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Following vaccination with adenoviral vector-based ChAdOx1 nCoV-19, serious neurological adverse events have been reported. Here we report two cases who presented with quadriparesis following the adenoviral vector-based ChAdOx1 nCoV-19 vaccine. A 55-year-old male patient presented with quadriparesis after 8 days of the second dose of ChAdOx1 nCoV-19 vaccination. Imaging showed features of stroke with right basilar artery thrombosis; he was started on anticoagulation following which the patient’s neurological status improved and he was discharged during the 7th week of hospital stay. A 19-year-old male patient presented with quadriparesis after 16 days of the first dose of ChAdOx1 nCoV-19 vaccination. Cerebral spinal fluid and nerve conduction study was suggestive of Guillain–Barre syndrome (GBS). Two doses of intravenous immunoglobulin were given, following which the patient’s neurological status improved and he was discharged in the 11th week of his hospital stay. Awareness of neurological adverse effects and emphasis on the underlying mechanism of vaccine-induced thrombotic thrombocytopenia (VITT) and molecular mimicry in patients presenting with quadriparesis following ChAdOx1 nCoV-19 vaccination is important.

Following vaccination with adenoviral vector-based ChAdOx1 nCoV-19, serious neurological adverse events have been reported. Here we report two cases who presented with quadriparesis following the adenoviral vector-based ChAdOx1 nCoV-19 vaccine. A 55-year-old male patient presented with quadriparesis after 8 days of the second dose of ChAdOx1 nCoV-19 vaccination. Imaging showed features of stroke with right basilar artery thrombosis; he was started on anticoagulation following which the patient's neurological status improved and he was discharged during the 7th week of hospital stay. A 19-year-old male patient presented with quadriparesis after 16 days of the first dose of ChAdOx1 nCoV-19 vaccination. Cerebral spinal fluid and nerve conduction study was suggestive of Guillain--Barre syndrome (GBS). Two doses of intravenous immunoglobulin were given, following which the patient's neurological status improved and he was discharged in the 11th week of his hospital stay. Awareness of neurological adverse effects and emphasis on the underlying mechanism of vaccine-induced thrombotic thrombocytopenia (VITT) and molecular mimicry in patients presenting with quadriparesis following ChAdOx1 nCoV-19 vaccination is important. [ABSTRACT FROM AUTHOR]

Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are rare, iatrogenic immune-mediated conditions with high rates of thrombosis-related morbidity and mortality. HIT is a long-recognized reaction to the administration of the common parenterally administered anticoagulant heparin (or its derivatives), while VITT is a new, distinct syndrome occurring in response to adenovirus-based vaccines against coronavirus disease 2019 and potentially other types of vaccines. A feature of both HIT and VITT is paradoxical thrombosis despite a characteristic low platelet count, mediated by the presence of platelet-activating antibodies to platelet factor 4. Several additional factors have also been suggested to contribute to clot formation in HIT and/or VITT, including monocytes, tissue factor, microparticles, endothelium, the formation of neutrophil extracellular traps, complement, procoagulant platelets, and vaccine components. In this review, we discuss the literature to date regarding mechanisms contributing to thrombosis in both HIT and VITT and explore the pathophysiological similarities and differences between the two conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. Case presentation We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. Conclusions Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.

Vaccine-induced thrombotic thrombocytopenia (VITT) has been recently linked with coronavirus disease (COVID-19) vaccines. It becomes crucial for the transplant communities to have a rigorous approach for accepting VITT donors, as the reports of such transplantation have been associated with thrombotic complications, graft loss, and deaths. The magnitude of facing a VITT donor in transplantation practices is unknown and also the management protocol. However, as per the limited data, it is better to avoid such transplants, and in the case of emergency transplants, the risk-benefit ratio should be weighed. All transplantation from VITT donors should be appropriately counseled before procurement. The organs should undergo deliberate examination for functionality by clinical, laboratory, and radiological parameters. In doubtful cases, a preimplantation biopsy is mandated to rule out any thrombosis. VITT donors are suggested to be treated with newer oral anti-coagulation and intravenous immunoglobulin. Platelet transfusion is best avoided in a VITT donor. There is no established protocol for any modification in surgical procedure, anesthesia, or immunosuppressive medicines in the recipients. The recipients should undergo extensive clinical and laboratory monitoring for any possible complications. No prophylactic therapy is recommended at present but candidates with a history of any COVID-19 vaccine within 30 days, should be avoided. In summary, the evidence for diagnosis and management of VITT donors is based only on a few reports, but with current knowledge, it is advisable to take a multidisciplinary approach to assess all benefits and risks before accepting or discarding organs.

