• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.189-193
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• 2006

This study was designed to assess the distribution of cytochrome P450 2E1 (CYP2E1) polymorphism among Korean patients on warfarin therapy. CYP2E1 polymorphism was analyzed at 5' flanking region of CYP2E1 gene using restriction fragment length polymorphism method. Patient characteristics including the measured internal normalized ratio (INR) were also evaluated. Based on the warfarin dose and the bleeding cases, the patients were grouped as the regular dose control, the regular dose bleeding, the low dose control, and the low dose bleeding. Total 96 patients were evaluated for both Pst I and Rsa I loci of the CYP2E1 gene and the results showed that both loci were tightly linked. Thirty-three patients(34.4%) were heterozygotes and 4 patients(4.2%) were homozygote. There was no significant difference in patient characteristics in the dose and bleeding case groups. CYP2E1 polymorphism showed a little difference among the groups but was not statistically significant, however, lower INR value was observed in homozygote genotype groups. It was also revealed that genotype allele frequencies of CYP2E1 in Korean was close to other Asian groups but was significantly different from other Caucasian and African-American populations.

• The Korean journal of helicobacter and upper gastrointestinal research
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• v.18 no.4
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• pp.219-224
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• 2018

New oral anticoagulants (NOACs) are now widely used for the prevention and treatment of venous thrombosis, and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. As compared with warfarin, NOACs have the advantage of rapid onset of action and less drug interaction. However, they carry a higher risk of gastrointestinal (GI) bleeding than warfarin. The risk of GI bleeding in patients using NOACs varies according to the type and dose of the drug. By contrast, apixaban and edoxaban are reported to carry similar risks as warfarin, and the risks with dabigatran and rivaroxaban are higher than that with warfarin. In patients using NOACs, old age, impaired renal function, impaired liver function, concurrent use of antiplatelet agents, and nonsteroidal anti-inflammatory drugs are considered major risk factors of GI bleeding, and gastroprotective agents such as histamine-2 receptor antagonist and proton pump inhibitor have preventive effects. To prevent GI bleeding associated with NOACs, the characteristics of each NOAC and the risk factors of bleeding should be recognized.

• Journal of Korean Biological Nursing Science
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• v.14 no.1
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• pp.66-75
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• 2012

Purpose: This study was conducted to measure medication adherence and perceptions of anticoagulation therapy and its relationship to patients taking warfarin. Methods: in a cross-sectional survey, 150 patients taking warfarin who had visited an outpatient clinic of a cardiovascular center in Seoul were included as research subjects. Medication adherence was measured using a visual analogue rating scale (VAS). Barriers and attitudes toward adherence, and oral anticoagulation knowledge, were measured using a structured questionnaire. Participants' medical records also were reviewed to identify clinical characteristics. Results: About one third of the participants (30.7%) reported medication adherence as 100%. The major barriers to adherence were identified as "Forgetting the time of medication" and "Not carrying their medication". Overall attitudes toward medication adherence were high, but oral anticoagulation therapy knowledge was low. To determine the relationship of medication adherence and perceptions of anticoagulation therapy, participants were stratified into three groups, based on their medication adherence levels (high adherence, moderate adherence, low adherence). Participants in the high adherent group more likely to be older (OR: 1.04, 95% CI: 1.005-1.071) and to have positive attitudes toward medication adherence (OR: 1.12, 95% CI:1.013-1.229) compared to the other two groups. Conclusion: The results show that age and attitude exerts significant influence on medication adherence in patients taking warfarin.

• Journal of Chest Surgery
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• v.38 no.11 s.256
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• pp.761-772
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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 objective of this study was to suggest a practical dosing guideline for 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, 1997 to September, 2000. Patients who were at least 6 months post-valve replacement and had nontherapeutic INR value (less than 2.0 or greater than 3.0) were included. The data on 688 patients (1,782 visits) requiring dosing adjustment without any known drug or food interaction with warfarin were analyzed. The amount of adjusted dose and INR changes based on the INR at the time of the event were calculated. Aortic valve replacements (AVR) patients and mitral or double valve replacement (MVR/DVR) patients were evaluated separately. Result: Two methods for the warfarin dosage adjustment were suggested: Guideline I (mg-based total weekly dose (TWD) adjustment), Guideline II (percentage-based TWD adjustment). The effectiveness of Guideline 1 was superior to Guideline II overall in patients with both AVR and MVR/DVR. Conclusion: The guideline suggested in this study could be useful when the dosage adjustment of wafarin is necessary in outpatients with mechanical heart valves.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.675-687
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• 2010

