Prediction of the international normalized ratio and maintenance dose during the initiation of warfarin therapy

Introduction. We present a case of concurrent spontaneous sublingual and intramural small bowel hematoma due to warfarin anticoagulation.Case. A 71-year-old man presented to the emergency department complaining of a swollen, painful tongue. He was on warfarin therapy. Physical examination revealed sublingual hematoma. His international normalized ratio was 11.9. The computed tomography scan of the neck demonstrated sublingual hematoma. He was admitted to emergency department observation unit, monitored closely; anticoagulation was reversed with fresh frozen plasma and vitamin K. 26 hours after his arrival to the emergency department, his abdominal pain and melena started. His abdomen tomography demonstrated intestinal submucosal hemorrhage in the ileum. He was admitted to surgical floor, monitored closely, and discharged on day 4.Conclusion. Since the patient did not have airway compromise holding anticoagulant, reversing anticoagulation, close monitoring and observation were enough for management of both sublingual and spontaneous intramural small bowel hematoma.

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Impact of CYP2C9 and VKORC1 Polymorphisms on Warfarin Sensitivity and Responsiveness in Jordanian Cardiovascular Patients during the Initiation Therapy

Genes ◽

10.3390/genes9120578 ◽

2018 ◽

Vol 9 (12) ◽

pp. 578 ◽

Cited By ~ 10

Author(s):

Laith AL-Eitan ◽

Ayah Almasri ◽

Rame Khasawneh

Keyword(s):

Warfarin Therapy ◽

Catalytic Properties ◽

Warfarin Dose ◽

International Normalized Ratio ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Haplotype Blocks ◽

Cardiovascular Patients ◽

Cyp2c9 Gene ◽

Vkorc1 Gene

Warfarin is an oral anticoagulant frequently used in the treatment of different cardiovascular diseases. Genetic polymorphisms in the CYP2C9 and VKORC1 genes have produced variants with altered catalytic properties. A total of 212 cardiovascular patients were genotyped for 17 Single Nucleotide Polymorphisms (SNPs) within the CYP2C9 and VKORC1 genes. This study confirmed a genetic association of the CYP2C9*3 and VKORC1 rs10871454, rs8050894, rs9934438, and rs17708472 SNPs with warfarin sensitivity. This study also found an association between CYP2C9 and VKORC1 genetic haplotype blocks and warfarin sensitivity. The initial warfarin dose was significantly related to the CYP2C9*3 polymorphism and the four VKORC1 SNPs (p < 0.001). There were significant associations between rs4086116 SNP and TAT haplotype within CYP2C9 gene and rs17708472 SNP and CCGG haplotype within VKORC1 gene and warfarin responsiveness. However, possessing a VKORC1 variant allele was found to affect the international normalized ratio (INR) outcomes during initiation of warfarin therapy. In contrast, there was a loose association between the CYP2C9 variant and INR measurements. These findings can enhance the current understanding of the great variability in response to warfarin treatment in Arabs.

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Fenofibrate Potentiates Warfarin Effects

Annals of Pharmacotherapy ◽

10.1177/106002800303700210 ◽

2003 ◽

Vol 37 (2) ◽

pp. 212-215 ◽

Cited By ~ 9

Author(s):

Karissa Y Kim ◽

Michael A Mancano

Keyword(s):

White Woman ◽

Chart Review ◽

Warfarin Therapy ◽

Dosage Reduction ◽

International Normalized Ratio ◽

Drug Regimen ◽

Warfarin Dosage ◽

Therapeutic Doses ◽

Anticoagulant Response

OBJECTIVE: To describe 2 patients in whom the initiation of fenofibrate potentiated warfarin's anticoagulant effects. CASE SUMMARY: A 71-year-old white woman and an 80-year-old white woman with multiple medical conditions were both stabilized on long-term warfarin therapy. During the course of anticoagulation, both patients were prescribed fenofibrate and experienced threefold and twofold increases in international normalized ratio (INR), respectively, requiring total weekly warfarin dosage reductions of 30–40%. Before starting fenofibrate therapy, both patients' coagulation values were within the therapeutic range. When interviewed, patients and caregivers denied bleeding, bruising, changes in diet, alcohol ingestion, nonadherence with therapy, or changes in drug regimen except for the addition of fenofibrate. Upon chart review, evaluation of potentially contributory parameters, such as other changes in drug therapy, thyroid function, liver function, and drug–disease interactions, showed that these parameters remained stable and were ruled noncontributory. DISCUSSION: The addition of fenofibrate in 2 patients on stable and therapeutic doses of warfarin increased the anticoagulant response to warfarin. A clear temporal relationship with the addition of fenofibrate and the appearance of the interaction was seen. Fenofibrate is highly protein bound, with the potential to displace warfarin from its binding protein, leading to an enhanced hypoprothrombinemic effect. Fenofibrate is also a mild to moderate inhibitor of CYP2C9, the enzyme responsible for warfarin metabolism. The combination of these effects — displacement of warfarin by fenofibrate coupled with decreased metabolism of warfarin — may increase the anticoagulant response to warfarin. Using the Naranjo probability scale, these interactions were designated as probable. CONCLUSIONS: We suggest serial monitoring of INR and consider an empiric 20% reduction in warfarin dosage when fenofibrate is initiated, with the possibility for a greater warfarin dosage reduction based on INR results.

