Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.

Sobel, Michael; McNeill, Paul M.; Carlson, Patricia; Kermode, John C.; Adelman, Burt; Conroy, Regina; Marques, Dalila

doi:10.1172/jci115198

Cited by 199 publications

(87 citation statements)

References 41 publications

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“…Heparin-binding proteins tend to build stronger bonds to UFH than to LMWH's (Lane et al, 1986;Preissner and Muller-Berghaus, 1987;Sobel et al, 1991), which actually increases the bioavailability of LMWH's in plasma even at lower doses. Moreover, the dose-dependent action of LMWH's (no reduction by plasma-protein binding) means they act in a much more predictable fashion (Handeland et al, 1990).…”

Section: Pharmacokinetics Of Lmwh'smentioning

confidence: 99%

“…The main mode of LMWH metabolism and excretion is through the kidney and urinary system (Palm and Mattsson, 1987;Boneu et al, 1988). LMWH's have a significantly lower affinity to von Wilebrandt factor (vWF) (Sobel et al, 1991) than UFH, which may decrease the probability of excessive bleeding complications at the same dose regimen (Esquivel et al, 1982;Andriuoli et al, 1985).…”

Section: Pharmacokinetics Of Lmwh'smentioning

confidence: 99%

“…In these models, LMWH's are slightly less effective than UFH; however, they cause significantly less systemic bleeding under standardized conditions (Esquivel et al, 1982;Ockelford et al, 1982;Hobbelen et al, 1987). Whenever these sulphated polysaccharides are compared to each other, their effect on platelets (Fabris et al, 1983;Fernandez et al, 1986;Sobel et al, 1991), as well as on blood vessel permeability (Blajchman et al, 1989) should be kept in mind.…”

Section: Efficacy and Safety Of Lmwh's In An Animal Modelmentioning

confidence: 99%

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Heparin and its derivatives in the treatment of arterial thrombosis: a review

Dvořák¹,

Vlašín²,

Dvorakova³

et al. 2010

Vet. Med. - Czech

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Arterial occlusion due to thrombosis caused by ruptured atherosclerotic plaques (Baba et al., 1975) has been recognized as a major cause of morbidity and mortality in western populations. Thrombosis may occur in various sections of arterial circulation, peripheral arteries of the limbs, coronary arteries, brain arteries, or both major and minor vessels within the abdominal cavity. The ultimate consequence is varying degrees of organ failure, mostly of ischemic origin. Arterial thrombosis represents a continuous problem, debilitating patients and decreasing their quality of life. Moreover, along with chronic heart failure, it can significantly decrease patient life expectancy. Arterial thrombosis results in ischemia, with serious systemic consequences, such as metabolic breakdown. The major goal of treatment remains fast and efficient recanalization -surgical, interventional or thrombolytic. To be able to prevent acute reocclusion with severe consequences (rhabdomyolysis, compartment syndrome, excessive tissue necrosis leading to limb amputation, etc.), several adjunctive treatment regimens have been advocated. Among others, thrombin inhibitors and platelet inhibitors have been widely used for both prophylaxis and adjunctive treatment. Direct thrombin inhibitors and antithrombin stimulators have been recognized as typical antithrombotic drugs. Direct (antithrombin-independent) thrombin inhibitors can be divided into two main categories: monovalent, active site inhibitors (argatroban, efegatran, inovastan, melagatran) and bivalent (hirudin, hirugen, hirulog, bivalirudin), while antithrombin stimulators represent standard (unfractionated) heparin (UFH) and its depolymerizing products -low molecular weight heparins (LMWH's). Recently, a clear change in the main use of heparin, as well as low-molecular weight heparins has been advocated representing a shift from treatment and prophylaxis of deep vein thrombosis to prophylaxis of thromboembolic disease following vascular, cardiovascular or orthopedic surgery, treatment of unstable angina and prevention of acute myocardial infarction. The main effect of heparins lies in their anticoagulant activity. Heparins are involved in different pathways of the coagulation cascade with anticoagulant, antithrombotic, profibrinolytic, anti-aggregative, as well as anti-inflammatory effects. Moreover, there is a little doubt about their anti-proliferative and anti-ischemic activity (Penka and Bulikova, 2006). Unlike standard heparin, low-molecular weight heparins do not affect the patient's general coagulation profile. Obviously, the difference in molecular weight results in different pharmacokinetic and pharmacodynamic properties of the agents.Key words: coagulation; arterial thrombosis; standard heparin; low-molecular weight heparins List of abbreviations ABI = axillary/...index, t-PA = tissue-type plasminogen activator, ADP = adenosin diphosphate, AG = angiography, AMI = acute myocardial infarction, APSAC = acylated plasminogen streptokinase activator complex, APTT = acti...

