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Clinical characteristics of patients with subsequent vaccine-induced immune thrombotic thrombocytopenia compared with patients without vaccine-induced immune thrombotic thrombocytopenia
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Aims
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but highly morbid complication after adenoviral vector-based SARS-CoV-2 vaccination. The pre-VITT syndrome is defined as vaccine-induced immune thrombocytopenia without thrombosis typically presenting with new-onset headache. This review aims to identify at-risk patients befor...
Context in source publication
Context 1
... addition to the initial case series with 11 patients (including the patient who was excluded from this review due to pre-existing vitamin K antagonist treatment), a recent literature search (as of January 1, 2022) found nine additional reports of patients who met the criteria for pre-VITT syndrome ( Table 1 and supplementary material online, Table 3). 14-20 All 19 patients reviewed here received anticoagulation but at different times during the disease course. ...Similar publications
Platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and throm...
Citations
... The presentation of VITT is frequently dominated by symptoms of thrombosis rather than isolated thrombocytopenia, with some individuals exhibiting pre-VITT, a syndrome characterized by new-onset headache without overt thrombosis. 48 A drop in the platelet count below 150×10 9 /L during the disease course aligns with the diagnosis of VITT as per the American Society of Hematology (ASH) criteria. 10 We found that a notable proportion of VITT patients experienced a platelet count nadir below 50×10 9 /L. ...
Anti-platelet factor 4 (PF4) disorders are a group of platelet-consumptive disorders characterized by platelet-activating antibodies against PF4, thrombocytopenia and an increased risk of thrombosis. PF4 is a chemokine released by platelet alpha granules upon activation, which can form immune complexes with negatively charged substances, such as heparin, cartilage components, nucleic acids, and viral and bacterial agents. Antibodies formed in response to PF4-polyanion complexes may display platelet-activating properties and cause pan-cellular activation, leading to the marked prothrombotic state of anti-PF4 disorders. In recent years, the landscape of anti-PF4 disorders has evolved to include classic heparin-induced thrombocytopenia (cHIT), autoimmune HIT (aHIT), spontaneous HIT (SpHIT), vaccine-induced immune thrombotic thrombocytopenia (VITT), and the newly recognized spontaneous VITT (SpVITT). These disorders have garnered increased attention due to their association with severe clinical outcomes. Recent discoveries have expanded the understanding of these conditions, highlighting the role of various triggers, such as upper respiratory tract infections and monoclonal gammopathy of undetermined significance, in their development. Compared to cHIT, the less common anti-PF4 disorders VITT, aHIT, SpHIT and SpVITT generally appear more severe, with aggressive disease courses, more severe thrombocytopenia and a higher frequency of bleeding, thrombosis at unusual sites, involvement of the central nervous system and of multiple vascular beds. Clinical suspicion and knowledge of the less well-known triggers of anti-PF4 disorders are pivotal to ordering the appropriate laboratory tests and initiating the necessary treatments. Herein, we will review cHIT, aHIT, SpHIT and VITT, focusing on their clinical presentation and therapeutic management.
... However, with raised awareness and prompt management, mortality has been reduced to about 5 % in Australia [52]. Pre-VITT (also known as VIT) may occur, where headache and thrombocytopenia are seen but thrombosis is not yet present [53,54]. ...
... This is consistent with what has been termed pre-VITT. Confirmation of anti-PF4 antibodies is required for Levels 1 and 2 of VITT [51,54]. ...
... Vaccine-induced thrombosis with thrombocytopenia syndrome (TTS) is caused by the platelet activation and consumption, triggered by anti-platelet factor-4 antibodies [27]. Headache is the most frequent symptom of TTS, and may even precede thrombosis [28,29]. The most specific feature to differentiate between the conventional vaccine-induced headache and TTS-related headache is the delayed onset of the headache, needed to produce the responsible antibodies [30]. ...
Introduction
Headache is a frequent symptom at the acute phase of coronavirus disease 2019 (COVID-19) and also one of the most frequent adverse effects following vaccination. In both cases, headache pathophysiology seems linked to the host immune response and could have similarities. We aimed to compare the clinical phenotype and the frequency and associated onset symptoms in patients with COVID-19 related-headache and COVID-19 vaccine related-headache.
Subjects and methods
A case-control study was conducted. Patients with confirmed COVID-19 infection and COVID-19-vaccine recipients who experienced new-onset headache were included. A standardised questionnaire was administered, including demographic variables, prior history of headaches, associated symptoms and headache-related variables. Both groups were matched for age, sex, and prior history of headache. A multivariate regression analysis was performed.
