Effect of Activated Prothrombin Complex Concentrate or Recombinant Factor VIIa on the Bleeding Time and Thrombus Formation During Anticoagulation with a Direct Thrombin Inhibitor

Elg, Margareta; Carlsson, Stefan; Gustafsson, David

doi:10.1016/s0049-3848(00)00397-2

Cited by 103 publications

(62 citation statements)

References 20 publications

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“…In an animal model of bleeding, activated prothrombin complex concentrate reduced bleeding after treatment with another thrombin inhibitor (melagatran). 47 In extreme cases, and where it is available, acute hemodialysis should be considered because only 35% of dabigatran is bound to plasma proteins. This strategy has been evaluated in patients with end-stage renal disease, who received 1 dose of 50 mg dabigatran and then had hemodialysis.…”

Section: Dabigatranmentioning

confidence: 99%

How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch

Schulman

Crowther

2012

Blood

223

197

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Two novel oral anticoagulants, dabigatran and rivaroxaban, have recently been approved. They differ in many ways from warfarin, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of need for monitoring, and no need for titration or dose adjustments. These novel agents represent a landmark shift in anticoagulant care; however, many aspects of their use will be unfamiliar to practicing clinicians, despite the imminent widespread use of these agents in the community. The management of these anticoagulants when transitioning from or back to warfarin, around surgery or in case of major hemorrhage, requires knowledge of their pharmacokinetics and mechanism of action. Unfortunately, there is a limited evidence base to inform decisions around management of these agents. We present our practice in these settings supported, where available, with literature evidence. (Blood. 2012;119(13): 3016-3023) IntroductionDabigatran has become available for long-term use in the United States and Canada at the end of 2010 and is the first novel antithrombotic agent approved for stroke prophylaxis in atrial fibrillation since the introduction of warfarin more than 50 years ago. 1 The Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) study provided high-quality evidence that, when administered at a dose of 150 mg twice daily, dabigatran is associated with a reduced risk of stroke and a similar risk of bleeding as warfarin when targeted to an international normalized ratio (INR) of 2.0 to 3.0. 2 When administered at a dose of 110 mg twice daily, the risk of stroke with dabigatran is similar to that of warfarin while producing less bleeding. This dose is approved in Canada but not in the United States because it did not reduce the risk of stroke compared with warfarin and stroke prevention was considered more important than the benefit of decreased risk for extracranial major bleeding. The dose of 75 mg twice daily is, however, recommended in the United States for patients with severe renal failure (calculated creatinine clearance 15-30 mL/ min). Dabigatran has also been approved for the prevention of deep vein thrombosis after orthopedic surgery in Canada, Europe, 3 and several other countries, and has been studied in the setting of long-term secondary prevention for venous thromboembolism. 4 Peer organization guidelines now recommend the use of dabigatran for many patients with atrial fibrillation. 5 The oral factor Xa inhibitor, rivaroxaban, has also been approved for prevention of stroke in atrial fibrillation and of venous thrombosis after orthopedic surgery. 6 Clinicians are intimately familiar with warfarin. It has 100% name recognition internationally, monitoring for its anticoagulant effect is routinely available, and physicians are aware of the need to interrupt warfarin for many interventional procedures. 7 There are established and highly effective treatment strategies for bleeding in patients receiving warfarin and for the management of unanticipated excess anticoagulant effe...

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Section: Dabigatranmentioning

confidence: 99%

How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch

Schulman

Crowther

2012

Blood

223

197

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“…Treatment with rFVIIa ex vivo restored abnormal thromboelastography parameters in blood samples from two patients treated with argatroban (Young et al, 2007). However, in an animal study of a different direct thrombin inhibitor (melagatran), rFVIIa had no effect on bleeding time whereas APCC reduced bleeding time (Elg et al, 2001). With yet another direct thrombin inhibitor, dabigatran, the drugs rVIIa, APCC and PCC exhibited activity in correcting the coagulopathy in animal models (Van Ryn et al, 2010a;Van Ryn et al, 2008).…”

Section: Argatrobanmentioning

confidence: 99%

Guideline on the management of bleeding in patients on antithrombotic agents

et al. 2012

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“…TAT and F1+2 were increased after the administration of MC710 indicating the activation of prothrombin in blood flow; however, similar increases were also observed after the administration of rFVIIa and APCC [54,55]. No serious or severe adverse events were observed within 4 weeks after the administration of MC710 and no subject discontinued treatment due to an adverse event.…”

Section: Dic and Other Safety Concernsmentioning

confidence: 58%

Prospective Efficacy and Safety of a Novel Bypassing Agent, FVIIa/FX Mixture (MC710) for Hemophilia Patients with Inhibitors

Tomokiyo¹,

Nakatomi²,

Hamamoto³

et al. 2012

Hemophilia

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Effect of Activated Prothrombin Complex Concentrate or Recombinant Factor VIIa on the Bleeding Time and Thrombus Formation During Anticoagulation with a Direct Thrombin Inhibitor

Cited by 103 publications

References 20 publications

How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch

How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch

Guideline on the management of bleeding in patients on antithrombotic agents

Prospective Efficacy and Safety of a Novel Bypassing Agent, FVIIa/FX Mixture (MC710) for Hemophilia Patients with Inhibitors

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