• Journal of Chest Surgery
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• v.51 no.2
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• pp.114-121
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• 2018

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin $(IL)-1{\beta}$ levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.

• 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.20 no.1
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• pp.13-21
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• 1987

To clarify the difference between the outcome of warfarin anticoagulation and the antiplatelet [Aspirin, Dipyridamole] therapy after bioprosthetic heart valve replacement, we compared the following two groups. Group I [Warfarin group] consisted of 557 patients undergone lonescu - Shiley valve replacement between January, 1979 and December, 1985, and treated with scheduled warfarin therapy at Seoul National University Hospital. Group II [Antiplatelet group] consisted of 128 patients undergone lonescu - Shiley, Carpentier - Edwards or Wessex bioprosthetic valve replacement between March, 1983 and December, 1986, and treated primarily with antiplatelet therapy [Aspirin plus Dipyridamole] at SeJong General Hospital. The two groups were similar with respect to age, number of valves utilized per patient, type of operation and risk factors of thromboembolism. In group I, 522 patients excluding 35 hospital death [hospital mortality 6.3%], and in group II, 119 survivors excluding 9 hospital death [hospital mortality 7.0%] were followed. In group I, there were 13 fatal complications, of which seven were thromboembolic [0.6% / pt-yr] and six hemorrhagic [0.5%/pt-yr] during the period of four years. In group II, there were 3 fatal thromboembolic complications [2.3%/pt-yr] during the period of four years. This showed no statistically significant difference. Apart from fatal complications, there were lots of warfarin related minor complications in group I comparing with those of group II. The actuarial probability of the freedom from thromboembolism and of the freedom from fatal complications were very similar at each corresponding years postoperatively. As a result, warfarin anticoagulation in patients with bioprosthetic valve replacement did not reveal any significant advantages over antiplatelet therapy.

• Journal of Korean Neurosurgical Society
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• v.60 no.6
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• pp.701-709
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• 2017

Objective : Chronic subdural hematoma is a common and relatively benign disease. However, recurrence is common after surgical treatment, and the recurrence rate varies from 5% to 33%. The aim of this study was to investigate the predictive factors for recurrence of chronic subdural hematoma. Methods : We analyzed data from 248 patients with chronic subdural hematoma who were treated by burr-hole craniostomy with a closed drainage system for hematoma evacuation in this five-year retrospective study. Results : Thirty-one (12.6%) patients underwent re-operation for recurrence of chronic subdural hematoma. Univariate analysis revealed that anticoagulation (p=0.0279), headache (p=0.0323), and preoperative midline shifting (p=0.0321) showed significant differences with respect to recurrent chronic subdural hematoma. We performed a multivariate logistic regression analysis and found that diabetes mellitus (odds ratio [OR], 2.618; 95% confidence interval [CI], 1.0899-6.2898; p=0.0314), anticoagulation (OR, 6.739; 95% CI, 1.1287-40.2369; p=0.0364), headache (OR, 2.951; 95% CI, 1.1464-7.5964; p=0.0249), and preoperative midline shifting (OR, 1.0838; 95% CI, 1.0040-1.1699; p=0.0391) were independent predictive factors for recurrence of chronic subdural hematoma. Conclusion : We showed that diabetes mellitus, anticoagulation, headache, and preoperative midline shifting were independent predictors of recurrence of chronic subdural hematoma.

• Journal of The Korean Dental Society of Anesthesiology
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• v.12 no.2
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• pp.99-104
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• 2012

Anticoagulation therapy with warfarin sodium is used to reduce the risk of thromboembolic events in patients with valvular heart disease, prosthetic heart valve, recurrent myocardiac infarction, etc. To keep anticoagulation state and minimize bleeding risk, patients with high risk of thromboembolism have been usually hospitalized for heparinization before oral surgery like extraction. However, this protocol requires time and high expense because of the long period of hospitalization and this is why low-molecular-weight heparin (LMWH) therapy is receiving attention in medical field as well as dentistry. LMWH has several advantages over unfractionated heparin (UFH) including predictable anticoagulant response which makes coagulation monitoring unnecessary in most patients and longer half-life than heparin which enables the patients to give themselves a subcutaneous injection once or twice daily. These advantages of LMWH make patients get oral surgery on an outpatient basis so that they can save time and cost. This case report introduces the use of LMWH in dental surgery and suggests proper use of LMWH. Though LMWH bridging therapy is widely used most of the previous studies are observational studies. Therefore randomized controlled trials are necessary to evaluate the safety and efficacy of LMWH bridging therapy.