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Section: Pharmacokinetics Of Lmwh'smentioning

confidence: 99%

Section: Pharmacokinetics Of Lmwh'smentioning

confidence: 99%

Section: Efficacy and Safety Of Lmwh's In An Animal Modelmentioning

confidence: 99%

See 1 more Smart Citation

Heparin and its derivatives in the treatment of arterial thrombosis: a review

Dvořák¹,

Vlašín²,

Dvorakova³

et al. 2010

Vet. Med. - Czech

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“…It is possible that at high shear rates, comparable with those in this ex vivo model, plasma von Willebrand factor (vWF) is required for adhesion of platelets to the roughened surface of the stents as well as to subendothelium, perhaps as a bridge between platelets and thrombogenic surface. 17 Heparin may supplement a moderate antiadhesive effect of magnesium by inhibiting vWF-dependent platelet function and vWF-platelet binding. 17 The addition of heparin to tirofiban produced a modest, but statistically significant, increase in antithrombotic effects compared with tirofiban alone.…”

Section: Incremental Effects Of Heparinmentioning

confidence: 99%

“…17 Heparin may supplement a moderate antiadhesive effect of magnesium by inhibiting vWF-dependent platelet function and vWF-platelet binding. 17 The addition of heparin to tirofiban produced a modest, but statistically significant, increase in antithrombotic effects compared with tirofiban alone. In contrast, heparin did not appear to produce an incremental effect on TW reduction when combined with eptifibatide.…”

Section: Incremental Effects Of Heparinmentioning

confidence: 99%

Comparative Antithrombotic Effects of Magnesium Sulfate and the Platelet Glycoprotein IIb/IIIa Inhibitors Tirofiban and Eptifibatide in a Canine Model of Stent Thrombosis

et al. 2002

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Background-Antithrombotic effects of glycoprotein IIb/IIIa inhibitors and magnesium are known, but their comparative effects on stent thrombosis are not known. Our objective was to compare the antithrombotic effects of the glycoprotein IIb/IIIa inhibitors tirofiban and eptifibatide with magnesium in an ex vivo canine arteriovenous shunt model of stent thrombosis. Methods and Results-Control nitinol stents were expanded to 2 mm in diameter in a tubular perfusion chamber interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100 s Ϫ1 for 20 minutes (nϭ398 perfusion runs in 24 experiments in 8 dogs). The animals were treated intravenously with MgSO 4 (2 g bolusϫ20 minutes followed by 2 g/h infusion), eptifibatide (double bolus of 180 g/kg 10 minutes apart followed by 2 g/kg per minute), or tirofiban (0.3 g/kg per minute), with or without heparin (50 U/kg). Effects of the test agents on thrombus weight, platelet aggregation (PA), platelet CD62 expression, bleeding time (BT), heart rate, and mean arterial blood pressure were assessed. Treatment with Mgϩheparin reduced stent thrombus weight by 78Ϯ10% compared with baseline (19Ϯ4 mg, PϽ0.001). The antithrombotic effect of Mgϩheparin was equivalent to that observed with tirofibanϩheparin (78Ϯ13%) and eptifibatideϩheparin (84Ϯ11%). Magnesium had no significant effect on PA and BT. Tirofiban and eptifibatide inhibited PA by Ͼ90% and prolonged BT up to 20 minutes. None of the test agents had effects on CD62 expression or activated clotting time. There were no significant bleeding or hemodynamic complications. Conclusion-Magnesium produced a significant reduction in acute stent thrombus formation that was equivalent in magnitude to that produced by clinically relevant doses of tirofiban and eptifibatide. Its potential use in percutaneous coronary intervention requires further study.

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Low-Molecular-Weight Heparins in the Management of Acute Coronary Syndromes

Zed¹,

Tisdale²,

Borzak³

1999

Arch Intern Med

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Acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition resulting in thrombosis. Aspirin and unfractionated heparin have traditionally been the treatments of choice for patients with acute coronary syndromes. Low-molecular-weight heparins offer potential advantages over unfractionated heparin, having proven equally effective for the treatment and prevention of many thromboembolic processes. Recently, a number of randomized controlled trials have been conducted to evaluate the role of low-molecular-weight heparins in the management of patients with unstable angina or non-Q-wave myocardial infarction. The purpose of this article is to review and evaluate the available literature on the use of low-molecular-weight heparins in the management of acute coronary syndromes to establish their role in therapy.

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Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.

Cited by 199 publications

References 41 publications

Heparin and its derivatives in the treatment of arterial thrombosis: a review

Heparin and its derivatives in the treatment of arterial thrombosis: a review

Comparative Antithrombotic Effects of Magnesium Sulfate and the Platelet Glycoprotein IIb/IIIa Inhibitors Tirofiban and Eptifibatide in a Canine Model of Stent Thrombosis

Low-Molecular-Weight Heparins in the Management of Acute Coronary Syndromes

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