title: Ancrod revisited: viscoelastic analyses of the effects of Calloselasma rhodostoma venom on plasma coagulation and fibrinolysis.
abstract: Fibrinogen depletion via catalysis by snake venom enzymes as a therapeutic strategy to prevent or treat thrombotic disorders was utilized for over four decades, with ancrod being the quintessential agent. However, ancrod eventually was found to not be of clinical utility in large scale stroke trial, resulting in the eventual discontinuation of the administration of the drug for any indication. It was hypothesized that ancrod, possessing thrombin-like activity, may have unappreciated robust coagulation kinetics. Using thrombelastographic methods, a comparison of equivalent tissue factor initiated thrombin generation and Calloselasma rhodostoma venom (rich in ancrod activity) on plasmatic coagulation kinetics was performed. The venom resulted in thrombi that formed nearly twice as fast compared to thrombin formed clots, and there was no difference in fibrinolytic kinetics initiated by tissue-type plasminogen activator. In plasma containing iron and carbon monoxide modified fibrinogen, which may be found in patients at risk of stroke, the coagulation kinetic differences observed with venom was still more vigorous than that seen with thrombin. These phenomena may provide insight into the clinical failure of ancrod, and may serve as an impetus to revisit the concept of fibrinogen depletion via fibrinogenolytic enzymes, not those with thrombin-like activity.
authors.affiliation: Department of Anesthesiology, The University of Arizona College of Medicine, P.O. Box 245114, 1501 North Campbell Avenue, Tucson, AZ, 85724-5114, USA. vgnielsen333@gmail.com.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
mesh_terms: D000347:Afibrinogenemia / Q000139:chemically induced; D000721:Ancrod / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D003435:Crotalid Venoms / Q000493:pharmacokinetics* / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D013916:Thrombelastography; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000502:physiology
chemical_list: D003435:Crotalid Venoms; D005340:Fibrinogen; D013925:Thromboplastin; D000721:Ancrod; D013917:Thrombin
keywords: Fibrinogen depleting agent; Fibrinolysis; Snake venom; Thrombelastography; Tissue-type plasminogen activator