Thromb Haemost 2004; 92(06): 1296-1302
DOI: 10.1160/TH03-11-0694
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

In vitro comparison of the effect of fondaparinux and enoxaparin on whole blood tissue factor-triggered thromboelastography profile

Grigoris T. Gerotziafas
1   Laboratoire d’Hématologie Biologique Hotel-Dieu de Paris, France
,
Tahar Chakroun
1   Laboratoire d’Hématologie Biologique Hotel-Dieu de Paris, France
,
Meyer M. Samama
1   Laboratoire d’Hématologie Biologique Hotel-Dieu de Paris, France
,
Ismail Elalamy
1   Laboratoire d’Hématologie Biologique Hotel-Dieu de Paris, France
› Author Affiliations
Further Information

Publication History

Received 15 November 2003

Accepted after resubmission 26 September 2004

Publication Date:
02 December 2017 (online)

Summary

Fondaparinux and enoxaparin are both effective and safe in preventing post-operative venous thromboembolism. However, neither of them significantly influence the conventional clotting tests. We compared the influence of clinically relevant concentrations of fondaparinux and enoxaparin on normal whole blood (WB) thromboelastographic profiles after triggering TF-pathway with minimal amount of thromboplastin. Diluted thromboplastin was added to WB samples supplemented with buffer (control), fondaparinux (0.25; 0.5; 1µg/ml), or enoxaparin (0.1; 0.5; 1anti-Xa lU/ml). Four parameters were analyzed, R: clotting time, K: time required to reach an amplitude of 20 mm, α angle: measurement reflecting clot development kinetics and MA: maximal amplitude. At concentrations used in prophylaxis, both enoxaparin (0.1 anti-Xa lU/ml) and fondaparinux (0.25 µg/ml which correspond to 0.27 anti-Xa lU/ml) significantly prolonged the R and K times, but did not significantly modify the a angle as compared to the control. At concentrations observed after administration of curative doses for the treatment of DVT (≥0.5 anti-Xa lU/ml for enoxaparin and ≥0.5 ug/ml for fondaparinux) both drugs induced a significant increase of R and K times, and a significant decrease of the α angle (p <0.05). In contrast to fondaparinux, enoxaparin at concentrations equal to or higher than 0.5 anti-Xa lU/ml significantly reduced MA. The present study provides evidence that the whole blood TF-triggered TEG assay is sensitive to the presence of clinically relevant concentrations of enoxaparin or fondaparinux. Moreover, the angle may be used in order to distinguish the effect of prophylactic and therapeutic concentrations, since it was significantly reduced by the later ones. Further studies are needed to evaluate the clinical usefulness of whole blood TF-triggered TEG assay for the monitoring of treatment with enoxaparin or fondaparinux.