Objective : Interaction of warfarin with herbal medicines still remains controversial. The aim of this study was to examine the effect of herbal medicines which contain ginseng on PT INR in patients being treated with warfarin. Method : We studied patients who take herbal medicines which contain ginseng with warfarin during their hospitalization. We retrospectively investigated the effect of herbal medicines which contain ginseng. 10 patients were assigned to receive one of the following adjuncts: Group A (n=4) that received Bojungikkitang-gagam, Group B (n=2) that received Ukgunjatang-gagam, and Group C (n=4) that received Shihogyeji-tang, Gamiondam-tang, Gwininaanshim-tang, and Saengpe-san together. We then investigated changes of PT INR in each group. Result : In group A, there were diminutions of PT INR in 3 cases, and increment in 1 case. In group B, there were increments of PT INR in both cases. In group C, there were increments of PT INR in 3 cases and there was no big change in 1 case. Conclusion : In this study, we found that the interaction of combined herbal medicine is very complicated. So, we must study further more study about interactions of combined herbal medicine on PT INR.

• Journal of Chest Surgery
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• v.32 no.11
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• pp.1023-1030
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• 1999

This is a retrospective study of 42 pregnancies from 33 women with prosthetic heart valves who were on anticoagulation regimen prior to or during their pregnancy. Material and Method: Of the 17 women with bioprosthesis, 15 had 21 pregnancies following cessation of the anticoagulation therapy which resulted in the delivery of 20 healthy babies and 1 abortion. Remaining 2 had 3 pregnancies maintained with heparin, resulting in 2 healthy babies and 1 spontaneous abortion. Result: Among 16 women with mechanical heart valves, there were 7 pregnancies during which warfarin was used and this was associated with 4 fetal wastages(2 therapeutic abortion, 1 spontaneous abortion and 1 stillbirth with cerebral hemorrhage). However, in pregnancies where heparin was used, there was no fetal wastage. A patient who did not take anticoagulant for the first trimester and took warfarin for the remaining period and a patient who did not take anticoagulant during pregnancy delivered normal babies. There was an other fetal wastage in a patient on anti-platelet therapy for the first trimester and warfarin therapy for the remaining periods. There was 1 minor petechial complication in a heparin administered group. Conclusion: The study indicates that woman with bioprosthetic heart valves can go through pregnancy without undue risks or complications. On the other hand, the use of warfarin during pregnancy in women with mechanical heart valves, was shown to be associated with unacceptable high risk for the fetus. However, in the same group of women, judicious use of heparin during pregnancy was accompanied by a much reduced risk. The safety and adequate therapeutic range of heparin usage under such circumstances are subject to further studies.

• Journal of Chest Surgery
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• v.9 no.2
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• pp.215-219
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• 1976

Anticoagulation therapy with Warfarin and Dipyridamole is useful after prosthetic heart valve replacement for the prevention of thromboembolic accidents. Here presented a case of right ovarian hematoma, 41 years old, female who has been already treated double valve replacement due to mitral insufficiency with 27 mm $Bj{\ddot{o}}rk-Shiley$ mitral, and 29 mm Hancock tricuspid valve successfully on 27th, April, 1976. Just after the operation, patient was treated the anticoagulation therapy with Dipyridamole 300 mg, and Heparin, and later switched to Warfarin 3.75 mg or 5 mg po, as the maintenance dose. Three and half months after the anticoagulation therapy, patient complained the lower abdominal pain and vaginal spotting and which revealed right ovarian hematoma due to ovulation, manifested due to anticoagulation therapy. Patient was discharged postoperative 15 th day with the maintenance dose 5 mg Warfarin and Dipyridamole 300mg po to maintain the prothrombin time 30%, after the uterus and both. ovaries and both adnexae are resected out for the prevention of the further hemorrhage of ovary.

• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.238-250
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• 2022

Objective: The aim of this study was to examine the impact of ATP-binding cassette subfamily B member 1 (ABCB1) C3435T polymorphism on the treatment response of patients to vitamin K antagonists (VKAs). Methods: In this systematic review and meta-analysis, the PubMed/Medline, Embase, and Cochrane Library databases were searched for eligible articles for the period up to November 2020. Articles that reported treatment response to VKAs according to the ABCB1 C3435T polymorphism were included in this study. Results: A total of 13 and 9 articles were included in the systematic review and meta-analysis, respectively. The weekly maintenance dose of warfarin was significantly lower in patients with the ABCB1 3435CT or TT polymorphism type than in those with the ABCB1 3435CC type (weighted mean difference [WMD], -2.53 mg/week; 95% confidence interval [CI], -3.64 to -1.43, p<0.001). However, the weekly maintenance dose of acenocoumarol was not significantly associated with the ABCB1 C3435T polymorphism (WMD, 1.02; 95% CI, -0.61 to 2.65, p=0.22). Conclusion: The ABCB1 C3435T polymorphism was significantly associated with the weekly maintenance dose of warfarin. Further research is needed to confirm the association between the ABCB1 C3435T polymorphism and the incidence rate of bleeding events.

