Additive Effect of the Combined Administration of Low Molecular Weight Heparin and Recombinant Hirudin on Thrombus Growth in a Rabbit Jugular Vein Thrombosis Model

Biemond, Bart J.; Levi, Marcel; Nurmohamed, Michael T.; Büller, Harry R.; Cate, J. W. Ten

doi:10.1055/s-0038-1648874

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…Combination of a low molecular weight heparin and recombinant hirudin was found to reduce successfully the thrombus growth in a rabbit jugular vein thrombosis model [29] . Finally, it was also shown experimentally that following hirudin treatment discontinuation, a hypercoagulation rebound occurred, possibly related to the persistence of factor Xa activity in the clot.…”

Section: Discussionmentioning

confidence: 96%

Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity

et al. 2012

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Islet and hepatocyte transplantation are associated with tissue factor-dependent activation of coagulation which elicits instant blood mediated inflammatory reaction, thereby contributing to a low rate of engraftment. The aim of this study was i) to evaluate the procoagulant activity of human adult liver-derived mesenchymal progenitor cells (hALPCs), ii) to compare it to other mesenchymal cells of extra-hepatic (bone marrow mesenchymal stem cells and skin fibroblasts) or liver origin (liver myofibroblasts), and iii) to determine the ways this activity could be modulated. Using a whole blood coagulation test (thromboelastometry), we demonstrated that all analyzed cell types exhibit procoagulant activity. The hALPCs pronounced procoagulant activity was associated with an increased tissue factor and a decreased tissue factor pathway inhibitor expression as compared with hepatocytes. At therapeutic doses, the procoagulant effect of hALPCs was inhibited by neither antithrombin activators nor direct factor Xa inhibitor or direct thrombin inhibitors individually. However, concomitant administration of an antithrombin activator or direct factor Xa inhibitor and direct thrombin inhibitor proved to be a particularly effective combination for controlling the procoagulant effects of hALPCs both in vitro and in vivo. The results suggest that this dual antithrombotic therapy should also improve the efficacy of cell transplantation in humans.

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Section: Discussionmentioning

confidence: 96%

Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity

et al. 2012

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“…Recombinant HV1 was shown to inhibit this effect. 52,53 Surprisingly, the inhibition continued beyond the time at which hirudin would have been removed from the circulation through excretion, and is therefore due to either an alteration to the amount of thrombin bound to the clot or the hirudin itself binding to and inhibiting any thrombin actually within in the clot. 54…”

Section: Venous Thrombosismentioning

confidence: 99%

Hirudins: From Leeches to Man

Wallis

1996

Semin Thromb Hemost

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Hirudins are a group of highly homologous polypeptides from the medicinal leech, Hirudo medicinalis. They have an extremely high and specific affinity for thrombin and are consequently potent anticoagulants. They inhibit platelet aggregation induced by thrombin and efficiently inhibit thrombin when it is bound to a fibrin clot. Recombinant hirudins have now been produced and have been used to show a wide range of effects on thrombosis in animal models. They are particularly effective against venous-type thrombi and have greater effects than heparins on the platelet-rich thrombi in arteries. Recombinant hirudins are currently undergoing clinical trails in deep venous thrombosis and acute coronary syndrome and as an adjunct to thrombolysis in myocardial infarction. Results from pilot trials indicate promising advantages over the currently used antithrombotic agents. Larger clinical trails have been initiated and we await with great interest their imminent publication.

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“…Indeed,o ral rivaroxaban 3.0mgkg -1 ,nadroparinand fondaparinux were similarly effectivea tr educing thrombin growth in the treatment model. Thenadroparindose waschosen in ordertoobtain therapeutic levels observedinpatients receiving nadroparin for the treatment of venous thrombosis (18)(19)(20).T he fondaparinux dose (42 µg kg -1 )had an equivalent antithrombotic effect to nadroparininthis experimental thrombosis model. It should be noted that fondaparinux 7.5 mg has beenapprovedfor treatment in patients with symptomatic DVTo ra cutep ulmonarye mbolism( 5, 25).…”

Section: Discussionmentioning

confidence: 99%

Prevention and treatment of experimental thrombosis in rabbits with rivaroxaban (BAY 597939) – an oral, direct factor Xa inhibitor

Biemond¹,

Perzborn²,

Friederich³

et al. 2007

Thromb Haemost

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Current anticoagulant therapies for the prevention and treatment of thromboembolic disorders have many drawbacks: vitamin K antagonists interact with food and drugs and require frequent laboratory monitoring, and heparins require parenteral administration. Oral rivaroxaban (BAY 597939) is a new, highly selective and potent direct factor-Xa (FXa) inhibitor with a predictable pharmacodynamic and pharmacokinetic profile and could therefore be an attractive antithrombotic drug. It was the objective of this study to investigate the antithrombotic efficacy of oral rivaroxaban in two rabbit models of experimental venous thrombosis. In the venous stasis (prevention) model, animals were randomized to receive oral rivaroxaban 0.3, 1.0, 3.0 or 10.0 mg/kg or vehicle control. Thrombosis was induced by jugular vein stasis and injection of thromboplastin into the ear vein. In the venous thrombosis (treatment) model, intravenous (1.0 and 3.0 mg/kg) and oral (3.0 mg/kg) rivaroxaban was compared with intravenous nadroparin (40 U bolus and 20 U/h), fondaparinux (42 microg/kg) and vehicle control. Thrombus growth was assessed by measuring the accretion of radiolabelled fibrinogen into preformed clots in the jugular veins. Bleeding was assessed using an ear bleeding model. In the prevention model, rivaroxaban reduced thrombus formation dose-dependently (calculated ED(50) 1.3 mg/kg). In the treatment model, oral rivaroxaban (3.0 mg/kg) reduced thrombus growth to a similar extent to intravenous rivaroxaban (1.0 mg/kg), nadroparin and fondaparinux. Oral rivaroxaban did not prolong bleeding time. In conclusion, the orally available selective, direct FXa inhibitor rivaroxaban is effective in the prevention and treatment of venous thrombosis in two well-established models of experimental thrombosis.

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Additive Effect of the Combined Administration of Low Molecular Weight Heparin and Recombinant Hirudin on Thrombus Growth in a Rabbit Jugular Vein Thrombosis Model

Cited by 7 publications

References 12 publications

Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity

Bivalirudin in Combination with Heparin to Control Mesenchymal Cell Procoagulant Activity

Hirudins: From Leeches to Man

Prevention and treatment of experimental thrombosis in rabbits with rivaroxaban (BAY 597939) – an oral, direct factor Xa inhibitor

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