scholarly journals Conservative Management of Overanticoagulation in Patients With Low–Moderate Risk for Bleeding Complications

2018 ◽  
Vol 24 (8) ◽  
pp. 1255-1260 ◽  
Author(s):  
Elise Schapkaitz ◽  
Susan Louw ◽  
Jessica Friedman ◽  
Johanna Sithole ◽  
Mavis Masebe ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Conservative Management ◽  
Low Dose ◽  
Low Risk ◽  
Moderate Risk ◽  
Oral Vitamin ◽  
Risk Of Bleeding ◽  
Dose Oral

Despite long-standing experience with warfarin, anticoagulation clinic services are often confronted with the challenging clinical situation of patients with overanticoagulation. This requires repeat international normalized ratio (INR) monitoring and in some cases administration of vitamin K to minimize the risk of bleeding. A study was performed to determine the safety and efficacy of outpatient management in order to provide guidance on the management of patients with prolonged INRs. Patients on stable warfarin therapy for more than 1 month attending a dedicated academic hospital anticoagulation clinic who had an INR ≥5 were identified over a 1-year period. Follow-up INR results and outcomes were recorded for 30 days. One hundred and ninety-five episodes of overanticoagulation in 148 patients were identified. Patients were classified as low risk (n = 85, 57.4%) and moderate risk of bleeding (n = 63, 42.6%). The mean index INR was 7.22 (1.88). Management with low-dose oral vitamin K (n = 32, 16.4%) did not significantly result in a more rapid correction of the INR when compared to conservative management (n = 163, 83.6%; P = .103). Follow-up INR testing was performed at a mean of 11.1 (8.9) days from the index measurement. A mean of 1.6 (0.9) follow-up INR tests were performed per episode. During the 30-day follow-up, there was 1 (0.5%) episode of major bleeding and 1 (0.5%) death. The management of asymptomatic outpatients with overanticoagulation is associated with a low risk of major bleeding within 30 days. Conservative management of overanticoagulation is as effective as utilizing low-dose oral vitamin K.

The Risk of Hemorrhage and the Frequency of Vitamin K Use in Asymptomatic Patients with Warfarin-Associated Coagulopathy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 527-527
Author(s):  
David A. Garcia ◽  
Mark A. Crowther ◽  
Elaine M. Hylek
Keyword(s):  
Vitamin K ◽  
Low Dose ◽  
Prosthetic Heart Valve ◽  
The United States ◽  
Oral Vitamin ◽  
Major Hemorrhage ◽  
Asymptomatic Patients ◽  
Number Of Patients ◽  
Dose Oral

Abstract Background: Warfarin, although highly effective in preventing thromboembolism, can cause hemorrhage. For warfarin-treated patients, the risk of bleeding increases as the International Normalized Ratio (INR) rises, particularly if the INR exceeds 4. Although low-dose oral vitamin K reliably decreases supratherapeutic INR values, previous surveys indicate that many providers choose not to administer vitamin K to asymptomatic patients who present with excessive INR prolongation. In effort to help guide the management of asymptomatic outpatients with elevated INRs, we assessed the rate of hemorrhage as well as the frequency of vitamin K use in an observational study. Methods: A prospective cohort of patients taking warfarin was assembled from 101 sites with personnel designated as warfarin managers across the United States during the period August 2000 to December 2001; 98 sites were community-based physician office practices. Enrolled practices participated in mandatory on-site study training and all patients provided written informed consent. Patients with a first observed episode of INR ≥5.0 were identified. For the two-week period following the index INR, provider-generated outpatient progress notes that pertained to anticoagulation (and were part of the medical record) were individually reviewed by one of the investigators. Outcomes included: site-specific management of elevated INR (recorded vitamin K use versus simple withholding of warfarin), and number of patients sustaining a major hemorrhage within the 2 weeks following the index INR value. Major hemorrhage was defined as fatal, necessitating hospitalization with transfusion of at least 2 units of packed red blood cells, or occurring at a critical site (e.g., intracranial, retroperitoneal). Results: During the study period, 6,792 patients were enrolled providing 5,961 person-years of follow-up. Of these, 979 had a first observed episode of an INR of more than 5. Thirty-nine % of these patients were receiving warfarin for atrial fibrillation and 29% had a prosthetic heart valve. Mean age was 69 years (range 20–94) and 50% were women. Ninety-six % (n=937) of the INRs were between 5 and 9. Ninety-eight % (n=963) were managed exclusively as outpatients; management could not be assessed in 16 patients who were hospitalized for unrelated reasons. Patients with an INR >9 were more likely to receive vitamin K compared to those with an INR of 5.0 to 9.0 (62% versus 7%). The mean INR for those patients known to have received vitamin K was 9.9 versus 6.2 among those for whom no vitamin K use was recorded. Of the 979 patients, 99.7% (n=976) had 14-day follow-up information. Nine patients sustained a major hemorrhage within the 2-week period (0.9%), mean INR 9.4, none were fatal. Conclusions: Among asymptomatic patients with warfarin-induced coagulopathy, an intervention known to reduce the INR (low-dose oral vitamin K) is used infrequently, particularly for patients whose INR value is 9 or less. For asymptomatic warfarin-treated individuals who are managed in the outpatient setting and whose INR is less than 9, the short-term risk of major bleeding appears to be low. Prospective, controlled trials are needed to determine the risks and benefits of administering vitamin K to this population.

