scholarly journals Factor VII Levels and International Normalized Ratios in the Early Phase of Warfarin Therapy

2010 ◽  
Vol 112 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Honorio T. Benzon ◽  
Michael J. Avram ◽  
Hubert A. Benzon ◽  
Misty Kirby-Nolan ◽  
Antoun Nader
Keyword(s):  
Epidural Catheter ◽  
Early Phase ◽  
Warfarin Therapy ◽  
Warfarin Dose ◽  
Patient Characteristics ◽  
International Normalized Ratio ◽  
Factor Vii ◽  
Clotting Factor ◽  
Epidural Catheter Placement ◽  
Epidural Catheters

Background Factor VII is the most affected clotting factor during the early phase of warfarin therapy. An international normalized ratio (INR) of more than 1.4 is considered unsafe for epidural catheter placement or removal, according to the American Society of Regional Anesthesia and Pain Medicine. The authors tested the hypothesis that factor VII activities would be consistent with safe removal of the epidural catheter on postoperative day (POD) 1 regardless of INR value. Methods Data from 121 patients who took warfarin after undergoing total joint surgery and had INRs and factor VII levels determined were reviewed. Patient characteristics and factor VII activities were compared between patients with INRs of more than 1.4 and those with INRs less than or equal to 1.4 on PODs 1, 2, and 3. Results Eleven patients had INRs of more than 1.4 on POD 1; their mean +/- SD factor VII activities were 60 +/- 28% (normal: 50-160%). On POD 2, 78 patients with INRs more than of 1.4 had factor VII activities of 32 +/- 15%, whereas on POD 3, 84 patients with INRs of more than 1.4 had factor VII activities of 44 +/- 19%. Variables included in the final multiple logistic regression model as predictors of an INR of more than 1.4 on POD 2 were warfarin dose on POD 1 and factor VII activity on POD 2. Conclusions The range of factor VII activities in the patients with INRs of more than 1.4 within 12 h of warfarin therapy was compatible with adequate hemostasis. The authors found no evidence that epidural catheters should not be removed even with INRs up to 1.9, the highest INR on POD 1 noted in their study.

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

Genes ◽  
2018 ◽  
Vol 9 (12) ◽  
pp. 578 ◽  
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.

scholarly journals Coagulation Disturbances in Patients with Argininemia

2018 ◽  
Vol 140 (4) ◽  
pp. 221-225 ◽  
Author(s):  
Ertugrul Kiykim ◽  
Tanyel Zubarioglu ◽  
Mehmet Serif Cansever ◽  
Tiraje Celkan ◽  
Johannes Häberle ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Urea Cycle ◽  
International Normalized Ratio ◽  
Factor Ix ◽  
Factor Vii ◽  
Clotting Factor ◽  
Clotting Factors ◽  
Hepatic Involvement ◽  
Prolonged Aptt ◽  
Liver Transaminases

Background: Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. Methods: In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. Results: All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. Conclusions: Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms.

Patient-Controlled Epidural Analgesia/Continuous Epidural Catheters

2016 ◽  
Author(s):  
Devin Peck
Keyword(s):  
Epidural Catheter ◽  
Local Anesthetics ◽  
Catheter Placement ◽  
Labor Pain ◽  
Abdominal Incision ◽  
Tumor Spread ◽  
Epidural Catheter Placement ◽  
Thoracic Epidural ◽  
Cord Injury ◽  
Epidural Catheters

Although useful for management of many types of pain, the most common indication for epidural catheter placement is for management of labor pain. High lumbar and thoracic epidural catheter placement has gained increasing popularity in recent years for the management of postoperative pain. The technique is most commonly employed for procedures in which a thoracic or an extensive abdominal incision is anticipated. Absolute contraindications for epidural catheter placement include patient refusal, uncorrected hypovolemia, increased intracranial pressure, local infection at the planned site of insertion, and patient allergy to amide/ester local anesthetics. Relative contraindications include coagulopathy, an uncooperative patient, severe anatomic abnormalities of the spine, sepsis, and hypertension. The advantages include attenuation of the sympathetic response to surgical stimulation and pain; effects on the cardiovascular, respiratory, and gastrointestinal systems; thromboprotective effects; and possibly limitation of tumor spread. The risks of epidural catheter placement include epidural hematoma, infection, nerve or spinal cord injury, dural puncture, or respiratory or cardiovascular depression from a high block. Epidural opioids provide analgesia without causing motor or sympathetic blockade. Epidurally administered local anesthetics may result in decreased postoperative ileus, nausea, vomiting, and sedation, which can be associated with opioids. Local anesthetics and opioids act additively or synergistically and, when used together, can lead to a reduction in the dose of each drug. 

