Pharmacokinetics of Heparin and Low Molecular Weight Heparins

Ambrosioni, Ettore; Strocchi, Enrico

doi:10.1159/000216165

Cited by 3 publications

(4 citation statements)

References 18 publications

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“…All LMWH have greater antiXa activity than antifactor IIa activity. In addition when antifactor IIa activity is undetectable, antiXa activity remains (Ambrosioni and Strocchi 1990;Coccheri 1990).…”

Section: Discussionmentioning

confidence: 99%

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Biological monitoring of three antithrombotic drugs: single dose therapy

Gopegui

Espada

Monreal

et al. 1997

Comparative Haematology International

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Abstract.A randomised study using 40 New Zealand White male rabbits was performed to compare the effects of three antithrombotic drugs on eight clinical haemostatic function tests. The animals were divided into four treatment groups. The treatment groups were saline (control), unfractioned heparin (UFH), lowmolecular-weight heparin (LMWH), and recombinant hirudin (r-hirudin).Blood samples were collected 2 and 12 h after administration of the drugs. The following tests were performed: bleeding time (BT), platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration (Fg), antithrombin III (ATIII), and antifactor Xa activity (antiXa activity). Effects attributable to drug treatment for each analyte were determined by comparison with the control group.At 2 h after medication, in the UFH treated group, TT was moderately prolonged (p<0.05) and antiXa activity was significantly higher (p<0.05) than the respective values of the control group. In the LMWHtreated group the antiXa activity was significantly higher (p<0.01) than that of the control group. In the r-hirudin-treated group, the APTT and TT were significantly prolonged (APTT, p<0.01; the TT samples did not clot) when compared to the control group. However, 12 h after administration, no significant differences (p>0.05) between groups were observed for any of the studied analytes. It might be concluded that the antiXa assay has the potential of being a sensitive screen Correspondence and offprint requests to: R. Ruiz de Gopegui, Unit of Experimental Thrombosis, Faculty of Veterinary Science, Universidad Autonoma Barcelona, 08193--Bellaterra, Barcelona, Spain.for heparin therapy and that the absence of changes in the bleeding time, antithrombin III, and antiXa assayswith a markedly prolonged thrombin time -indicates that, in vivo, r-hirudin acts as a specific inhibitor of thrombin.

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Section: Discussionmentioning

confidence: 99%

“…LMWH proportionately inhibits factor Xa more than it inhibits thrombin (Coccheri 1990). Thus LMWH can be administered to effect half as often as UFH (Thomas 1986;Bergqvist et al 1988;Ambrosioni and Strocchi 1990).…”

Section: Introductionmentioning

confidence: 99%

Biological monitoring of three antithrombotic drugs: single dose therapy

Gopegui

Espada

Monreal

et al. 1997

Comparative Haematology International

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“…In contrast, subcutaneously administered LMWHs achieve a bioavailability in excess of 90%. 10 Unfractionated heparin binds more readily and extensively to plasma proteins and endothelial cells, which reduces its anticoagulant activity; this phenomenon explains the wide variation observed in UFH's dose-response relationship. 9 Because LMWHs bind less extensively to plasma proteins and endothelial cells, they produce a much more predictable and consistent anticoagulant response.…”

Section: Ufh and Lmwhsmentioning

confidence: 99%

Limitations of Traditional Anticoagulants

Hawkins

2004

Pharmacotherapy

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Warfarin and unfractionated heparin have been in clinical use for more than 50 years. Both are effective anticoagulants, but their use is associated with a number of impediments, including the need for intensive coagulation monitoring, wide variation in dose-response relationships, multiple drug interactions (in the case of warfarin), and serious immune-mediated thrombocytopenia (in the case of heparin). The introduction of low-molecular-weight heparins 10 years ago advanced anticoagulation therapy by enhancing efficacy and eliminating the need for intensive coagulation monitoring. Fondaparinux, the first selective factor Xa inhibitor, represents yet another improvement in anticoagulation therapy with even greater efficacy and safety.

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“…Also LMWH have a longer plasma half-life [29,30] and a more favourable antithrombotic to haemorrhagic risk ratio; they maintain their antithrombotic effect prob ably through anti-Xa activity but cause less clinical bleeding by a reduced action on the APTT and overall clotting [28,31,32]. These properties might allow LMWH to be administered once daily without laboratory monitoring.…”

Section: Low Molecular Weight Heparins (Lmwh)mentioning

confidence: 99%

New developments in the treatment of deep venous thrombosis

Janssen¹,

Nováková²,

Verbruggen³

et al. 1997

The Netherlands Journal of Medicine

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An initial course of standard heparin (SH) or low-molecular-weight heparins (LMWH) is regarded as the treatment of choice for patients with deep venous thrombosis (DVT). LMWH have better bioavailability after subcutaneous administra tion, have a longer half-life, and show higher and more predictable anticoagulant activity. As a result they can be given subcutaneously and without laboratory control, using a dose that is determined by body weight. Because of these multiple advantages of LMWH they will replace SH in the future and subsequently home treatment with LMWH of selected patients seems feasible. The currently accepted approach is to start with SH or LMWH therapy combined with oral anticoagulant therapy (OAT) at the time of diagnosis. The course of SH or LMWH should continue for at least 5 days, provided that international normalized ratio (INR) is in the therapeutic range on 2 consecutive days. OAT should be continued for at least 3 months to prolong the prothrombin time to an INR of 2 -3 . When oral anticoagulants are either contraindicated or inconvenient, SH or LMWH can be used at the middosing interval. The role of anti-platelet treatment is not yet established 4 and should be compared with coumarin therapy in the future.

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Pharmacokinetics of Heparin and Low Molecular Weight Heparins

Cited by 3 publications

References 18 publications

Biological monitoring of three antithrombotic drugs: single dose therapy

Biological monitoring of three antithrombotic drugs: single dose therapy

Limitations of Traditional Anticoagulants

New developments in the treatment of deep venous thrombosis

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