Vaccine-induced thrombotic thrombocytopenia (VITT) has been recently linked with coronavirus disease (COVID-19) vaccines. It becomes crucial for the transplant communities to have a rigorous approach for accepting VITT donors, as the reports of such transplantation have been associated with thrombotic complications, graft loss, and deaths. The magnitude of facing a VITT donor in transplantation practices is unknown and also the management protocol. However, as per the limited data, it is better to avoid such transplants, and in the case of emergency transplants, the risk-benefit ratio should be weighed. All transplantation from VITT donors should be appropriately counseled before procurement. The organs should undergo deliberate examination for functionality by clinical, laboratory, and radiological parameters. In doubtful cases, a preimplantation biopsy is mandated to rule out any thrombosis. VITT donors are suggested to be treated with newer oral anti-coagulation and intravenous immunoglobulin. Platelet transfusion is best avoided in a VITT donor. There is no established protocol for any modification in surgical procedure, anesthesia, or immunosuppressive medicines in the recipients. The recipients should undergo extensive clinical and laboratory monitoring for any possible complications. No prophylactic therapy is recommended at present but candidates with a history of any COVID-19 vaccine within 30 days, should be avoided. In summary, the evidence for diagnosis and management of VITT donors is based only on a few reports, but with current knowledge, it is advisable to take a multidisciplinary approach to assess all benefits and risks before accepting or discarding organs. [ABSTRACT FROM AUTHOR]

Acute pulmonary embolism in presence of thrombocytopenia poses a challenging situation to manage. Concomitant presence of right atrial thrombus and thrombocytopenia will further complicate the situation. We hereby report a case of large right atrial thrombus with massive saddle bilateral pulmonary artery embolism with severe thrombocytopenia managed surgically with successful outcome. [ABSTRACT FROM AUTHOR]

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.

Background: Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. Case presentation: We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. Conclusions: Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions. [ABSTRACT FROM AUTHOR]

Transplantation outcome in recipients engrafted with organs recovered from the first French deceased donor with a SARS-COV-2 vaccine-induced thrombotic thrombocytopenia. Kidney transplantation, organ donation, SARS-CoV-2, vaccine, vaccine-induced thrombotic thrombocytopenia Keywords: kidney transplantation; organ donation; SARS-CoV-2; vaccine; vaccine-induced thrombotic thrombocytopenia EN kidney transplantation organ donation SARS-CoV-2 vaccine vaccine-induced thrombotic thrombocytopenia 1 4 4 12/23/22 20221201 NES 221201 Abbreviations ATG anti-thymocyte globulin BPR biopsy-proven rejection DGF delayed graft function DSA donor-specific antibodies ECDs expanded-criteria donors ER emergency room ITP immune thrombocytopenic purpura IVIG intravenous immunoglobulins MM mismatches PF4 platelet factor 4 PLT platelets PRA panel-reactive antibodies TMA transplant-mediated alloimmune thrombocytopenia VITT vaccine-induced thrombosis and thrombocytopenia INTRODUCTION In march 2021, fatal cases of thrombosis associated with thrombocytopenia following anti-SARS-CoV2 adenoviral vaccines administration have been reported especially in younger people, the so-called vaccine-induced thrombosis and thrombocytopenia (VITT).[1] This has raised the challenge of accepting VITT-deceased patients as organ donors, taking into account potential risks associated with transplantation, such as the occurrence of microangiopathic thrombosis of the graft, or the development of transplant-mediated alloimmune thrombocytopenia (TMA).[2] Here, we present two cases of kidney transplantation from donors deceased as a consequence of VITT. [Extracted from the article]

