***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 
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    Input: BACKGROUND Prothrombin complex concentrate ( PCC ) can substantially shorten the time needed to reverse antivitamin K oral anticoagulant therapy ( OAT ) . OBJECTIVES . To determine the effectiveness and safety of emergency OAT reversal by a balanced pasteurized nanofiltered PCC ( Beriplex P/N ) containing coagulation factors II , VII , IX , and X , and anticoagulant proteins C and S. PATIENTS AND METHODS Patients receiving OAT were eligible for this prospect i ve multinational study if their International Normalized Ratio ( INR ) exceeded 2 and they required either an emergency surgical or urgent invasive diagnostic intervention or INR normalization due to acute bleeding . Stratified 25 , 35 , or 50 IU kg(-1 ) PCC doses were infused based on initial INR . Study endpoints included INR normalization ( < /=1.3 ) by 30 min after PCC infusion and hemostatic efficacy . RESULTS Forty-three patients , 26 requiring interventional procedures and 17 experiencing acute bleeding , received PCC infusions at a median rate of 7.5 mL min(-1 ) ( 188 IU min(-1 ) ) . At 30 min thereafter , INR declined to < /=1.3 in 93 % of patients . At all postinfusion time points through 48 h , median INR remained between 1.2 and 1.3 . Clinical hemostatic efficacy was classified as very good or satisfactory in 42 patients ( 98 % ) . Prompt and sustained increases in circulating coagulation factors and anticoagulant proteins were observed . One fatal suspected pulmonary embolism in a patient with metastatic cancer was judged to be possibly PCC-related . CONCLUSIONS PCC treatment serves as an effective rapid hemorrhage control re source in the emergency anticoagulant reversal setting . More widespread availability of PCC is warranted to ensure its benefits in appropriate patients 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 A rapid method of reversal is required for patients on warfarin who suffer acute bleeding or require emergency surgery .  Prothrombin complex concentrates ( PCCs ) have recently been recommended by the Canadian Blood Services for use at a fixed low dose of 1000 IU of Factor (F)IX activity . The main goal of this study was to investigate both the effectiveness and the safety of fixed low-dose PCCs . STUDY DESIGN AND METHODS We retrospectively review ed charts from 103 patients who received PCCs for reversal of warfarin therapy .  RESULTS A total of 103 patients were treated with PCC at a single fixed dose of 1000 IU of F IX activity . Fifty patients ( 48.5 % ) had a final international normalized ratio ( INR ) response of not more than 1.5 and an additional 45 patients ( 43.7 % ) had a final INR response between 1.6 and 2.0 . However , 86 patients ( 83.5 % ) had an excellent clinical response consisting of control of bleeding without the requirement of additional measures . In a multivariable model , patients who received fresh-frozen plasma and patients who were given doses greater than 1000 IU of PCC were both identified as predictors of a poor clinical response ( odds ratio [ OR ] 3.48 , 95 % confidence interval [ CI ] 0.76 - 15.89 , p = 0.11 ; and OR 10.8 , 95 % CI 2.08 - 56.28 , 95 % CI , p = 0.005 , respectively ) . There were five adverse events up to 30 days after PCC use . CONCLUSION At a fixed dose of 1000 IU of F IX activity , PCC seems to be effective and safe but r and omized controlled trials , specifically examining different doses of PCC , are required to confirm the above observations BACKGROUND Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications . We studied the frequency of bleeding complications in out patients treated routinely in anticoagulation clinics . METHODS In a prospect i ve cohort from thirty-four Italian anticoagulation clinics , 2745 consecutive patients were studied from the start of their oral anticoagulation ( warfarin in 64 % , acenocourmarol in the rest ) . The target anticoagulation-intensity was low ( international normalised ratio [ INR ] < or = 2.8 ) in 71 % of the patients and high ( > 2.8 ) in the remainder . We recorded demographic details and the main indication for treatment and , every 3 - 4 months , INR and outcome events . Such events included all complications ( bleeding , thrombosis , other ) , although only bleeding events are reported here , and deaths . We divided bleeding into major and minor categories . FINDINGS 43 % of the patients were women . Nearly three-fifths of the patients were aged 60 - 79 ; 8 % were over 80 . The main indication for treatment was venous thrombolism ( 33 % ) , followed by non-ischaemic heart disease ( 17 % ) . Mean follow-up was 267 days . Over 2011 patient-years of follow-up , 153 bleeding complications occurred ( 7.6 per 100 patient-years ) . 