DIAGNOSTIC USE OF THE PROTEIN C ACTIVATOR FROM<i>AGKISTRODON CONTORTRIX</i>

Abstract

Disturbances within the protein C pathway due to coagulation factor V Leiden mutation and deficiency of protein C or protein S are the most frequent abnormalities in hereditary thrombophilia (hypercoagulable states). Furthermore, acquired dysfunctions of the protein C system may predispose an individual to an increased thrombotic risk. For diagnostic or research purposes, abnormalities of the protein C natural anticoagulant system are based on measuring protein C, protein S, and activated protein C resistance. Most of the assays contain the protein C activator Protac® from Agkistrodon contortrix contortrix (southern copperhead). Unlike the physiological, thrombin-catalyzed protein C activation reaction that requires thrombomodulin as a cofactor, Protac® directly converts the zymogen protein C into the catalytically active form that can easily be determined by means of coagulation or chromogenic substrate techniques. Protein C activators have been detected in several snake venoms. Most of them have been purified from venom of snake species belonging to the Agkistrodon or Gloydius genus. Due to its features, the fast-acting protein C activator Protac® has found a broad application in assays for research and in clinical practice to identify patients with defects of the protein C system.