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Association between satisfaction with and adherence to warfarin therapy on the control of international normalized ratio: A hospital-based study in Saudi Arabia

Saudi Pharmaceutical Journal ◽

10.1016/j.jsps.2017.11.010 ◽

2018 ◽

Vol 26 (1) ◽

pp. 145-149 ◽

Cited By ~ 5

Author(s):

Balkhi Balkhi ◽

Mabrouk Al-Rasheedi ◽

Abuabker Ibrahim Elbur ◽

Ahmad Alghamadi

Keyword(s):

Saudi Arabia ◽

Warfarin Therapy ◽

International Normalized Ratio

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The Effect of Demographic Factors and VKORC1 1639 G>A Genotypes on Estimated Warfarin Maintenance Dose in Iranian Patients Under Warfarin Therapy

Indian Journal of Hematology and Blood Transfusion ◽

10.1007/s12288-018-0987-0 ◽

2018 ◽

Vol 35 (1) ◽

pp. 167-171 ◽

Cited By ~ 1

Author(s):

Fariba Rad ◽

Mohsen Hamidpour ◽

Akbar Dorgalaleh ◽

Behzad Poopak

Keyword(s):

Maintenance Dose ◽

Warfarin Therapy ◽

Demographic Factors ◽

Warfarin Maintenance Dose ◽

Iranian Patients

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International normalized ratio in anticoagulant therapy: understanding the issues

American Journal of Critical Care ◽

10.4037/ajcc1997.6.2.88 ◽

1997 ◽

Vol 6 (2) ◽

pp. 88-92 ◽

Cited By ~ 2

Author(s):

AL Severson ◽

LR Baldwin ◽

TG DeLoughery

Keyword(s):

Anticoagulant Therapy ◽

Warfarin Therapy ◽

Healthcare Providers ◽

Anticoagulation Therapy ◽

International Normalized Ratio ◽

Laboratory Methods ◽

Current Monitoring

Recently, a change in anticoagulation therapy occurred that is still partially ignored by the healthcare community. Understanding the controversy over the use of the internal normalized ratio in monitoring patients receiving warfarin therapy is important for nurses who provide care to these patients. Five questions related to current monitoring of patients treated with anticoagulants are addressed. Nurses must recognize the importance to their practice of changes in laboratory methods and move toward using the most useful measures available to influence patients' outcomes. The international normalized ratio is the most appropriate way to evaluate the effects of warfarin therapy. All healthcare providers should use this ratio as the standard in evaluating the effects of anticoagulation therapy.

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De Ritis ratio as a significant prognostic factor of international normalized ratio ≥4 in the initial 10 days of warfarin therapy

Biomarkers in Medicine ◽

10.2217/bmm-2019-0033 ◽

2019 ◽

Vol 13 (18) ◽

pp. 1599-1607

Author(s):

Yide Cao ◽

Ganyi Chen ◽

Huangshu Li ◽

Yafeng Liu ◽

Zhonghao Tao ◽

...

Keyword(s):

Valve Replacement ◽

Heart Valve ◽

Warfarin Therapy ◽

Anticoagulation Therapy ◽

International Normalized Ratio ◽

Heart Valve Replacement ◽

Significant Prognostic Factor ◽

Replacement Surgery ◽

The Relationship ◽

Valve Replacement Surgery

Aim: To assess the relationship between the De Ritis ratio on admission and warfarin sensitivity in the initial 10 days of anticoagulation therapy. Methods: We retrospectively reviewed data from 906 patients who underwent heart valve replacement surgery. Results: A De Ritis ratio of 1.19 was identified as the optimal cutoff according to the ROC curve. Patients with a high De Ritis ratio achieved an international normalized ratio (INR) ≥4 more easily and earlier than those with a low De Ritis ratio in the initial 10 days of warfarin therapy. Multivariate analysis showed that a high De Ritis ratio was an independent predictor of an INR ≥4 (HR: 2.567; p < 0.001). Conclusion: A De Ritis ratio ≥1.19 on admission was significantly associated with an INR ≥4 in the initial 10 days of warfarin therapy among patients underwent heart valve replacement surgery.

