Thrombotic and Thromboembolic Complications After Vaccination Against COVID-19: A Systematic Review.

Thromboembolic complications after the COVID-19 vaccination have been reported from all over the world. We aimed to identify the thrombotic and thromboembolic complications that can arise after receiving various types of COVID-19 vaccines, their frequency, and distinguishing characteristics. Articles published in Medline/PubMed, Scopus, EMBASE, Google Scholar, EBSCO, Web of Science, the Cochrane Library, the CDC database, the WHO database, ClinicalTrials.gov, and servers like medRxiv.org and bioRxiv.org, as well as the websites of several reporting authorities between December 1, 2019, and July 29, 2021, were searched. Studies were included if they reported any thromboembolic complications post-COVID-19 vaccination and excluded editorials, systematic reviews, meta-analyses, narrative reviews, and commentaries. Two reviewers independently extracted the data and conducted the quality assessment. Thromboembolic events and associated hemorrhagic complications after various types of COVID-19 vaccines, their frequency, and distinguishing characteristics were assessed. The protocol was registered at PROSPERO (ID-CRD42021257862). There were 59 articles, enrolling 202 patients. We also studied data from two nationwide registries and surveillance. The mean age of presentation was 47 ± 15.5 (mean ± SD) years, and 71.1% of the reported cases were females. The majority of events were with the AstraZeneca vaccine and with the first dose. Of these, 74.8% were venous thromboembolic events, 12.7% were arterial thromboembolic events, and the rest were hemorrhagic complications. The most common reported event was cerebral venous sinus thrombosis (65.8%), followed by pulmonary embolism, splanchnic vein thrombosis, deep vein thrombosis, and ischemic and hemorrhagic stroke. The majority had thrombocytopenia, high D-dimer, and anti-PF4 antibodies. The case fatality rate was 26.5%. In our study, 26/59 of the papers were of fair quality. The data from two nationwide registries and surveillance revealed 6347 venous and arterial thromboembolic events post-COVID-19 vaccinations. COVID-19 vaccinations have been linked to thrombotic and thromboembolic complications. However, the benefits far outweigh the risks. Clinicians should be aware of these complications because they may be fatal and because prompt identification and treatment can prevent fatalities.

An Unusual Case of Combined Thrombosis and Amegakaryocytopenia Resembling Thrombosis With Thrombocytopenia Syndrome Following COVID-19 Infection in an Unvaccinated Patient.

As a global community, we have learned that the manifestations of severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), infection, or coronavirus disease 2019 (COVID-19), extends far beyond respiratory compromise. Thrombocytopenia is thought to occur secondary to increased platelet consumption. Platelet activation and platelet-mediated immune inflammation contribute towards the thromboembolic complications seen in COVID-19 patients. In this report, the authors present the unusual case of a 75-year-old female with a history of COVID-19 infection who presented with a transient ischemic attack, thrombocytopenia, and amegakaryocytopenia.

Cerebral Sinus Thrombosis and Immune Thrombocytopenia Post COVID-19 Vaccination: A Case Report and Narrative Review.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following the adenoviral vector COVID-19 vaccine is a rare adverse event. Although the risk of VITT following the COVID-19 vaccine appears to be low, early diagnosis and management can be lifesaving. We present a case of VITT in a young female who presented with persistent headaches and fevers followed by anisocoria and right-sided hemiplegia. Initial imaging was unremarkable, and labs showed thrombocytopenia and elevated d-dimers. Repeat imaging revealed thrombosis in the left transverse and superior sagittal sinuses, and she was diagnosed with VITT. She received combined treatment with intravenous immunoglobulins and systemic anticoagulation, resulting in an increased platelet count and resolution of her neurological symptoms.

Immune Thrombocytopenia and Cerebral Venous Sinus Thrombosis Following COVID-19 Vaccination: A Case Report.

Mass vaccination against coronavirus disease 2019 (COVID-19) has been safe and effective. The ongoing emergence of vaccine-induced complications has challenged the public trust in vaccination programs and, though uncommon, can lead to significant morbidity and mortality. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare and fatal complication of the COVID-19 vaccine. We present a rare case of VITT in a young female who presented with worsening headache, body rash with deteriorating neurological deficit after 12 days of the second dose of the ChAdOx1 COVID-19 vaccine. Initial blood tests showed thrombocytopenia with deranged clotting time and D-dimer levels. Her computed tomography venogram showed thrombosis in the left transverse sinus, and she was diagnosed with a provisional diagnosis of VITT. She initially managed with dexamethasone, intravenous immunoglobulins, and apixaban to reverse the autoimmune process. Our case highlights the clinical course, diagnosis, and management of VITT, which will assist physicians in the timely recognition and adequate management of VITT.

