OC-14 Pregnancy related thrombosis risk in patients with protein C deficiency

Background: Venous thrombosis (VT) continues to be one of the leading causes of maternal morbidity and mortality in countries with good perinatal care. The incidence of pregnancy related VT is approximately 1 per 1000 pregnancies. Major complications from VT are post-thrombotic syndrome and death from pulmonary embolism. Limited data exist on thrombophilia and the risk of VT during pregnancy and postpartum, and further, whether biomarkers associated with VT are associated with different risk for deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods: The present study is a substudy of the Venous Thromboembolism in Pregnancy (VIP) study. 313 cases with objectively verified first time VT and 353 controls were selected from a source population of 377155 women with 613232 pregnancies. When we analyzed phenotypic hemostatic parameters, women with conditions known to influence coagulation parameters were excluded. Furthermore, women diagnosed with VT at unusual sites were excluded when we analyzed the risk for DVT and PE. Percentiles were defined in controls. Results: The odds ratios (ORs) for pregnancy related VTwas increased for women with factor VIII and factor IX above the 90th percentile, ORs 1.9; 95% CI 1.2-3.1 and 2.1; 95% CI 1.3-3.4, respectively. ORs for VT for endogenous thrombin potential and D-dimer values above the 90th percentile were 2.1; 95% CI 1.3-3.3 and 2.3; 95% CI 1.4-3.7, respectively. Women with low levels of protein S had increased risk for PE, ORs 2.1; 95% CI 1.1-4.3. Low levels of protein S were not associated with DVT. Similarly, high levels of fibrinogen were associated with PE, OR 2.5; 95% CI 1.3-4.9, whereas the risk for DVT as compared with controls was not increased. Women carrying factor V Leiden polymorphism (F5 rs6025) had increased risk for DVT, OR 7.7; 95% CI 4.7-12.7, whereas the risk for PEwas not increased. Analyzing only non-carriers of F5 rs6025, reduced sensitivity to activated protein C (aPC) was associated with increased risk for DVT, OR 3.5; 95% CI 2.2-5.4, whereas the risk for pulmonary embolism was not increased. Comment: Women with a history of pregnancy related VT showed activation of coagulation and had elevated factor VIII and IX. Furthermore, reduced sensitivity to aPC in absence of F5 rs6025, or carrying F5 rs6025 were risk factors for DVT, but not for PE, whereas high levels offibrinogen and low levels of free protein Swere associated with increased risk for PE, but not for DVT.