Inhibition of thrombin generation in recalcified plasma

Blood Coagul Fibrinolysis. 2007 Dec;18(8):751-60. doi: 10.1097/MBC.0b013e3282f09e6f.

Abstract

Eight inhibitors of thrombin generation were compared in recalcified unfrozen plasma. Individual or pooled normal citrated plasma was supplemented on polystyrol flat-bottom wells (23 degrees C) with increasing concentrations of low-molecular-weight heparin, heparin, danaparoid, fondaparinux, hirudin, argatroban, corn trypsin inhibitor, or aprotinin. Thrombin was generated by addition of 5 microl fresh 250 mmol/l CaCl2 to 50 microl plasma in polystyrol flat-bottom wells and incubation for 20 min at 37 degrees C (recalcified coagulation activity assay). Arginine stopped hemostasis activation and then the generated thrombin activity was specifically quantified. The approximate 50% inhibitory concentrations of plasmatic anticoagulants for individual or pooled normal plasma are, respectively, 0.6 or 3.7 mIU/ml low-molecular-weight heparin, 0.3 or 1.6 mIU/ml heparin, 0.7 or 6.1 mU/ml danaparoid, 0.023 or 0.18 microg/ml fondaparinux, 75 or 230 pg/ml hirudin, 0.026 or 0.24 microg/ml argatroban, 1 or 2 U/ml corn trypsin inhibitor, and 2 or 4 KIU/ml aprotinin. The 50% inhibitory concentration values for corn trypsin inhibitor or aprotinin at plasmatic concentrations above 4-100 U/ml might increase pathologically the thrombin generation. The recalcified coagulation activity assay is a sensitive method to measure prothrombotic tendencies of blood or subtle concentrations of any plasmatic anticoagulant. It is suggested to analyze the individual patient's sensibility to certain plasmatic anticoagulants.

MeSH terms

  • Anticoagulants / pharmacology*
  • Aprotinin / pharmacology
  • Arginine / analogs & derivatives
  • Blood Coagulation Tests / methods*
  • Chondroitin Sulfates / pharmacology
  • Dermatan Sulfate / pharmacology
  • Fondaparinux
  • Heparin / pharmacology
  • Heparitin Sulfate / pharmacology
  • Hirudins / pharmacology
  • Humans
  • Pipecolic Acids / pharmacology
  • Plant Proteins / pharmacology
  • Plasma / chemistry
  • Plasma / drug effects
  • Plasma / enzymology*
  • Polysaccharides / pharmacology
  • Sulfonamides
  • Thrombin* / analysis
  • Thrombin* / physiology

Substances

  • Anticoagulants
  • Hirudins
  • Pipecolic Acids
  • Plant Proteins
  • Polysaccharides
  • Sulfonamides
  • trypsin inhibitor, Zea mays
  • Dermatan Sulfate
  • Heparin
  • Chondroitin Sulfates
  • Heparitin Sulfate
  • Aprotinin
  • Arginine
  • danaparoid
  • Thrombin
  • argatroban
  • Fondaparinux