title: Hydroxyethyl starch enhances argatroban-mediated decreases in clot propagation and strength by diminishing thrombin-fibrinogen interactions.
abstract: Direct thrombin inhibitors (DTIs) have been administered for anticoagulation during cardiopulmonary bypass for patients with heparin-induced thrombocytopenia. While DTIs prolonged clot initiation and decreased clot propagation, clot strength did not change. Hydroxyethyl starches (HES), however, significantly decreased clot propagation and strength. We hypothesized that DTI with HES could significantly decrease hemostasis more than DTI alone. Plasma was exposed to 0 or 5 microg/ml argatroban with 0 or 30% dilution with 0.9% NaCl, 10% pentastarch or 6% Voluven. Additional argatroban-exposed samples diluted with HES had addition of alpha-thrombin (0.25 U/ml) and fibrinogen (150 mg/ml). Clot kinetics were determined via thrombelastography. While dilution with 0.9% NaCl significantly (P < 0.05) decreased the clot strength by 17% compared with samples only exposed to argatroban, dilution with pentastarch and Voluven significantly (P < 0.05) markedly decreased clot strength (53 and 78%, respectively). Voluven dilution significantly increased the time to clot initiation and decreased the velocity of clot propagation compared with samples only exposed to argatroban. Addition of alpha-thrombin/fibrinogen restored clot strength. DTI/HES administration diminished hemostasis to a greater extent than DTI exposure alone. Further investigation is warranted to determine whether this therapeutic approach can improve the safety of anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia.
authors.affiliation: Department of Anesthesiology, The University of Alabama at Birmingham, Alabama 35249-6810, USA. vnielsen@uab.edu
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: James K
authors.initials: JK
authors.lastname: Kirklin
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004357:Drug Synergism; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013449:Sulfonamides; D013917:Thrombin / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D006895:Hydroxyethyl Starch Derivatives; D010875:Pipecolic Acids; D013449:Sulfonamides; D005340:Fibrinogen; D006493:Heparin; D001120:Arginine; D013917:Thrombin; C031942:argatroban