Branch retinal vein occlusion following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine.

PURPOSE: To present a case of branch retinal vein occlusion (BRVO) following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) Vaccine. METHODS: Case report. RESULTS: A 60-year old otherwise healthy Caucasian male, presented to the ophthalmology emergency clinic complaining of sudden, painless vision loss in his right eye of 24 h" duration. The patient had received Vaxveria seven days prior. The clinical and fundus examination of the right eye established the diagnosis of BRVO. CONCLUSION: The present case descibes the occurrence of BRVO soon after the vaccination with the Oxford-AstraZeneca vaccine. The close temporal relationship between the BRVO incidence and the vaccination is reinforced by the lack of othe subjective cause to justify the episode.

Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation.

Several vaccines were developed and rolled out at an unprecedented rate in response to the coronavirus disease-2019 (COVID-19) pandemic. Most vaccines approved globally by WHO for emergency use to combat the pandemic were deemed remarkably effective and safe. Despite the safety, rare incidences of vaccine-induced thrombosis and thrombocytopenia (VITT), sometimes known as vaccine-induced prothrombotic thrombocytopenia (VIPIT), have been reported. We report a case of young female with prothrombotic conditions and suspected VITT who developed catastrophic cerebral venous sinus thrombosis (CVST) and progressed to brain death. We highlight hurdles of organ retrieval from a brain-dead patient with suspected SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. There is limited data and lack of substantial evidence regarding transplantation of organs from brain-dead patients with suspected VITT. How to cite this article: Tiwari AM, Zirpe KG, Gurav SK, Bhirud LB, Suryawanshi RS, Kulkarni SS. Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation. Indian J Crit Care Med 2022;26(4):514-517.

Post COVID-19 Vaccine Related Cerebral Venous Sinus Thrombosis and Thrombocytopenia.

During the height of the COVID-19 pandemic, there was great relief with the global mass rollout of the Covid-19 vaccination programs. While they have proven to be safe and effective, the gradual emergence of side effects to the vaccines has undermined public trust in the vaccination program and, whilst rare, can lead to significant morbidity and mortality. The most serious was the emergence of vaccine-induced immune thrombocytopenia and thrombosis (VITT), also known as thrombosis with thrombocytopenia syndrome (TTS) or vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). VITT is a serious and often fatal complication of some COVID vaccines that seem more prevalent in younger people and women. We present a case of a 48-year-old woman who presented with VITT following COVID vaccination.

Long-term follow-up after successful treatment of vaccine-induced prothrombotic immune thrombocytopenia.

BACKGROUND: Cases of ChAdOx1 nCoV-19 (AstraZeneca) vaccinated patients with thrombocytopenia, elevated D-dimer, and elevated platelet factor 4 (PF4) antibody levels with- and without thrombosis have been reported. No recommendations regarding the duration of anticoagulation have been made, because data on the long-term course beyond the first weeks is lacking. OBJECTIVE: To report on the treatment, medical course, and longitudinal follow-up of laboratory parameters in patients with vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). PATIENTS: We followed VIPIT patients with- (n = 3) and without (n = 3) venous thromboembolism fulfilling the aforementioned laboratory criteria. RESULTS: Elevated D-dimer (median: 35.10 µg/ml, range: 17.80-52.70), thrombocytopenia (42 G/l, 20-101), and strong positivity in the platelet factor 4 (PF4)/heparin-enzyme-immunoassay (2.42 optical density [OD], 2.06-3.13; reference range < 0.50) were present in all patients after vaccination (10 days, 7-17). Routine laboratory parameters rapidly improved upon initiation of treatment (comprising therapeutic non-heparin anticoagulation in all patients and high dose immunoglobulins ± corticosteroids in 5 patients). PF4 antibody levels slowly decreased over several weeks. Patients were discharged in good physical health (8 days, 5-13). VIPIT did not recur during follow-up (12 weeks, 8-17). Five of 6 patients fully recovered (in 2 patients thrombosis had resolved, in 1 patient exertional dyspnea persisted). CONCLUSIONS: Remissions without sequelae can be achieved upon rapid initiation of treatment in patients with VIPIT. Platelet factor 4 antibody levels slowly decreased over several weeks but VIPIT did not recur in any of our patients. Continuation of anticoagulation in VIPIT patients at least until PF4 antibody negativity is reached seems reasonable.

