What's New in Anticoagulation?

WHAT’S NEW IN ANTICOAGULATION?

Peter Steinberg, M.D.
Harvard Medical Faculty Physicians (HMFP) at Beth Israel Deaconess Medical Center

Urologists often care for aging patients with a slew of co-morbid medical conditions. Managing patients on chronic anticoagulation, usually for atrial-fibrillation or a history of venous thromboembolic disease (VTE), in the peri-operative period is a tremendous challenge. In recent years a variety of new anticoagulant agents have emerged, with distinct mechanisms from the standbys of warfarin and heparin, and knowledge of these drugs is essential.

Agents: The latest generation of anticoagulants includes Factor Xa inhibitors and direct thrombin inhibitors. Factor Xa inhibitors exist in direct and indirect forms.

Direct Thrombin Inhibitors: Direct thrombin inhibitors bind to thrombin in both free and bound forms and prevent the conversion of fibrinogen to fibrin. Additionally, they prevent clot stabilization via thrombin mediated Factor XIII pathways.

Direct thrombin inhibitors include lepirudin, argatroban, desirudin, bivalrudin, and dabigatran.

Thrombin time and possibly the partial thromboplastin time (PTT) may be a good means of monitoring these agents.

Uses: Patients with heparin induced thrombocytopenia (HIT) who require anticoagulation. VTE prevention after orthopaedic surgery. Dabigatran, the only oral direct thrombin inhibitor, is FDA approved for anticoagulation in atrial fibrillation.

Reversal of action: In the face of normal renal function, the half-life is approximately 12 hours, so cessation is usually the best means of reversal. In renal failure, dialysis can remove these drugs. In the event of severe hemorrhage either prothrombin complex concentrate (PCC) or recombinant activated Factor VIIa may be utilized.

Factor Xa Inhibitors: The direct Factor Xa inhibitors include rivaroxaban, apixaban, and edoxaban. The indirect Factor Xa inhibitors are fondaparinux, idraparinux, and idrabiotaparinux, though only fondaparinux has found use in the United States.

Indirect Factor Xa inhibitors enhance the activity of Antithrombin (AT), whereas direct inhibitors bind to Factor Xa that is either free or part of a clot.

Uses: Fondaparinux is dosed daily, has a low risk of causing HIT and does not require monitoring. It is used for both VTE prophylaxis and as therapeutic treatment of VTE. Direct Factor Xa inhibitors are also dosed daily, have a rapid onset of action, do not require monitoring and do not require bridging with heparin. These agents are also used for VTE prophylaxis and are now being touted as anticoagulation in patients with atrial fibrillation, as the rate of stroke is lower than warfarin based therapy.

Reversal of action: Monitoring these agents can be done with antii-factor Xa levels if necessary. There are no reversal agents for either class of Factor Xa inhibitors. In the face of normal renal function, Fondaparinux should be metabolized within 24 hours of administration; however, recombinant Factor VIIa has been used emergently when surgery has been required. The direct Factor Xa inhibitors have a consistent pharmacology, thus stopping these agents one day before surgery is usually all that is needed. Emergently, PCC has been utilized anecdotally to manage hemorrhage from these agents, but this has been scrutinized.

Conclusion: Both Factor Xa and direct thrombin inhibitors will have a larger role in urologic patients in the future. They require less monitoring and have a more consistent onset of action than heparin and warfarin; however, cessation appears to be the only consistent means of halting their anticoagulant properties before surgery.

References:

1. Louise Yeung, Emily Miraflor, Alden Harken. Confronting the chronically anticoagulated, acute care surgery patient as we evolve into the post-warfarin era. Surgery, Volume 153, Issue 3, March 2013, Pages 308-315.

2. Fadi E. Shamoun, Elvis N. Martin, Samuel R. Money. The novel anticoagulants: The surgeons' prospective. Surgery, Volume 153, Issue 3, March 2013.

Peter Steinberg, M.D.
Harvard Medical Faculty Physicians (HMFP) at Beth Israel Deaconess Medical Center