Hydroxyethyl starch enhances fibrinolysis in human plasma by diminishing alpha2-antiplasmin-plasmin interactions.
Hydroxyethyl starch (HES) solutions are effective volume expanders but are also associated with poorly understood coagulopathy. Enhanced fibrinolysis following dilution with HES has been demonstrated. This investigation sought to identify the interactions of HES with critical fibrinolytic/antifibrinolytic enzymes. Normal plasma or plasmas deficient in factor XIII, thrombin activatable fibrinolysis inhibitor or alpha2-antiplasmin were either not diluted or were diluted 20% with 0.9% NaCl, 5% human albumin, high-molecular-weight HES (HES 450) or low-molecular-weight HES (HES 130). Plasma was activated with celite and exposed to 75 IU/ml tissue-type plasminogen activator. Coagulation growth/disintegration kinetics were determined with thrombelastography. Compared with undiluted plasma, diluted plasma had a significant decrease in the clot lysis time and the time to maximum rate of lysis in all plasma types except in alpha2-antiplasmin-deficient plasma. The hierarchy of the decrease in clot lysis time and time to maximum rate of lysis was HES 450 = HES 130 > 5% human albumin = 0.9% NaCl. In conclusion, HES dilution enhances fibrinolysis by diminishing alpha2-antiplasmin-plasmin interactions. Further laboratory and clinical investigation is warranted to better define the mechanisms by which HES enhances clot disintegration and to find new therapeutic roles for HES to either prevent or treat thrombosis.
Nielsen
Vance G
VG
Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama 35249-6810, USA. vnielsen@uab.edu
D000925:Anticoagulants / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D001809:Blood Viscosity / Q000187:drug effects; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects*; D006438:Hemodilution; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D007700:Kinetics; D010952:Plasma Substitutes / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013916:Thrombelastography / Q000295:instrumentation / Q000379:methods; D013917:Thrombin / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D000979:alpha-2-Antiplasmin; D013917:Thrombin; D005341:Fibrinolysin