Results
A total of 238 patients fulfilled eligibility criteria (143 patients with COVID-19 related-headache and 95 subjects experiencing COVID-19 vaccine related-headache). Patients with COVID-19 related-headache exhibited a higher frequency of arthralgia, diarrhoea, dyspnoea, chest pain, expectoration, anosmia, myalgia, odynophagia, rhinorrhoea, cough, and dysgeusia. Further, patients with COVID-19 related-headache had a more prolonged daily duration of headache and described the headache as the worst headache ever experienced. Patients with COVID-19 vaccine-related headache, experienced more frequently pain in the parietal region, phonophobia, and worsening of the headache by head movements or eye movements.
Conclusion
Headache caused by SARS-CoV-2 infection and COVID-19 vaccination related-headache have more similarities than differences, supporting a shared pathophysiology, and the activation of the innate immune response. The main differences were related to associated symptoms.
... Meanwhile, the immune process underlying the cause of VITT was elucidated in detail, allowing a more specific treatment regime with anticoagulation and immunomodulation [15][16][17]. Specific treatment as well as early identification may have contributed to a declining mortality of patients with VITT [18][19][20]. However, despite these advances in treating patients with VITT-associated severe CVST, case series continued reporting high rates of fatal courses in patients with VITT-associated CVST and DS, which has led to the impression that this approach could not influence the fatal course [21,22]. ...
Background:
Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome.
Methods:
This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS.
Results:
Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission (p = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months (p = 0.043).
Conclusions:
Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.
Coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization. The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Establishing a direct correlation (the cause‐effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on the main adverse effects observed after vaccination, including anaphylaxis, myocarditis, vaccine‐induced thrombotic thrombocytopenia, Guillain–Barré syndrome, and transverse myelitis reported in the context of COVID‐19 vaccination. We highlight the symptoms, laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments for these adverse effects. The aim of this work is to increase awareness among healthcare personnel about the serious adverse events that may arise post‐vaccination. Regardless of the ongoing discussion about the safety of COVID‐19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications.
Vaccine-induced immune thrombotic thrombocytopenia (VITT) was recognized around two years ago, at the beginning of the anti-SARS-CoV-2 vaccination campaign, as a rare but life-threatening complication of adenoviral vector vaccines. Two years later the COVID-19 pandemic has been tamed, although not defeated, and the vaccines provoking VITT have been abandoned in most high-income countries, thus why should we still speak about VITT? Because a significant fraction of the world population has not been vaccinated yet, especially in low/middle-income countries that can only afford adenoviral vector-based vaccines, because the adenoviral vector platform is being used for the development of a large series of new vaccines for other transmissible diseases, and lastly because there are some clues suggesting that VITT may not be exclusive to anti-SARS-CoV-2 vaccines. Therefore a deep understanding of this new syndrome is highly warranted as well as the awareness that we still miss some crucial insight into its pathophysiology and on some aspects of its management. This snapshot review aims to portray our knowledge on VITT, focusing on its clinical presentation, pathophysiological insight, diagnostic and management strategies and to pinpoint the main unmet needs, highlighting the aspects on which research should focus in the near future.
Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome, is a potentially fatal reaction to coronavirus disease 2019 (COVID-19) vaccines, which occurs disproportionately in response to vaccination with non-replicating adenovirus vector (AV) vaccines. The mechanism of VITT is not well defined and it has not been resolved why cases of VITT are predominated by vaccination with AV vaccines. However, virtually all VITT patients have positive platelet-activating anti-platelet factor 4 (PF4) antibody titers. Subsequently, platelets are activated and depleted in an Fcγ-receptor IIa (FcγRIIa or CD32a)-dependent manner, but it is not clear why or how the anti-PF4 response is mounted. This review describes the pathogenesis of VITT and provides insight into possible mechanisms that prompt the formation of a PF4/polyanion complex, which drives VITT pathology, as an amalgam of current experimental data or hypotheses.
Within the first months of the Covid-19 vaccination campaign, previously healthy recipients were identified who developed severe thrombosis (often cerebral and/or splanchnic vasculature) and thrombocytopenia typically after adenoviralvector-based vaccination. Similarities between this syndrome, vaccine-induced thrombocytopenia and thrombosis (VITT), and heparin-induced thrombocytopenia, prompted recognition of the role of anti-platelet factor 4 (PF4) antibodies and management strategies based on intravenous immunoglobulin and non-heparin anticoagulants, which improved outcome. We update current understanding of VITT and potential involvement of anti-PF4 antibodies in thrombotic disorders.
