• Journal of Chest Surgery
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• v.38 no.11 s.256
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• pp.746-760
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• 2005

Background: Following the implantation of heart valve prostheses, it is important to maintain therapeutic INR to reduce the risk of thromboembolism. The objectives of this study were to determine the causes of nontherapeutic INRs, and to identify the factors associated with nonadherences to warfarin therapy in Korean outpatients with prosthetic heart valves managed by a pharmacist-run anticoagulation service (ACS). Material and Method: A retrospective chart review was completed for all patients enrolled in the ACS at Seoul National University Hospital from March, 1997b to September, 2000. The data on 868 patients (5,304 visits) who were at least 6 months post-valve replacement were included. All possible causes of nontherapeutic INRs were documented for each patient visit. The association of covariates to noncompliance was investigated by univariate analysis. Result: The reasons for nontherapeutic INRs were identified as follows: inadequate dosage adjustment $(21\%)$, nonadherences to dosing regimen $(13\%)$, drug/herbal interactions $(12\%)$, changes in diet $(7\%)$, and indeterminate cause $(42\%)$. Younger age, shorter duration of ACS and longer duration of warfarin therapy were associated with nonadherence. Conclusion: In this study, nonadherence and interactions between diet and medications were found to be important factors influencing nontherapeutic INRs. Longer duration of enrollment in the ACS affected the adherence to warfarin therapy Positively whereas younger age and longer duration of warfarin therapy affected negatively.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.135-140
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• 1995

Glycation occurs by covalent binding between the carbonyl group of monosaccharides and the epsilon amino group of amino acid. It can alter the physiological function of proteins and causes the development of diabetic complications. In this study, the influence of glycation on protein binding of warfarin and dansylsarcosine was studied by equilibrium dialysis which was performed for 3 hours at $37^{\circ}C$ in the water bath. The high glycated albumin which contained $50{\pm}16%$ of glycated albumin bound less than natural albumin which contained $8.5{\pm}5.28%$ of glycated albumin, if drugs concentration were more than the albumin concentration. But only warfarin binding showed a significant difference of 6% (P<0.05) when the molar concentration ratio of warfarin per albumin was 3. In consideration of low therapeutic concentrations, low glycated albumin concentrations in the body, and rapid elimination of excessive free drugs, these small increaes of free warfarin concentrations by glycation of albumin are not considered as risk. factors for drug intoxication for diabetics, if renal functions are intact.

• Journal of Chest Surgery
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• v.18 no.3
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• pp.446-455
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• 1985

A total and consecutive 156 patients have undergone cardiac valve surgery including 13 closed mitral commissurotomy, 13 open mitral commissurotomy, one mitral annuloplasty, 75 mitral valve replacement, one aortic annuloplasty, 24 aortic valve replacement, 3 tricuspid valve replacement, 25 double valve replacement and one triple valve replacement. 155 prosthetic valves were replaced in a period between September 1976 and August 1985. There were 68 males and 88 females with age range from 8 to 69 yrs [mean 36.5 yr]. Out of replaced valves, 61 was tissue valve including 54 Carpentier-Edwards, and 4 was mechanical valves including 74 St. Jude Medical, and the position replaced was 101 valves for mitral, 46 for aortic and 8 for tricuspid. Single valve replacement in 102 cases, double valve replacement in 25 cases [17 for AVR+MVR, and 8 for MVR+TVR], and only one case was noted in the triple valve replacement. Early mortality within 30 days after operation was noted in 11 cases [7%]; 7 after MVR, 2 after DVR, and each one after open mitral commissurotomy and mitral annuloplasty. Cause of death was valve thrombus, cerebral air embolism, low output syndrome, uncontrollable arrhythmia, parapneumonic sepsis, acute cardiac tamponade and left atrial rupture. 7 late deaths were noted during the follow-up period from 1 to 104 months [average 48 month]; three due to valve and left atrial thrombus formation, two due to CVA from overdose of warfarin, and each one due to congestive heart failure and chronic constrictive pericarditis, Anticoagulants after prosthetic valve replacement were maintained with warfarin, dipyridamole and aspirin to the level of around 50% of normal prothrombin time in 79 cases, and Ticlopidine with aspirin in 47 cases to compare the result of each group. There were 11 major thromboembolic episodes including 3 deaths in the warfarin group. Two cases of CVA due to overdose of warfarin was noted in the warfarin group. In the ticlopidine group, there was only one left atrial thrombus confirmed at the time of autopsy. Among the survived 138 cases, nearly all cases[136 cases] were included in NYHA functional class I and II during the follow-up period. In conclusion, surgical treatment of the cardiac valve disease in 156 clinical cases revealed excellent result with acceptable operative risk and late mortality. Prevention of thrombus formation with anti-platelet aggregator Ticlopidine has better result than warfarin group presently with no specific side effect such as bleeding or gastrointestinal trouble.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.307-309
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• 1999

