Medline ® Abstracts for References 73,74
of 'Perioperative management of patients receiving anticoagulants'
Perioperative hemostatic management of patients treated with vitamin K antagonists.
Levy JH, Tanaka KA, Dietrich W
Clinicians, including anesthesiologists, surgeons, and intensivists, are frequently called on to correct coagulopathy in patients receiving oral anticoagulation therapy. Before elective surgery, anticoagulation reversal may be undertaken over several days by discontinuing warfarin or vitamin K treatment, but rapid correction is required in an emergency. European and American guidelines recommend prothrombin complex concentrates (PCCs) for anticoagulation reversal in patients with life-threatening bleeding and an increased international normalized ratio. Compared with human fresh frozen plasma, PCCs provide quicker correction of the international normalized ratio and improved bleeding control. Although there are historic concerns regarding potential infectious and thrombotic risks with PCCs, current PCC formulations are much improved. Recombinant activated factor VII is a potential alternative to PCCs, but preclinical comparisons suggest that PCCs are more effective in correcting coagulopathy. Although many patients who require rapid reversal of warfarin are currently treated with fresh frozen plasma, PCCs should be considered as an alternative therapy.
Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322-1061, USA. email@example.com
Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study.
Sarode R, Milling TJ Jr, Refaai MA, Mangione A, Schneider A, Durn BL, Goldstein JN
Circulation. 2013 Sep;128(11):1234-43. Epub 2013 Aug 9.
BACKGROUND: Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal.
METHODS AND RESULTS: In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8-20.0) for the 4F-PCC group and 3.60 (1.9-38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% [95% confidence interval, -5.8 to 19.9]). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% [95% confidence interval, 39.4 to 65.9]). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (P<0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced≥1 adverse event.
CONCLUSIONS: 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708435.
University of Texas Southwestern Medical Center, Dallas (R.S.); Seton/University of Texas Southwestern Clinical Research Institute of Austin, Dell Children's Medical Center, University Medical Center at Brackenridge, Austin, TX (T.J.M.); University of Rochester Medical Center, Rochester, NY (M.A.R.); CSL Behring LLC, King of Prussia, PA (A.M., B.L.D.); CSL Behring GmbH, Marburg, Germany (A.S.); and Massachusetts General Hospital, Boston (J.N.G.).