Examining the Evidence
Q Does acute infection raise the risk of venous thromboembolism?
<huc>A</huc> Yes. Acute urinary or respiratory tract infection is linked to a substantial but reversible increase in the risk of venous thromboembolism. The risk increased significantly in the first 2 weeks after acute infection and gradually returned to baseline over 12 months.
In this study, the incidence ratio for deep venous thrombosis (DVT) following urinary tract infection was 2.10 (95% confidence interval [CI] 1.56–2.82), and for respiratory tract infection, it was 2.86 (95% CI 2.05–3.97).
The incidence ratio for pulmonary embolism (PE) following urinary tract infection was 2.11 (95% CI 1.38–3.23). Although the risk of PE following respiratory tract infection was 11-fold higher, possible misdiagnosis of PE as a respiratory infection precluded reliable estimates of the precise risk.
Details of the study
The study assessed the risk of a first-ever DVT or PE after acute urinary tract infection or acute systemic respiratory infection, excluding pharyngitis and coryza.
Data were from the United Kingdom’s Health Improvement Network, which has complete diagnostic and prescribing information, and covered the years 1987 to 2004, or approximately 20 million person-years.
One strength was use of a self-controlled case series method, which allowed patients to serve as their own controls, thus eliminating variation among individuals in risk factors for venous thromboembolism.
Patients were observed for 12 months after an acute urinary or respiratory tract infection to determine whether a thromboembolic event had occurred. Incidence ratios and confidence intervals were calculated, and the study had adequate power at 5% significance to detect a 4-fold difference during the first 2 weeks after acute infections.
The exact mechanism of thrombosis is still unknown, and the possibility of a common pathway not linked to a specific infection is intriguing. Uncovering the mechanism could help us direct therapy to a particular biochemical process.
Virchow proposed his triad of precipitating factors 150 years ago: venous stasis, increased coagulability of the blood, and vessel wall damage.1 It now seems entirely plausible that damage to the vessel wall need not be physical damage, but could include factors, such as inflammation, that affect endothelial function. As the authors noted, “Inflammation is a key determinant of endothelial function in both arteries and veins, and a link between infection and venous thrombosis via endothelial activation has been suggested.” In fact, earlier studies already identified infection as a potential risk factor for venous thromboembolism.2,3
Thromboembolic events occur at a rate of about 0.5 cases per 1,000 person-years and cause considerable morbidity and mortality.
How long to continue prophylaxis?
The study by Smeeth and colleagues should help ObGyns determine the level of prophylaxis appropriate for hospitalized patients. Less clear is whether thromboprophylaxis should be offered to women who have acute infections in an ambulatory setting. Although earlier studies suggested that thromboprophylaxis may be appropriate, I believe the question of whether every patient should receive preventive therapy remains unanswered.
Another unresolved issue: If prophylaxis is initiated, how long should it continue? Because the risk of a thromboembolic event does not return to baseline levels for 1 year, the duration of therapy could be lengthy. At the same time, the risks of anticoagulation are not inconsequential and may increase with extended therapy. As the greatest risk occurs during the first 8 weeks after infection, prophylaxis is most beneficial during this time.
Given the data thus far, I do not believe therapy is warranted for every patient with an acute infection. Selective therapy may be justified.
1. Virchow RLK. Thrombosis and Emboli. Matzdorff AC, Bell WR, trans. Canton, Mass: Science History Publications; 1998.
2. Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med. 2000;160:3415-3420.
3. Alikhan R, Cohen AT, Combe S, et al. Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch Intern Med. 2004;164:963-968.