Bleeding times and the antithrombotic effects of high-dose aspirin, hirudin and heparins in the rat

Lavelle, S. M.; MacIomhair, Maura

doi:10.1007/bf02937415

Cited by 7 publications

(11 citation statements)

References 14 publications

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“…This agrees with other experimental studies in rats, other animals, and humans [16,18,[26][27][28] . In this experiment, there was no signifi cant alteration of BT in the enoxaparin groups compared with controls.…”

Section: Discussionsupporting

confidence: 82%

See 1 more Smart Citation

Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

Carelli¹,

Maffei²,

Mattar³

et al. 2005

Pathophysiol Haemos Thromb

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Synergism between low-molecular-weight heparin and low doses of unfractionated heparin (UH) enhancing anti-factor Xa activity and the release of tissue factor pathway inhibitor was observed. The aim of this study was to verify whether this association is effective in preventing experimental venous thrombosis. Seventy rats were allocated into 7 groups: the control group treated with distilled water, the H₃₅₀ group treated with UH 350 IU/kg, the E₂ group treated with enoxaparin 2 mg/kg, the H₁₇₅ group treated with UH 175 IU/kg, the E₁ group treated with enoxaparin 1 mg/kg, the H₁₇₅ + E₁ group treated with UH 175 IU/kg plus enoxaparin 1 mg/kg, and the H₁₀₀ + E_0.5 group treated with UH 100 IU/kg plus enoxaparin 0.5 mg/kg. Forty minutes after subcutaneous injection, thrombosis was induced in vena cava. Three hours later, if present, thrombi were withdrawn and weighed. Bleeding time, activated partial thromboplastin time, thrombin time (TT), and anti-factor Xa were measured at the beginning and end of the experiment. Forty-eight other animals were treated, but without inducing thrombus, and tests were performed 40 min after injection. Thrombus developed in 90.9% of control animals, 20% of the H₃₅₀ group, 22.2% of the E₂ group, 10% of the H₁₇₅ + E₁ group, and 30% of the H₁₀₀ + E_0.5 group; there was a difference between group C and the other groups. Only in the H₃₅₀ and H₁₇₅ + E₁ groups were TT and activated partial thromboplastin time prolonged in relation to control at the end of the experiment. Forty minutes after injection, TT was prolonged in the H₃₅₀ and H₁₇₅ + E₁ groups. In conclusion, combinations of low doses of low-molecular-weight heparin and low doses of UH were as effective as high doses of each one used alone in preventing thrombus development in rat vena cava.

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Section: Discussionsupporting

confidence: 82%

“…A 3-mm-long and 2-mm-deep incision was made in the ventral side of the tail, 8-9 cm from the extremity, and BT was measured from the time of incision until bleeding stopped [16][17][18][19] .…”

Section: Bleeding Timementioning

confidence: 99%

Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

Carelli¹,

Maffei²,

Mattar³

et al. 2005

Pathophysiol Haemos Thromb

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“…All drugs were administered in an intravenous bolus dose followed by repeatedly subcutaneous injection in an equivalent dose for 3 days (twice a day). Group 1 was infused with normal saline as the control; group 2 was infused with abciximab 0.2 mg/kg; group 3 was infused with wt-hirudin 1.0 mg/kg; group 4 was infused with r-RGD-hirudin 0.2 mg/kg; group 5 was infused with r-RGD-hirudin 0.5 mg/kg and group 6 was infused with r-RGD-hirudin 1.0 mg/kg [ 13 , 14 ].…”

Section: Methodsmentioning

confidence: 99%

A novel hirudin derivative characterized with anti-platelet aggregations and thrombin inhibition

Zhang

Chen

et al. 2008

J Thromb Thrombolysis

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Background Hirudin is an anti-coagulative product of the salivary glands of the medicinal leech Hirudo medicinalis. It is a powerful and specific thrombin inhibitor. Peptides containing the RGD motif competitively inhibit the binding of fibrinogen to GP IIb/IIIa on the platelets, thus inhibiting platelet aggregation. Results We have constructed a recombinant RGD-hirudin (r-RGDhirudin) by fusing the tripeptide RGD sequence to the native hirudin (wt-hirudin). The r-RGD-hirudin was expressed at high levels in Pichia pastoris, and was purified to *97% homogeneity. The specific anti-thrombin activity of purified r-RGD-hirudin is 12,000 ATU/mg, which is equivalent to wt-hirudin, but only r-RGD-hirudin can inhibit platelet aggregation. The biological effects of r-RGD-hirudin on Thrombin Time (TT), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Bleeding Time (BT), maximum platelet aggregation (PAGm) induced by ADP were studied in rabbit model and compared with that of wt-hirudin. The rabbits were infused r-RGD-hirudin had prolonged TT, PT, and aPTT which were similar to that of wt-hirudin; but only r-RGD-hirudin was capable of inhibiting PAGm. Histopathological analyses showed that r-RGD-hirudin was two to three times more effective than wt-hirudin in preventing thrombosis. Conclusions r-RGD-hirudin can potentially be used as a novel anti-coagulant for the prevention of thrombosis after carotid artery anastomosis or in other thrombotic events.

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“…Tail vein transection experiments in haemophilic mice provide a measure of in vivo haemostatic efficacy [18–22]. Plasma‐derived FVIII, PEGLip‐formulated pdFVIII, or saline were injected into the tail veins of haemophilic mice.…”

Section: Resultsmentioning

confidence: 99%

Enhancement of haemostatic efficacy of plasma‐derived FVIII by formulation with PEGylated liposomes

2009

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We have shown previously that PEGylated liposomes (PEGLip) bind recombinant FVIII (rFVIII) with high affinity and specificity. This binding resulted in a significant extension of the biological activity of rFVIII as demonstrated in animal models and in clinical trials. In the present study we found that PEGLip bind plasma-derived factor VIII (pdFVIII). PEGLip binding did not affect potency or stability in vitro and did not alter levels of FVIII activity in vivo immediately after injection. However, formulation of pdFVIII with PEGLip led to several important improvements. Twenty-four and 30 hours after injection, FVIII activity levels were significantly higher in haemophilic mice injected with PEGLip-pdFVIII than in mice injected with standard pdFVIII. Half life, area under the curve and mean residence time were increased while clearance was decreased. In vivo efficacy was evaluated in a tail vein transection assay performed in haemophilic mice. Prophylactic treatment with PEGLip-pdFVIII was much more effective in prolonging survival in this assay than similar treatment with standard pdFVIII. These results suggest that formulation of pdFVIII with PEGLip has the potential to improve patient care by prolonging the biological efficacy of pdFVIII and reducing the frequency of FVIII infusions.

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Bleeding times and the antithrombotic effects of high-dose aspirin, hirudin and heparins in the rat

Cited by 7 publications

References 14 publications

Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

A novel hirudin derivative characterized with anti-platelet aggregations and thrombin inhibition

Enhancement of haemostatic efficacy of plasma‐derived FVIII by formulation with PEGylated liposomes

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