Warfarin-induced skin necrosis is a rare complication caused by transient hypercoagulable state. This state is a result of rapid decline of the protein C activity relative to that of coagulation factor II, IX, and X during initiation of oral anticoagulant therapy. We experienced a case of warfarin-induced skin necrosis involving both breasts in a patient who underwent double valve replacement 1 month before. Warfarin was replaced to a low- molecular weight heparin and the necrotic breast lesion was healed spontaneously. Low-dose warfarin was restarted and gradually increased, after which a low molecular weight heparin discontinued..

• Korean Journal of Clinical Pharmacy
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• v.20 no.2
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• pp.159-164
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• 2010

Radiofrequency ablation (RA) is being used to manage atrial fibrillation (AF) with patients failed at the $1^{st}$-line anti-arrhythmic medications. Patients undergoing this procedure are at increased risk of thromboembolism after ablation, and anticoagulation management surrounding the ablation remains controversial. Although no conclusive recommendations can be made, published guidelines and data support therapeutic anticoagulation with warfarin. The purpose of this study was to analyze effectiveness of current therapy and to find factors fluctuate International Normalized Ratio (INR) values in patients undergone RA followed by anticoagulation service (ACS). Retrospective review was conducted utilizing database in a hospital. Among 110 patients under warfarin around ablation between January 2006 to September 2007, 54 patients were selected and allocated into 2 groups: Group A included 47 who discontinued warfarin after ablation, while 7 in B continued the medication. Information on demographics, amount and length of warfarin dosing, INR values and measuring frequencies, and the causing factors on INR fluctuation were abstracted. Differences were analyzed using chi-squared test, Fisher's Exact test, and unpaired Student t-test. Mean amount of warfarin before and after surgery was 4.0 mg, 4.1 mg in Group A and was 5.1 mg, 4.6 mg in Group B, respectively. Average duration of warfarin doing before ablation was 73.7 days in Group A, 129.9 days in B with no significant difference (p = 0.312). The duration time of warfarin on groups after ablation lasted several months. The number of checking INRs was 4.1 and 7.6, respectively. Inter-individual variability of INR fluctuations were $2.1{\pm}0.6$ in Group A and $2.2{\pm}0.7$ in B which were not significantly different (p = 0.062). 164 cases of decreased INR were: 'omission in taking medication, stressfulness and headache, 'increased intake of high vitamin K foods', 'lifestyle change of increased physical activities', and 'increase of food-intakes'. To the contrary, 36 cases of increased INR were: 'reduce of food-intake', 'use of non-prescription drugs', 'reduction in physical activities', and 'excessive restriction on food-intake', consecutively. In conclusion, the study validated therapeutic outcomes of RA patients who we treated with standard guideline and demonstrated 9 factors of INR fluctuations in the patient. A well-trained, pharmacist-monitored anticoagulation service could reduce the risk of adverse effects and prevent complications in patients with AF around RA operation.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.21 no.1
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• pp.584-592
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• 2020

The purpose of this study is to explore the relationship between warfarin-related knowledge, self-efficacy, and medication adherence among patients who underwent heart valve replacement surgery. The patients who underwent heart valve surgery and warfarin therapy were included in this study. The data was collected by administering questionnaires, and the data was then analyzed using the SPSS WIN 22.0 program. There was a positive relationship between warfarin-related knowledge and the adherence to medication (r=.285, p=004). Medication adherence was also positively correlated with warfarin-related knowledge (r=.250, p=.046) and self-efficacy (r=.292, p=.019) for elderly patients under 70 years of age. Further, medication adherence of elderly patients over 70 years of age was correlated with only warfarin-related knowledge (r=.358, p=.032). The results of this study show that in order to improve medication adherence, elderly people should be provided with warfarin-related knowledge through individually tailored education and nursing interventions that strengthen self-efficacy, as well as the knowledge that is needed in the elderly group under 70 years old.

