***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background — Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin , respectively . Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results . A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation . This study evaluated the potential of prothrombin complex concentrate ( PCC ) to reverse the anticoagulant effect of these drugs . Methods and Results — In a r and omized , double-blind , placebo-controlled study , 12 healthy male volunteers received rivaroxaban 20 mg twice daily ( n=6 ) or dabigatran 150 mg twice daily ( n=6 ) for 2½ days , followed by either a single bolus of 50 IU/kg PCC ( Cofact ) or a similar volume of saline . After a washout period , this procedure was repeated with the other anticoagulant treatment . Rivaroxaban induced a significant prolongation of the prothrombin time ( 15.8±1.3 versus 12.3±0.7 seconds at baseline ; P<0.001 ) that was immediately and completely reversed by PCC ( 12.8±1.0 ; P<0.001 ) . The endogenous thrombin potential was inhibited by rivaroxaban ( 51±22 % ; baseline , 92±22 % ; P=0.002 ) and normalized with PCC ( 114±26 % ; P<0.001 ) , whereas saline had no effect . Dabigatran  increased the activated partial thromboplastin time , ecarin clotting time ( ECT ) , and thrombin time . Administration of PCC did not restore these coagulation tests . Conclusion — Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study . Clinical Trial Registration — URL : http://www.trialregister.nl . Unique identifier : NTR2272 BACKGROUND Fresh frozen plasma ( FFP ) and prothrombin complex concentrates ( PCC ) reverse oral anticoagulants . We compared PCC and FFP intraoperative administration in patients undergoing heart surgery with cardiopulmonary bypass ( CPB ) . METHODS Forty patients [ with international normalized ratio (INR)≥ 2·1 ] assigned semi-urgent cardiac surgery were r and omized to receive either FFP ( n = 20 ) or PCC ( n = 20 ) . Prior to CPB , they received either 2 units of FFP or half of the PCC dose calculated according to body weight , initial INR and target INR ( ≤ 1·5 ) . After CPB and protamine administration , patients received either another 2 units of FFP or the other half PCC dose . Additional doses were administered if INR was still too high ( ≥ 1·5 ) . RESULTS Fifteen minutes after CPB , more patients reached INR target with PCC ( P = 0·007 ) : 7/16 patients vs. 0/15 patients with FFP ; there was no difference 1 h after CPB ( 6/15 patients with PCC vs. 4/15 patients with FFP reached target ) . Fifteen minutes after CPB , median INR ( range ) decreased to 1·6 ( 1·2 - 2·2 ) with PCC vs. 2·3 ( 1·5 - 3·5 ) with FFP ; 1 h after CPB both groups reached similar values [ 1·6 ( 1·3 - 2·2 ) with PCC and 1·7 ( 1·3 - 2·7 ) with FFP ] . With PCC , less patients needed additional dose ( 6/20 ) than with FFP ( 20/20 ) ( P < 0·001 ) . Both groups differed significantly on the course of factor II ( P = 0·0023 ) and factor X ( P = 0·008 ) over time . Dilution of coagulation factors was maximal at CPB onset . Safety was good for both groups , with only two related oozing cases with FFP . CONCLUSION PCC reverses anticoagulation safely , faster and with less bleeding than FFP BACKGROUND Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures . The optimum means of VKA reversal has not been established in comparative clinical trials . We compared the efficacy and safety of four-factor prothrombin complex concentrate ( 4F-PCC ) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures . METHODS In a multicentre , open-label , phase 3b r and omised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure . We r and omly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC ( Beriplex/Kcentra/Confidex ; CSL Behring , Marburg , Germany ) or plasma , with dosing based on international normalised ratio ( INR ) and weight . The primary endpoint was effective haemostasis , and the co- primary endpoint was rapid INR reduction ( ≤1·3 at 0·5 h after infusion end ) . The analyses were intended to evaluate , in a hierarchical fashion , first non-inferiority ( lower limit 95 % CI greater than -10 % for group difference ) for both endpoints , then superiority ( lower limit 95 % CI > 0 % ) if non-inferiority was achieved . Adverse events and serious adverse events were reported to days 10 and 45 , respectively . This trial is registered at Clinical Trials.gov , number NCT00803101 . FINDINGS 181 patients were r and omised ( 4F-PCC n=90 ; plasma n=91 ) . The intention-to-treat efficacy population comprised 168 patients ( 4F-PCC , n=87 ; plasma , n=81 ) . Effective haemostasis was achieved in 78 ( 90 % ) patients in the 4F-PCC group compared with 61 ( 75 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 14·3 % , 95 % CI 2·8 - 25·8 ) . Rapid INR reduction was achieved in 48 ( 55 % ) patients in the 4F-PCC group compared with eight ( 10 % ) patients in the plasma group , demonstrating both non-inferiority and superiority of 4F-PCC over plasma ( difference 45·3 % , 95 % CI 31·9 - 56·4 ) . The safety profile of 4F-PCC was generally similar to that of plasma ; 49 ( 56 % ) patients receiving 4F-PCC had adverse events compared with 53 ( 60 % ) patients receiving plasma . Adverse events of interest were thromboembolic adverse events ( six [ 7 % ] patients receiving 4F-PCC vs seven [ 8 % ] patients receiving plasma ) , fluid overload or similar cardiac events ( three [ 3 % ] patients vs 11 [ 13 % ] patients ) , and late bleeding events ( three [ 3 % ] patients vs four [ 5 % ] patients ) . INTERPRETATION 4F-PCC is non-inferior and superior to plasma for rapid INR reversal and effective haemostasis in patients needing VKA reversal for urgent surgical or invasive procedures . FUNDING CSL Behring Background and Purpose — Intracranial hemorrhage is the most devastating complication of anticoagulation . Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined . Methods — Analysis of 18 113 participants with atrial fibrillation in the R and omized Evaluation of Long-term anticoagulant therapY ( RE-LY ) trial assigned to adjusted-dose warfarin ( target international normalized ratio , 2–3 ) or dabigatran ( 150 mg or 110 mg , both twice daily ) . Results — During a mean of 2.0 years of follow-up ,  154 intracranial hemorrhages occurred in 153 participants : 46 % intracerebral ( 49 % mortality ) , 45 % subdural ( 24 % mortality ) , and 8 % subarachnoid ( 31 % mortality ) . The rates of intracranial hemorrhage were 0.76 % , 0.31 % , and 0.23 % per year among those assigned to warfarin , dabigatran 150 mg , and dabigatran 110 mg , respectively ( P<0.001 for either dabigatran dose versus warfarin ) . Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg ( n=13 and n=11 , respectively ) versus warfarin ( n=32 ; P<0.01 for both ) . Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran ( 11 patients with each dose ) compared with warfarin ( 24 patients ; P<0.05 for both dabigatran doses versus warfarin ) . Independent predictors of intracranial hemorrhage were assignment to warfarin ( relative risk , 2.9 ; P<0.001 ) , aspirin use ( relative risk , 1.6 ; P=0.01 ) , age ( relative risk , 1.1 per year ; P<0.001 ) , and previous stroke/transient ischemic attack ( relative risk , 1.8 ; P=0.001 ) . Conclusions — The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran . Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin . Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage Introduction Prothrombin complex concentrates ( PCC ) are haemostatic blood preparations indicated for urgent anticoagulation reversal , though the optimal dose for effective reversal is still under debate . The latest generation of PCCs include four coagulation factors , the so-called 4-factor PCC . The aim of this study was to compare the efficacy and safety of two doses , 25 and 40 IU/kg , of 4-factor PCC in vitamin K antagonist ( VKA ) associated intracranial haemorrhage . Methods We performed a phase III , prospect i ve , r and omised , open-label study including patients with objective ly diagnosed VKA-associated intracranial haemorrhage between November 2008 and April 2011 in 22 centres in France . Patients were r and omised to receive 25 or 40 IU/kg of 4-factor PCC . The primary endpoint was the international normalised ratio ( INR ) 10 minutes after the end of 4-factor PCC infusion . Secondary endpoints were changes in coagulation factors , global clinical outcomes and incidence of adverse events ( AEs ) . Results A total of 59 patients were r and omised : 29 in the 25 IU/kg and 30 in the 40 IU/kg group . Baseline demographics and clinical characteristics were comparable between the groups . The mean INR was significantly reduced to 1.2 - and ≤1.5 in all patients of both groups - 10 minutes after 4-factor PCC infusion . The INR in the 40 IU/kg group was significantly lower than in the 25 IU/kg group 10 minutes ( P = 0.001 ) , 1 hour ( P = 0.001 ) and 3 hours ( P = 0.02 ) after infusion . The 40 IU/kg dose was also effective in replacing coagulation factors such as PT ( P = 0.038 ) , FII ( P = 0.001 ) , FX ( P < 0.001 ) , protein C ( P = 0.002 ) and protein S ( 0.043 ) , 10 minutes after infusion . However , no differences were found in haematoma volume or global clinical outcomes between the groups . Incidence of death and thrombotic events was similar between the groups . Conclusions Rapid infusion of both doses of 4-factor PCC achieved an INR of 1.5 or less in all patients with a lower INR observed in the 40 IU/kg group . No safety concerns were raised by the 40 IU/kg dose . Further trials are needed to evaluate the impact of the high dose of 4-factor PCC on functional outcomes and mortality . Trial registration Eudra CT number 2007 - 000602 - 73 BACKGROUND Four-factor prothrombin complex concentrates ( PCCs ) , which contain factor II , FVII , FIX , and FX , have shown the potential to reverse the anticoagulant effect of  rivaroxaban in healthy volunteers . The purpose of this study was to determine whether a three-factor PCC , which contains little FVII , has a similar effect . METHODS AND RESULTS We performed an open-label , single-center , parallel-group study comparing the effect of a three-factor PCC ( Profilnine SD ) with that of a four-factor PCC ( Beriplex P/N ) on the pharmacodynamics of  rivaroxaban in  
    Output:
    
This review supports the use of PCC for VKA reversal , specifically for 4F-PCC over FFP for laboratory reversal .