Comparison of Published Guidelines for the Diagnosis and the Management of Vaccine-Induced Immune Thrombotic Thrombocytopenia.

The development of thrombocytopenia and thrombosis after the administration of the AstraZeneca and Johnson & Johnson/Janssen vaccines has been recently described. This new condition has been called vaccine-induced immune thrombotic thrombocytopenia. The objective of this review is to summarize the clinical characteristics and therapeutic options of vaccine-induced immune thrombotic thrombocytopenia based on available published case series. Furthermore, we provide a comparison of the diagnostic pathway and treatment recommendations provided by six major medical societies. DATA SOURCES: We searched MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases. STUDY SELECTION: We included case series and case reports on patients who developed vaccine-induced immune thrombotic thrombocytopenia. We also included guidelines for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia from major medical societies. DATA EXTRACTION: We examined baseline risk factors, symptoms, physical signs, laboratory and imaging findings, and treatment in patients with vaccine-induced immune thrombotic thrombocytopenia reported in the case series. We also analyzed the diagnostic and treatment recommendations provided by major societal guidelines on the management of vaccine-induced immune thrombotic thrombocytopenia. DATA SYNTHESIS: Patients who developed vaccine-induced immune thrombotic thrombocytopenia were more likely to be young women (age 20-50) who were given the AstraZeneca or Johnson & Johnson/Janssen 4-28 days prior to presentation. Patients showed signs, symptoms, and imaging findings consistent with cerebral venous sinus thrombosis and splanchnic thrombosis. Laboratory findings showed thrombocytopenia, low fibrinogen, and elevate d-dimer levels, while positive platelet factor 4 antibodies were always positive. Major societal guidelines recommend avoidance of heparin and platelets. Treatment with nonheparin anticoagulants and IV immunoglobulin is also recommended. CONCLUSIONS: Vaccine-induced immune thrombotic thrombocytopenia is a rare but highly morbid complication related to the administration of the AstraZeneca and Johnson & Johnson/Janssen vaccines. Clinicians should be prepared for the early identification of patients with suspicious symptoms and prompt treatment should be initiated to avoid catastrophic deterioration. Major societal guidelines provide useful recommendations for the diagnosis and management of patients with vaccine-induced immune thrombotic thrombocytopenia.

A rare case of vaccine-induced immune thrombosis and thrombocytopenia and approach to management.

BACKGROUND: The use of the COVID-19 vaccines Vaxzevria from AstraZeneca and Covishield from Janssen has been associated with sporadic reports of thrombosis with thrombocytopenia, a complication referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT) or vaccine-induced prothrombotic immune thrombocytopenia. It presents commonly as cerebral sinus venous thrombosis (CSVT), within 4-30 days of vaccination. Females under 55 years of age are considered to be especially at high risk. Mortality up to 50% has been reported in some countries. Identification of early warning signs and symptoms with prompt medical intervention is crucial. CASE DESCRIPTION: We report here a case of VITT in a young female who presented 11 days after receiving the first dose of the Covishield vaccine, with severe headache and hemiparesis. She was diagnosed with CSVT with a large intraparenchymal bleed, requiring decompressive craniectomy and extended period on mechanical ventilation. CONCLUSION: The patient was successfully treated with intravenous immunoglobulin and discharged after 19 days in ICU. Although she was left with long-term neurological deficits, an early presentation and a multidisciplinary approach to management contributed toward a relatively short stay in hospital and avoided mortality.

Addressing Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following COVID-19 Vaccination: A Mini-Review of Practical Strategies.

In response to the COVID-19 pandemic, several vaccines were developed and rolled out at unprecedented speed, and notwithstanding this rapid pace of development, the results from initial clinical trials involving tens of thousands of adult subjects generally indicated that most vaccines were remarkably effective and safe, with no major safety warnings noted. However, with more than 2 billion vaccination doses administered to date, reports of rare adverse events following immunization (AEFI) are beginning to emerge. In late February 2021, atypical thrombotic events following immunization with the adenoviral vector-based ChAdOx1 nCov-19 vaccine were first reported, and similar events have also been observed in recipients of the adenoviral vector-based Ad26.COV2.S vaccine and the mRNA-based BNT162b2 and mRNA-1273 vaccines. These manifestations of atypical thrombosis and thrombocytopenia following COVID-19 vaccine immunization are now collectively referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Although the reported incidence remains very low and does not affect the overall benefit of immunization, it is also true that if left untreated, VITT can be debilitating or even fatal. Therefore, this review seeks to provide a comprehensive overview regarding the incidence, pathogenesis, presentation, diagnosis, and treatment of VITT, as well as considerations for special populations, based on the currently available evidence in the literature. It is hoped that this will enhance awareness of this vaccine side effect, so that cases of VITT may be identified and treated in a timely and appropriate manner.

