***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: To determine the best way to reverse the excessive effect of regular anticoagulation in patients with INR > 5 and no bleeding complications , 23 patients with INR > 5 were r and omly subdivided into two groups : group A ( n = 12 ) discontinued warfarin for one day and group B ( n = 11 ) received 2 mg of vitamin K1 orally in addition to the usual warfarin dose .  INR was determined after 24 h ( day 1 ) , after which both groups continued with their usual dose of warfarin . After 48 h ( day 2 ) , warfarin dosage was changed according to the INR value . On day 9 , INR values were determined again . Five out of twelve patients in group A had INR values > 5 on day 1 . One patient in group A had an INR value < 5 both on days 1 and 2 . All eleven patients in group B had INR values < 5 on day 1 , and all but one on day 2 . On day 9 , INR values were acceptable ( INR 2.0 - 4.5 ) in ten group A patients and eight group B patients . These findings suggest that a low oral dose of vitamin K1 is a convenient treatment for excessive anticoagulation in patients with no bleeding complications 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 BACKGROUND Excessive anticoagulation increases the risk of hemorrhagic complications associated with oral anticoagulant therapy . Oral or parenteral phytonadione is used to reverse excessive anticoagulation . Intravenous ( IV ) phytonadione , while effective , is associated with a small risk of serious anaphylactic reactions . Subcutaneous ( SC ) administration is safer , but there is little information on its relative efficacy in small doses . METHODS Twenty-two patients with asymptomatic prolongation of prothrombin time were prospect ively r and omized and treated with 1 mg of phytonadione IV or 1 mg SC .  Prothrombin time was measured at baseline and at 8 and 24 hours after phytonadione administration and expressed as international normalized ratio ( INR ) . RESULTS Mean INR at baseline was 8.0 and 8.5 in the IV and SC groups , respectively ( P = .70 ) . At 8 hours , mean INR was 4.6 in the IV group and 8.0 in the SC group ( P = .006 ) , and at 24 hours , mean INR was 3.1 in the IV group and 5.0 in the SC group ( P = .009 ) . Mean decrease in INR 8 hours after administration of phytonadione was 3.4 in the IV group and 0.4 in the SC group ( P = .02 ) , and mean decrease in INR after 24 hours was 4.9 in the IV group and 3.4 in the SC group ( P = .18 ) . CONCLUSIONS For patients who are excessively anticoagulated with warfarin , small doses of SC phytonadione may not correct the INR as rapidly or as effectively as when administered IV . Higher doses must be considered for more rapid and complete reversal of anticoagulation by the SC route We performed a prospect i ve , r and omized , open study in 109 out patients under chronic anticoagulation with acenocoumarine , presenting with International Normalized Ratios ( INRs ) ⩾ 6.0 and no or minor bleeding . All the patients withheld one dose of acenocoumarine ; in addition , a treated group also received 1 mg oral vitamin K1 . We aim ed at a post-intervention INR < 6.0 , with a target zone of 2.0–4.0 . The INRs were lowered from a mean of 8.1 ± 1.7 to 4.9 ± 2.5 in the controls ( P= 0.0000 ) and from 8.4 ± 2.4 to 3.3 ± 3 in the treated patients ( P= 0.0000 ) . There were no differences in the percentage of patients with post-intervention INRs < 6.0 or within the therapeutic zone . One-third of the treated patients and only 2 % of the controls reached INRs < 2.0 ( P= 0.0003 ) . Oral vitamin K1offered no advantage to the simple discontinuation of one dose of acenocoumarine . A substantial number of treated patients were consequently exposed to under-anticoagulation STUDY OBJECTIVE To compare the efficacy of managing excessive anticoagulation  in the absence of bleeding by either omitting warfarin therapy alone or administering oral phytonadione in addition to omitting warfarin therapy . DESIGN R and omized , double-blind , placebo-controlled study . SETTING Clinical pharmacy anticoagulation service in a group model health maintenance organization . SUBJECTS Thirty nonbleeding patients with international normalized ratios ( INRs ) ranging from 6.0 - 10.0 . INTERVENTIONS Patients were r and omized to receive either a single oral dose of phytonadione 2.5 mg or placebo .  