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Les héparines sont les cheffes de files des anticoagulants injectables. Elles sont très largement utilisées, en curatif comme en préventif pour leur action immédiate.Cependant comme tous les médicaments elles présentent des effets indésirables qui ne sont pas négligeables. Leur spécificité est de pouvoir entraîner une réaction allergique, qui se traduit par la formation de thrombus, pouvant se situer dans les veines/artères au niveau des membres inférieurs mais également dans les poumons. Nous parlons de Thrombopénie Induite par l’Héparine, dite « T.I.H ». Cette complication reste méconnue par une grande partie de la population, mais également par certains professionnels de santé, ce qui peut rendre sa prise en charge compliquée. En effet, elle se diagnostique principalement par une chute des plaquettes qui seront suractivées mais également par l’apparition de thromboses entraînant notamment des thromboses veineuses profondes ou des embolies pulmonaires. Sa prise en charge repose sur l’arrêt du traitement héparinique dans les plus brefs délais, et la mise en place d’un relais avec un autre anticoagulant injectable, plus particulièrement l’ORGARAN®. Le pharmacien d’officine est le professionnel de santé le plus accessible pour les patients. Il peut être sollicité pour un conseil ou un problème de traitement, il permet également de faire le lien entre le patient et le médecin lorsque cela est nécessaire. Son rôle auprès de la population est en constante évolution, notamment pendant la pandémie de la Covid-19. Comme d’autres professionnels de santé, le pharmacien d’officine se trouve au centre de la prévention de la Covid-19 via la vaccination. Il se doit de mettre à jour ses connaissances afin d’informer et de conseiller au mieux les patients. Cela se confirme par l’apparition de thrombocytopénie et de thrombose immunitaire induite par le vaccin, dite « V.I.T.T ». Cette complication survient chez des personnes ayant reçu une dose de vaccin du laboratoire d’Astrazeneca. Le pharmacien doit jouer un rôle dans la prévention des complications engendrées par les maladies, les traitements qu’ils soient chroniques ou non, ainsi que par la vaccination.

Platelet factor 4 (PF4), a protein stored in the alpha-granules of platelets and released upon activation, forms cationic tetramers that bind with various polymeric anions, including heparin. Some individuals develop antibodies against PF4 in complex with heparin (PF4/H), which potentially lead to the onset of heparin induced thrombocytopenia (HIT). In some patients, this may cause activation and aggregation of platelets, promoting pathological thrombosis, in a process called heparin induced thrombocytopenia with thrombosis ('HITT'). Laboratories can assess for the presence of these antibodies using many PF4 antibody tests, including by enzyme linked immunosorbent assay (ELISA), latex immunoassay (LIA), chemiluminescence immunoassay (CLIA) and even rapid nanoparticle based lateral flow immunoassays. All these assays can identify such antibodies with high sensitivity, but methods may have variable specificity. For example, several studies have shown CLIA assays to have higher specificity to HITT than ELISA assays. Very recently, a new 'HITT-like' syndrome has been described in some individuals receiving adenovirus based COVID-19 (coronavirus disease 2019) vaccines. This condition has been given several names, including vaccine induced thrombotic thrombocytopenia (VITT) and thrombosis with thrombocytopenia syndrome (TTS), and also involves a mechanism mediated by antibodies formed against PF4. These antibodies can also be detected by PF4 antibody tests, but detection sensitivity appears to favour ELISA assays, with most other tests (including CLIA and LIA) not generally capable of detecting such antibodies. Additional functional assays assessing for PF4 mediated platelet activation may also be performed. The current review is focussed on laboratory testing for PF4 antibodies, in particular to distinguishing patterns in HITT versus VITT.

Objective We 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. Methods A 42-year-old woman developed acute left hemiparesis (NIHSS 12) 9 days after the first vaccine dose. Results The 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. Discussion Healthcare 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. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05800-3.

We report a case of massive cerebral venous sinus thrombosis in the contest of vaccine-induced immune thrombotic thrombocytopenia that required the rapid coordination of many specialists from different departments, notably emergency, neurology, neuroradiology, hematology, and neurosurgery. The patient was rapidly treated with steroids, immunoglobulin, and fondaparinux. She underwent within 6 h after hospital admission a mechanical thrombectomy in order to allow flow restoration in cerebral venous systems. Neuroendovascular treatment in cerebral venous thrombosis related to VITT has never been described before. It can represent a complementary tool along with the other therapies and a multidisciplinary approach.

