This article is presented by Firstline, a point of care tool for infectious diseases.

Last updated: May 25, 2021

Since early March of 2021, a global pharmacovigilance initiative has been underway to better understand rare cases of thrombosis with thrombocytopenia correlated with the AstraZeneca and Johnson & Johnson COVID-19 Vaccines. The majority of pharmacovigilance data will be related to the AstraZeneca COVID-19 vaccine and this blog will focus on published and regulatory reported evidence that has grown regarding Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT).

Brief Overview of Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)

VITT type blood clots are a rare adverse event following administration of COVID-19 vaccines that use the adenoviral vector including the AstraZeneca/COVISHIELD as well as the Johnson & Johnson vaccines.1 These clots are aggressive and are more likely to result in morbidity, disability and death than commonly diagnosed venous thromboembolic events.1 Please see The AstraZeneca COVID-19 Vaccine and Thrombosis: What You Should Know blog for information regarding an overview of these types of clots as well as timeline covering until the end of April 2021.

Prevalence of VITT after AstraZeneca/COVISHIELD and Johnson & Johnson COVID-19 Vaccines: Global

AstraZeneca Data

In Germany as of March 29th 2021, a total of 19 cases of VITT were reported out of 2.2 million doses (incidence of 1:116,000).2 In the UK as of April 7th 2021, 79 VITT cases have been reported out of a total of 20.2 million doses (incidence of 1:250 000).2 A report out of Norway found 5 cases of VITT out of more than 130,000 (incidence of 1:26,000).3

Currently the prevalence of VITT varies by pharmacovigilance database with the Ontario Science Table noting that the incidence is from 1 case per every 26,000 to 1 case per 127,000 doses administered of the AstraZeneca/COVISHIELD vaccines1 and another recently published review notes the incidence could range from approximately 1 in 250,000 to 1 in 1 million of vaccinated cases after the first dose.2

Johnson & Johnson Data

In the USA as of April 21st a total of 7.89 million doses of the Johnson & Johnson COVID-19 vaccine had been administered and 15 cases of VITT (or alternately named Thrombosis with Thrombocytopenia Syndrome (TTS) in the USA) had been reported according to a CDC Morbidity and Mortality Weekly Report to the Vaccine Event Reporting System (VAERS) database.4

Prevalence of VITT after First Dose of the AstraZeneca COVID-19 Vaccine: Canada

According to the Ontario Science Table1 and the National Advisory Committee on Immunization (NACI),5 the rate of VITT in Canada has been estimated to be approximately 1 in every 100,000 doses administered. With respect to general prevalence of an adverse event following immunization (AEFI) as defined by Health Canada,6 this adverse event is occurring in less than 0.01% of individuals based on the ranges noted above and by definition is considered very rare.

In Canada, as of May 14, 2021 there have been 2 194,754 doses of the AstraZeneca/ COVISHEILD vaccines administered and of these there have been 22 reported cases of VITT after AstraZeneca/ COVISHEILD doses administered. This results in an incidence of 1/100,000 doses. Symptom onset has ranged from 4 to 28 days after vaccination with a reported date range in Canada of 6 to 24 days after vaccination.1

The changing prevalence of VITT in Canada overtime from 1/250,000 to 1/100,000 is based on improved understanding and awareness of this AEFI and the fact that the adverse outcome takes days to develop; therefore, in order to gain a better understanding of prevalence, the total number of doses administered today would need to be correlated to the total number of VITT cases in 28 days time.

Current Canadian NACI guidance estimates a mortality rate of between 20 to 40% for all individuals who have VITT. This may change over time with increased recognition and treatment of VITT cases.5

Prevalence of VITT after Second Dose of the AstraZeneca/COVISHIELD COVID-19 Vaccine

According to data from the UK, the risk of VITT after the second dose appears to be 1 in 600,000 vaccinations and as of May 21, 2021 the Ontario government is resuming second dose administration of the AstraZeneca COVID-19 vaccine for those who received their first dose between March 10th and March 19th 2021.

Are There Predisposing Factors to VITT?

There are no clear correlations of specific patient factors that predispose to VITT. When VITT was first reported, the predominance was in young females, however this may have been due to an overrepresentation of the population in reporting countries after vaccination initiatives that focused on health care workers, who are predominantly female.1

Are there Contraindications to the Viral Vector Vaccines in Canada?