Use of Low Dose Oral Vitamin K in the Treatment of Patients with INR Values of More Than 10.0.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 547-547
Author(s):  
Mark A. Crowther ◽  
David Garcia ◽  
Walter Ageno ◽  
Daniel M. Witt ◽  
Sam Schulman ◽  
...  
Keyword(s):  
Vitamin K ◽  
Low Dose ◽  
Coagulation Factor ◽  
Study Drug ◽  
Additional Patient ◽  
Oral Vitamin ◽  
Risk Of Bleeding ◽  
Dose Oral ◽  
The Mean ◽  
The Impact

Abstract The optimal therapy for patients who present with markedly prolonged INR values during warfarin therapy is undefined. Evidence suggests that the risk of bleeding increases directly with the degree of prolongation of the INR. Traditional therapy for patients with excessive warfarin associated anticoagulation has included warfarin withdrawal with or without vitamin K, transfusion therapy and admission to the hospital. As part of an ongoing international study, we prospectively enrolled 32 consecutive warfarin-treated patients presenting with an INR of more than 10.0. Eligible patients had no evidence of active bleeding or need for immediate correction of their INR. All patients received 2.5 mg of oral vitamin K, were not treated with coagulation factor replacement, and were followed over 90 days for clinical events and their INR response. Seventeen of the 32 patients were women, with an average age of 65.8 (range 31 to 89). Treatment of venous thrombosis and atrial fibrillation (12 patients each) were the most common indications for warfarin. Twenty-five patients had a target INR of 2.0 to 3.0; the remainder had a target of 2.5 to 3.5. The mean INR at presentation was 12.9 (range 10.0 to 21.2). Of the 25 patients with a recorded INR value on the day following vitamin K, 19 (76%) had an INR of 6.0 or less (range 1.6 to 17.5, mean 5.0, 2 less than 2.0). On day 7 after study drug, the mean INR was 3.5 (range 1.6 to 17.5). Six (19%) patients reported bleeding over the 90 days after study drug: 1 (3%) bleed was major (retroperitoneal hemorrhage diagnosed the day after study drug) and 3 patients reported epistaxis or bruising within three days of study drug. Two patients reported late bleeding; one had a fall on day 8 at which time the INR was 10.5, and the other had bleeding associated with a surgical procedure 25 days after study drug. No patients had suspected or confirmed thrombosis, and no patients died during follow-up. This the first prospective study of vitamin K monotherapy for patients with INR values above 10, and confirms prior retrospective analyses which suggest that low dose oral vitamin K effectively lowers the INR in such patients. Our preliminary results also suggest that coagulation factor replacement may be unneeded in such patients. The true risk of bleeding, and the impact of degree of prolongation of the INR on the vitamin K response, will require additional patient recruitment.

scholarly journals Low Dose Oral Vitamin K Does Not Increase Time in Therapeutic Range: Results of a Multicentre Clinical Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2872-2872
Author(s):  
Mark A. Crowther ◽  
Luqi Wang ◽  
Alejandro Lazo Langer ◽  
Kovacs Michael ◽  
Erik Yeo ◽  
...  
Keyword(s):  
Placebo Group ◽  
Vitamin K ◽  
Therapeutic Range ◽  
Research Funding ◽  
Low Dose ◽  
Warfarin Dose ◽  
Oral Vitamin ◽  
Time In Therapeutic Range ◽  
Dose Oral

