Project description:BackgroundVaccine-induced thrombotic thrombocytopenia (VITT) is a rare but devastating adverse event following adenoviral vector-based vaccinations for COVID-19, resulting in thrombosis, especially of the cerebral and splanchnic vasculature. Despite the progress in laboratory techniques for early diagnosis, VITT remains a clinical diagnosis supplemented by coagulation studies. We report on VITT for the first time from India.CaseWe describe cortical venous sinus thrombosis and intracerebral bleed associated with severe thrombocytopenia in two young men who had no other contributory cause besides a recent ChAdOx1 nCoV-19 vaccination. The diagnosis was supported with PF-4 antibodies in one patient. The second patient's test could not be processed to technical limitations. Both patients were treated with IVIG at 1 g/kg for 2 days and anticoagulation (Apixaban). One patient fully recovered with no residual deficits, and the other is under treatment and recovering.ConclusionVITT can cause devastating fatality and morbidity in otherwise healthy patients via potential immune-mediated effects. Clinicians should have a high suspicion index and treat VITT in the appropriate setting even if the PF-4 antibody testing by ELISA is unavailable or delayed. Though counterintuitive, clinicians must not delay the administration of non-heparin anticoagulation, IVIG and restrict platelet transfusion even in the presence of intracerebral haemorrhage.
Project description:The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.
Project description:PurposeWe reported the first described post Ad26.COV2.S (Janssen, Johnson & Johnson) vaccine-induced immune thrombocytopenia (VITT) case outside US. CASE DESCRIPTION: CA young woman without any medical history presented association of deep vein thrombosis and thrombocytopenia at day 10 after vaccine injection. The patient was treated with low-molecular weight heparin at a first medical institution. Twelve days post Ad26.COV2.S vaccination, the patient was admitted at our hospital for neurological deterioration and right hemiplegia. Medical imaging using MRI showed thrombosis of the major anterior part of the sagittal superior sinus with bilateral intraparenchymal hemorrhagic complications. Screening tests for antibodies against platelet factor 4 (PF4)-heparin by rapid lateral flow immunoassay and chemiluminescence techniques were negative. Platelet activation test using heparin-induced multiple electrode aggregometry confirmed the initial clinical hypothesis. Despite immediate treatment with intravenous immunoglobulin, dexamethasone, danaparoid and attempted neurosurgery the patient evolved toward brain death.ConclusionEven though it is an extremely rare complication of vaccination physicians should maintain a high index of suspicion of VITT in patients who received an adenovirus-vector-based SARS-CoV-2 vaccine within the last 30 days with persistent complains compatible with VITT or thromboembolic event associated with thrombocytopenia. The diagnosis should not be excluded if the rapid anti-PF4 immunological nor chemiluminescence techniques yield negative results. An adapted functional assay should be performed to confirm the diagnosis. Early treatment with intravenous immunoglobulin and non-heparin anticoagulants is essential as delayed diagnosis and administration of appropriate treatment is associated with poor prognosis.
Project description:Historical records document medieval immigration from North Africa to Iberia to create Islamic al-Andalus. Here, we present a low-coverage genome of an eleventh century CE man buried in an Islamic necropolis in Segorbe, near Valencia, Spain. Uniparental lineages indicate North African ancestry, but at the autosomal level he displays a mosaic of North African and European-like ancestries, distinct from any present-day population. Altogether, the genome-wide evidence, stable isotope results and the age of the burial indicate that his ancestry was ultimately a result of admixture between recently arrived Amazigh people (Berbers) and the population inhabiting the Peninsula prior to the Islamic conquest. We detect differences between our sample and a previously published group of contemporary individuals from Valencia, exemplifying how detailed, small-scale aDNA studies can illuminate fine-grained regional and temporal differences. His genome demonstrates how ancient DNA studies can capture portraits of past genetic variation that have been erased by later demographic shifts-in this case, most likely the seventeenth century CE expulsion of formerly Islamic communities as tolerance dissipated following the Reconquista by the Catholic kingdoms of the north.
Project description:ObjectiveWe describe a severe case of vaccine-induced immune thrombotic thrombocytopenia (VITT) after the first dose of the ChAdOx1 nCoV-19 vaccine leading to massive ischemic stroke.MethodsA 42-year-old woman developed acute left hemiparesis (NIHSS 12) 9 days after the first vaccine dose.ResultsThe blood tests revealed low platelets (70 103/μL) and severe increment of D-dimer (70,745 ng/mL FEU). Brain non-contrast computed tomography and multiphasic CT angiography demonstrated a right middle cerebral artery occlusion. The patient was treated with primary thrombectomy, steroids, immunoglobulin, and fondaparinux. Despite the treatment, the neurological status deteriorated and underwent decompressive hemicraniectomy. She was transferred to the rehab's unit 52 days after the onset.DiscussionHealthcare providers should be aware of the possibility of ischemic stroke as a manifestation of VITT. Awareness on this very rare and possibly fatal complication should be reinforced on both the vaccine recipients and general practitioners.
Project description:The involvement of viruses and SARS-CoV-2 in autoimmune diseases is well known. The recent demonstration that ChAdOx1 nCoV-19 Covid-19 (AstraZeneca) vaccine (ChA) favors the production of anti-platelet factor 4 (anti-PF4) antibodies, blood clots, and thrombocytopenia raises the question of whether other anti-CoViD-19 vaccines favor the same patterns of events. We assessed the frequency of severe adverse events (SAEs) documented in the EudraVigilance European database up to April 16, 2021 related to thrombocytopenia, bleeding, and blood clots in recipients of ChA compared to that of recipients of the BNT162b2 Covid-19 (Pfizer/BioNTech) vaccine (BNT). ChA administration was associated with a much higher frequency of SAEs in each AE Reaction Group as compared with that elicited by BNT. When considering AEs caused by thrombocytopenia, bleeding and blood clots, we observed 33 and 151 SAEs/1 million doses in BNT and ChA recipients, respectively. When considering patients with AEs related to cerebral/splanchnic venous thrombosis, and/or thrombocytopenia, we documented 4 and 30 SAEs and 0.4 and 4.8 deaths/1 million doses for BNT and ChA recipients, respectively. The highest risk following ChA vaccination is in young people and, likely, women of reproductive age, as suggested by hypothesized scenarios. In conclusion, the immune reaction promoted by ChA vaccine may lead to not only thrombocytopenia and cerebral/splanchnic venous thrombosis but also other thrombotic and thromboembolic SAEs. These events are not favored by BNT vaccine. Our study may help in the evaluation of the benefit/risk profile of the ChA vaccine considering the epidemic curve present in a country.