Abstract

The thrombotic thrombocytopenia syndrome (TTS), a complication of COVID-19 vaccines, involves thrombosis (often cerebral venous sinus thrombosis) and thrombocytopenia with occasional pulmonary embolism and arterial ischemia. TTS appears to mostly affect females aged between 20 and 50 years old, with no predisposing risk factors conclusively identified so far. Cases are characterized by thrombocytopenia, higher levels of D-dimers than commonly observed in venous thromboembolic events, inexplicably low fibrinogen levels and worsening thrombosis. Hyper fibrinolysis associated with bleeding can also occur. Antibodies that bind platelet factor 4, similar to those associated with heparin-induced thrombocytopenia, have also been identified but in the absence of patient exposure to heparin treatment. A number of countries have now suspended the use of adenovirus-vectored vaccines for younger individuals. The prevailing opinion of most experts is that the risk of developing COVID-19 disease, including thrombosis, far exceeds the extremely low risk of TTS associated with highly efficacious vaccines. Mass vaccination should continue but with caution. Vaccines that are more likely to cause TTS (e.g., Vaxzevria manufactured by AstraZeneca) should be avoided in younger patients for whom an alternative vaccine is available.

Highlights

  • A new deadly virus of the coronavirus family was first identified in December 2019 and named SARS-2-CoV-2; this virus caused severe acute respiratory syndrome and is known as COVID-19

  • Further evidence comes from Scotland which has seen deaths from COVID-19 falling in all locations, with the fastest decreases occurring in long-term care homes where deaths fell by 62% in the three weeks leading to 14 February 2021, approaching a level last observed near the end of October 2020

  • thrombocytopenia syndrome (TTS) is an extremely rare but increasingly recognized serious adverse event related to unusual sites of thromboembolism, such as cerebral venous sinus thrombosis (CVST) or abdominal thromboses, all of which are associated with thrombocytopenia

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Summary

Background

A new deadly virus of the coronavirus family was first identified in December 2019 and named SARS-2-CoV-2; this virus caused severe acute respiratory syndrome and is known as COVID-19. Patients presented with variable symptoms, ranging from asymptomatic carriers to life-threatening/changing consequences. Rare but life-threatening events such as thrombosis with thrombocytopenia syndrome (TTS) ( called VITT—vaccine induced thrombocytopenia and thrombosis) have been reported with some COVID-19 vaccines. Recent reviews of TTS following COVID-19 vaccinations have not included clinical management guidelines [1,2]. To this end, this review summarizes the available data on the pathophysiology of COVID-19 and thrombosis, the different types of vaccines used to prevent COVID-19, the proposed mechanisms of TTS and some clinical management recommendations

COVID-19 and Thrombosis
Vaccinations
Vaccines and Serious Adverse Events
Thrombosis with Thrombocytopenia Syndrome
Possible Pathophysiology of TTS
Heparin Induced Thrombocytopenia with Thrombosis
Prevalence of Platelet Factor 4 Antibody in the General Population
Microangiopathic Haemolytic Anaemia
Disseminated Intravascular Coagulopathy
10. Thrombocytopenia following Vaccine Administration in Children
11. Post COVID-19 Syndrome and Risk of Thrombosis
12. Current Management Recommendations
13. Evolving Clinical and Laboratories Studies
15. Conclusions
Findings
18. Covid-19
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