A Comparison of Recombinant Hirudin with a Low-Molecular-Weight Heparin to Prevent Thromboembolic Complications after Total Hip Replacement

Eriksson, Bengt I.; Wille‐Jørgensen, Peer; Kälebo, Peter; Mouret, P; Rosencher, Nadia; Bösch, Peter; Baur, Markus; Ekman, Steffan; Bach, Doris; Lindbratt, Siv; Close, Philippe

doi:10.1056/nejm199711063371901

Cited by 361 publications

(204 citation statements)

References 18 publications

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“…4 Indeed, long-term subcutaneous administration of specific ATs may prove even more efficacious than low-molecular-weight heparins. 33 Although further modifications of drug delivery are desirable for clinical application, the present observations raise the possibility of extended oral dosing with heparins or specific ATs. 34,35 They may also have a broader relevance to the absorption of macromolecules in general.…”

Section: Discussionmentioning

confidence: 86%

Oral Delivery of Anticoagulant Doses of Heparin

Baughman

Kapoor²,

Agarwal³

et al. 1998

Circulation

116

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Background-Parenteral heparin is the anticoagulant of choice in hospitalized patients. Continued anticoagulation is achieved by subcutaneous administration of low-molecular-weight heparin or with an orally active anticoagulant such as warfarin. An oral heparin formulation would avoid the inconvenience of subcutaneous injection and the unfavorable drug interactions and adverse events associated with warfarin. A candidate delivery agent, sodium N-[8(-2-hydroxybenzoyl)amino]caprylate (SNAC), was evaluated with escalating oral heparin doses in a randomized, double-blind, controlled clinical study for safety, tolerability, and effects on indexes of anticoagulation. Methods and Results-Increases in activated partial thromboplastin time (aPTT), anti-factors IIa and Xa, and tissue factor pathway inhibitor (TFPI) concentrations were detected when normal volunteers were dosed with 10.5 g SNAC/20 000 IU heparin by gavage in some subjects. For the entire group, 30 000 IU SNAC and heparin elevated TFPI from 74.9Ϯ7.6 to 254.2Ϯ12.3 mg/mL (PϽ0.001) 1 hour after dosing (PϽ0.001). Similar changes occurred in anti-factor IIa and anti-factor Xa. aPTT rose from 28Ϯ0.5 to 42.2Ϯ6.3 seconds 2 hours after dosing (PϽ0.01). No significant changes in vital signs, physical examination, ECGs, or clinical laboratory values were observed. Neither 30 000 IU heparin alone nor 10.5 g SNAC alone altered the hemostatic parameters. Emesis was associated with 10.5 g SNAC. A taste-masked preparation of SNAC 2.25 g was administered orally with heparin 30 000 to 150 000 IU. Both aPTT and anti-factor Xa increased with escalating doses of heparin. This preparation was well tolerated. Conclusions-Heparin, administered orally in combination with the delivery agent SNAC, produces significant elevations in 4 indexes of anticoagulant effect in healthy human volunteers. These results establish the feasibility of oral delivery of anticoagulant doses of heparin in humans and may have broader implications for the absorption of macromolecules.

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Section: Discussionmentioning

confidence: 86%

Oral Delivery of Anticoagulant Doses of Heparin

Baughman

Kapoor²,

Agarwal³

et al. 1998

Circulation

116

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“…Compared to argatroban, its use is not recommended in patients with renal failure, as it is cleared primarily by the kidneys, but it can be used in patients with impaired liver function [117]. Desirudin is used for VTE prophylaxis in patients undergoing total hip replacement [118]. Hirudin use for ACS has been studied, but not yet approved [119].…”

Section: Desirudin (Iprivask)mentioning

confidence: 99%

Management of antithrombotic agents in patients undergoing flexible bronchoscopy

et al. 2017

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Bleeding is one of the most feared complications of flexible bronchoscopy. Although infrequent, it can be catastrophic and result in fatal outcomes. Compared to other endoscopic procedures, the risk of morbidity and mortality from the bleeding is increased, as even a small amount of blood can fill the tracheobronchial tree and lead to respiratory failure. Patients using antithrombotic agents (ATAs) have higher bleeding risk. A thorough understanding of the different ATAs is critical to manage patients during the peri-procedural period. A decision to stop an ATA before bronchoscopy should take into account a variety of factors, including indication for its use and the type of procedure. This article serves as a detailed review on the different ATAs, their pharmacokinetics and the pre-and post-bronchoscopy management of patients receiving these medications.

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“…Two randomized, double-blind, multi-centre clinical studies compared the efficacy and safety of desirudin (15 mg s.c. twice daily injections) with unfractionated heparin (UFH) (5000 units s.c. three times daily) and enoxaparin (40 mg s.c. daily) for the prophylaxis of DVT in patients undergoing major orthopaedic surgeries. Desirudin was superior to both heparin anticoagulants (P < 0.001 for both) after 8-12 days of treatment, while showing a similar safety profile [18,19]. Desirudin is also currently under investigation as a potential anticoagulant for patients with HIT with or without thrombosis.…”

Section: Figurementioning

confidence: 99%

Direct Thrombin Inhibitors

Maffrand

2005

N Engl J Med

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Heparins and vitamin K antagonists have been the primary agents used for anticoagulation in certain cardiovascular and thromboembolic diseases for over 50 years. However, they can be difficult to administer and are fraught with limitations. In response to the need for new anticoagulants, direct thrombin inhibitors (DTIs) have been developed and investigated for their utility in prophylaxis and treatment of venous thromboembolism (VTE), heparin-induced thrombocytopenia (HIT), acute coronary syndromes (ACS), secondary prevention of coronary events after ACS, and nonvalvular atrial fibrillation. Currently, four parenteral direct inhibitors of thrombin activity are FDA-approved in North America: lepirudin, desirudin, bivalirudin and argatroban. Of the new oral DTIs, dabigatran etexilate is the most studied and promising of these agents. This review discusses the clinical indications and efficacy of these direct thrombin inhibitors as well as future directions in anticoagulant therapy.

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A Comparison of Recombinant Hirudin with a Low-Molecular-Weight Heparin to Prevent Thromboembolic Complications after Total Hip Replacement

Abstract: When administered 30 minutes before total hip replacement surgery, desirudin is more effective than enoxaparin in preventing deep-vein thrombosis.

Cited by 361 publications

References 18 publications

Oral Delivery of Anticoagulant Doses of Heparin

Oral Delivery of Anticoagulant Doses of Heparin

Management of antithrombotic agents in patients undergoing flexible bronchoscopy

Direct Thrombin Inhibitors

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