5 were fatal ( all cerebral haemorrhages , 0.25 per 100 patient-years ) , 23 were major ( 1.1 ) , and 125 were minor ( 6.2 ) . The rate of events was similar between sexes , coumarin type , size of enrolling centre , and target INR . The rate was higher in older patients : 10.5 per 100 patient-years in those aged 70 or over , 6.0 in those aged under 70 ( relative risk 1.75 , 95 % Cl 1.29 - 2.39 , p < 0.001 ) . The rate was also higher when the indication was peripheral and /or cerebrovascular disease than venous thromboembolism plus other indications ( 12.5 vs 6.0 per 100 patient-years ) ( 1.80 , 1.2 - 2.7 , p < 0.01 ) , and during the first 90 days of treatment compared with later ( 11.0 vs 6.3 , 1.75 , 1.27 - 2.44 , p < 0.001 ) . A fifth of the bleeding events occurred at low anticoagulation intensity ( INR < 2 , rate 7.7 per 100 patient-years of follow-up ) . The rates were 4.8 , 9.5 , 40.5 , and 200 at INRs 2.0 - 2.9 , 3 - 4.4 , 4.5 - 6.9 , and over 7 , respectively ( relative risks for INR > 4.5 , 7.91 , 5.44 - 11.5 , p < 0.0001 ) . INTERPRETATION We saw fewer bleeding events than those recorded in other observational and experimental studies . Oral anticoagulation has become safer in recent years , especially if monitored in anticoagulation clinics . Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Introduction In  vitamin K antagonist (VKA)-treated patients with severe hemorrhage , guidelines recommend prompt VKA reversal with prothrombin complex concentrate ( PCC ) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on seven-day mortality . Methods Data from consecutive patients treated with PCC were prospect ively collected in 44 emergency departments .  Type of hemorrhage , coagulation parameters , type of treatment and seven-day mortality mortality were recorded . Guideline -concordant administration of PCC and vitamin K ( GC-PCC-K ) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of eight hours after admission . Multivariate analysis was used to assess the effect of appropriate reversal on seven-day mortality in all patients and in those with intracranial hemorrhage ( ICH ) . Results Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months .  Bleeding was gastrointestinal ( 32 % ) , intracranial ( 32 % ) , muscular ( 13 % ) , and “ other ” ( 23 % ) . In the whole cohort , seven-day mortality was 13 % and 33 % in patients with ICH . GC-PCC-K was performed in 38 % of all patients and 44 % of ICH patients . Multivariate analysis showed a two-fold decrease in seven-day mortality in patients with GC-PCC-K ( odds ratio ( OR ) = 2.15 ( 1.20 to 3.88 ) ; P = 0.011 ) ; this mortality reduction was also observed when only ICH was considered ( OR = 3.23 ( 1.53 to 6.79 ) ; P = 0.002 ) . Conclusions Guideline -concordant VKA reversal with PCC and vitamin K within eight hours after admission was associated with a significant decrease in seven-day mortality Introduction Prothrombin Complex Concentrate ( PCC ) is a key treatment in the management of bleeding related to Vitamin K antagonists ( VKA ) . This study aim ed to evaluate prospect ively PCC use in patients with VKA-related bleeding in view of the French guidelines published in 2008 . Methods All consecutive patients with VKA-related bleeding treated with a 4-factor PCC ( Octaplex ® ) were selected in 33 French hospitals . Collected data included demographics , site and severity of bleeding , modalities of PCC administration , International Normalized Ratio ( INR ) values before and after  PCC  administration , outcomes and survival rate 15 days after infusion . Results Of 825 patients who received PCC between August 2008 and December 2010 , 646 had severe bleeding .  The main haemorrhage sites were intracranial ( 43.7 % ) and abdominal ( 24.3 % ) . Mean INR before PCC was 4.4 ± 1.9 ; INR was unavailable in 12.5 % of patients . The proportions of patients who received a PCC dose according to guidelines were 15.8 % in patients with initial INR 2 - 2.5 , 41.5 % in patients with INR 2.5 - 3 , 40.8 % in patients with INR 3 - 3.5 , 26.9 % in patients with INR > 3.5 , and 63.5 % of patients with unknown INR  . Vitamin K was administered in 84.7 % of patients . The infused dose of PCC did not vary with initial INR ; the mean dose was 25.3 ± 9.8 IU/Kg . Rates of controlled bleeding and target INR achievement were similar , regardless of whether or not patients were receiving PCC doses as per the guidelines . No differences in INR  after PCC treatment were observed , regardless of whether or not vitamin 
    Output:
    
PCC reduced the time to reach INR correction in comparison with FFP or no treatment .
Four-factor PCC is an effective and safe option in reversal of VKA bleeding events