Do COVID-19 (Coronavirus Disease 2019) vaccines increase the risk of thrombosis (blood clots)?

COVID-19 Vaccines and Risk of Blood Clots

COVID-19 vaccines are associated with a rare but serious risk of vaccine-induced immune thrombocytopenia and thrombosis (VITT), primarily with adenoviral vector-based vaccines, while mRNA vaccines have not shown disproportionate reporting of thromboembolic events. 1

Types of Vaccine-Related Thrombotic Complications

Adenoviral Vector-Based Vaccines (AstraZeneca, Johnson & Johnson)

• VITT (Vaccine-Induced Immune Thrombocytopenia and Thrombosis):
  • Incidence: 14.9 cases per million after first dose, 1.8 cases per million after second dose 1
  • Timing: Symptoms begin 5-30 days post-vaccination 1
  • Pathophysiology: Caused by anti-platelet factor 4 (PF4) antibodies that lead to intense activation of platelets and coagulation system 1
  • Clinical presentation:
    • Severe or unusual headaches (most common)
    • New unexplained pinprick bruising or bleeding
    • Shortness of breath
    • Leg swelling
    • Persistent abdominal pain 1
  • Thrombosis characteristics:
    • Cerebral venous sinuses affected in 50% of cases
    • Any arterial or venous vascular bed may be involved
    • About one-third of patients have thrombosis in multiple sites 1

mRNA Vaccines (Pfizer-BioNTech, Moderna)

• No disproportional reporting of thromboembolic events compared to background rates 2
• In a US-based analysis of 13.6 million women aged ≤50 years who received mRNA vaccines, only 61 cases with 68 thromboembolic events were reported (1 case per 222,951 vaccinated) 2
• Comparative studies show lower risk compared to adenoviral vector vaccines 3

Diagnostic Approach for Suspected VITT

1. Clinical suspicion: Symptoms 5-30 days after adenoviral vector vaccination
2. Laboratory testing:
   • Recommended: Anti-PF4 enzyme immunoassays (Class 1 recommendation, Level B-NR) 1
   • Not recommended: Rapid heparin-induced thrombocytopenia assays such as particle gel immunoassay, lateral-flow assay, latex-enhanced immunoturbidimetric assay, or chemiluminescence immunoassay (Class 3: No benefit, Level B-NR) 1
3. Presumptive diagnosis when testing unavailable: High D-dimer, thrombocytopenia (<150,000/μL), and thrombosis occurring 5-30 days after adenoviral vector vaccination 1

Management of VITT

1. Anticoagulation:

   • Start non-heparin based anticoagulants as soon as possible 1
   • When non-heparin anticoagulants are unavailable, UFH or LMWH is reasonable (Class 2a recommendation, Level C-LD) 1

2. Immunomodulation:

   • Intravenous immunoglobulin may be considered for reducing risk of death (Class 2b recommendation, Level C-LD) 1

Important Clinical Considerations

Risk Stratification

• Higher risk in younger adults: Incidence rate in adults aged 18-49 years is twice that of adults ≥50 years after first dose 1
• Female predominance: 71.1% of reported cases are in females 4

Common Pitfalls to Avoid

1. Misattributing common post-vaccination symptoms to VITT:

   • Pain at injection site, fatigue, headache, and fever commonly occur immediately after vaccination and usually resolve within 2-3 days - these are NOT related to VITT 1

2. Delaying treatment:

   • Early recognition and treatment are critical as VITT can be life-threatening
   • Case fatality rate reported as high as 26.5% 4

3. Unnecessary prophylaxis:

   • For patients with thrombophilia who receive COVID-19 vaccines, prophylaxis with anticoagulants or antiplatelet agents is not recommended (Class 3: No benefit, Level B-NR) 1

4. Confusing VITT with other thrombocytopenic disorders:

   • Important to distinguish from antiphospholipid syndrome, thrombotic thrombocytopenic purpura, immune thrombocytopenic purpura, systemic lupus erythematosus, and hemophagocytic syndrome 5

Conclusion

While COVID-19 vaccines have been associated with thrombotic complications, these events are rare. The risk is primarily associated with adenoviral vector-based vaccines rather than mRNA vaccines. Healthcare providers should be aware of the symptoms of VITT, which typically occur 5-30 days after vaccination, and should initiate prompt diagnosis and treatment when suspected.