 
  • References

  • 1 Samama MM, Gerotziafas GT. Evaluation of the pharmacological properties and clinical results of the synthetic pentasaccharide (Fon-aparinux). Thromb Res 2003; 109: 1-11.
  • 2 Bauer KA, Eriksson BI, Lassen MR. et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med 2001; 345: 1305-10.
  • 3 Eriksson BI, Bauer KA, Lassen MR. et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med 2001; 345: 1298-304.
  • 4 Thorevska N, Amoateng-Adjepong Y, Sabahi R. et al. Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin. Chest 2004; 125: 856-63.
  • 5 Turpie AG, Bauer KA, Eriksson BI. et al. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized doubleblind studies. Arch Intern Med 2002; 162: 1833-40.
  • 6 Linkins LA, Julian JA, Rischke J. et al. In vitro comparison of the effect of heparin, enoxaparin and fondaparinux on tests of coagulation. Thromb Res 2002; 107: 241-4.
  • 7 Bara L, Planes A, Samama MM. Occurrence of thrombosis and haemorrhage, relationship with anti-Xa, anti-IIa activities, and D-dimer plasma levels in patients receiving a low molecular weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery. Br J Haematol 1999; 104: 230-40.
  • 8 Hartert H. Blutgerinnungessstudien mit der thrombelastographie, einem neuen Untersu chungsverfahren. Klein Wochenchr 1948; 26: 577-83.
  • 9 Marchal G, Leroux ME, Samama MM. Interêt de thrombodynamographie (Thromboelas tographie) dans l’étude des syndromes hemorragiques. Pat Biol 1958; 951-53.
  • 10 Kang YG, Martin DJ, Marquez J. et al. Intraoperative changes in blood coagulation and thromboelastographic monitoring in liver transplantation. Anesth Analg 1985; 64: 888-96.
  • 11 Tuman KJ, McCarthy RJ, Djuric M. et al. Evaluation of coagulation during cardiopulmonary bypass with heparinase-modified thromboelastographic assay. J Cardiothorac Vasc Anesth 1994; 08: 144-49.
  • 12 Shore-Lesserson L, Manspeizer HE, DePerio M. et al. Thromboelastography-guided transfusion algorithm reduces transfusion in complex cardiac surgery. Anesth Analg 1999; 88: 312-19.
  • 13 Bowbrick VA, Mikhailidis DP, Stansby G. The use of citrated whole blood in thromboelastog-raphy. Anesth Analg 2000; 90: 1086-88.
  • 14 Rapaport SI, Rao LV. The tissue factor pathway: how it has become a prima ballerina. Thromb Haemost 1995; 74: 7-17.
  • 15 Giesen PLA, Rauch U, Bohrmann B. et al. Blood borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999; 96: 2311-15.
  • 16 Depasse F, Gerotziafas GT, Busson J. et al. Assessment of three chromogenic and one clotting assays for measurment of synthetic pentasaccharide fondaparinux (Arixtra) anti-Xa activity. J Thromb Haemost 2004; 02: 346-8.
  • 17 Mallett SV, Cox DJ. Thromboelastography. Br J Anaesth 1992; 69: 307-13.
  • 18 Vig S, Chitolie A, Bevan DH. et al. Throm boelastography: a reliable test?. Blood Coagul Fibrinolysis 2001; 12: 555-61.
  • 19 Rand MD, Lock JB, van’t Veer C. et al. Blood clotting in minimally altered whole blood. Blood 1996; 88: 3432-45.
  • 20 Holmes MB, Schneider DJ, Hayes MG. et al. Novel, bedside, tissue factor-dependent clotting assay permits improved assessment of combination antithrombotic and antiplatelet therapy. Circulation 2000; 102: 2051-7.
  • 21 Zambruni A, Thalheimer U, Leandro G. et al. Thromboelastography with citrated blood: comparability with native blood, stability of citrate storage and effect of repeated sampling. Blood Coagul Fibrinolysis 2004; 15: 103-7.
  • 22 Boneu B, Necciari J, Cariou R. et al. Pharmacokinetics and tolerance of the natural pentasaccharide (SR90107/ORG31540) with high affinity to antithrombin III in man. Thromb Haemost 1995; 74: 1468-73.
  • 23 Donat F, Duret JP, Santoni A. et al. The pharmacokinetics of Fondaparinux sodium in healthy volunteers. Clin Pharmacokinet 2002; 41 (Suppl. 02) 1-9.
  • 24 Bendetowicz AV, Kai H, Knebel R. et al. The effect of subcutaneous injection of unfractionated and low molecular weight heparin on thrombin generation in platelet rich plasma - a study in human volunteers. Thromb Haemost 1994; 72: 705-12.
  • 25 Gerotziafas GT, Depasse F, Chakroun T. et al. The role of tissue factor on the inhibition of prothrombin activation and thrombin generation by the synthetic pentasaccharide (fonda parinux). XIXth Congress of the International Society on Thrombosis and Haemostasis, 12-18/7/2003, Birmingham, UK. J Thromb Haemost. 2003 suppl 01.
  • 26 Gerotziafas GT, Depasse F, Chakroun T. et al. Comparison of the effect of fondaparinux and enoxaparin on thrombin generation during invito clotting of whole blood and platelet-rich plasma. Blood Coagul Fibrinolysis 2004; 15: 149-56.
  • 27 Sorensen B, Johensen P, Christiansen K. et al. Whole blood coagulation thromboelasto graphic profiles employing minimal tissue factor activation. J Thromb Haemost 2003; 01: 551-58.
  • 28 Lindahl AK, Abildgaard U, Larsen ML. et al. Extrinsic pathway inhibitor (EPI) and the post-heparin anticoagulant effect in tissue thromboplastin induced coagulation. Thromb Res 1991; 14: 39-48.
  • 29 Zmuda K, Neofotistos D, Ts’ao C-H. Effects of unfractionated heparin, low molecular weight heparin, and danaparoid on thromboelastographic assay of blood coagulation. Am J Clin Pathol 2000; 113: 725-31.
  • 30 Khurana S, Mattson JC, Westley S. et al. Monitoring platelet glycoprotein Ilb/IIIa-fibrin interaction with tisuue factor-activated thromboelastography. J Lab Clin Med 1997; 130: 401-11.
  • 31 Engelmann B, Luther T, Muller I. Intravascular tissue factor pathway - a model for rapid initiation of coagulation within the blood vessel. Thromb Haemost 2003; 89: 3-8.