Vein Thrombosis In Patients With Activated Protein C Resistance (apc-r) And The Anticoagulant Protein Defects

BACKGROUND: Thromboembolic disease has become a major cause of death in human being. It is reported that venous thrombosis is a common disease with an estimated annual incidence of 1 in 1000 populations. The pathogenesis of a thrombotic event is the final result of multiple interactions between different genetic and environmental components. Thrombotic disease becomes a very important issue because it has a high incidence and affects many people. It is crucial to deeply investigate the pathogenesis of venous thrombosis .Prior to 1993, a hereditary disorder could be identified in only about 15% of patients under age 50 presenting with unexplained venous thrombosis . The major disorders known at that time were deficiencies of antithrombin III, protein C, or protein S. Deficiencies of other anticoagulant protein were very rare. So far no explanation could be found for 85% of families predisposed to thrombosis. The concept of resistance to activated protein C(APC-R)was first introduced in 1993 by Dahlback. It was defined as a poor anticoagulant response of plasma to the addition of APC. The phenotype of APC resistance are present in about 40%~60% of thrombophilic patients. In 1994 Bertina reported that more than 80% of the cases with activated protein C resistance were carriers of the same mutation in the gene of factor V,viz a G→A transition in position 1691, in exon 10, that causes a replacement of Arg 506 by Gln in the factor V molecule (named Factor V Leiden). This inherited factor V mutation results in the loss of an activated protein C cleavage site at residue 506 , thus causing resistance to activated protein C. It is reported that more than 80%~90% of cases of activated protein C resistance are caused by factor V Leiden mutation in western countries.The prevalence of factor V Leiden is about 2%-6% in European populations, and 20%-40% thrombotic patients in European. It appears to be rare among individuals of most other races and outside Europe. So deepening...