After the vaccination campaign initiation in Europe and the UK, reports of rare cases of atypical thrombosis, including sinus vein thrombosis and splanchnic venous thrombosis, began to appear in association with the use of vector vaccines AstraZeneca (ChAdOx1) and Johnson & Johnson/Janssen. The syndrome called VITT (vaccine-induced immune thrombotic thrombocytopenia) manifested as thrombosis simultaneously with a decrease in platelet count, a significant increase in D-dimer levels and a detection of factor 4 platelet (PF4) antibodies. We present a detailed review of the epidemiology, pathogenesis, clinical presentation, diagnostics and treatment of VITT, which is by its nature an immune complication, similar to the processes occurring in heparin-induced thrombocytopenia (HIT). All international and national organizations and regulatory authorities, including experts in the field of thrombosis and hemostasis and the VITT expert council recommend continuing the prompt mass vaccination against COVID-19 as the only method that can reduce the incidence of severe cases, stop the spread of COVID-19 infection and the emergence of new dangerous mutations in the viral genome. Failure to vaccinate poses an incomparably greater risk of fatal thrombotic and inflammatory complications associated with infections, compared with the risks of extremely rare adverse events that can occur after vaccination. It should be noted that information on VITT, described as a sporadic phenomenon of an abnormal immune response to some variants of vaccines against COVID-19, cannot be translated to other vaccines (including registered in the Russian Federation) and even more cannot be a reason for refusal to use them.

Background Current vaccines for the Coronavirus Disease of 2019 (COVID-19) have demonstrated efficacy with low risk of adverse events. However, recent reports of thrombosis with thrombocytopenia syndrome (TTS) associated with adenovirus vector vaccines have raised concern. Objective This narrative review summarizes the current background, evaluation, and management of TTS for emergency clinicians. Discussion TTS, also known as vaccine-induced immune thrombotic thrombocytopenia, is a reaction associated with exposure to the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and AD26.COV2·S (Johnson & Johnson) vaccine, which may result in thrombocytopenia and thrombotic events. There are several case series of patients diagnosed with TTS, but the overall incidence is rare. TTS is characterized by exposure to one of the aforementioned vaccines 4–30 days prior to presentation, followed by thrombosis, mild-to-severe thrombocytopenia, and a positive platelet factor-4 (PF4)-heparin enzyme-linked immunosorbent assay (ELISA). Thrombosis typically involves atypical locations, including cerebral venous thrombosis and splanchnic vein thrombosis. Evaluation should include complete blood count, peripheral smear, D-dimer, fibrinogen, coagulation panel, renal and liver function, and electrolytes, as well as PF4-heparin ELISA if available. Consultation with hematology is recommended if suspected or confirmed. Treatment may include intravenous immunoglobulin and anticoagulation, while avoiding heparin-based agents and platelet transfusion. Conclusions With increasing vaccine distribution, it is essential for emergency clinicians to be aware of the evaluation and management of this condition.

Contains fulltext : 238068.pdf (Publisher’s version ) (Open Access) Historically, the vaccination strategies developed in the second half of the 20th century have facilitated the eradication of infectious diseases. From the onset of COVID-19 pandemic to the end of April 2021, more than 150 million cases and 3 million deaths were documented worldwide with disruption of the economic and social activity, and with devastating material, physical, and psychological consequences. Reports of unusual and severe thrombotic events, including cerebral and splanchnic venous thrombosis and other autoimmune adverse reactions, such as immune thrombocytopenia or thrombotic microangiopathies in connection with some of the SARS-CoV-2 vaccines, have caused a great deal of concern within the population and the medical community. This report is intended to provide practical answers following an overview of our knowledge on these thrombotic events that are extremely rare but have serious consequences. Vaccine hesitancy threatens to reverse the progress made in controlling vaccine-preventable diseases. These adverse events must be put into perspective with an objective analysis of the facts and the issues of the vaccination strategy during this SARS-CoV-2 pandemic. Health care professionals remain the most pertinent advisors and influencers regarding vaccination decisions; they have to be supported to provide reliable and credible information on vaccines. We need to inform, reassure, and support our patients when the prescription is made. Facing these challenges and observations, a panel of experts express their insights and propose a tracking algorithm for vaccinated patients based on a 10-point guideline for decision-making on what to do and not to do.

