Contribution of factor V deficiency to the thrombotic risk associated with factor V HR2

Abstract number: P1026

Faioni^* E. M., Castaman† G., Asti‡ D., Lussana^* F., Rodeghiero† F.

^*Hematology and Thrombosis Unit, Ospedale San Paolo, Italy; †Hematology Division, San Bortolo Hospital, Vicenza, Italy; ‡Hemophilia and Thrombosis Center, Ospedale Maggiori, Italy

Background  

Factor V HR2 possesses decreased cofactor activity to activated protein C, and an increased ratio of factor V1 to factor V2. Increased resistance to activated protein C (APC) and reduced factor V concentration have also been associated with HR2. According to some studies HR2 confers an increased, though mild, risk of venous thromboembolism (VTE). Inconsistency in the results of the epidemiological studies on HR2 possibly stems from failure to identify other variables which, when present together with HR2, may lead to an increased risk of thrombosis. Candidate variables are other factor V defects.

Aim of the study  

To establish if factor V deficiency concurs to the risk of venous thromboembolism when associated with HR2.

Methods  

Four hundred and ninety-seven patients with venous thromboembolism (median age 47 years, range 15–78, 296 women, 201 men) and 498 controls with no thrombosis (median age 46 years, range 16–84, 278 women, 220 men) were enrolled in two Thrombosis Centers in Italy during 1 year. Laboratory tests included: anti-thrombin, protein C, protein S, factor V Leiden, prothrombin 20210A, resistance to APC, HR2, factor V (in carriers of HR2). The risk of developing venous thromboembolism was estimated as odds ratio (OR).

Results  

HR2 was present in 12.5% of patients and 10.4% of controls. Factor V deficiency was associated with HR2 in 4.8% of patients and 1.0% of controls. OR for HR2 alone was 1.2 (95%CI 0.8–1.7), while it was 4.5 (95%CI 1.7–11.8) for HR2 plus factor V deficiency and it remained statistically significant even after taking into account all other prothrombotic defects by logistic regression. Patients with HR2 and factor V deficiency developed a thrombotic event earlier (median age 35 years) than patients with HR2 alone (median age 43 years, P = 0.018). Factor V Leiden was associated with HR2 in 2.4% of patients and none of the controls. Normalized ratios of APC resistance were lower in carriers of HR2 than in non carriers (0.97 vs. 1.00, P = 0.045), and more so in patients (normalized ratio 0.94) than in controls (1.03, P = 0.003), independently of factor V Leiden or factor V levels.

Conclusions  

Double heterozygosity for HR2 and a factor V defect, including factor V deficiency, increases the thrombotic risk afforded by HR2.