Hemostasis and Thrombosis Issues

DECEMBER 07, 2011
Charles H. Brown, MSPharm, RPh, CACP

RivaRoxaban’s New Indication

In a November 4, 2011, press release, the FDA announced the approval of rivaroxaban (Xarelto, Janssen Pharmaceuticals) for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation (AF). The approval was based largely on data from ROCKET-AF. 1 Because discontinuing the drug can increase stroke risk, a boxed warning was placed on rivaroxaban to emphasize that patients should not stop taking it before talking to their health care professional.

The FDA states that rivaroxaban is now the first oral anticoagulant available in the United States for the AF indication that can be given once daily without anticoagulation monitoring. Rivaroxaban and apixaban are in a new class of drugs called factor Xa inhibitors. Factor X is an enzyme that promotes clotting, so blocking it helps to prevent strokes and systemic embolisms.

New Study Examines Aspirin and Stroke Prevention in AF Patients

In a study published in the October 2011 issue of Thrombosis and Haemostasis, researchers reported more evidence that aspirin is neither safe nor effective for the prevention of stroke in patients with AF. These results counter the longstanding claims that aspirin is a safer alternative to oral anticoagulation for stroke prevention.

This study is reportedly the largest published cohort study looking at the use of aspirin and oral anticoagulation in AF patients, and it clearly shows the net clinical benefit for aspirin is not positive at any level of stroke risk. The researchers state that unless aspirin is needed in patients for other indications, such as having a stent, there is no requirement to add aspirin on top of warfarin in AF patients. PT

US Dabigatran Label Updated

Revised drug labeling for dabigatran etexilate (Pradaxa, Boehringer Ingelheim) advises US physicians to assess a patient’s renal function prior to prescribing and to assess renal function in clinical situations associated with declines in kidney function. In patients 75 years and older and those with creatinine clearance (CrCl) <50 mL/min, the revised label also states that renal function should be assessed prior to starting therapy and tested annually. In addition, physicians should consider using the 75-mg twice-daily dose in patients with moderate renal impairment who are also taking systemic ketoconazole or dronedarone. The concomitant use of dabigatran and permeabilityglycoprotein inhibitors in patients with severe renal impairment (CrCl 15-30 mL/min) should be avoided.

Once bottles are opened, according to the new label, dabigatran can be safely stored for 4 months. The label also states that international normalized ratio (INR) testing should be avoided in patients treated with dabigatran because it is unreliable. 2

PCCS to Reverse Warfarin-Related Bleeding 

Warfarin-related bleeding, especially intracranial hemorrhage, can be catastrophic. New studies show that prothrombin complex concentrates (PCCs) lower INRs more rapidly than fresh frozen plasma (FFP).

Currently, the US, British, and French guidelines for the reversal of warfarin-related bleeding recommend PCC as the treatment of choice to accompany vitamin K. PCC 4-factor products demonstrate the best evidence for superior effectiveness in stopping bleeding coupled with low incidence of thrombotic events.

PCC 4-factor concentrate contains factors II, VII, IX, and X, but the composition of PCC products is variable. Those PCC products available in the United States include clotting factors II, IX, and X, but only small amounts of factor VII (3-factor PCC). Due to the lack of factor VII, supplementing PCC with FFP to replace factor VII has been employed to reverse warfarinrelated bleeding. 3,4

Mr. Brown is professor emeritus of clinical pharmacy and a clinical pharmacist at Purdue University College of Pharmacy, Nursing, and Health Sciences, Department of Pharmacy Practice, West Lafayette, Indiana. This column’s information is based on current studies and references, but it may be changed without notice with newer studies or with different patient populations.


  1. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. NEJM. 2011:365;883-891.
  2. US dabigatran label updated, including renal-function recommendations. TheHeart.org. www.theheart.org/article/1306579.do. Accessed November 10, 2011.
  3. Bershad EM, Suarez JI. Prothrombin complex concentrates for oral anticoagulant therapy-related intracranial hemorrhage: a review of the literature. Neurocrit Care. 2010;12:403.
  4. Schick KS, Fertmann JM, Jauch K, Hoffman JN. Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care. 2009;13:R191.

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