Vaccine induced thrombotic thrombocytopenia: The shady chapter of a success story.

The recognition of the rare but serious and potentially lethal complication of vaccine induced thrombotic thrombocytopenia (VITT) raised concerns regarding the safety of COVID-19 vaccines and led to the reconsideration of vaccination strategies in many countries. Following the description of VITT among recipients of adenoviral vector ChAdOx1 vaccine, a review of similar cases after Ad26.COV2·S vaccination gave rise to the question whether this entity may constitute a potential class effect of all adenoviral vector vaccines. Most cases are females, typically younger than 60 years who present shortly (range: 5-30 days) following vaccination with thrombocytopenia and thrombotic manifestations, occasionally in multiple sites. Following initial incertitude, concrete recommendations to guide the diagnosis (clinical suspicion, initial laboratory screening, PF4-polyanion-antibody ELISA) and management of VITT (non-heparin anticoagulants, corticosteroids, intravenous immunoglobulin) have been issued. The mechanisms behind this rare syndrome are currently a subject of active research and include the following: 1) production of PF4-polyanion autoantibodies; 2) adenoviral vector entry in megacaryocytes and subsequent expression of spike protein on platelet surface; 3) direct platelet and endothelial cell binding and activation by the adenoviral vector; 4) activation of endothelial and inflammatory cells by the PF4-polyanion autoantibodies; 5) the presence of an inflammatory co-signal; and 6) the abundance of circulating soluble spike protein variants following vaccination. Apart from the analysis of potential underlying mechanisms, this review aims to synopsize the clinical and epidemiologic features of VITT, to present the current evidence-based recommendations on diagnostic and therapeutic work-up of VITT and to discuss new dilemmas and perspectives that emerged after the description of this entity.

COVID-19 vaccines and thrombosis with thrombocytopenia syndrome.

INTRODUCTION: To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination. AREAS COVERED: This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS. EXPERT OPINION: : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity. PLAIN LANGUAGE SUMMARY: What is the context?Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines.TTS mainly occurs in patients aged < 55 years and is associated with high morbidity and mortality.What is new?TTS mimics autoimmune heparin-induced thrombocytopenia and can be mediated by platelet-activating antibodies against platelet factor 4. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) should be considered as the treatment of choice if the platelet count is > 50 × 109/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated.What is the impact?TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.

COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A review of the potential mechanisms and proposed management.

With over 600 million coronavirus (COVID-19) vaccine doses administered globally, adverse events are constantly monitored. Recently however, reports of thrombosis and thrombocytopenia following vaccination with the ChAdOx1 nCoV-19 vaccine have emerged. This paper aims to review the available literature and guidelines pertaining to vaccine-induced immune thrombotic thrombocytopenia (VITT) and the proposed guidelines, while offering a potential approach that unifies the available evidence. While the risk of VITT remains extremely low and the benefits outweigh the risks, experimental studies are needed to clarify the pathophysiology behind VITT and possibly decrease the risk of thrombosis and other adverse events occurring. However, treatment should not be delayed in suspected cases, and IV immunoglobulin and non-heparin anticoagulation should be initiated.

Successful treatment of vaccine-induced prothrombotic immune thrombocytopenia (VIPIT).

Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV-19 vaccine (AstraZeneca) have been reported. The term vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high-dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet-activating properties of ChAdOx1 nCoV-19 vaccine induced antibodies. Here, we report a case of a 62-year-old woman who had received this vaccine and developed VIPIT. She visited the emergency ward because of petechiae and hematomas. In the laboratory work-up, thrombocytopenia, low fibrinogen, elevated D-dimer, and positivity in the platelet factor 4/heparin-enzyme-immunoassay were present. Signs and symptoms of thrombosis were absent. Upon immediate therapy with non-heparin anticoagulation, high-dose IVIG, and prednisolone, laboratory parameters steadily improved and the patient was discharged from hospital without thrombotic complications. We conclude that early initiation of VIPIT treatment results in a swift response without thrombotic complications.