Patient Factors That Influence Warfarin Dose Response

2010 ◽  
Vol 23 (3) ◽  
pp. 194-204 ◽  
Author(s):  
Pamela J. White
Keyword(s):  
Dose Response ◽  
Warfarin Therapy ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
Therapeutic Index ◽  
International Normalized Ratio ◽  
Patient Factors ◽  
Disease States ◽  
Treatment And Prevention ◽  
Number Of Factors

Warfarin has long been the mainstay of oral anticoagulation therapy for the treatment and prevention of venous and arterial thrombosis. The narrow therapeutic index of warfarin, and the complex number of factors that influence international normalized ratio (INR) response, makes optimization of warfarin therapy challenging. Determination of the appropriate warfarin dose during initiation and maintenance therapy requires an understanding of patient factors that influence dose response: age, body weight, nutritional status, acute and chronic disease states, and changes in concomitant drug therapy and diet. This review will examine specific clinical factors that can affect the pharmacokinetics and pharmacodynamics of warfarin, as well as the role of pharmacogenetics in optimizing warfarin therapy.

Increased Sensitivity of Prothrombin Time Using Recombinant Tissue Thromboplastin Reagents: Implications for Plasma Transfusion.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4058-4058
Author(s):  
Adam C. Seegmiller ◽  
Ravindra Sarode
Keyword(s):  
Prothrombin Time ◽  
International Normalized Ratio ◽  
Fresh Frozen Plasma ◽  
Factor Vii ◽  
Clotting Factor ◽  
Factor Ii ◽  
Fresh Frozen ◽  
Tissue Homogenates ◽  
Tissue Thromboplastin ◽  
Clinically Significant

Abstract Acquired coagulopathies are often treated with fresh frozen plasma (FFP) transfusion. Standards for the tranfusion of FFP vary, but are often based on coagulation tests, especially prothrombin time (PT). Previously, the PT test was performed using tissue thromboplastin (TT) reagents derived from human or animal tissue homogenates (hTT). These preparations were fairly crude and varied between manufacturers and lots. Recently, these have been replaced with recombinant TT (rTT) reagents that are more consistent. However, anecdotal reports suggest that rTT is more sensitive to mildly decreased clotting factor levels, leading to longer PTs and increases in FFP transfusion. The purpose of this study is to test the hypothesis that rTT reagents are more sensitive and to determine if thresholds for FFP transfusion should be increased. Fifty plasma samples from patients with prolonged PTs (range 13.0–27.6 seconds; normal 9.2–12.8 seconds) were randomly selected. PTs for each sample were re-measured using rTT (Innovin, Dade-Behring, Liederbach, Germany; ISI=0.91) and hTT (Thromboplastin Reagent, Helena Laboratories, Beaumont, Texas; ISI=2.07) on the same instrument (Start 4 benchtop coagulation analyzer, Diagnostica Stago, Parsippany, New Jersey). These measured PTs are compared in Fig. 1. At the lower end of the PT range (beginning at ~13 seconds), the rTT PTs are shorter, on average, than the hTT PTs. However, the average rTT PT increases at a 1.4 times greater rate than the hTT PT, such that the average PT of the two reagents is equivalent at 16.4 seconds and longer for rTT thereafter. This suggests that the rTT reagent is indeed more sensitive. A similar pattern is seen when factor II and VII levels for each sample are plotted against the corresponding PT (Fig. 2). At high factor levels, the rTT PT is lower, on average, than the hTT PT. However, as factor levels decrease, the rTT PT rises about twice as fast as the hTT PT. The PTs for the two reagents are equivalent at 66% factor II (PT=15.7) and 46% factor VII (PT=17.7). The important thresholds for risk of surgical bleeding are 40% factor II and 25% factor VII. The equivalent PTs in this study are 20.5 (rTT) and 18.1 (hTT) for 40% factor II and 22.3 (rTT) and 19.6 (hTT) for 25% factor VII. These differences are not corrected by converting PTs to the international normalized ratio (INR). Instead, INRs are higher for hTT than rTT, and the degree of difference between the two reagents is greater. The equivalent INRs are 1.90 (rTT) and 2.54 (hTT) for 40% factor II activity, and 2.05 (rTT) and 2.98 (hTT) for 25% factor VII activity. The results of this study confirm that PTs measured using rTT are more sensitive to changes in clotting factor levels than those measured using hTT, especially at clinically significant factor levels. This suggests that thresholds for the transfusion of FFP should be raised at those institutions using rTT. Fig. 1: Comparison of PTs measured Using rTT and hTT Reagents Fig. 1:. Comparison of PTs measured Using rTT and hTT Reagents Fig. 2: Correlation of Prothrombin Time and Factor Levels Fig. 2:. Correlation of Prothrombin Time and Factor Levels

scholarly journals Measurements of Epidural Space Depth Using Preexisting CT Scans Correlate with Loss of Resistance Depth during Thoracic Epidural Catheter Placement

