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...Continue Reading
References
Dec 1, 1994·Toxicon : Official Journal of the International Society on Toxinology·Y M DambisyaP Gopalakrishnakone
Jun 1, 1994·The Annals of Thoracic Surgery·A H O-YurvatiL B McGrath
Aug 1, 1993·Critical Reviews in Oncology/hematology·R L Soutar, J S Ginsberg
Jan 1, 1997·Drugs·W R Bell
May 18, 2000·JAMA : the Journal of the American Medical Association·D G ShermanD E Levy
Jan 5, 2002·Thrombosis Research·C E DempfleM Borggrefe
May 24, 2005·Thrombosis Research·Norbert LubenowHarry N Magnani
Apr 12, 2006·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Vance G NielsenEli Cohen
Nov 28, 2006·Lancet·Michael G HennericiUNKNOWN ESTAT investigators
Dec 21, 2006·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Truitt C EllisJames K Kirklin
Feb 10, 2007·Journal of Cardiothoracic and Vascular Anesthesia·Glenn S Murphy, Jesse H Marymont
Oct 31, 2009·Stroke; a Journal of Cerebral Circulation·David E LevyWarren W Wasiewski
Aug 27, 2011·Stroke; a Journal of Cerebral Circulation·Shuo LiuMark J Fisher
Sep 19, 2014·ASAIO Journal : a Peer-reviewed Journal of the American Society for Artificial Internal Organs·Ryan W MatikaMachaiah Madhrira
May 20, 2015·Journal of Thrombosis and Thrombolysis·Nirmish ShahVance G Nielsen
Aug 22, 2015·CNS & Neurological Disorders Drug Targets·Vance G NielsenRyan W Matika
Oct 16, 2015·Basic & Clinical Pharmacology & Toxicology·Vance G NielsenPatrick K Boyle
Oct 21, 2015·PloS One·Junzhou FuFeng He
Nov 18, 2015·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Vance G Nielsen, Leslie V Boyer
Feb 5, 2016·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Vance G NielsenPatrick K Boyle
Citations
Oct 28, 2016·Journal of Thrombosis and Thrombolysis·Vance G Nielsen, Charles M Bazzell
Sep 11, 2017·Journal of Thrombosis and Thrombolysis·Vance G Nielsen
Nov 30, 2018·Toxins·Fernanda G AmorimSuely V Sampaio
May 13, 2020·Neurotoxicity Research·Richard J HarrisBryan G Fry
Jan 2, 2021·Journal of Translational Autoimmunity·Carlos A CañasGabriel J Tobón
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jacinthe FrangiehCésar Mattei
Oct 15, 2020·Current Topics in Medicinal Chemistry·Yana LernerNir Qvit