Researchers evaluated the occurrence of venous thromboembolism (VTE) in patients with thrombophilia undergoing orthopedic surgery and identified factors associated with greater VTE risk. Findings were reported in the Journal of Thrombosis and Haemostasis.

Information on patient characteristics and outcomes was obtained from the population-based Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study conducted across 6 anticoagulation clinics in the Netherlands. The MEGA study was case controlled, and for this analysis 4721 cases and 5638 controls were reviewed.

Orthopedic surgery was performed in 263 (5.6%) of the cases and 94 (1.7%) of the controls from the MEGA study. The risk for VTE overall was nearly 4 times greater in the year before the study’s index date for anyone who had undergone an orthopedic surgery, compared with those who did not have surgery (adjusted odds ratio [aOR], 3.7; 95% CI, 2.9-4.8).

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Deep vein thrombosis showed the highest level of risk with surgery, being increased by approximately 14-fold in the first 90 days after surgery (aOR, 13.9; 95% CI, 8.8-21.8). The risk for pulmonary embolism was increased approximately 8-fold in the first 90 days following surgery (aOR, 7.9; 95% CI, 4.8-13.0). Risks with both were also elevated over the course of the first year after surgery. VTE risk was elevated with multiple types of orthopedic surgery, but it was greatest with knee surgery.

Risks for VTE with surgery and in the context of thrombophilic factors were examined for 4096 cases and 4418 controls who had been evaluated for thrombophilia. Patients with thrombophilia who underwent orthopedic surgery had a nearly 6-fold increased risk for VTE (OR, 5.8; 95% CI, 3.7-9.1), while patients with thrombophilia who did not undergo surgery had an almost 4-fold elevated risk for VTE (OR, 3.6; 95% CI, 3.1-4.0).

Certain factors were associated with greater risks for VTE in patients undergoing surgery compared with patients who did not undergo surgery. These included elevated factor VIII plasma levels (aOR, 18.6; 95% CI, 7.4-46.9), factor V Leiden (aOR, 17.5; 95% CI, 4.1-73.6), and presence of a non-O blood type (aOR, 11.2; 95% CI, 3.4-34.0).

Presence of 1 or more thrombophilic factors was associated with an approximately 13-fold elevated VTE risk with surgery, vs absence of surgery (OR, 13.3; 95% CI, 7.2-24.7). This relative VTE risk of 13.3 translated into an estimated absolute VTE risk of 3.5% within 1 year, or an incidence of 34.6/1000 person-years, for patients with thrombophilia who undergo orthopedic surgery. Without thrombophilia, the absolute VTE risk was estimated to be 1.0% within 1 year following orthopedic surgery.

“In conclusion, we showed a high risk of VTE in patients with factor V Leiden, high levels of factor VIII, or non-O blood group undergoing orthopedic surgery,” wrote the researchers in their report. They continued, “[t]hese data can be used to identify high-risk patients for whom a tailored thromboprophylactic strategy may be needed.”


Zambelli R, Nemeth B, Touw CE, Rosendaal FR, Rezende SM, Cannegieter SC. High risk of venous thromboembolism after orthopedic surgery in patients with thrombophilia. J Thromb Haemost. Published online November 10, 2020. doi:10.1111/jth.15163