***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: Objective Intracranial hemorrhage in patients receiving oral anticoagulant ( OAC ) therapy  is associated with poor neurological outcome . Prothrombin complex concentrate ( PCC ) is the gold – st and ard therapy to normalize hemostasis but remains underused . Ultra-rapid reversal of anticoagulation could reduce the time to biological and surgical hemostasis , and might improve outcome . We report the use of bolus infusions of PCC to immediately reverse anticoagulation and allow for urgent neurosurgical care . Design Prospect i ve , observational study . Setting Neurosurgical intensive care unit , university hospital . Patients and participants Eighteen patients with OAC-associated intracranial hemorrhage requiring urgent neurosurgical intervention . Interventions All patients received 20 UI/kg of PCC as an intravenous bolus infusion ( 3 min ) and 5 mg of enteral vitamin K. Surgery was started immediately , without waiting for blood sample results . Measurements and results Serial blood sample s were performed to assess prothrombin time . Coagulation was considered normal when the international normalized ratio was ≤ 1.5 . All patients , including nine who were over-anticoagulated , had complete reversal of anticoagulation immediately after the bolus of PCC . No hemorrhagic or thrombotic adverse effect was observed intra- or postoperatively . Conclusions A bolus infusion of PCC  completely reverses anticoagulation within 3 min . Neurosurgery can be performed immediately in OAC-related intracranial hemorrhage . This study shows that OAC – treated patients can be managed as rapidly as non – anticoagulated patients Background Co-fact © , prothrombin complex concentrate , is used for restoring the international normalized ratio ( INR ) in patients on vitamin K antagonists ( VKA ) presenting with acute bleeding . In this prospect i ve cohort study , we evaluated whether adequate INR values were reached in ED patients using the Sanquin ( Federation of Dutch Thrombosis Services ) treatment protocol . Methods We evaluated this protocol for two target INR groups : group 1 , target INR ≤ 1.5 ( for life-threatening bleeding/immediate intervention ) ; group 2 , target INR 1.6 - 2.1 ( in cases of a minor urgent surgery or serious overdosing of anticoagulant ) . We specifically wanted to identify both under- and over-treated patients . Reversing VKA anticoagulation therapy to unnecessarily low INR values may involve thrombotic risks . Apart from this risk , the patient is also administered an excess amount of the drug . This means unnecessary costs and may present problems with restoring an anticoagulated state at a later time . Results In our cohort , the Sanquin dosing protocol was followed for 45/60 patients . It appeared that out of the 41 patients in group 1 ( target INR ≤ 1.5 ) , 35 ( 85 % ) achieved the goal INR . This occurred more often than for the 19 patients in group 2 ( target INR 1.6–2.1 ) , where only 6 ( 32 % ) achieved the goal INR . Using the protocol result ed in a positive trend toward better INR reversal in group 1.In group 2 , no relation between using the protocol and achieving the desired INR value was detected . Physicians ignoring the proposed dose of Co-fact © prescribed significantly less Co-fact © ( even when correcting for patient weight ) . It appeared that patients in group 1 had a significantly lower baseline INR than patients in group 2 . Group 2 patients , on the other h and , had a baseline INR > 7.5 in 53 % of the cases . Conclusion In our cohort , for most patients in INR group 2 treated with Co-fact © , the achieved INR value was outside the desired range of 1.6 - 2.1 . The supra-therapeutic range of baseline INR in group 2 may have contributed to the different kind of bleeding witnessed in this patient group . Our results support the idea that treatment of patients on vitamin K antagonists with Co-fact © could benefit from a slightly different approach , taking into account the INR value to which the patient needs to be reversed 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 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 INTRODUCTION Prothrombin complex concentrates ( PCCs ) are used for the urgent reversal of oral vitamin K antagonists in patients with life-threatening bleeding or prior to urgent procedures /surgery . PCCs offer rapid and complete reversal without the disadvantages of volume overload and adverse reactions seen with fresh frozen plasma ( FFP ) . There is concern about the risk of thrombosis associated with the use PCCs ; data on this is limited at present . OBJECTIVES To determine the incidence of objective ly confirmed arterial or venous thromboembolism within 30 days following the administration of PROTHROMBINEX ® -VF ( PTX-VF ) to acutely reverse a prolonged INR . MATERIAL S/ METHODS A prospect i ve observational study was conducted at two teaching hospitals in Auckl and , NZ . All patients who received PTX-VF  for the acute reversal of prolonged INR were eligible . Baseline patient demographics and reasons for PTX-VF administration were recorded . Patients were review ed at days 7 and 30 , to confirm/exclude thromboembolism or adverse events . RESULTS 173 patients were enrolled from August 2008 to March 2009 . The most frequent indication for reversal was acute bleeding . At 30 days 4.6 % ( 8/173 ) patients had a definite/probable thrombotic event , and 16.7 % had died either due to the presenting bleed ( intracranial haemorrhage ) or a complication of their presenting complaint ( e.g. sepsis , renal failure ) . CONCLUSIONS Acute reversal of anticoagulant therapy with PTX-VF is associated with a significant rate of thromboembolism ( 4.6 % ) within 30 days . These events can be explained by ongoing cessation of anticoagulant therapy in patients with ongoing risk factors for arterial or venous thrombosis , rather than directly attributable to PTX-VF therapy 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 ( 4 
    Output:
    
Relatively good clinical and INR outcomes were reported with the use of any treatment protocol while less good results were reported for INR outcome when a predefined protocol was missing ( doctor strategy ) .
Lowest PCC dosages were infused in the fixed dose strategy .
In emergency VKA reversal , a predefined PCC dosing protocol seems essential .
We found no evidence that one dosing strategy is superior .