Resistance to activated protein C a novel risk factor for venous thrombosis

University dissertation from Dept for Coagulation Disorders, University Hospital, S-205 02 Malmö, Sweden

Abstract: Activated protein C resistance (APC resistance) is the most common hereditary condition associated with venous thrombosis. The syndrome known as APC resistance is perfectly linked to a mutation in the gene coding coagulation FV (FV:Q506) mutation changing Arg 506 to Gln in the APC cleavage site. APC-resistance is associated with a hypercoagulable state and life-long increased risk of thrombosis. APC resistance was found to be associated with venous thrombosis in approximately 45% of a large cohort of patients, and the mode of inheritance was confirmed to be autosomal dominant. The risk of thrombosis was shown to be 10-fold greater among APC-resistant family members than among non-APC-resistant family members, and survival analysis showed 50% of APC-resistant family members to have had their first thrombosis before the age of 50. Relationship was found to exist between the presence of APC resistance and the occurrence of thrombosis in 59% of cases of pregnancy-related thrombosis, and in 32% of cases of oral contraceptive-related thrombosis, as well as in 28% of consecutive outpatients with verified thrombosis, and in 38% of patients under 60 years of age. A modified APC-resistance test was shown to manifest almost 100% sensitivity and specificity for the FV:Q506 mutation, which means that it is suitable for screening purposes where high sensitivity and specificity are required. In patients undergoing elective hip arthroplasty, the risk of thrombosis was higher among carriers of FV:Q506 mutation than among non-carriers (41% vs. 23%). This risk was completely neutralized with prolonged anticoagulation treatment.

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