Hemorrhagic doses of heparin and other glycosaminoglycans induce a platelet defect

Fernandez, F.; Nguyen, Philip V.; Ryn, Joanne van; Ofosu, Frederick A.; Hirsh, Jack; Buchanan, Michael R.

doi:10.1016/0049-3848(86)90094-0

Cited by 144 publications

(45 citation statements)

References 4 publications

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“…Heparin binds to platelets in vitro and has been shown to induce a platelet function defect in a dose-dependent manner (Fernandez et al, 1986). Thus is it possible that heparin will have a greater anticoagulant effect in assay systems that include platelets.…”

Section: Discussionmentioning

confidence: 99%

Monitoring heparin anticoagulation in the acute phase response

2010

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Summary The anticoagulant effect of unfractionated heparin (UFH) is monitored using the activated partial thromboplastin time (APTT). An APTT of 1·5–2·5 times the control is usually taken as the therapeutic range and assumed to reflect an anti‐activated factor X (anti‐Xa) level of 0·35–0·7 u/ml. However, in some cases, despite administration of sufficient heparin to achieve a therapeutic anti‐Xa assay level, the APTT remains sub‐therapeutic. This ‘apparent heparin resistance’ is commonly due to high levels of factor VIII (FVIII). In these situations, the anti‐Xa is usually preferred for monitoring in order to avoid, what might be, dangerously high levels of heparin. We hypothesized that at high FVIII levels, the heparin resistance encountered may be genuine rather than apparent and that higher doses of heparin may indeed be needed for an equivalent anticoagulant effect. The relationship between heparin level, APTT and anticoagulant effect at different FVIII concentrations was determined using thrombelastography and the thrombin generation assay. Thromboelastographic and thrombin generation parameters concurred with APTT, demonstrating a genuine heparin resistance in the presence of high FVIII levels. This suggests that APTT may be a more accurate measure of anticoagulant effect in vivo than anti‐Xa.

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Section: Discussionmentioning

confidence: 99%

Monitoring heparin anticoagulation in the acute phase response

2010

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“…Unfractionated heparin also inhibits the hemostatic system via release of tissue factor pathway inhibitor, 5 which results in inhibition of contact activation 6 and, in the majority of patients, probably directly or indirectly inhibits platelet function, especially when higher plasma concentrations ([ 3-4 UÁmL -1 ) are achieved. [7][8][9][10][11] This inhibition may be mediated via attenuation of collagen-mediated aggregation, 7,8 factor VIII-associated platelet aggregation, 11 or von Willebrand factor-related mechanisms. 10 Although low concentrations of UFH do not effectively inhibit thrombin bound to fibrin, this can be overcome if higher concentrations are achieved 12 during CPB.…”

Section: Indirect Vs Direct Thrombin Inhibitionmentioning

confidence: 99%

“…76 Moreover, the transfusion rate at day 7 was 84%, with platelets (mean of 8.6 ± 7.2 concentrates/patient, range 1-23) being the blood component used most often. 76 Each transfused patient also received FFP and PRBC (mean of 6.0 ± 4.7 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and 5.6 ± 3.8 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16], respectively). 76 The CHOOSE-OFF trial was a prospective, multicentre, open-label study with no comparator arm assessing bivalirudin anticoagulation in OPCAB patients with confirmed or prior HIT/thrombotic syndrome (HIT/TS) and/or anti-PF4/UFH antibodies.…”

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confidence: 99%

Utilisation de la bivalirudine en chirurgie cardiaque – de l’inhibition indirecte à l’inhibition directe de la thrombine

Anand

Viles-González

Mahboobi

et al. 2010

Can J Anesth/J Can Anesth

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Purpose Bivalirudin use for anticoagulating patients undergoing cardiac surgery, particularly those with or at risk for heparin-induced thrombocytopenia, has expanded over the past several years. The purpose of this review is to provide a summary of the following: the differences between indirect and direct thrombin inhibition, unfractionated heparin's limitations (i.e., heparin-induced thrombocytopenia), bivalirudin's pharmacology, recent cardiac surgery trials comparing bivalirudin and unfractionated heparin as anticoagulants, the growing role of bivalirudin-mediated anticoagulation for various surgical procedures, and the potential of bivalirudin-mediated vascular graft patency.

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“…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%

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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Hemorrhagic doses of heparin and other glycosaminoglycans induce a platelet defect

Cited by 144 publications

References 4 publications

Monitoring heparin anticoagulation in the acute phase response

Monitoring heparin anticoagulation in the acute phase response

Utilisation de la bivalirudine en chirurgie cardiaque – de l’inhibition indirecte à l’inhibition directe de la thrombine

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

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