Influenza‑Associated Venous Thromboembolism Risk and Management

Risk Magnitude

Severe viral pneumonias such as influenza H1N1 are associated with an 18‑ to 23‑fold higher incidence of VTE compared with patients without severe infection (observational cohort data) 1, 2.
This multi‑fold increase applies specifically to severe influenza‑related pneumonia and acute respiratory syndromes (prospective/retrospective analyses) 3, 4, 5.
In patients with influenza H1N1‑related ARDS, therapeutic anticoagulation reduced VTE events by roughly 33‑fold relative to standard prophylactic dosing (comparative cohort study) 3, 4, 5.

All hospitalized individuals with influenza‑associated pneumonia should be regarded as high‑risk for VTE and assessed for thromboprophylaxis (expert consensus) 3, 1.
The VTE risk is particularly elevated in intensive‑care settings, in those with severe pneumonia, and in patients experiencing respiratory failure (ICU‑based cohort) 3, 4, 5.
Clinicians should suspect VTE in influenza patients who develop unexplained worsening of respiration, markedly elevated D‑dimer (> 6 × upper limit of normal), or acute limb symptoms (clinical observation) 3.

Universal pharmacologic thromboprophylaxis with low‑molecular‑weight heparin (LMWH) or unfractionated heparin (UFH) is advised for all hospitalized patients with severe influenza pneumonia, unless absolute contraindications exist (guideline‑type recommendation) 1.
Standard‑dose prophylaxis is appropriate for non‑ICU patients, while intermediate‑dose LMWH may be considered for critically ill patients (dose‑adjustment guidance) 3, 1.

Objective imaging (CT pulmonary angiography, ventilation‑perfusion scan, or Doppler ultrasound) should be employed based on clinical suspicion rather than routine screening (diagnostic algorithm) 1, 2.
Routine screening using D‑dimer levels or ultrasound in asymptomatic hospitalized influenza patients is not recommended (negative recommendation) 1.

The endothelial injury, inflammatory cascade activation, and pro‑coagulant state observed with influenza A (including H1N1) also apply to severe influenza B infections, supporting a common mechanistic basis for VTE risk (biological plausibility) 3, 1, 4, 5.

VTE risk is greatest in patients with severe influenza pneumonia requiring hospitalization, especially those admitted to the ICU or developing ARDS (severity‑stratified data) 3, 4, 5.
Out‑patient individuals with mild influenza are presumed to have minimal additional VTE risk (implicit from lack of data).

The European Society of Cardiology considers pneumonia a moderate risk factor for venous thromboembolism (VTE), with an odds ratio of 2-9 6

The standard diagnostic tests (CT pulmonary angiography, V/Q scintigraphy, Doppler ultrasound) should be used to diagnose VTE based on clinical suspicion, as recommended by guidelines from the Journal of Thrombosis and Haemostasis 7, 8
Routine screening for VTE using Doppler ultrasound of the lower extremities or based on elevated D-dimer levels is not recommended, according to the Journal of Thrombosis and Haemostasis 7, 8

Universal thromboprophylaxis should be considered in hospitalized patients with severe pneumonia, especially in the ICU, due to the increased risk of VTE, as suggested by the Journal of Thrombosis and Haemostasis 9, 10

Patients with severe COVID-19 pneumonia are at particularly high risk of VTE, with an incidence of up to 27% (95% CI: 17-37) in some studies, according to the Journal of Thrombosis and Haemostasis 8, 11
This risk is consistent with high rates of VTE in patients with other severe viral pneumonias, such as influenza H1N1, who had an 18-23 times higher risk of VTE compared to control patients, as reported by the Journal of Thrombosis and Haemostasis 9