Since the emergence of the COVID-19 pandemic at the end of 2019, a massive vaccination campaign has been undertaken rapidly and worldwide. Like other vaccines, the COVID-19 vaccine is not devoid of side effects. Typically, the adverse side effects of vaccination include transient headache, fever, and myalgia. Endocrine organs are also affected by adverse effects. The major SARS-CoV-2 vaccine-associated endocrinopathies reported since the beginning of the vaccination campaign are thyroid and pancreas disorders. SARS-CoV-2 vaccine-induced pituitary diseases have become more frequently described in the literature. We searched PubMed/MEDLINE for commentaries, case reports, and case series articles reporting pituitary disorders following SARS-CoV-2 vaccination. The search was reiterated until September 2022, in which eight case reports were found. In all the cases, there were no personal or familial history of pituitary disease described. All the patients described had no previous SARS-CoV-2 infection prior to the vaccination episode. Regarding the type of vaccines administered, 50% of the patients received (BNT162b2; Pfizer–BioNTech) and 50% received (ChAdOx1 nCov-19; AstraZeneca). In five cases, the pituitary disorder developed after the first dose of the corresponding vaccine. Regarding the types of pituitary disorder, five were hypophysitis (variable clinical aspects ranging from pituitary lesion to pituitary stalk thickness) and three were pituitary apoplexy. The time period between vaccination and pituitary disorder ranged from one to seven days. Depending on each case's follow-up time, a complete remission was obtained in all the apoplexy cases but in only three patients with hypophysitis (persistence of the central diabetes insipidus). Both quantity and quality of the published data about pituitary inconveniences after COVID-19 vaccination are limited. Pituitary disorders, unlike thyroid disorders, occur very quickly after COVID-19 vaccination (less than seven days for pituitary disorders versus two months for thyroid disease). This is partially explained by the ease of reaching the pituitary, which is a small gland. Therefore, this gland is rapidly overspread, which explains the speed of onset of pituitary symptoms (especially ADH deficiency which is a rapid onset deficit with evocative symptoms). Accordingly, these pilot findings offer clinicians a future direction to be vigilant for possible pituitary adverse effects of vaccination. This will allow them to accurately orient patients for medical assistance when they present with remarkable symptoms, such as asthenia, polyuro-polydipsia, or severe headache, following a COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Since March 2021, cases with unusual clots, particularly cerebral venous sinus thrombosis and splanchnic vein thrombosis, have been reported worldwide following adenoviral vector-based coronavirus disease 2019 (COVID-19) vaccination. This entity has been termed vaccine-induced thrombotic thrombocytopenia (VITT). We report a 23-year-old healthy female who developed seizures, altered sensorium, and left hemiparesis, 20 days after receiving the first dose of adenoviral vector-based COVID-19 vaccine “Covishield™.” The patient had transient thrombocytopenia. The D-dimer level was 2460 ng/mL. Magnetic resonance imaging (MRI) demonstrated occlusion of M2 segment of the middle cerebral artery and cerebral infarction. Platelet factor-4 antibodies level was normal. Treatment with aspirin and antiepileptic drugs resulted in a remarkable recovery. This is the first Indian case report of ischemic stroke and transient thrombocytopenia following SARS-CoV-2 ChAdOx1 nCoV-19 vaccination. Our case had clinical features consistent with the diagnosis of probable VITT. Familiarity with VITT is crucial because timely treatment with non-heparin anticoagulants and intravenous immunoglobulin improves the outcome.

Ella H Leung,1 Jason Fan,2 Harry W Flynn Jr,2 Thomas A Albini2 1Georgia Retina, Atlanta, GA, USA; 2Bascom Palmer Eye Institute/University of Miami, Miami, FL, USACorrespondence: Ella H LeungGeorgia Retina, 833 Campbell Hill St NW, Suite 300, Marietta, GA, 30328, USATel +1 770-218-1888Email eleung@garetina.comAbstract: There is increasing information available about the effects of the SARS-CoV-2 virus on the systemic and ocular health of patients, as well as the effects of delayed health care. This mini-review summarizes the potential complications and treatments of COVID-19. Systemic findings include respiratory illness, risk of thromboembolic events, and neurologic findings. Some patients may develop persistent symptoms even after the infection resolves. Effective treatment options include glucocorticoids, antivirals, interleukin-6 antagonists, monoclonal antibodies, Janus kinase inhibitors and vaccines. Potential ocular findings of COVID-19 include conjunctivitis, cranial nerve palsies, and microvascular changes in the retina; most symptoms resolved over time. During the lockdown periods, teleophthalmology was utilized to triage non-urgent issues; patients who did present to emergency departments tended to have more severe disease with worse visual prognoses. While transient delays in outpatient ophthalmic care may be tolerated in some patients, others experienced significant vision loss with interruptions in treatments. Resumption of ophthalmic care as soon as possible may help mitigate the effects of delayed care due to the pandemic.Keywords: COVID-19, SARS-CoV-2, quarantine, steroids, interleukin 6, tocilizumab, monoclonal antibodies, casirivimab, imdevimab, antiviral, remdesivir; teleophthalmology; vaccine; trauma

