Background: Low molecular weight heparin (LMWH) has a more convenient delivery method (subcutaneous) for outpatient use and improved efficacy and safety as compared to unfractionated heparin in thromboembolic disorders. Different manufacturing methods of LMWH result in significant differences in their molecular weight distribution and sulfation levels. LMWH act at multiple sites including inhibition of factor Xa, inhibition of thrombin, and via the increase in cellular release of tissue factor pathway inhibitor (TFPI). Tinzaparin have relatively higher molecular weight fractions as compared to other LMWH. The present study was undertaken to compare the efficacy of various LMWH as well different heparin molecular weight fractions (3,000 - 12,000 dalton) on TF or endotoxin (LPS)-induced platelet-fibrin mediated-clot formation and strength. 

Methods: Thromboelastography was used to determine the ability of platelets and fibrin to augment the shear elastic modulus of human blood clots under conditions of maximal platelet activation during clot formation accelerated by TF or LPS. Comparative efficacy between different LMWH including Tinzaparin, Enoxaparin, Fraxiparin on TF or LPS-induced clot formation and strength in human whole blood using TEG was determined. 

Results: Data demonstrated the potency of the different LMWH in inhibiting TF or LPS-induced clot formations and strength under shear in addition to their potent effects in inhibiting Xa and Ila-mediated clot retraction. The absolute potency of the various heparin molecular weight fractions in inhibiting both TF and LPS-induced clot retraction was shown to be enhanced as a function of the molecular weight distribution, with optimal potency at 8,000 Dalton.The highly sulfated heparinase manufactured LMWH Tinzaparin demonstrated significantly (P < 0.01) higher potency (2-3 folds) in inhibiting TF or LPS -induced clot formation and strength under shear as compared to Enoxaparin or Fraxiparin. These data suggest a broader efficacy of LMWH as compared with other specific anticoagulant mechanisms. Additionally, these data indicated a differential efficacy among different LMWH in blunting Endotoxin or tissue factor-mediated platelet-fibrin clot formation and strength under shear.