• Journal of The Korean Society of Clinical Toxicology
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• v.7 no.2
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• pp.164-171
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• 2009

Purpose: The number of patients who take warfarin is growing and so is the number of complications. Hemorrhage is the major complication, but the clinical characteristics and outcomes have not been determined for Korean patients. Therefore, we tried to evaluate the characteristics of the patients with hemorrhagic complications after taking warfarin as anticoagulation therapy. Methods: We retrospectively reviewed the medical records of the patients who visited the emergency room with bleeding complications after taking warfarin anticoagulation at the out-patient clinic for 1 year from 1 st January 2008. We compared between two groups (the major hemorrhage group vs. the minor hemorrhage group) according to the clinical criteria, the unstable vital signs that required blood transfusion, transfusion more than 2 units of blood, the need for further laboratory follow-up, the need for interventional treatment and the development of critical complications or death due to bleeding. Results: There were 150 patients who met the criteria and had acute hemorrhagic complications (the major group: 90 patients and the minor group: 60 patients). In the major hemorrhage group, the frequent sites of bleeding were the gastro-intestinal system (40 patients), lung (14 patients) and intracranium (7 patients). At the emergency room, the major group showed a higher initial INR of the activated prothrombin time than did the minor group (p=0.02). The bleeding sites of the fatal cases were the gastro-intestinal system (3 patients), lung (3 patients) and intracranium (3 patients), but the percentage of fatality was the highest for intracranium bleeding. Conclusion: In the major hemorrhage group, gastrointestinal bleeding was the most frequent complication and fatality was the highest for intracranium bleeding. An initially higher INR showed a greater risk of major bleeding, but not more fatalities.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.179-204
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• 1998

The purpose of this research was to investigate the efficacy of Goiwhasan extract powder on the gastric injuries, antiulcer, gastrointestinal tract and blood hemostasis. Animals were used through this studies mice and rats. All animals were divided into 3 groups, contol group(no treatment), sample Ⅰ group(375mg/kg administration), sample Ⅱ group(750mg/kg administration). The gastric injuries and ulcer have been made by using pyloric ligation, indomethacin, HCI-ethanol, acetic acid and then The histological observation was followed. In the gastrointestinal tract, gastric juice secretion, gastric acidity, pepsin output, blood gastrin and secretin level, transport potentials in the small and large intestine were checked. And studies on blood hemostasis were performed on normal hemostatic activities and plasma prothrombin time, plasma recalcification time, plasma fibrinogen levels in the hypoprothrombinemic mice induced by warfarin. The results were as follows: 1. The antigastric ulcer effects on the pyloric ligation, indomethacin, HCl-ethanol, acetic acid induced gastric injuries were shown in Sample Ⅱ group(p<0.05). 2. Through the morphologic examination on the acetic acid induced ulcer, Sample Ⅰ group showed mild regeneration of epithelium and slight decrease of periulcer edema then that of Control group, while Sample Ⅱ group showed more retraction of round ulcer site, remarkable loss of swelling and edema then that of Control group, and revealing the regenerated epithelium in the surrounding ulcer site. Thus it was noted that both Sample groups have antigastriculcer effects on the experimentally induced gastric ulcer. 3. The inhibitory effects on gastric juice were noted in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.01). However, only Sample Ⅱ group showed the inhibitory effects on total acidity and pepsin output(p<0.05). 4. The significant inhibition of blood gastrin level showed at 30 min.(P<0.05) and 90 min.(P<0.05) after starting medication in only Sample Ⅱ group, but significance of blood secretin level in both groups was not recognized. 5. Any significant changes in barium sulfate transport in the small intestine of mice was not recognized in both groups, but the significantly inhibitory effect in large intestine was recognized in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.001). 6. In hemostatic effect on both normal mice and hypoprothrombinemic mice induced by warfarin, the significantly shortening effect on coagulation time was seen in only Sample Ⅱ group(p<0.01). 7. On plasma prothrombin time in hypoprothrombinemic rat induced by warfarin, Sample Ⅱ group have shortened the prothrombin time significantly(p<0.001). 8. On plasma reclcification time in hypoprothrombinemic rat induced by warfarin, the recalcification time have been shortened significantly in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.01). 9. On plasma fibrinogen levels in hypoprothrombinemic rat induced by warfarin, the fibrinogen contents in Sample Ⅱ have been decreased significantly(p<0.01). Overall the above results suggest that Goiwhasan has an therapeutic efficacy on antigastric ulcer and blood hemostasis. Further studies would be needed on the interaction of its herbal medicine and its mechanism in the future.