From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees, India, to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision-making. VITT is a rare entity, but a meticulous approach should be taken by the organ procurement organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities (NOTTO) as a resource for data collection and ensuring compliance with protocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be considered to be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and a treating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the risk‒benefit equation based on limited experience. An appropriate written informed consent of potential recipients and family members should be obtained before the transplantation of organs from suspected or proven VITT donors.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a well-known complication of adenoviral vector COVID-19 vaccines including ChAdOx1 nCoV-19 (AstraZeneca) and Ad26. COV2.S (Janssen, Johnson & Johnson). To date, only a few cases of mRNA COVID-19 vaccine such as mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech)-induced VITT have been reported. We report a case of VITT with acute cerebral venous thrombosis and hemorrhage after a booster of mRNA-1273 (Moderna) vaccine in a patient previously vaccinated with two doses of the AstraZeneca vaccine. A 42-year-old woman presented with sudden onset of weakness of the right upper limb with focal seizure. She had received two doses of AstraZeneca vaccines and a booster with Moderna vaccine 32 days before presentation. She had also undergone a laparoscopic myomectomy 12 days previously. Laboratory examinations revealed anemia (9.5 g/dl), thrombocytopenia (31 × 103/µl), and markedly elevated d-dimer (>20.0 mg/L; reference value <0.5 mg/L). The initial brain computed tomography (CT) was normal, but a repeated scan 10 h later revealed hemorrhage at the left cerebrum. Before the results of the blood smear were received, on suspicion of thrombotic microangiopathy with thrombocytopenia and thrombosis, plasmapheresis and pulse steroid therapy were initiated, followed by intravenous immunoglobulin (1 g/kg/day for two consecutive days) due to refractory thrombocytopenia. VITT was confirmed by positive anti-PF4 antibody and both heparin-induced and PF4- induced platelet activation testing. Clinicians should be aware that mRNA-1273 Moderna, an mRNA-based vaccine, may be associated with VITT with catastrophic complications. Additionally, prior exposure to the AstraZeneca vaccine and surgical procedure could also have precipitated or aggravated autoimmune heparin-induced thrombocytopenia/VITT-like presentation. [ABSTRACT FROM AUTHOR]