SARS-CoV-2, which originated in China in late 2019, has spread rapidly resulting in a global pandemic. Multiple vaccines have been developed to help prevent COVID-19 infection. Similar to other vaccines, common side effects including fever, fatigue, myalgias have occurred; however, episodes of more serious side effects have been noted. One such potentially serious sequalae is vaccine-induced thrombocytopenia (VITT), an autoimmune-mediated phenomenon hypothesized to occur due to molecular mimicry and the production of platelet PF4 antibodies, ultimately leading to thrombocytopenia and easy bruising. In this report, we present the case of a 34-year-old, otherwise, healthy female who presented with easy bruising and thrombocytopenia following completion of the two-dose Moderna COVID-19 vaccine, suspicious for a diagnosis of VITT. The patient was managed conservatively with steroids. Steroids and intravenous immune globulin therapy have been reported in the literature. This report highlights that VITT should be considered in the differential diagnosis for patient presenting with increased bruising in the setting of recent COVID-19 vaccine administration, and furthermore highlights the diagnostic workup and management options for such patients.

Refereed/Peer-reviewed Since the start of the pandemic, thrombotic events have been a well-known and severe complication associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nevertheless, the initiation of vaccination programs brought another rare yet highly fatal thrombotic event, vaccine-induced immune thrombotic thrombocytopaenia, which has caused extensive debate regarding the safety of vaccines. This review defines the thromboembolic events following infection and vaccination, identifies their risk factors, describes their pathophysiology, and discusses their management, treatment, and prevention.

Vaccine-induced thrombotic thrombocytopenia (VITT) is triggered by vaccination against COVID-19 with adenovirus vector vaccines (ChAdOx1 nCoV-19; Ad26.COV2-S). In this observational study, we followed VITT patients for changes in their reactivity of platelet-activating antiplatelet factor 4 (PF4) immunoglobulin G (IgG) antibodies by an anti-PF4/heparin IgG enzyme immunoassay (EIA) and a functional test for PF4-dependent, platelet-activating antibodies, and new thrombotic complications. Sixty-five VITT patients (41 females; median, 51 years; range, 18-80 years) were followed for a median of 25 weeks (range, 3-36 weeks). In 48/65 patients (73.8%; CI, 62.0% to 83.0%) the functional assay became negative. The median time to negative functional test result was 15.5 weeks (range, 5-28 weeks). In parallel, EIA optical density (OD) values decreased from median 3.12 to 1.52 (P.0001), but seroreversion to a negative result was seen in only 14 (21.5%) patients. Five (7.5%) patients showed persistent platelet-activating antibodies and high EIA ODs for11 weeks. None of the 29 VITT patients who received a second vaccination dose with an mRNA COVID-19 vaccine developed new thromboses or relevant increase in anti-PF4/heparin IgG EIA OD, regardless of whether PF4-dependent platelet-activating antibodies were still present. PF4-dependent platelet-activating antibodies are transient in most patients with VITT. VITT patients can safely receive a second COVID-19 mRNA-vaccine shot.

The novel coronavirus pandemic has taken a toll on the global healthcare systems and economy. Safety precautions, along with vaccination, are the most effective preventive measures. The global vaccination program against COVID-19 has dramatically reduced the number of deaths and cases. However, the incidence of thrombotic events and thrombocytopenia post-COVID-19 vaccination known as vaccine-induced thrombotic thrombocytopenia has raised safety concerns. This has led to an element of vaccine hesitancy. The exact mechanism for vaccine-induced thrombotic thrombocytopenia is unknown. Although the incidence of thrombosis associated with COVID-19 vaccination is low, it still requires attention, especially in older people, smokers, and people with preexisting comorbidities. This study aims to review the pathophysiology, diagnosis, and management of vaccine-induced thrombotic thrombocytopenia, to provide a concise and comprehensive update.

Summary: Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse event of SARS-CoV-2 vaccination. We describe the characteristics of patients reported in Germany based on the Brighton Collaboration (BC) case definition criteria for Thrombosis and Thrombocytopenia Syndrome (TTS) and focus on patients with complete anti-platelet factor 4 (PF4)-antibody laboratory work up. Methods: The adverse drug reaction database of the Paul-Ehrlich Institute was queried for TTS cases following ChAdOx1 nCoV-19 vaccination from February 1, until May 21, 2021. Cases with reports from the Greifswald laboratory were analysed in detail. Findings: PF4 antibody tests were available for 69 suspected TTS cases reported to the Paul-Ehrlich Institute, of whom 52 patients fulfilled the BC case definition; 37 (71%) women, 15 (29%) men, median age 46·0 years (interquartile range 31·0-60·3 years). Cerebral venous sinus thrombosis was confirmed in 37 (71%), (additional) multiple thromboses in 19 (37%) patients. Twelve patients died. Non-survivors showed lower platelet counts compared to survivors (median nadir 15,000/µL vs 49,000/µL; p

