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SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia

THROMBOSIS RESEARCH (2022)

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Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia

Andreas Greinacher et al.

Summary: The mechanism underlying vaccine-induced immune thrombotic thrombocytopenia (VITT) primarily involves the formation of PF4/vaccine complexes and the proinflammatory environment stimulated by the vaccine, leading to the production of high-titer anti-PF4 antibodies in the body and consequent thrombosis.

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Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines A Systematic Review and Meta-analysis

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Prothrombotic immune thrombocytopenia after COVID-19 vaccination

Andreas Tiede et al.

Summary: This study reports 5 cases of prothrombotic immune thrombocytopenia following vaccination with AZD1222. Patients presented with various clinical manifestations, including thrombocytopenia and elevated D-dimer levels. Treatment experience suggests that anticoagulation may be effective, but there is also a risk of unusual and severe thromboembolic events.

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Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

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Summary: This study found that patients with cerebral venous sinus thrombosis after COVID-19 vaccination who met the criteria for TTS had distinct clinical characteristics, high prevalence, and high mortality rates.

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US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021

Isaac See et al.

Summary: Cases of CVST with thrombocytopenia following Ad26.COV2.S vaccination have been reported in the US, leading to serious outcomes. This case series may provide guidance for clinical management and further investigation into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

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An observational study to identify the prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in Norwegian health care workers after COVID-19 vaccination

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Summary: This study investigated the prevalence of thrombocytopenia and anti-PF4/polyanion antibodies in a population recently vaccinated with AZD1222. The results showed a low prevalence of both conditions among Norwegian health care workers after vaccination with AZD1222, with the majority of participants having normal platelet counts and negative immunoassay results.

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Article Hematology

Recommendations for the clinical and laboratory diagnosis of VITT against COVID-19: Communication from the ISTH SSC Subcommittee on Platelet Immunology

Ishac Nazy et al.

Summary: Vaccine administration is ongoing worldwide to combat the COVID-19 pandemic, with newly developed vaccines showing high effectiveness but concerns over rare thrombotic events associated with the AstraZeneca ChadOx1 nCov-19 vaccine. The ISTH SSC Subcommittee on Platelet Immunology has outlined guidelines on how to recognize, diagnose, and manage patients with VITT, which presents clinically and pathologically similar to heparin-induced thrombocytopenia.

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Vaccine-induced immune thrombotic thrombocytopenia: Consider IVIG batch in the treatment

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Nina H. Schultz et al.

Summary: This study reports five cases of venous thrombosis and thrombocytopenia occurring 7 to 10 days after receiving the ChAdOx1 nCoV-19 vaccine, suggesting a rare vaccine-induced immune thrombotic thrombocytopenia. The condition, which can lead to catastrophic outcomes such as cerebral venous sinus thrombosis, may be treated with intravenous immune globulin.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

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Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

Andreas Greinacher et al.

Summary: After vaccination with ChAdOx1 nCov-19, rare immune thrombotic thrombocytopenia can occur due to platelet-activating antibodies against PF4, resulting in various thrombotic events. Most patients in this case series were women, with fatal outcomes such as cerebral venous thrombosis and intracranial hemorrhage. Additional studies are needed to further investigate and understand this phenomenon.

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Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): Targeting Pathomechanisms with Bruton Tyrosine Kinase Inhibitors

Philipp von Hundelshausen et al.

Summary: Rare thromboembolic incidents following COVID-19 vaccination have led to temporary suspensions. A pathomechanism involving platelet-activating antibodies has been identified, with proposed treatments including high-dose IV immunoglobulin G and Btk inhibitors. This emergency repurposing of approved drugs in COVID-19 may provide a safe option for treating VITT.

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Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients — United States, April 2021

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Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine Reported to EudraVigilance Database

Mansour Tobaiqy et al.

Summary: The development of safe and effective vaccines against COVID-19 is crucial in the fight against the pandemic. Although some thrombotic adverse reactions were associated with the Oxford-AstraZeneca vaccine, the European Medicines Agency affirmed the vaccine's safety and effectiveness, with the benefits outweighing the risks. Conducting further analyses based on more detailed thrombotic adverse event reports may help evaluate causality with higher specificity.

VACCINES (2021)

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Article Hematology

Anti-Platelet Factor 4 Antibodies Causing VITT do not Cross-React with SARS-CoV-2 Spike Protein

Andreas Greinacher et al.

BLOOD (2021)

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Article Cardiac & Cardiovascular Systems

Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia

Sverre Holm et al.

Summary: The study revealed that the formation of thrombus in VITT patients is associated with massive innate immune activation, particularly the activation of neutrophils including NETosis. These findings suggest a potential relationship between VITT pathogenesis and abnormal immune response.