COVID-19 patients often develop coagulopathies including microclotting, thrombotic strokes or thrombocytopenia. Autoantibodies are present against blood-related proteins including cardiolipin (CL), serum albumin (SA), platelet factor 4 (PF4), beta 2 glycoprotein 1 (β2GPI), phosphodiesterases (PDE), and coagulation factors such as Factor II, IX, X and von Willebrand factor (vWF). Different combinations of autoantibodies associate with different coagulopathies. Previous research revealed similarities between proteins with blood clotting functions and SARS-CoV-2 proteins, adenovirus, and bacterial proteins associated with moderate-to-severe COVID-19 infections. This study investigated whether polyclonal antibodies (mainly goat and rabbit) against these viruses and bacteria recognize human blood-related proteins. Antibodies against SARS-CoV-2 and adenovirus recognized vWF, PDE and PF4 and SARS-CoV-2 antibodies also recognized additional antigens. Most bacterial antibodies tested (group A streptococci [GAS], staphylococci, Escherichia coli [E. coli], Klebsiella pneumoniae, Clostridia, and Mycobacterium tuberculosis) cross-reacted with CL and PF4. while GAS antibodies also bound to F2, Factor VIII, Factor IX, and vWF, and E. coli antibodies to PDE. All cross-reactive interactions involved antibody-antigen binding constants smaller than 100 nM. Since most COVID-19 coagulopathy patients display autoantibodies against vWF, PDE and PF4 along with CL, combinations of viral and bacterial infections appear to be necessary to initiate their autoimmune coagulopathies. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has led to unprecedented demand on the global healthcare system. Remarkably, at the end of 2021, COVID-19 vaccines received approvals for human use in several countries worldwide. Since then, a solid base for response in the fight against the virus has been placed. COVID-19 vaccines have been shown to be safe and effective drugs. Nevertheless, all kinds of vaccines may be associated with the possible appearance of neurological complications, and COVID-19 vaccines are not free from neurological side effects. Neurological complications of COVID-19 vaccination are usually mild, short-duration, and self-limiting. However, severe and unexpected post-vaccination complications are rare but possible events. They include the Guillain-Barré syndrome, facial palsy, other neuropathies, encephalitis, meningitis, myelitis, autoimmune disorders, and cerebrovascular events. The fear of severe or fatal neurological complications fed the "vaccine hesitancy" phenomenon, posing a vital communication challenge between the scientific community and public opinion. This review aims to collect and discuss the frequency, management, and outcome of reported neurological complications of COVID-19 vaccines after eighteen months of the World Health Organization's approval of COVID-19 vaccination, providing an overview of safety and concerns related to the most potent weapon against the SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Fast-track approval has led to serious concerns on the perception of COVID-19 vaccines' safety among the public. Common adverse drug reactions (ADRs) of COVID-19 vaccines are minor localized reactions, while systemic ADRs have been reported rarely. The serious ADRs include anaphylaxis, vaccine-induced immune thrombotic thrombocytopenia syndrome (VITTS), and reactions related to the pharmaceutical excipients present in the vaccine. A comprehensive review on the safety of COVID-19 vaccines would help in early identification and better management of ADRs. This literature review was conducted using PubMed, Google Scholar, COVID-19 Vaccine package inserts, and UpToDate. This article provides various aspects of COVID-19 vaccine safety and offers strategies to prevent and clinically manage suspected ADRs related to COVID-19 vaccines. A careful consideration of contraindications and patient education on early identification of serious ADRs are the cornerstones in tackling safety concerns associated with COVID-19 vaccines. Most of the mild ADR cases are manageable with over-the-counter medications, while the serious ones may require physician oversight and hospitalization. It is also mandatory to report all ADRs to the local pharmacovigilance centers, with a higher priority given to the moe significant ones, in order to improve vaccine safety data. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Vaccine-induced thrombotic thrombocytopenia (VITT) is a condition similar to heparin-induced thrombocytopenia (HIT), but it is associated with prior administration of COVID-19 vaccines without prior exposure to heparin. The incidence of VITT is not certain, but it appears to be extremely rare. 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. We would like to present 4 clinical cases of VITT, hospitalized and treated in intensive care unit (ICU) of University clinic of cardiology in Skopje. [ABSTRACT FROM AUTHOR]

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.

In 2020, the SARS‐COV‐2 disease (COVID‐19) imposed huge challenges on the health, economic, and political systems, and by the end of the year, hope had been born with the release of COVID‐19 vaccines aimed at bringing the pandemic to an end. However, the COVID‐19 vaccination programs have sparked several concerns and ongoing debates over safety issues. Here, we presented three cases of patients with serious adverse events, encephalopathy, vaccine‐induced thrombotic thrombocytopenia, and leukocytoclastic vasculitis, after receiving the ChAdOx1 nCoV‐19 vaccine. Therefore, it is critical to investigate and report the occurrence of adverse reactions following vaccination, particularly serious ones, as it contributes to the growing body of research and assists clinicians in better diagnosing and managing them. [ABSTRACT FROM AUTHOR]

From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees, India, to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision-making. VITT is a rare entity, but a meticulous approach should be taken by the organ procurement organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities (NOTTO) as a resource for data collection and ensuring compliance with protocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be considered to be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and a treating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the risk-benefit equation based on limited experience. An appropriate written informed consent of potential recipients and family members should be obtained before the transplantation of organs from suspected or proven VITT donors. [ABSTRACT FROM AUTHOR]

