Inherited resistance to activated protein C caused by presence of the FV:Q506 allele as a basis of venous thrombosis.
Inherited resistance to activated protein C (APC) was recently discovered as a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. In a majority of cases, APC resistance is associated with a single point mutation in the factor V gene, which results in substitution of arginine (R) at position 506 by glutamine (Q) (FV:Q506). The mutation renders factor Va partially resistant to degradation by activated protein C (APC), which leads to a hypercoagulable state and a life-long 5-10-fold increased risk of venous thrombosis. The previously known inherited deficiencies of antithrombin, protein S or protein C, are in western societies together found in less than 10-15% of thrombosis patients, whereas APC resistance is present in 20 to 60% of the patients. A functional APC resistance test, which includes predilution of the patient plasma with factor V deficient plasma, is 100% sensitive and specific for the presence of FV:Q506. The FV:Q506 allele is common in populations of Caucasian origin (prevalence ranging between 1 and 15%), whereas it is not found in certain other ethnic groups such as in Japanese and Chinese. The thrombotic risk in individuals with APC resistant may be further increased by other genetic defects such as protein C or protein S deficiency and by exposure to circumstantial risk factors such as oral contraceptives, pregnancy, immobilisation and surgery.
Dahlbäck
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B
Department of Clinical Chemistry, Lund University, University Hospital Malmö, Sweden.
Zöller
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Hillarp
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A
D000293:Adolescent; D001780:Blood Coagulation Tests; D002648:Child; D004198:Disease Susceptibility; D004789:Enzyme Activation; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic; D011486:Protein C / Q000502:physiology*; D018455:Protein S Deficiency / Q000150:complications; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D013924:Thrombophlebitis / Q000097:blood / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D013927:Thrombosis / Q000209:etiology / Q000401:mortality
D011486:Protein C; C095381:factor V Leiden; D005165:Factor V