Both groups omitted warfarin doses until the INR became less than or equal to 4.0 . MEASUREMENTS AND RESULTS The mean calculated time to reach an INR of 4.0 was significantly greater in the placebo than the phytonadione group ( 2.6 vs 1.4 days , p=0.006 ) . Overcorrection of anticoagulation was significantly more common in patients receiving phytonadione . Overt warfarin resistance was not observed in either group after reinitiating warfarin therapy . No major bleeding or thromboembolic complications occurred , and minor bleeding episodes were similar in both groups . CONCLUSION The addition of oral phytonadione 2.5 mg reduced the time to achieve an INR of 4.0 by approximately 1 day compared with omitting warfarin therapy alone . Adverse events did not differ between the two groups . Both strategies were effective in managing asymptomatic patients with INRs of 6.0 - 10.0 . Oral phytonadione may be most appropriate for patients at high risk for bleeding in whom the benefit of prompt INR reduction would outweigh the thromboembolic risk associated with INR overcorrection Low dose oral vitamin K rapidly reverses warfarin-associated coagulopathy . Its effect in patients receiving acenocoumarol  is uncertain . We compared the effect of withholding acenocoumarol and administering 1 mg oral vitamin K with simply withholding acenocoumarol in asymptomatic patients presenting with INR values between 4.5 and 10.0 . The primary end-point of the study was the INR value on the day following r and omisation . We found that patients receiving oral vitamin K  had more sub-therapeutic INR levels than controls ( 36.6 % and 13.3 % , respectively ; RR 1.83 , 95 % confidence interval 1.16 , 2.89 ) and a lower , but non-significant , proportion of INR values in range ( 50 % and 66.6 % , respectively ) on the day following r and omisation . After 5 + /- 1 days , there were more patients with an INR value in range in the vitamin K group than in controls ( 74.1 % and 44.8 % , respectively ) . There were no clinical events during 1 month follow-up . We conclude that the omission of a single dose of acenocoumarol is associated with an effective reduction of the INR in asymptomatic patients presenting with an INR value of 4.5 to 10.0 . Furthermore , the use of a 1 mg dose of oral vitamin K results in an excessive risk of over-reversal of the INR BACKGROUND Warfarin-associated coagulopathy is a frequent clinical complication . We aim ed to assess whether treatment with vitamin K is safe and more effective than placebo in rapidly lowering the international normalised ratio ( INR ) into the therapeutic range in over anticoagulated patients receiving warfarin . METHODS We did a multicentre , double-blind , placebo-controlled , r and omised trial in five tertiary care hospitals . In this study , patients receiving warfarin who had an INR value between 4.5 and 10.0 , and who did not have an indication for the immediate normalisation of their INR , had their warfarin withheld , and were r and omly allocated to receive either 1 mg of vitamin K or placebo orally . The primary outcome measure was the INR value on the day after treatment . Secondary outcome measures included INR values on subsequent days , and the risk of haemorrhage and recurrent thrombosis over a 3 month follow-up period . FINDINGS Patients given vitamin K had a more rapid decrease in the INR than those given placebo ( 25 of 45 ( 56 % ] vs nine of 44 [ 20 % ] patients with INR values of 1.8 - 3.2 on the day after treatment , respectively , p=0.001 ; odds ratio [ OR ] 0.21 , 95 % CI 0.07 - 0.57 ) . Fewer patients given vitamin K had bleeding episodes during the follow-up period than those given placebo ( two [ 4 % ] vs eight [ 17 % ] patients , respectively , p=0.050 ; OR 0.87 , 95 % CI 0.019 - 0.999 ) . INTERPRETATION Low dose oral vitamin K is more effective than placebo for the rapid lowering of raised INR values in patients taking warfarin Unanticipated elevation of the INR is common in patients receiving warfarin .  We performed a prospect i ve cohort study of 107 warfarin-treated patients with INR values of more than 10 who received a single 2.5 mg dose of oral vitamin K.  During the first week , one patient experienced major bleeding , and one died . In the first 90 days after enrolment four patients had major bleeding ( 3.7 % , 1.0 % to 9.3 % ) , eight patients ( 7.5 % , 3.3 % to 14.2 % ) died and two had objective ly confirmed thromboembolism . Based on our low rate of observed major bleeding we conclude that 2.5 mg of oral vitamin K is a reasonable treatment for patients with INR values of more 
    Output:
    
Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation