title: APC-resistance as measured by a Textarin time assay: comparison to the APTT-based method.
abstract: Protein C is a major regulatory protein critical to physiologic anticoagulation. When activated, it selectively degrades the activated forms of factors V and VIII, thereby, down-regulating blood coagulation. Using an activated partial thromboplastin time (APTT) assay, Dahlback et al. recently reported that some individuals with thrombophilia show a poor in vitro anticoagulant response to activated protein C (APC-Resistance). Subsequent studies identified a point mutation in the gene for factor V as the underlying cause of APC-Resistance. The incidence of APC-Resistance in patients with recurrent thromboembolic events approaches 50%. The APC-Resistance phenotype is also present in approximately 5% of normal Caucasian subjects. In an attempt to develop a more sensitive and specific test system, we evaluated an assay based on Textarin(Pentapharm, Basel, Switzerland). Textarin, a protein fraction of Pseudonaja textilis venom (Australian Eastern Brown Snake) activates prothrombin in the presence of phospholipid (PL), factor V and calcium ions. Based on Textarin's requirement for factor V, we developed a Textarin time assay to test for APC-Resistance. We evaluated this test system in normal subjects and the following patient populations: stable orally anticoagulated, previously diagnosed factor V Leiden, and therapeutically heparinized samples. We found the Textarin assay to be a sensitive and specific test system to identify APC-Resistance. The phenotypic Textarin APC-Resistance test correlated more closely with the genotypic abnormality of factor VR506Q than the APTT-APC-Resistance test.
authors.affiliation: Muncie Center for Medical Education, Indiana University School of Medicine, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Hoagland
authors.forename: D A
authors.initials: DA
authors.lastname: Triplett
authors.forename: F
authors.initials: F
authors.lastname: Peng
authors.forename: L
authors.initials: L
authors.lastname: Barna
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D001780:Blood Coagulation Tests; D002118:Calcium / Q000097:blood; D004198:Disease Susceptibility; D004546:Elapid Venoms / Q000494:pharmacology; D004789:Enzyme Activation; D005165:Factor V / Q000235:genetics / Q000378:metabolism; D005166:Factor V Deficiency / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D015994:Incidence; D010314:Partial Thromboplastin Time; D010743:Phospholipids / Q000097:blood; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011486:Protein C / Q000378:metabolism*; D011516:Prothrombin / Q000187:drug effects; D012016:Reference Values; D012680:Sensitivity and Specificity; D013923:Thromboembolism / Q000097:blood / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D004546:Elapid Venoms; D010743:Phospholipids; D011486:Protein C; C095381:factor V Leiden; C037525:textilotoxin; D005165:Factor V; D011516:Prothrombin; D006493:Heparin; D002118:Calcium