Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents

Abstract

To cite this article: Levi M, Eerenberg E, Kamphuisen PW. Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents. J Thromb Haemost 2011; 9: 1705-12.Summary. The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In the case of severe bleeding in a patient who uses anticoagulant agents or when a patient on anticoagulants needs to undergo an urgent invasive procedure, it may be useful to reverse anticoagulant treatment. Conventional anticoagulants such as vitamin K antagonists may be neutralized by administration of vitamin K or prothrombin complex concentrates, whereas heparin and heparin derivatives can be counteracted by protamine sulphate. The anti-hemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors as well as new antiplatelet agents have been introduced and these drugs show promising results in clinical studies. A limitation of these new agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although experimental studies show hopeful results for some of these agents.

Nucleic acid scavengers inhibit thrombosis without increasing bleeding

“…A major unmet clinical need exists for developing improved antithrombotic agents because the anticoagulants currently utilized may also cause side effects such as severe and fatal bleeding, adverse immunological responses, and thrombocytopenia, as well as have unpredictable pharmacokinetics (23,24,26). We observe that at concentrations that limit thrombosis, PAMAM G-3 does not significantly increase bleeding in a murine tail-transection model.…”

“…Most of the commonly used antithrombotic agents come with an inherent risk of severe or fatal bleeding (21)(22)(23)(24). To assess the effect of PAMAM G-3 administration on bleeding, we surgically challenged mice treated with the NABP PAMAM G-3 by tail transection and monitored blood loss.…”

Guideline on the management of bleeding in patients on antithrombotic agents

“…In an in vitro experiment using the calibrated automated thrombogram, rFVIIa failed to correct the suppressed thrombin generation induced by dabigatran in spiked platelet-rich plasma samples (Perzborn & Harwardt, 2007). In experiments on healthy volunteers, rFVIIa failed to correct the reduced thrombin generation of melagatran, another direct thrombin inhibitor (Wolzt et al, 2004), and more recently Guideline ª 2012 Blackwell Publishing Ltd this failure was also observed with a PCC Levi et al, 2011). At present the data on rFVIIa and APCC is preliminary and inconclusive and not based on bleeding humans, nevertheless until new knowledge becomes available it is reasonable to try these products in patients with life-threatening bleeding on dabigatran, having made a risk-benefit decision on an individual basis.…”

The European Heart Rhythm Association Practical Guide on the Use of New Oral Anticoagulants in Patients with Non-valvular Atrial Fibrillation – A Brief Summary

“…21 Restoration of haemostasis should occur within 12-24 hours after the last dose. It is therefore important to establish the exact time of last intake and factors influencing plasma concentration, such as co-medications and CKD.…”