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Nathaniel H. Greene ◽  
Benjamin G. Cobb ◽  
Ken F. Linnau ◽  
Christopher D. Kent
Keyword(s):  
Epidural Catheter ◽  
Strong Association ◽  
Epidural Catheter Placement ◽  
Thoracic Epidural ◽  
Thoracic Surgical Procedures ◽  
Spine Imaging ◽  
Thoracic Epidural Catheter ◽  
Loss Of Resistance ◽  
Resolution Imaging ◽  
Epidural Catheters

Background.Thoracic epidural catheters provide the best quality postoperative pain relief for major abdominal and thoracic surgical procedures, but placement is one of the most challenging procedures in the repertoire of an anesthesiologist. Most patients presenting for a procedure that would benefit from a thoracic epidural catheter have already had high resolution imaging that may be useful to assist placement of a catheter.Methods.This retrospective study used data from 168 patients to examine the association and predictive power of epidural-skin distance (ESD) on computed tomography (CT) to determine loss of resistance depth acquired during epidural placement. Additionally, the ability of anesthesiologists to measure this distance was compared to a radiologist, who specializes in spine imaging.Results.There was a strong association between CT measurement and loss of resistance depth (P<0.0001); the presence of morbid obesity (BMI>35) changed this relationship (P=0.007). The ability of anesthesiologists to make CT measurements was similar to a gold standard radiologist (all individualICCs>0.9).Conclusions.Overall, this study supports the examination of a recent CT scan to aid in the placement of a thoracic epidural catheter. Making use of these scans may lead to faster epidural placements, fewer accidental dural punctures, and better epidural blockade.

scholarly journals Genetic-based dosing in orthopedic patients beginning warfarin therapy

Blood ◽  
2007 ◽  
Vol 110 (5) ◽  
pp. 1511-1515 ◽  
Author(s):  
Eric A. Millican ◽  
Petra A. Lenzini ◽  
Paul E. Milligan ◽  
Leonard Grosso ◽  
Charles Eby ◽  
...  
Keyword(s):  
Warfarin Therapy ◽  
Smoking Status ◽  
Warfarin Dose ◽  
Therapeutic Index ◽  
International Normalized Ratio ◽  
Narrow Therapeutic Index ◽  
Therapy Initiation ◽  
Estimated Blood Loss ◽  
Epoxide Reductase ◽  
Orthopedic Patients

AbstractHigh variability in drug response and a narrow therapeutic index complicate warfarin therapy initiation. No existing algorithm provides recommendations on refining the initial warfarin dose based on genetic variables, clinical data, and international normalized ratio (INR) values. Our goal was to develop such an algorithm. We studied 92 patients undergoing primary or revision total hip or knee replacement. From each patient we collected a blood sample, clinical variables, current medications, and preoperative and postoperative laboratory values. We genotyped for polymorphisms in the cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase (VKORC1) genes. Using stepwise regression, we developed a model for refining the warfarin dose after the third warfarin dose. The algorithm explained four fifths of the variability in therapeutic dose (R2adj of 79%). Significant (P > .05) predictors were INR value after 3 doses (47% reduction per 0.25-unit rise), first warfarin dose (+7% per 1 mg), CYP2C9*3 and CYP2C9*2 genotype (−38% and −17% per allele), estimated blood loss (interacting with INR3), smoking status (+20% in current smokers), and VKORC1 (−11% per copy of haplotype A). If validated, this model should provide a safer, more effective process for initiating warfarin therapy.

