Thrombophilia gene mutations predict venous thromboembolism in ambulatory cancer patients receiving chemotherapy

Background: Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear.

Objectives: Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy.

Methods: We conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated.

Results: Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding.

Conclusion: Our results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.