Severe acute respiratory syndrome coronavirus type 2 has been responsible for an unprecedented pandemic, and nowadays, several vaccines proved to be effective and safe, representing the only available strategy to stop the pandemic. While millions of people have safely received vaccine, rare and unusual thrombotic events have been reported and are undergoing investigations to elucidate their nature. Understanding initial trigger, underlying pathophysiology and the reasons for specific site localization of thrombotic events are a matter of debate.We here propose that rare cases of cerebral venous sinus thrombosis, a clinical event that may rapidly evolve to brain death, reported after COVID-19 vaccine, might be consequent to an immune response resulting in inflamed/damaged endothelium, an event similar to that described for cases of cerebral venous sinus thrombosis reported during COVID-19 and not necessarily related to anti-Platelets Factor 4 antibodies, as recently described. Remarkably, in the two patients presenting at our hospital with cerebral venous sinus thrombosis and evolved to brain death, proper tissue perfusion and function maintenance allowed organ donation despite extensive thrombosis in the organ donors, with favorable outcome at 6 months.Increased vigilance, close multidisciplinary collaboration, and further prospective research will help to better elucidate a very rare and still not fully understood pathophysiological event associated with vaccines for severe acute respiratory syndrome coronavirus 2.

Background Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is triggered by nCOV-19 adenovirus-vectored vaccines against SARS-CoV2. Pathogenesis has been mainly related to platelet activation via PF4-reactive antibodies that activate platelets and may cross-react with heparin. Data concerning optimal anticoagulation are anecdotal, and so far, there are scattered reports of danaparoid use in VITT management. Danaparoid has good efficacy and safety in treatment of heparin-induced thrombocytopenia. We report here our experience of the administration and monitoring danaparoid in VITT. Methods We diagnosed a series of six hospitalized cases of VITT, based on the international diagnostic guidance. All VITT-related data were from the local electronic medical and laboratory record system and were analyzed with IBM SPSS Statistics. Results Predominately women in their late 40’s developed VITT on average 24 days (range 9–59) after the first ChAdOx1 dose. Clinical presentation included single or multiple venous and/or arterial thrombosis, moderate thrombocytopenia and high D-dimer levels. After detecting PF4 antibodies subcutaneous danaparoid was our first-line antithrombotic treatment with an average duration of three weeks. The median plasma anti-FXa activity was in the lower part of the therapeutic range and during the first week of danaparoid administration clinical symptoms, platelet counts, and fibrin turnover resolved or significantly improved. The average duration of hospital admission was 10 days [2–18]. One patient died but the other five patients recovered completely. Conclusions The clinical outcomes of our small cohort align with the earlier published reports, and support danaparoid as a rational option for the initial anticoagulation of VITT patients.

VITT is a rare, life-threatening syndrome characterized by thrombotic symptoms in combination with thrombocytopenia, which may occur in individuals receiving the first administration of adenoviral non replicating vectors (AVV) anti Covid19 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by high levels of serum IgG that bind PF4/polyanion complexes, thus triggering platelet activation. Therefore, identification of the fine pathophysiological mechanism by which vaccine components trigger platelet activation is mandatory. Herein, we propose a multistep mechanism involving both the AVV and the neo-synthetized Spike protein. The former can: i) spread rapidly into blood stream, ii), promote the early production of high levels of IL-6, iii) interact with erythrocytes, platelets, mast cells and endothelia, iv) favor the presence of extracellular DNA at the site of injection, v) activate platelets and mast cells to release PF4 and heparin. Moreover, AVV infection of mast cells may trigger aberrant inflammatory and immune responses in people affected by the mast cell activation syndrome (MCAS). The pre-existence of natural antibodies binding PF4/heparin complexes may amplify platelet activation and thrombotic events. Finally, neosynthesized Covid 19 Spike protein interacting with its ACE2 receptor on endothelia, platelets and leucocyte may trigger further thrombotic events unleashing the WITT syndrome.