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare coagulation disorder reported after administration of COVID-19 adenovirus-vectored vaccines. VITT is mediated by anti-platelet factor 4 (PF4) antibodies activating platelets through the Fcγ-receptor II (FcγRII), and it is associated with strong fibrin turnover. The complement system is involved in several other immunothrombotic entities, but its impact on VITT is not established. To assess antibodies in interaction with the activation of platelets and complement triggered by VITT. Antibodies against adenovirus type 2 hexon protein, ChAdOx1 adenoviral vector-specific IgG and PF4 were analyzed by enzyme immunoassays from VITT patients (n = 5). The EDTA plasma samples of the patients and controls were used to measure both terminal complement complexes (TCC) by ELISA and aggregation of healthy donor platelets. We studied the effects of human immunoglobulin (IVIG) and glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa) on spontaneous and collagen-induced platelet aggregation supplemented with VITT plasma. None of the patients had experienced a COVID-19 infection. Antibody analyses confirmed the immunogenicity of the adenovirus-vectored ChAdOx1 vaccine. Moreover, VITT plasma had anti-PF4 antibodies and elevated TCC levels as a sign of complement activation. In isolated healthy donor platelets, VITT patient plasma caused marked, spontaneous aggregation of platelets, which was abolished by eptifibatide and high-dose therapeutic IVIG. Our findings suggest that VITT is triggered by antibodies against adenovirus vector and PF4-polyanion complexes which strongly co-activate complement and platelets. The spontaneous platelet aggregation was suppressed by IVIG or eptifibatide, indicating that besides FcγRII, also GPIIb/IIIa receptor exerts platelet procoagulant role in VITT. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract In 2020, the SARS‐COV‐2 disease (COVID‐19) imposed huge challenges on the health, economic, and political systems, and by the end of the year, hope had been born with the release of COVID‐19 vaccines aimed at bringing the pandemic to an end. However, the COVID‐19 vaccination programs have sparked several concerns and ongoing debates over safety issues. Here, we presented three cases of patients with serious adverse events, encephalopathy, vaccine‐induced thrombotic thrombocytopenia, and leukocytoclastic vasculitis, after receiving the ChAdOx1 nCoV‐19 vaccine. Therefore, it is critical to investigate and report the occurrence of adverse reactions following vaccination, particularly serious ones, as it contributes to the growing body of research and assists clinicians in better diagnosing and managing them.

COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenoviral vector (ChAdOx1 nCoV-19) vaccine administration. It is presented as thrombocytopenia and thrombotic manifestations in various sites, especially in cerebral veins. Pulmonary emboli have been reported rarely. We present a case of a young male patient who developed severe thrombocytopenia and pulmonary embolism 12 days after the first dose of the vaccine. Severe thrombocytopenia, skin hematomas, and segmental pulmonary emboli were detected. Anti-platelet factor 4 (aPF-4) antibody was highly positive supporting the diagnosis of VITT. Prompt treatment with fondaparinux, intravenous immunoglobulin, and prednisone led to a marked improvement of clinical condition and thrombocytes count. We report the first known case of VITT in Slovakia.

Abstract Background Vaccination with ChAdOx1 n‐CoV‐19 is associated with a rare syndrome called vaccine‐induced immune thrombotic thrombocytopenia (VITT). VITT has been reported mainly in Western countries, whereas the report of VITT in Asians is sparse. Objectives To report a case series of VITT following ChAdOx1 n‐CoV‐19 in Thailand and to estimate the incidence of VITT among Asian countries. Methods We retrieved the number of VITT patients and the total inoculation doses from the database of the Thai Ministry of Public Health. We performed a literature search including published articles and gray literature to estimate the incidence of VITT. The incidences of VITT by countries and respective confidence intervals were calculated. Results By the end of August 2021, five VITT cases occurred after 15 million doses of ChAdOx1 n‐CoV‐19 in Thailand. The median age was 31 years, and 60% were women. The incidence of VITT is estimated at 1 in 3 million. In other Asian countries, only a few cases of VITT have been reported. The incidence of VITT is much lower than in those of Western countries, which is estimated at 1 in 100, 000. The fatality rate was 44% in this study. Conclusions Although the incidence of VITT in Asians is low, the mortality rate is substantially higher. We urge that public awareness of this syndrome be raised, as early recognition and appropriate treatment of this syndrome following ChAdOx1 n‐CoV‐19 are crucial to improve the outcome.