• Journal of Chest Surgery
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• v.41 no.3
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• pp.354-359
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• 2008

Background: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin-rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. Material and Method: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan '1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). Result: The average INR of all the patient before rifampin administration was $2.25{\pm}0.52$ $(mean{\pm}SD)$, and that value for the first 100 days after rifampin administration was $1.98{\pm}0.28$. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was $2.19{\pm}0.34$, and the value after rifampin cessation was $2.49{\pm}0.43$. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range. Conclusion: The warfarin dose adjustment equation of before and after warfarin-rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.161-161
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• 2008

• Korean Journal of Clinical Pharmacy
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• v.26 no.3
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• pp.201-206
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• 2016

Objective: Direct current cardioversion for atrial fibrillation could be associated with the risk of thromboembolic events. Anticoagulation therapy with warfarin (INR 2.0-3.0) is recommended 3 weeks before and 4 weeks after cardioversion to reduce the risk of thromboembolism. This study evaluated warfarin therapy in pharmacist-managed anticoagulant services (ACS). Methods: This retrospective study was performed in 106 patients with atrial fibrillation from 2012 to 2013. The primary efficacy endpoint was the composite of stroke, transient ischemic attack, myocardial infarction, and cardiovascular death. The primary safety measure was major bleeding. To evaluate the peri-procedural effects of warfarin treatment, we studied whether target INR was maintained, as well as the maintenance period of the therapeutic range. Quality of treatment was measured by time in therapeutic range (TTR) by using the Rosendaal method. Results: There were no thromboembolic events, but TEE examination at time of cardioversion showed a left atrial thrombus in three patients (2.8%). Bleeding complications after cardioversion occurred in 2 patients (1.9%). The average INR value at the time of cardioversion was $2.59{\pm}0.8$, and was within the therapeutic range in 83 patients (78%). Analysis of the patients in whom the value was within the therapeutic range twice consecutively showed that the ratio of TTR was 80% and the therapeutic range was maintained in 67 patients (63%) for an average of 4.90 weeks prior to cardioversion. Similarly, 76 patients (72%) had a stable INR within the therapeutic range for an average of 5.70 weeks and a mean TTR of 83%. Conclusion: Pharmacists significantly contributed to appropriate warfarin treatment with close monitoring during cardioversion. Likewise, active pharmacist monitoring and systemic management should be considered to reduce thromboembolism and bleeding complications in the peri-cardioversion period.

• Korean Journal of Clinical Pharmacy
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• v.5 no.2
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• pp.17-31
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• 1995

Pharmacist-managed Anticoagulation Service(ACS) was estabilished and the effectiveness of warfarin monitoring by ACS in maintaining therapeutic INR was evaluated. The primary goal of ACS is to maximize the control of therapy, to maintain therapeutic INR and to decrease morbidity and hospitalization caused by inadequate dosage regimen. Clinical pharmacists performed chartreview, laboratory interpretation, recommendations for warfarin dosage adjustments, physician and patient education, and coordination of follow-up in ACS. Patients receiving warfarin sodium were evaluated via retrospective chart review. Sixty-two patients were referred to ACS by primary physicians were compared with 117 patients in the physician-amtrolled group. The ACS patients maintained $88.6\%$ in the therapeutic range for anticoagulant therapy and the control group maintained $63.7\%$, where the difference was statistically significant.(P<0.001) The ACS improved warfarin dose determination, PT stability, patient compliance and provided improved therapy compared with the control group. ACS offers safe and efficient anticoagulant therapy in the ambulatory setting.