• The Korean Journal of Food And Nutrition
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• v.22 no.1
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• pp.20-28
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• 2009

According to traditional oriental medicine, only non-coagulated native deer blood is said to be effective, and coagulated deer blood is ineffective. Thus, a drying and tablet-producing method for deer blood was developed to maintain its physiological and therapeutic activity, and so that after drying, it can be redissolved and protected from coagulation. Proteases such as trypsin, pepsin, chymotrypsin, and aminopeptidase were added to the deer blood indicating that it coagulated in an hour, as shown by the reference. Wax gourd extract, which is high in protease, was added to the blood resulting in anticoagulation for 31 hours. Also, additions of 1% EDTA, 0.38% sodium citrate, 0.16% calcium oxalate, 1.2% ethanol, and 0.006% heparin to the deer blood resulted in anticoagulation for 1 hour, 4 hours, 2 hours, 1 hour, and 31 hours, respectively. In an experiment using 0.19% sodium citrate plus 1% wax gourd extract, and 0.006% heparin plus 1% wax gourd extract, anticoagulation was maintained for up to 72 hours. However, since heparin can not be used in food, the deer blood tablet was made with the addition of 0.19% sodium citrate and 1% wax gourd extract, followed by freeze drying. The dissolution rate for the tablet manufactured in this manner was 96.7%. And the dissolution rates for spray-dried deer blood, vacuum-dried deer blood, and marketed deer blood tablets were 85%, 81%, and 25.5%, respectively. The composition of the tablet produced from the freeze-dried deer blood was 56.4% protein, 18.7% lactose, 1.2% amino acids, 1.0% glucose, 0.7% lipids, 180 mg/100 g of iron, 13 mg/100 g of potassium, 39.1 mg/100 g of calcium, 480 mg/100 g of sodium, 368 mg/100 g of chloride, each.

• Korean Journal of Clinical Pharmacy
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• v.23 no.3
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• pp.232-238
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• 2013

Background: Although thromboembolism is common and one of the major causes of mortality in cancer patients, maintaining therapeutic anticoagulation effect with warfarin is challenging. This study aimed to determine the prevalence and the causes of non-therapeutic INR (International Normalized Ratio) in cancer patients. Methods: Medical and pharmacy records for cancer patients managed by the pharmacist-run anticoagulation service (ACS) between May, 2010 and April, 2011 at Seoul National University Hospital were retrospectively reviewed. The causes of non-therapeutic INR were identified and compared with the results from a former study with mechanical heart valve patients. Results: A total of 335 cancer patients and 6,737 patient-visits were analyzed producing 68% (n=4,590) of non-therapeutic INR readings. Eighty-five percent of the non-therapeutic INR readings were categorized as sub-therapeutic. Frequent causes linked to non-therapeutic INR included inadequate dosage adjustment (21.8%), changes in health status (11.8%), dietary changes (8.1%), and drug interactions (4.2%). More than half of the non-therapeutic INR values had no known etiology. As causes for non-therapeutic INR, changes in health status (p<0.0001), adverse reactions (p<0.0001), and dietary changes (p=0.017) were statistically more frequent in cancer patients than in patients with mechanical heart valves. Furthermore, exposure to sub-therapeutic INR were more prevalent in cancer patients than in patients with mechanical heart valve (p<0.0001). Conclusions: This study shows that there is a tendency to keep the level of INR low and that health status change, dietary change, and drug interactions are found to be frequent causes for non-therapeutic INR in cancer patients.

• The Journal of the Korean dental association
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• v.57 no.10
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• pp.613-622
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• 2019

The vitamin K antagonist (VKA), cumadin, or warfarin, is the only antithrombotic drug that can be orally administered and has excellent effective for decades. However, it is cumbersome to periodically inspect the prothrombin time (PT) order to maintain adequate concentrations that do not cause bleeding, takes a few days to indicate therapeutic effects, gets affected by several factors such as food and drugs etc, and narrow in the therapeutic range. Although recently in development, the non-vitamin K antagonist anticoagulants(NOACs) exhibit a rapid onset of action and have relatively short half- lives compared to Coumadin. Because of these pharmacokinetic properties, it is possible to modify an individual's anticoagulation status quite rapidly, minimizing the period where the anticoagulation activity is therapeutically suboptimal. And the short half -lives of these drug allow for the relatively rapid reduction of their anticoagulation effects. There are currently no published clinical trials specifically assessing the bleeding risks associated with dental procedures for patients taking the NOACs. It is not necessary to interrupt NOAC medication for dental procedures that are likely to cause bleeding, but which have a low risk of bleeding complications. Because the bleeding risk for these procedures is considered to be low, the balance of effects is in favour of continuing the NOAC treatment without modification, to avoid increasing the risk of a thromboembolic event. The patients should be advised to miss(apixaban or dabigatran) or delay(rivaroxaban) a dose of their NOAC prior to dental procedures that are likely to cause bleeding and which have a higher risk of bleeding complications. Because the risk of bleeding complications for these procedures is considered to be higher, the balance effects is in favour of missing or delaying the pretreatment NOAC dose. The interruption is only for a short time to minimize the effect on thromboembolic risk.