EUROPEAN HEART JOURNAL (2021)

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Thrombosis with Thrombocytopenia Syndrome associated with viral vector COVID-19 vaccines

Marco Cattaneo

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Kiran T. Thakur et al.

Summary: This study conducted a collaborative review among a global group of expert neurologists and hematologists to identify strategies for rapid evaluation and treatment of CVT in the context of potential VITT, including measurements of inflammatory markers, PF4 assays, and non-heparin anticoagulation.

JOURNAL OF THE NEUROLOGICAL SCIENCES (2021)

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Article Medicine, General & Internal

Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study

Richard J. Perry et al.

Summary: The study documented cases of cerebral venous thrombosis after COVID-19 vaccination, finding that patients with VITT were younger, had more intracranial and extracranial thrombosis, and experienced worse outcomes compared to non-VITT patients. Treatments with non-heparin anticoagulants and intravenous immunoglobulin may improve outcomes in VITT-associated cerebral venous thrombosis.

LANCET (2021)

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Article Multidisciplinary Sciences

Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia

Angela Huynh et al.

Summary: Alanine-scanning mutagenesis is used to identify the PF4 epitope that is recognized by anti-PF4 antibodies in patients with vaccine-induced immune thrombotic thrombocytopaenia, revealing that the epitope corresponds to the heparin-binding site on PF4. VITT anti-PF4 antibodies show stronger binding response compared to HIT anti-PF4 antibodies, potentially contributing to platelet activation and thrombosis by mimicking the effect of heparin binding on PF4. The findings suggest a potential mechanism for VITT development related to immune complexes formation and platelet activation via Fc gamma receptor IIa.

NATURE (2021)

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Article Medicine, General & Internal

Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis

Sue Pavord et al.

Summary: Phenotypes of VITT were defined in 220 patients in the United Kingdom who presented a median of 14 days after the first ChAdOx1 nCoV-19 vaccination. Half had cerebral venous sinus thrombosis, a third of whom also had intracranial hemorrhage. Mortality was 22%. Intravenous immune globulin may reverse VITT.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Letter Medicine, General & Internal

Vaccine-Induced Thrombocytopenia with Severe Headache

Farid Salih et al.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Letter Medicine, General & Internal

Therapeutic Plasma Exchange in Vaccine-Induced Immune Thrombotic Thrombocytopenia

Christopher J. Patriquin et al.

Summary: Therapeutic plasma exchange was effective in treating refractory VITT in three patients, who showed poor response to initial therapy with anticoagulants and intravenous immune globulin. Their conditions improved and they were discharged from the hospital after the treatment.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Letter Medicine, General & Internal

Decline in Pathogenic Antibodies over Time in VITT

Linda Schoenborn et al.

Summary: The study found that pathogenic antibodies in VITT patients decreased after receiving adenoviral vector Covid-19 vaccines, with improvements in platelet activation despite persistent positivity on ELISA. Additionally, 5 patients received additional vaccination without any sequelae.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Medicine, General & Internal

Adjunct Immune Globulin for Vaccine-Induced Immune Thrombotic Thrombocytopenia

Alex Bourguignon et al.

Summary: High-dose intravenous immune globulin (IVIG) combined with anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), showing a good response in reducing antibody-induced platelet activation, particularly in cases of VITT induced by ChAdOx1 nCoV-19 vaccine.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Editorial Material Clinical Neurology

Cerebral Vein Thrombosis With Vaccine-Induced Immune Thrombotic Thrombocytopenia

James E. Siegler et al.

Summary: In the spring of 2021, rare cases of venous thrombosis linked to ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to temporary suspensions in some countries. These events were associated with thrombocytopenia and anti-PF4 antibodies, resulting in vaccine-induced immune thrombotic thrombocytopenia.

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Review Biochemistry & Molecular Biology

Coagulopathies after Vaccination against SARS-CoV-2 May Be Derived from a Combined Effect of SARS-CoV-2 Spike Protein and Adenovirus Vector-Triggered Signaling Pathways

Ralf Kircheis

Summary: The global pandemic of the novel coronavirus has led to the approval and application of various vaccines, but some rare blood clot side effects have been reported, potentially correlated with interactions between vaccine components and the immune system.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Medicine, General & Internal

Adjunct Immune Globulin for Vaccine-Induced Immune Thrombotic Thrombocytopenia

Alex Bourguignon et al.

Summary: The use of high-dose IVIG plus anticoagulation is recommended for the treatment of VITT, a rare side effect of adenoviral vector vaccines against Covid-19. Response to IVIG therapy in VITT patients showed reduced platelet activation and improvement in symptoms.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Clinical Neurology

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Suzanne M. Silvis et al.

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IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia

Anand Padmanabhan et al.

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Polyphosphate/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia

Douglas B. Cines et al.

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Theodore E. Warkentin et al.

AMERICAN JOURNAL OF MEDICINE (2008)

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