Abstract Warfarin remains the most commonly used oral anticoagulant. Its efficacy is closely correlated with the time in therapeutic range (TTR) of the international normalized ratio (INR). Excellent anticoagulant management systems can achieve TTRs in excess of 80%: however, in day-to-day clinical practice TTR values in the range of 50 to 60% are more commonly seen. Strategies to increase TTR are widely sought; one such intervention is the daily administration of low dose vitamin K (VK) administered to reduce variations in VK intake and thus reduce fluctuations in the INR due to such variability. In this multicentre, blinded, randomized controlled trial we allocated patients on chronic warfarin therapy to receive either 0.150 mg of daily oral VK, or matching placebo. After a one month “run in period” to allow adjustment of the warfarin dose, patients were followed for a maximum of 9 months (mean 6 months), their INR was determined, their TTR calculated and their mean warfarin dose calculated. A total of 253 patients were enrolled at 4 clinical centres between Aug 19, 2010 and Aug 30, 2013; 18 (9 in each group) were excluded from this analysis due to inadequate follow-up data, mostly as a result of withdrawal from the study during the run in period. Of the 117 analyzable patients allocated to VK, 66 were male (average age 66.9 yrs). Of the 118 analyzable patients allocated to placebo 59 were male (average age 65.7 yrs). Indications for warfarin were similar between the two groups, as was the frequency of renal insufficiency and the presence of cancer. Patients allocated to placebo were more likely to report a history of bleeding (7% vs 3%). Mean TTR over the 6 months prior to enrollment to the study was 54.6% in the placebo group, and 51.8% in the VK group. Mean TTR over an average follow-up of 6 months after completion of the 1 month run-in period was 66% in the placebo group, and 65.1% in the VK group. We conclude that inclusion in this study resulted in a statistically (and likely clinically) significant improvement in the TTR. The improvement in the TTR we observed appeared to be predominately as a result of attentive clinical management, rather than administration of VK. Our findings do not support the use of daily, low dose oral vitamin K administered in an effort to improve TTR. Disclosures Crowther: Portola: Consultancy; Leo: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; AKP America: Consultancy; Heart and Stroke Foundation: Career Investigator award Other; Celgene: Honoraria; Shire: Honoraria; CSL Behring: Honoraria. Lazo Langer:Pfizer: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Leo Pharma: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria; Alexion: Research Funding; Daichii Sankyo: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Yeo:Bayer: Honoraria. Schulman:Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Bayer HealthCare: Consultancy, Honoraria, Research Funding.

Low Dose Oral Vitamin K to Reverse Acenocoumarol-induced Coagulopathy: A Randomized Controlled Trial

2002 ◽  
Vol 88 (07) ◽  
pp. 48-51 ◽  
Author(s):  
M. Crowther ◽  
L. Steidl ◽  
C. Ultori ◽  
V. Mera ◽  
F. Dentali ◽  
...  
Keyword(s):  
Vitamin K ◽  
Low Dose ◽  
Controlled Trial ◽  
Significant Proportion ◽  
Oral Vitamin ◽  
Clinical Events ◽  
Asymptomatic Patients ◽  
Dose Oral ◽  
Excessive Risk

SummaryLow 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 randomisation. 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 randomisation. 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 overreversal of the INR.

Low-dose oral vitamin K is safe and effective for outpatient management of patients with an INR>10

2004 ◽  
Vol 113 (3-4) ◽  
pp. 205-209 ◽  
Author(s):  
Karen E Gunther ◽  
Gladys Conway ◽  
Linda Leibach ◽  
Mark A Crowther
Keyword(s):  
Vitamin K ◽  
Low Dose ◽  
Outpatient Management ◽  
Oral Vitamin ◽  
Dose Oral

Derivation and validation of a novel bleeding risk score for elderly patients with venous thromboembolism on extended anticoagulation

2017 ◽  
Vol 117 (10) ◽  
pp. 1930-1936 ◽  
Author(s):  
Andreas Limacher ◽  
Marie Méan ◽  
Hans-Jürg Beer ◽  
Joseph Osterwalder ◽  
Beat Frauchiger ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Elderly Patients ◽  
Major Bleeding ◽  
Clinical Score ◽  
Low Risk ◽  
University Hospital ◽  
Moderate Risk ◽  
Internal Validation ◽  
Risk Of Bleeding

SummaryExisting clinical scores do not perform well in predicting bleeding in elderly patients with acute venous thromboembolism (VTE). We sought to derive an easy-to-use clinical score to help physicians identify elderly patients with VTE who are at high-risk of bleeding during extended anticoagulation (>3 months). Our derivation sample included 743 patients aged ≥65 years with VTE who were enrolled in a prospective multicenter cohort study. All patients received extended anticoagulation with vitamin K antagonists. We derived our score using competing risk regression, with the time to a first major bleeding up to 36 months of extended anticoagulation as the outcome, and 17 candidate variables as predictors. We used bootstrapping methods for internal validation. Sixty-six (9%) patients suffered major bleeding. The clinical score is based on seven clinical factors (previous bleeding, active cancer, low physical activity, anemia, thrombocytopenia, antiplatelet drugs/NSAIDs, and poor INR control). Overall, 48% of patients were classified as low-risk, 37% as moderate-risk, and 15% as high-risk of bleeding. The rate of major bleeding was 1.4 events in low-risk, 5.0 events in moderate-risk, and 12.2 events per 100 patientyears in high-risk patients. The c-statistic was 0.78 at 3 months and 0.71 at 36 months of extended anticoagulation. Model calibration was excellent (p=0.93). Internal validation showed similar results. This simple clinical score accurately identified elderly patients with VTE who are at high risk of major bleeding and who may not benefit from extended anticoagulation. Further validation of the score is important before its implementation into practice. The study is registered to https://clinicaltrials.gov as NCT00973596.This work was carried out at the Department of General Internal Medicine in the Bern University Hospital, Switzerland.

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