Although there are currently no contraindications to the viral vector vaccines, the product monograph for the AstraZeneca and COVISHIELD vaccines in Canada notes that individuals with previous CVST or heparin induced thrombocytopenia (HIT) should only receive the viral vector vaccines if the potential benefit significantly outweighs potential risk. This would suggest that a discussion with the individual’s primary care provider or specialist is merited to allow for an informed decision to be made.

How is VITT Treated?

In Canada, the Ontario Science Table1 provides fantastic guidance for treating presumed VITT and suggests a similar treatment approach to HIT. Until VITT is ruled out, the recommendation is to avoid anticoagulation with heparinoids (unfractionated heparin and low molecular weight heparin) and avoid platelet transfusion. First-line anticoagulants suggested are the direct oral factor Xa inhibitors including apixaban and rivaroxaban and administration of IVIG 1g/kg of actual body weight for at least 2 days is recommended (confirmation using a HIT ELISA assay is suggested prior to IVIG). Consultation with hematology is strongly recommended to discuss treatment, HIT ELISA testing and functional testing.

In the USA, the American Society of Hematology has created a resource for VITT or Thrombosis with Thrombocytopenia Syndrome (TTS) that includes requirements for diagnosis, incidence, signs and symptoms indicating urgent need for medical evaluation, as well as diagnostic and treatment alternatives.7 This guidance notes that an individual who presents with thrombosis that meets the criteria for diagnosis but has a normal platelet count may be in early stages of TTS therefore continued assessment and use of non-heparinoid anticoagulation may be indicated.

As the understanding of VITT evolves over time, prevalence and treatment algorithms may also change. The primary objective of this global pharmacovigilance process is to continue to monitor vaccine safety and inform public health policy around the world amidst the COVID-19 pandemic.

Biographies:

Dr. Mira Maximos (PharmD) completed a hospital pharmacy residency at London Health Sciences Centre concomitantly with a Master of Science in Pharmacy and went on to pursue a Doctor of Pharmacy degree at the University of Waterloo. Dr. Maximos works at Woodstock Hospital in Ontario as the Antimicrobial Stewardship Pharmacy Lead, with @firstline as the Knowledge Mobilization pharmacist. Dr. Maximos lectures at the University of Waterloo in areas such as drug induced disease and infectious diseases in the elderly.

Conflicts of Interest: Mira Maximos is employed with Firstline Mobile Health as a Knowledge Mobilization pharmacist

This blog post is for information/educational purposes only, and does not substitute professional medical advice. Also please note that opinions are those of the authors and do not necessarily reflect that of their employers.

References:

  1. Pai M, Chan B, Stall NM, et al. Vaccine-induced immune thrombotic thrombocytopenia (VITT) following adenovirus vector COVID-19 vaccination. Science Briefs of the Ontario COVID-19 Science Advisory Table. 2021;2(17). (Accessed May 20, 2021) ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  2. Franchini M, Liumbruno GM, Pezzo M. COVID-19 Vaccine-associated Immune Thrombosis and Thrombocytopenia (VITT): diagnostic and therapeutic recommendations for a new syndrome. Eur J Haematol. Published online May 2021. ↩ ↩2 ↩3

  3. Schultz NH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, Wiedmann M, Aamodt AH, Skattør TH, Tjønnfjord GE, Holme PA. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. N Engl J Med. 2021 Apr 9:NEJMoa2104882. ↩

  4. MacNeil JR, Su JR, Broder KR, et al. 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. MMWR Morb Mortal Wkly Rep. 2021;70(17):651-656. (Accessed May 21, 2021). ↩

  5. National Advisory Committee on Immunization (NACI). An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI): Recommendations on the use of COVID-19 Vaccines. Published online 2021:1-106. (Accessed May 19, 2021) ↩ ↩2

  6. Vaccine safety and pharmacovigilance: Canadian Immunization Guide. Public Health Agency of Canada. Government of Canada. Last revised December 2019. (Accessed May 19, 2021). ↩

  7. American Society of Hematology Resource on Thrombosis with Thrombocytopenia Syndrome (also termed Vaccine-Induced Thrombotic Thrombocytopenia). ↩