© European Stroke Organisation 2021. Article reuse guidelines: sagepub.com/journals-permissions, Severe cases of cerebral venous thrombosis (CVT) with thrombocytopenia and anti-platelet factor 4 (PF4) antibodies occurring after adenoviral vector anti-SARS-CoV-2 vaccines have been recently reported. We aim to present a guidance document on the diagnosis and treatment of patients presenting with CVT after vaccination against SARS-CoV-2 infection. We reviewed the available evidence which consists on case reports, small case series, expert opinion and analogy with heparin-induced thrombocytopenia (HIT) management. Because of the low level of evidence, this is an interim document, based only on expert opinion consensus. In patients presenting with CVT after being vaccinated against SARS-CoV-2 infection, if there is thrombocytopenia a reliable HIT PF4 Antibody ELISA test should be performed, to confirm vaccine-induced immune thrombotic thrombocytopenia (VITT). In patients with CVT and thrombocytopenia, in whom VITT is suspected or confirmed, heparin (unfractionated or low molecular weight) should be avoided and non-heparin anticoagulants are preferred. If possible, platelet transfusions should be avoided. If the diagnosis of VITT is confirmed or suspected, early intravenous immunoglobulins are indicated. This expert opinion is supported by low quality evidence. It should be periodically updated, or changed to a formal guideline, as new and higher quality evidence is eventually produced. Because of their potential unfavourable clinical course, patients developing symptoms and signs suggestive of CVT after being vaccinated against SARS-CoV-2 virus should undergo urgent clinical and neuroimaging evaluation. In cases of suspected or confirmed VITT, non-heparin anticoagulants should be used, platelet transfusions avoided and intravenous immunoglobulin started early.

Summary The coronavirus disease 2019 (Covid‐19) pandemic has had devastating effects on public health worldwide, but the deployment of vaccines for Covid‐19 protection has helped control the spread of SARS Coronavirus 2 (SARS‐CoV‐2) infection where they are available. The common side effects reported following Covid‐19 vaccination were mostly self‐restricted local reactions that resolved quickly. Nevertheless, rare vaccine‐induced immune thrombotic thrombocytopenia (VITT) cases have been reported in some people being vaccinated against Covid‐19. This review summarizes the thromboembolic events after Covid‐19 vaccination and discusses its molecular mechanism, incidence rate, clinical manifestations and differential diagnosis. Then, a step‐by‐step algorithm for diagnosing such events, along with a management plan, are presented. In conclusion, considering the likeliness of acquiring severe SARS‐CoV‐2 infection and its subsequent morbidity and mortality, the benefits of vaccination outweigh its risks. Hence, if not already initiated, all governments should begin an effective and fast public vaccination plan to overcome this pandemic.

Purpose We 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. Conclusion Even 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.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is associated with high titers of immunoglobulin G class antibodies directed against the cationic platelet chemokine platelet factor 4 (PF4). These antibodies activate platelets via FcγIIa receptors. VITT closely resembles heparin-induced thrombocytopenia. Inflammation and tissue trauma substantially increase the risk for forming pathogenic PF4 antibodies. We therefore propose the use of therapeutic plasma exchange as rescue therapy in VITT to deplete antibodies plus factors promoting inflammation such as excess cytokines in the circulation as well as extracellular vesicles derived from activated platelets.

En mars 2021, l’EMA a alerte sur des cas de thrombocytopenie et de thrombose, souvent dans des sites atypiques, survenus apres l’administration de Vaxzevria (ChAdOx1 nCoV-19, AstraZeneca). En date du 4 avril 2021, 169 cas de thrombose veineuse cerebrale (TVC) et 53 cas de thrombose de la veine splanchnique ont ete signales. Dans la majorite des cas, une thrombopenie, parfois marquee, etait associee. Ce syndrome thrombotique, denomme thrombocytopenie immuno-thrombotique induite par le vaccin (VITT), affecte principalement les femmes (80 %) et les personnes âgees de moins de 55 ans. Tres vite, la pathophysiologie du VITT a ete decryptee, et des etudes recentes ont montre des niveaux eleves d’anticorps plaquettes (PF4) chez les personnes affectees, en l’absence d’une exposition anterieure a l’heparine. Dans cet expose, nous preciserons les donnees physiopathologiques de ce VITT, et presenterons les demarches, notamment menees en France, pour mieux guider les demarches diagnostiques et therapeutiques de ce syndrome.

Objectives Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication after adenoviral vector vaccination against COVID-19 reported up to 24 days after ChAdOx1 nCOV-19 (AZD1222) vaccination. This report describes a case with a significantly later onset of VITT with cerebral venous sinus thrombosis. Case description We report a 42-year-old woman presenting to the emergency department 53 days after AZD1222 vaccination with sudden onset sensory aphasia and an 18-day history of headache. Cranial computed tomography (CT) showed acute intracranial hemorrhage and CT venogram demonstrated thrombosis of the left vein of Labbé and transverse and sigmoid sinus. D-dimers were elevated and despite a normal platelet count, platelet-activating anti-PF4 antibody testing was positive, confirming the diagnosis of VITT. The patient was treated with intravenous immunoglobulins and argatroban, and was discharged without any neurological deficit on day 12. Conclusion Our report of VITT with symptom onset on day 35 and diagnosis of cerebral sinuous thrombosis on day 53 after AZD1222 vaccination significantly enhances the time window during which VITT may occur.