We present two cases of ChAdOx1 nCov-19 (AstraZeneca)-associated thrombotic thrombocytopenia syndrome (TTS) and cerebral venous sinus thrombosis (CVST). At the time of emergency room presentation due to persistent headache, blood serum levels revealed reduced platelet counts. Yet, 1 or 4 days after the onset of the symptom, the first MR-angiography provided no evidence of CVST. Follow-up imaging, performed upon headache refractory to nonsteroidal pain medication verified CVST 2–10 days after initial negative MRI. Both the patients received combined treatment with intravenous immunoglobulins and parenteral anticoagulation leading to an increase of platelet concentration in both the individuals and resolution of the occluded cerebral sinus in one patient. [ABSTRACT FROM AUTHOR]

Aims The clinical manifestation and outcomes of thrombosis with thrombocytopenia syndrome (TTS) after adenoviral COVID-19 vaccine administration are largely unknown due to the rare nature of the disease. We aimed to analyse the clinical presentation, treatment modalities, outcomes, and prognostic factors of adenoviral TTS, as well as identify predictors for mortality. Methods and Results PubMed, Scopus, Embase, and Web of Science databases were searched and the resulting articles were reviewed. A total of 6 case series and 13 case reports (64 patients) of TTS after ChAdOx1 nCoV-19 vaccination were included. We performed a pooled analysis and developed a novel scoring system to predict mortality. The overall mortality of TTS after ChAdOx1 nCoV-19 vaccination was 35.9% (23/64). In our analysis, age ≤60 years, platelet count <25 × 103/µL, fibrinogen <150 mg/dL, the presence of intracerebral haemorrhage (ICH), and the presence of cerebral venous thrombosis (CVT) were significantly associated with death and were selected as predictors for mortality (1 point each). We named this novel scoring system FAPIC (fibrinogen, age, platelet count, ICH, and CVT), and the C-statistic for the FAPIC score was 0.837 (95% CI 0.732–0.942). Expected mortality increased with each point increase in the FAPIC score, at 2.08, 6.66, 19.31, 44.54, 72.94, and 90.05% with FAPIC scores 0, 1, 2, 3, 4, and 5, respectively. The FAPIC scoring model was internally validated through cross-validation and bootstrapping, then externally validated on a panel of TTS patients after Ad26.COV2.S administration. Conclusions Fibrinogen levels, age, platelet count, and the presence of ICH and CVT were significantly associated with mortality in patients with TTS, and the FAPIC score comprising these risk factors could predict mortality. The FAPIC score could be used in the clinical setting to recognize TTS patients at high risk of adverse outcomes and provide early intensive interventions including intravenous immunoglobulins and non-heparin anticoagulants. [ABSTRACT FROM AUTHOR]

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We present two cases of ChAdOx1 nCov-19 (AstraZeneca)-associated thrombotic thrombocytopenia syndrome (TTS) and cerebral venous sinus thrombosis (CVST). At the time of emergency room presentation due to persistent headache, blood serum levels revealed reduced platelet counts. Yet, 1 or 4 days after the onset of the symptom, the first MR-angiography provided no evidence of CVST. Follow-up imaging, performed upon headache refractory to nonsteroidal pain medication verified CVST 2–10 days after initial negative MRI. Both the patients received combined treatment with intravenous immunoglobulins and parenteral anticoagulation leading to an increase of platelet concentration in both the individuals and resolution of the occluded cerebral sinus in one patient.

The Medicines and Healthcare products Regulatory Agency (MHRA) of the UK has approved the use of three vaccines to combat COVID-19 (SARS-CoV-2). There have been rare reports of thrombosis after vaccination with the AstraZeneca vaccine. We present three cases of vaccine-induced thrombotic thrombocytopenia (VITT) in one UK district general hospital following administration of this vaccine. Two of the patients had asymptomatic pulmonary emboli, while the other is the first known case of both renal vein thrombosis and pulmonary embolism.

