There are no risk models available yet that accurately predict a person's risk for developing venous thrombosis. Our aim was therefore to explore whether inclusion of established thrombosisassociated single nucleotide polymorphisms (SNPs) in a venous thrombosis risk model improves the risk prediction. We calculated genetic risk scores by counting risk-increasing alleles from 31 venous thrombosis-associated SNPs for subjects of a large case-control study,

See also Spencer FA, Goldberg RJ. Asymptomatic thrombophilia-a family affair. This issue, pp 457-8.Summary. Background: Reliable risk estimates for venous thrombosis in families with inherited thrombophilia are scarce but necessary for determining optimal screening and treatment policies. Objectives: In the present analysis, we determined the risk of a first venous thrombotic event in carriers of a thrombophilic defect (i.e. antithrombin-, protein C-or protein S deficiency, or factor V Leiden). Patients and methods: The asymptomatic carriers had been tested prior to this study in nine European thrombosis centers because of a symptomatic carrier in the family, and were followed prospectively for 5.7 years on average between March 1994 and January 2001. Annually, data were recorded on the occurrence of risk situations for venous thrombosis and events (e.g. venous thrombosis, death). Results: Twenty-six of the 575 asymptomatic carriers (4.5%) and seven of the 1118 controls (0.6%) experienced a first deep venous thrombosis or pulmonary embolism during follow-up. Of these events, 58% occurred spontaneously in the carriers compared with 43% in the controls. The incidence of first events was 0.8% per year (95% CI 0.5-1.2) in the carriers compared with 0.1% per year (95% CI 0.0-0.2) in the controls. The highest incidence was associated with antithrombin deficiency or combined defects, and the lowest incidence with factor V Leiden. Conclusions: The incidence of venous events in asymptomatic individuals from thrombophilic families does not exceed the risk of bleeding associated with long-term anticoagulant treatment in the literature (1-3%).

To cite this article: Brummel-Ziedins KE, Vossen CY, Butenas S, Mann KG, Rosendaal FR. Thrombin generation profiles in deep venous thrombosis.J Thromb Haemost 2005; 3: 2497-505.

Summary. Background and objectives: The range of plasma concentrations of hemostatic analytes in the population is wide. In this study these components of blood coagulation phenotype are integrated in an attempt to predict clinical risk. Methods: We modeled tissue factor (TF)-induced thrombin generation in the control population (N ¼ 473) from the Leiden Thrombophilia Study utilizing a numerical simulation model. Hypothetical thrombin generation curves were established by modeling pro-and anticoagulant factor levels for each individual. These curves were evaluated using parameters which describe the initiation, propagation and termination phases of thrombin generation, i.e. time to 10 nM thrombin (approximate clot time), total thrombin and the maximum rates and levels of thrombin generated. Results and conclusions: The time to 10 nM thrombin varied over a 3-fold range (2.9-9.5 min), maximum levels varied over a 4-fold range (200-800 nM), maximum rates varied 4.8-fold (90-435 nM min ) within this control population. Thrombin generation curves, defined by the clotting factor concentrations, were distinguished by sex, age, body mass index (BMI) and oral contraceptive (OC) use. Our results show that the capacity for thrombin generation in response to a TF challenge may represent a method to identify an individual's propensity for developing thrombosis.