• Journal of Chest Surgery
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• v.13 no.4
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• pp.422-434
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• 1980

Since 1968 up to the end of October 1980, 448 valves were replaced in 354 patients in Seoul National University Hospital. There were 238 mitral, 38 aortic, 7 tricuspid, 45 aortic with mitral, 23 tricuspid with mitral, and 3 triple valve replacement aortic mitral and tricuspid cases. Annual increase of mitral valve replacement cases and decrease of operative maortality were remarkable. Recently operative mortality of mitral valve replacement is about 5%. Sex ratio of mitral valve replacement is almost equal and there were 12 cases of pediatric patients (5%) among 238 cases, and patients under the age of 20 years were 34 (14.3%). Mitral valve replacement was done for 199 single mitral, 38 double valve and one triple valve lesions. Among 238 mitral valve replacement paients left atrial thrombus in 23(9.7%), atrial fibrillation in 132 (55.5%), and reoperation after blind mitral commissurotomy in 12(5%) cases were noted. In recent cases bioprosthetic valves, mainly lonescu-shiley valve were utilized to overcome the difficulties of postoperative late complications in anticoagnuation, especially for the rural patients and pediatric cases, in addition to the hemodynamic advantages of lonesocu valve. Among 354 patients 16 cases were congenital heart anomaly related, 5 ventricular septal defect related aortic and 4 Ebstein related tribuspid valve replacement cases. There were 2 congenital anomaly related mitral valve replacements, one for congenital mitral insufficiency of 7 years old boy and one for corrected transposition of the great vessels associated with mitral insufficiency. Among total 354 valve replacements 49 operative deaths (13.3%) were noted and in 238 mitral valve replacement 24 operative deaths occurred (10.1%). In 39 patients among 354 total valve replacements late complications were found. In 238 mitral valve replacement cases late complications were noted in 26 patients, among whom 16 cases expired. Main late complications were thrombe-embolism, subacute becteerial endocarditis, arrythmia cerebral hemorrhage due to unsatisfactory anticoagulation, and congestive heart failure in the incipient period of valve replacement were also noted. In mitral valve replacement cases long-term survival rate was 83.2% who showed marked clinical improvement. Ther were no evidences of calcification during the 2 years follow-up period for the lonescu-valve replacement cases among 19 pediatric patients. In conclusion 238 cases of mitral valve replacement were done with 24 operative deaths and 26 late complication cases among whom 16 expired. The long term survival was 83.2% of the cases. In pediatric cases in place of coumadin anticoagulation Persantin **** 75 and aspirin were administered after valve replacement. In adult cases who have difficulaties with coumadin anticoagulation and for those even with bioprosthetic heart valve replacement who needs long-term or permanent anticoagulation persantin 75 and aspirin combination regimen were administered with antisfactory results.

• Quality Improvement in Health Care
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• v.4 no.1
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• pp.82-103
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• 1997

Background : With increased concerns about variation among physician's practice pattern and their impact on the quality of care, clinical practice guidelines have been developed by many different organizations, with differing aims and incentives. From the same point of view, there is growing interest in the development of clinical practice guidelines in Korea, but with only a few examples. As a result, there is not much exploration on the incentive and barrier to develop guidelines as well as description on the development process. The purposes of this study are to describe the process of the four different clinical practice guidelines in a hospital setting, and to identify incentives and barriers in the development of guidelines. Methods : For this research, a clinical practice guideline development committee and four clinical practice guideline development teams were organized in a university hospital which has more than 1,200 bead. Twenty eight doctors, three nurses, and one technician participated as members of development teams for eight months. Four to six meetings were held, and three to seven departments in the hospital were involved. Results : The topics which developed into clinical practice guidelines were cardiopulmonary resuscitation(CPR), blood transfusion, anticoagulation, and angiography. The main goals set by teams were education(CPR, angiography), risk management(blood transfusion), and to enhance quality of care(anticoagulation). Among four teams, only in the team for anticoagulation guideline medical record review and pilot-testing were performed. Also literature review was not carried out systematically. However, all the guidelines were developed by multidisciplinary be used as standard protocols in the practice. Conclusion : Experience and skill in developing process has to be improved to have a more valid and useful practice guideline. In particular, literature review and problem identification by examining medical record should be emphasized. Also further studies on the clinical outcomes of the guidelines application and changes in physicians' behaviors would be required.