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Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613443 ◽

2003 ◽

Vol 89 (02) ◽

pp. 278-283 ◽

Cited By ~ 95

Author(s):

Kazuo Minematsu ◽

Hiroaki Naritomi ◽

Toshiyuki Sakata ◽

Takenori Yamaguchi ◽

Masahiro Yasaka

Keyword(s):

Logistic Regression Model ◽

Prothrombin Complex Concentrate ◽

Warfarin Therapy ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Predisposing Factors ◽

Predisposing Factor ◽

Fresh Frozen ◽

Cerebral Hematoma ◽

Frozen Plasma

SummaryTo elucidate predisposing factors for enlargement of intra-cerebral hematoma (ICH) during warfarin therapy, we reviewed 47 patients on warfarin who developed acute ICH and determined relationships among ICH enlargement, INR reversal and clinical data. Among 36 patients treated to counteract the effects of warfarin within 24 h of onset, ICH increased in 10 patients (enlarged group), but remained unchanged in the remaining 26 (unchanged group), while ICH remained unchanged in another 11 patients in whom the effect of warfarin was reversed after 24 h. The international normalized ratio (INR) was counteracted immediately in 11 patients treated with prothrombin complex concentrate (PCC) but gradually in the other 36 treated by reducing the dose of warfarin, or by administering vitamin K or fresh frozen plasma. Multivariate analysis with a logistic regression model showed an INR value <2.0 at admission or for 24 h after immediate INR correction with PCC prevented ICH enlargement (OR 0.069, 95%CI 0.006-0.789, p = 0.031). An INR value of >2.0 within 24 h of ICH seems an important predisposing factor for ICH enlargement.

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Analysis of Warfarin Therapy in Pediatric Patients: A Prospective Cohort Study of 319 Patients

Blood ◽

10.1182/blood.v94.9.3007 ◽

1999 ◽

Vol 94 (9) ◽

pp. 3007-3014 ◽

Cited By ~ 200

Author(s):

W. Streif ◽

M. Andrew ◽

V. Marzinotto ◽

P. Massicotte ◽

A.K.C. Chan ◽

...

Keyword(s):

Enteral Nutrition ◽

Warfarin Therapy ◽

Pediatric Patients ◽

Pediatric Population ◽

International Normalized Ratio ◽

Target Range ◽

Age Group ◽

Older Children ◽

Effect Of Age ◽

Fontan Patients

Abstract This study details warfarin use in a large pediatric population followed in a central anticoagulation clinic. A prospective, consecutive cohort of nonselected children were studied. Patients were divided into groups by age, target international normalized ratio (INR) range, disease, medications, and vitamin K supplemented enteral nutrition use. Groups were analyzed on multiple aspects of warfarin therapy using multivariate methods. A total of 319 patients received 352 warfarin courses representing 391 treatment years. Age independently influenced all aspects of therapy. When compared with all older children, the ≤1 year of age group required increased warfarin doses, longer overlap with heparin, longer time to achieve target INR ranges, more frequent INR testing and dose adjustments, and fewer INR values in the target range. Although significantly different than children ≤1 year, children 1 to 6 years of age showed the same findings when compared with 7- to 18-year-olds. Fontan patients required 25% decreased dosage as compared with other congenital heart disease patients. Children on corticosteroids had less INRs in the target range and children on phenobarbital/carbamazepine required increased maintenance dosages of warfarin. Also, patients receiving enteral nutrition required increased dosages of warfarin. Serious bleeding occurred in 2 children (0.5% per patient year). Recurrent thromboembolic events (TEs) occurred in 8 children. Two children had recurrences while receiving warfarin (1.3% per patient year). This study outlines the profound effect of age and relative complexity of clinical management of warfarin therapy in children.

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A Protocol for the Rapid Normalization of INR in Trauma Patients with Intracranial Hemorrhage on Prescribed Warfarin Therapy

The American Surgeon ◽

10.1177/000313480807400919 ◽

2008 ◽

Vol 74 (9) ◽

pp. 858-861 ◽

Cited By ~ 20

Author(s):

Michael Kalina ◽

Glen Tinkoff ◽

Adebayo Gbadebo ◽

Paula Veneri ◽

Gerard Fulda

Keyword(s):

Intracranial Hemorrhage ◽

Prothrombin Complex Concentrate ◽

Warfarin Therapy ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Operative Intervention ◽

Trauma Patients ◽

Number Of Patients ◽

Fresh Frozen ◽

Factor Concentrate

Trauma patients on prescribed warfarin therapy sustaining intracranial hemorrhage can be difficult to manage. Rapid normalization of coagulopathy is imperative to operative intervention and may affect outcomes. To identify and expedite warfarin reversal, we designed a protocol to administer a prothrombin complex concentrate. A Proplex T protocol was instituted in May 2004. It dictated that trauma patients with an International Normalized Ratio (INR) greater than 1.5, history of prescribed warfarin therapy, and intracranial hemorrhage on CT scan receive a prothrombin complex concentrate for reversal of their coagulopathy. Neither the protocol nor the factor concentrate was validated for use in this subset of trauma patients; therefore, adherence to the protocol and use of the factor concentrate was not mandatory. Patients not administered the prothrombin complex concentrate received vitamin K and fresh-frozen plasma. The protocol resulted in an increased number of patients receiving Proplex T (54.3% vs 35.4%, P = 0.047). Protocol patients had improved times to normalization of INR (331.3 vs 737.8 minutes, P = 0.048), number of patients with reversal of coagulopathy (73.2% vs 50.9%, P = 0.026), and time to operative intervention (222.6 vs 351.3 minutes, P = 0.045) compared with control subjects. There were no differences in intensive care unit (ICU) days, hospital days, or mortality. The Proplex T protocol increased the number of patients who received prothrombin complex concentrate, provided rapid normalization of INR, and improved time to operative intervention.

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