Dietary Vitamin K Variability Affects International Normalized Ratio (INR) Coagulation Indices

2006 ◽  
Vol 76 (2) ◽  
pp. 65-74 ◽  
Author(s):  
Rebecca Couris ◽  
Gary Tataronis ◽  
William McCloskey ◽  
Lynn Oertel ◽  
Gerard Dallal ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Vitamin K ◽  
Warfarin Therapy ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Adverse Outcomes ◽  
Dietary Vitamin ◽  
Prescription Medications ◽  
Oral Warfarin

Background: Changes in daily vitamin K intake may contribute to marked variations in the International Normalized Ratio (INR) coagulation index in patients receiving oral warfarin anticoagulant therapy, with potentially serious adverse outcomes. Thus, patients receiving warfarin therapy are routinely counseled regarding this drug-nutrient interaction and are instructed to maintain consistent vitamin K intakes, though little quantitative information about this relationship is available. Objective: To determine the quantitative impact of variability in dietary vitamin K1 (phylloquinone) intake, assessed by a validated patient self-monitoring instrument, on weekly INR in patients receiving warfarin anticoagulant therapy. Methods: A prospective dietary assessment study was conducted at the Massachusetts General Hospital in Boston. Sixty outpatients (37 males and 23 females) were selected with a mean age 60.3 ± 16.8 years, who began oral warfarin anticoagulant therapy within 14 days prior to their first clinic visit to an outpatient anticoagulation therapy unit. Exclusion criteria included more than 2 drinks of alcohol per day, inability to speak English, and concurrent disease states affecting warfarin therapy such as liver disease and terminal illness. Over the five-week study period, participants recorded daily intakes in specified amounts of all food items appearing on a validated dietary self-assessment tool. Concomitant use of prescription and/or non-prescription medications was also obtained. Concurrent daily warfarin dose and adherence to the drug regimen, concomitant use of prescription and/or non-prescription medications known to interact with warfarin, and weekly INR were obtained. Week-to-week changes in vitamin K intake, warfarin dose, and INR were determined and cross-correlated. Results: Forty-three patients (28 males and 15 females) completed the study and 17 dropped out. Pearson’s correlation coefficient revealed the variability in INR and changes in vitamin K intake were inversely correlated (r = –0.600, p < 0.01). Multiple regression analysis (r = 0.848) indicated that a weekly change of 714 mug dietary vitamin K significantly altered weekly INR by 1 unit (p < 0.01) and a weekly change of 14.5 mg warfarin significantly altered weekly INR by 1 unit (p < 0.01) after adjustment for age, sex, weight, height, and concomitant use of medications known to interact with warfarin. Conclusions: Patients taking warfarin and consuming markedly changing amounts of vitamin K may have a variable weekly INR with potentially unstable anticoagulant outcomes.

Evaluation of an Initiation Regimen of Warfarin for International Normalized Ratio Target 2.0 to 3.0

2021 ◽  
pp. 875512252110341
Author(s):  
Sahimi Mohamed ◽  
Chan Mei Fong ◽  
Yew Jie Ming ◽  
Ahlam Naila Kori ◽  
Sopian Abdul Wahab ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Warfarin Therapy ◽  
Warfarin Dose ◽  
Asian Population ◽  
International Normalized Ratio ◽  
Efficacy And Safety ◽  
Risk Of Bleeding ◽  
Number Of Patients ◽  
Inpatient Settings ◽  
The Mean

Background: he number of patients on warfarin therapy is rising steadily. Although warfarin is beneficial, it carries a high risk of bleeding, especially if the international normalized ratio (INR) values exceed 3.0. Currently, no warfarin initiation regimens have been developed for the Asian population, especially for Malaysians. Objective: This article describes the efficacy and safety of a new initiation regimen for warfarin among warfarin-naive patients. Method: Data were retrospectively collected from the ambulatory and inpatient settings. Results: A total of 165 patients who each had a target INR of 2.0 to 3.0 were included in the study. The mean age was 57.2 years and 94 patients were male. A total of 108 patients used Regimen 1 (5 mg/5 mg/3mg) and the rest of the patients used Regimen 2 (5 mg/3 mg/3 mg). Most patients used warfarin either for atrial fibrillation (52.1%) or for venous thromboembolism (29.7%). Overall, 88 of the patients had INR values above 50% from the baseline on Day 4. Additionally, 13 patients had INR values of >3.2, which required withholding and lower dose of warfarin. The predicted weekly maintenance warfarin dose (23 ± 0.5 mg/week) was found to have correlated closely with the actual maintenance dose (22.8 ± 0.5 mg/week; r2 = 0.75). Nearly two thirds (70.3%) of the patients achieved the target INR on Day 11. Conclusion: The warfarin initiation regimens in this study was simple, safe, and suitable to be used in both ambulatory and inpatient settings for managing warfarin therapy.

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