Can viruses increase the risk of bleeding?

Can Viruses Increase Bleeding Risk?

Yes, viral infections can increase bleeding risk through multiple mechanisms, including direct effects on hemostasis, immune-mediated thrombocytopenia, disseminated intravascular coagulation (DIC), and hepatocellular injury affecting coagulation factor production. 1, 2

Mechanisms of Virus-Associated Bleeding

Viral infections affect all aspects of the coagulation cascade—primary hemostasis, coagulation, and fibrinolysis—leading to hemorrhagic complications through several pathways 1:

• Immune-mediated thrombocytopenia is a common mechanism where viruses trigger immune destruction of platelets, manifesting as thrombocytopenic purpura 2
• Disseminated intravascular coagulation (DIC) occurs in severe viral infections, consuming clotting factors and platelets while generating microthrombi 2
• Hepatocellular injury from hepatitis viruses decreases production of multiple coagulation factors and impairs hepatic modulation of hemostasis 2
• Direct endothelial damage and inflammatory responses alter the balance between pro-thrombotic and pro-hemorrhagic states 1

COVID-19 Specific Bleeding Risk

Baseline Bleeding Incidence

In COVID-19 patients, the pooled incidence of bleeding is 7.8% for all types of bleeding and 3.9% for major bleeding, with no clear difference between critically ill and ward patients 3. In ICU cohorts, major bleeding rates reach 14.8%, though this risk does not differ significantly from other severe viral infections (HR 1.26; 95% CI 0.86-1.86) 3.

Temporal Pattern of Bleeding Risk

A critical temporal relationship exists between thrombotic and hemorrhagic risks in COVID-19 3:

• Thrombotic events occur at a median of 7.0 days (5.9-8.2 days) after hospital admission 3
• Hemorrhagic events occur later at a median of 11.4 days (8.6-14.1 days) after admission 3
• This pattern reflects initial hypercoagulability with increased thrombin generation and decreased fibrinolysis during the first week, followed by gradual normalization and increased bleeding risk 3

Risk Factors for Major Bleeding in COVID-19

Specific predictors of major bleeding in hospitalized COVID-19 patients include 4:

• D-dimer levels >10 times the upper normal range (HR 2.23; 95% CI 1.38-3.59) 4
• Ferritin levels >500 ng/ml (HR 2.01; 95% CI 1.02-3.95) 4
• Critical illness/ICU admission (HR 1.91; 95% CI 1.14-3.18) 4
• Therapeutic-intensity anticoagulation (HR 1.43; 95% CI 1.01-1.97) 4
• Higher HAS-BLED scores correlate with increased GI bleeding risk and transfusion requirements 5

Anticoagulation-Related Bleeding

The use of anticoagulation for thromboprophylaxis in COVID-19 increases bleeding risk 3:

• Postdischarge prophylactic-intensity anticoagulation may increase major bleeding risk (relative risk 2.09; 95% CI 1.33-3.27), corresponding to 4-13 more major bleeding episodes per 1000 patients depending on baseline risk 3
• Among hospitalized patients receiving intermediate or therapeutic-dose anticoagulation, 5.7% developed major bleeding with a 30-day mortality rate of 45% 4
• The risk of major bleeding was 3% in anticoagulated versus 1.9% in non-anticoagulated patients 3

Clinical Implications

Risk Stratification

Clinicians should assess bleeding risk using validated tools and COVID-19-specific markers 5:

• Calculate HAS-BLED scores (excluding alcohol/drug components if data unavailable) to stratify GI bleeding risk 5
• Monitor D-dimers, ferritin, platelet count, prothrombin time, and fibrinogen to identify high-risk patients 3
• Recognize that DIC is associated with increased bleeding risk and should prompt dose reduction of anticoagulation 3

Monitoring Strategy

For critically ill COVID-19 patients, implement sequential monitoring 3:

• Monitor D-dimers every 24-48 hours during the first 7-10 days when thrombotic risk predominates 3
• Monitor platelet count, prothrombin time, and fibrinogen every 24-72 hours in the acute phase 3
• Consider sequential anticoagulation strategy: increased prophylaxis for 7-10 days, then decreased to standard dose as bleeding risk increases 3

Common Pitfalls

• Avoid therapeutic-dose anticoagulation in unselected patients as bleeding complications may outweigh benefits, particularly given the temporal shift from thrombotic to hemorrhagic risk 3
• Do not ignore elevated inflammatory markers (D-dimer >10x ULN, ferritin >500 ng/ml) as these strongly predict major bleeding 4
• Recognize that critically ill COVID-19 patients are at high risk for both thrombosis AND bleeding, making risk-benefit assessment challenging without individualized evaluation 3