The amazing effort of vaccination against COVID-19, with more than 2 billion vaccine doses administered all around the world as of 16 June 2021, has changed the history of this pandemic, drastically reducing the number of severe cases or deaths in countries were mass vaccination campaign have been carried out. However, the people's rising enthusiasm has been blunted in late February 2021 by the report of several cases of unusual thrombotic events in combination with thrombocytopenia after vaccination with ChAdOx1 nCov-19 (Vaxzevria), and a few months later also after Ad26.COV2. S vaccines. Of note, both products used an Adenovirus-based (AdV) platform to deliver the mRNA molecule - coding for the spike protein of SARS-CoV-2. A clinical entity characterized by cerebral and/or splanchnic vein thrombosis, often associated with multiple thromboses, with thrombocytopenia and bleeding, and sometimes disseminated intravascular coagulation (DIC), was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). VITT was mainly observed in females under 55 years of age, between 4 and 16 days after receiving only Adenovirus-based vaccine and displayed a seriously high fatality rate. This prompted the Medicine Regulatory Agencies of various countries to enforce the pharmacovigilance programs, and to provide some advices to restrict the use of AdV-based vaccines to some age groups. This point-of view is aimed at providing a comprehensive review of epidemiological issues, pathogenetic hypothesis and treatment strategies of this rare but compelling syndrome, thus helping physicians to offer an up-to dated and evidence-based counseling to their often alarmed patients. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has led to unprecedented demand on the global healthcare system. Remarkably, at the end of 2021, COVID-19 vaccines received approvals for human use in several countries worldwide. Since then, a solid base for response in the fight against the virus has been placed. COVID-19 vaccines have been shown to be safe and effective drugs. Nevertheless, all kinds of vaccines may be associated with the possible appearance of neurological complications, and COVID-19 vaccines are not free from neurological side effects. Neurological complications of COVID-19 vaccination are usually mild, short-duration, and self-limiting. However, severe and unexpected post-vaccination complications are rare but possible events. They include the Guillain-Barré syndrome, facial palsy, other neuropathies, encephalitis, meningitis, myelitis, autoimmune disorders, and cerebrovascular events. The fear of severe or fatal neurological complications fed the “vaccine hesitancy” phenomenon, posing a vital communication challenge between the scientific community and public opinion. This review aims to collect and discuss the frequency, management, and outcome of reported neurological complications of COVID-19 vaccines after eighteen months of the World Health Organization’s approval of COVID-19 vaccination, providing an overview of safety and concerns related to the most potent weapon against the SARS-CoV-2.

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. [ABSTRACT FROM AUTHOR]

Platelets play an important role in hemostasis by forming clots and stopping bleeding. In immune thrombotic conditions, platelets and leukocytes are aberrantly activated by pathogenic antibodies resulting in platelet aggregates and NETosis, leading to thrombosis and thrombocytopenia. A simple assay that assesses platelet function and antibody activity is light transmission aggregometry. This assay can be used to determine antibody activity in patients with disorders such as heparin-induced thrombocytopenia (HIT) and vaccine-induced thrombotic thrombocytopenia (VITT). Briefly, for detection of pathogenic antibody, platelet-rich plasma (PRP) is treated with a specific agent (e.g., patient sera or purified patient antibodies) with constant stirring. Upon activation, platelets undergo a shape change and adhere to each other forming aggregates. This causes a reduction in opacity allowing more light to pass through PRP. Light transmission through the cuvette is proportional to the degree of platelet aggregation and is measured by the photocell over time. The advantage of this protocol is that it is a simple, reliable assay that can be applied to assess antibody activity in thrombotic conditions. Light transmission aggregometry does not require the use of radioactive reagents and is technically less demanding compared with 14 C-serotonin release assay, another common assay for detecting antibody activity. Key features • This protocol can be used to assess platelet function and to detect platelet activating antibodies in diseases such as HIT and VITT. • Does not require radioactive reagents, requires an aggregometer; based on the light transmission aggregometry protocol, adapted for detection of VITT and other platelet-activating antibodies. • Two positive controls are required for reliable detection of antibodies in diseases such as HIT/VITT, namely a weak HIT/VITT antibody and a physiological agonist. • For detection of HIT/VITT antibodies, it is essential to use donors known to have platelets reactive to these antibodies to avoid false negative results., Competing Interests: Competing interestsThe authors of this manuscript declare that there are no conflicts of interest or competing interests., (©Copyright : © 2023 The Authors; This is an open access article under the CC BY-NC license.)