 patients) in extracranial vessels, such as the carotid artery, in the absence of underlying atherosclerotic disease. Acute reperfusion therapy was performed in 7 of the 17 patients with LVO (41%). One patient with a normal platelet count underwent intravenous thrombolysis with alteplase, while 6 patients underwent mechanical thrombectomy. A malignant infarct occurred in 9 patients and decompressive hemicraniectomy was performed in 7 patients. Five patients died (21%). <b><i>Conclusion:</i></b> Our study points out that, in addition to cerebral venous thrombosis, adenoviral vector-based vaccines also appear to have a cerebral arterial thrombotic risk, and clinicians should be aware that ischemic stroke with LVO, although rare, could represent a clinical presentation of VITT.

Acute ischemic stroke and vaccine-induced immune thrombotic thrombocytopenia post COVID-19 vaccination; a systematic review

“…Seven cases of AIS with LVO who have thrombocytopenia underwent mechanical thrombectomy successfully and safely among our studied patients, 6 of them did not receive IV tPA prior to thrombectomy [ 29 , 108 , [110] , [111] , [112] ]. Cascio Rizzo et al also indicated that despite that re-occlusion after revascularization may happen due to the hypercoagulative state, mechanical thrombectomy is a feasible and safe treatment in patients with VITT and AIS [ 113 ]. It is suggested not to use intravenous heparin throughout the thrombectomy procedure in these patients [ 108 ].…”

Investigation of Neurological Complications after COVID-19 Vaccination: Report of the Clinical Scenarios and Review of the Literature

“…Thrombosis combined with thrombocytopenia after vaccination has been termed vaccine-induced prothrombotic immune thrombocytopenia (VIPIT), VITT, or thrombosis with thrombocytopenia syndrome (TTS). VITT has been mostly reported after immunization with adenovirus vector-based vaccines against COVID-19 [ 13 , 14 , 15 , 16 , 17 ]. The mean age of patients with VITT was 45.6 years (95% CI 43.8–47.4, I2 = 57%), with a female predominance (70%) [ 15 ].…”

“…The mean age of patients with VITT was 45.6 years (95% CI 43.8–47.4, I2 = 57%), with a female predominance (70%) [ 15 ]. Another systemic review presented a median age of 45.5 years [ 17 ]. One systemic review included 27 patients with the occurrence or relapse of thrombotic thrombocytopenic purpura (TTP) [ 16 ].…”

COVID-19 Vaccine-Associated Immune Thrombosis and Thrombocytopenia (VITT): Diagnostic Discrepancies and Global Implications

“…For example, negative or obscure results for ELISA have been used in several cases. 42 43 In Scully et al's publication in June 2021, an individual with elevated D-dimer, low fibrinogen, and deep venous thrombosis and bilateral adrenal hemorrhage had an ambiguous ELISA level of 0.156 optical density on the Asserachrom HPIA IgG assay. 20 Likewise, a clinically indistinguishable individual tested negative on ELISA (Lifecodes PF4 IgG assay) and functional HIT assay.…”