Warfarin 복용 고령 환자의 출혈 현황 및 위험성 예측

남주연,최경숙,정영미,남궁형욱,이은숙,이병구,신완균 한국병원약사회 2010 병원약사회지 Vol.27 No.3

Warfarin, an effective agent for the prevention of serious thromboembolism, frequently causes bleeding complication, especially in elderly patients. In the literature, a number of different bleeding risk indices were proposed to predict the bleeding risk in patients with warfarin. However, the predictability of these indices has not been systemically evaluated in Korean patients. Therefore, the aims of the study were to determine the bleeding rate in elderly Korean patients treated with warfarin and to evaluate the predictability of the bleeding risk indices by comparing the indices with the actual bleeding rate. Electronic Medical Records(EMRs) of the patients enrolled in Anti-Coagulation Service(ACS) in Seoul National University Bundang Hospital(SNUBH) between May 10, 2003 and March 31, 2007 were reviewed. Patients, who were over the age of 65 years and received warfarin for at least 90 days with a targeted therapeutic International Normalized Ratio(INR) of 2.0~3.0, were participated in the present study. The patients were divided into 3 risk groups(i.e., low, moderate, high), as defined by the indices. Bleeding was considered ‘major’if the location was either intracranial or retroperitoneal, if the bleeding was associated with a decline in hemoglobin concentration of at least 2g/dL, or if a transfusion of 2U or more of red blood cells was necessary. Within one year, out of 323 patients, 94(29%) patients have experienced bleeding; 11 cases were classified as major bleeding. Major bleeding rates according to Shireman et al were 2.5%(5/197) and 5.2%(6/116) for the groups with low and moderate risk, respectively. No major bleeding was found in the high risk group based on the Shireman index. Major bleeding rates according to Kuijer et al were 3.3%(10/306) and 5.9%(1/17) for the groups with moderate and high risk, respectively. Major bleeding rates according to Beyth et al were 3.3%(9/271) and 3.8%(2/52) for the groups with moderate and high risk, respectively. There was no statistically significant difference among the bleeding risk groups. Further study will be necessary for the development of bleeding risk index optimized for elderly Korean patients.

출혈성 소화성 궤양에서 재출혈 혹은 지속출혈의 위험인자

박선미,윤세진,채희복,오상우,이정아 충북대학교 의과대학 충북대학교 의학연구소 1999 忠北醫大學術誌 Vol.9 No.2

연구목적: 소화성 궤양에 의한 출혈은 대부분 저절로 멈추고 회복되지만 일부는 재출혈 혹은 지속 출혈을 하고 불량한 임상 경과를 보인다. 출혈성 소화성 궤양에서 재출혈 혹은 지속 출혈을 예측할 수 있는 위험인자를 파악하고자 본 연구를 시행하였다. 대상 및 방법: 출혈성 소화성 궤양으로 내원한 위궤양 97예, 십이지장 궤양 46예를 후향적으로 분석하였다. 출혈의 유형은 단회 출혈, 재출혈, 및 지속 출혈로 분류하고 각 유형에 따른 경과를 조사하였다. 재출혈 혹은 지속 출혈과 연관된 위험 인자들로서 대상 예들의 임상적 특성, 초회 출혈 후 혈류 동태의 불완전성, 초회 출혈량, 궤양의 위치, 초회 출혈후 내시경적 최근 출혈의 징후 등에 대해 단변량 및 다변량 분석을 하였다. 결과: 출혈의 유형은 단회 출혈이 104예(72.7%), 재출혈이 31예(21.7%), 그리고 지속 출혈이 8예(5.6%)였다. 지속 출혈 1예는 사망하였고 재출혈 10예와 지속 출혈 7예는 외과적 수술로, 나머지는 보존적인 치료로 호전되었다. 단변량 분석상 재출혈 혹은 지속 출혈의 위험인자는 흡연력, 비스테로이드성 함염증제를 복용한 병력, 토혈, 저혈압, 고질소혈증, 위궤양, 그리고 활동성 출혈 혹은 비출혈성 노출 혈관 등이었다. 다변량 분석상 저혈압, 위궤양, 활동성 출혈 혹은 비출혈성 노출 혈관 등이 의미있는 위험인자들이었다. 위험인자의 개수가 많아질수록 재출혈 혹은 지속 출혈율은 의미있게 증가하였다. 결론: 초회 출혈 후 저혈압이 있거나 위궤양이거나 활동성 출혈 혹은 비출혈성 노출 혈관 등 내시경 소견상 최근 출혈의 징후가 있는 소화성 궤양은 재출혈 혹은 지속 출혈을 할 위험성이 높으므로 집중적인 관찰과 치료가 요구된다. Purpose: Although the most of patients with bleeding peptic ulcers show self-limited course, a subgroup of patients presenting with persistent or rebleeding have poor outcome. The aims of this study are to determine the clinical outcomes of bleeding peptic ulcer and to identify the risk factors of persistent or rebleeding after an episode. Materials and Method: One hundred forty-three patients of bleeding peptic ulcers, 97 gastric ulcer cases and 46 duodenal ulcer cases, were studied retrospectively. Bleeding patterns were divided into single bleeding, rebleeding, and persistent bleeding. The clinical, laboratory and endoscopic variables were evaluated for the risk factors of persistent or rebleeding in univariate and multivariate analysis. Results: The three patterns of bleeding were single bleeding in 104 cases (68.4%), rebleeding in 31 cases (25.7%), and persistent bleeding in 8 cases (5.9%). One half of patients with persistent or rebleeding showed fatal outcomes (17 operations and 1 deaths), whereas all patients with single bleeding were improved completely. In univariate analysis, the history of smoking, nonsteroidal antiinflammatory drugs, hematemesis, hypotension, elevated BUN, gastric ulcer, and active bleeding or nonbleeding visible vessel proved to be risk factors for persistent or rebleeding. Miltivariate analysis identified three risk factors for persistent or rebleeding: hypotension, gastric ulcer, and active bleeding or nonbleeding visible vessel. The numbers of risk factors were closely related to the rates of persistent or rebleeding. Conclusion: The patients at a high risk for persistent or rebleeding needed early therapeutic intervention and intensive care.

출혈성 소화성 궤양의 위험인자 분석

김인한(In Han Kim),김범수(Pum Soo Kim),권계숙(Sook Kwon),이돈행(Don Haeng Lee),최원(Won CHoi),조현근(Hyeon Guen Cho),김형길(Hyung Gil Kim),신용운(Yong Woon Shin),김영수(Young Soo Kim),김영배(Young Bae Kim) 대한소화기학회 2000 대한소화기학회지 Vol.35 No.2

Background/Aims: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to be associated with a high incidence of upper gastrointestinal tract bleeding in the elderly. Increase in prevalence of Helicobacter pylori (H. pylori) infection according to age, implicates that an interaction between use of NSAIDs and H. pylori infection may explain the higher incidence of ulcer complications in the elderly. In the present study, we analysed risk factors existed in peptic ulcer patients with upper gastrointestinal bleeding. Methods: A retrospective study was performed for 420 consecutive peptic ulcer patients (bleeding: 98, nonbleeding: 322). The bleeding group had bleeding symptoms and endoscopic stigmata of bleeding. Use of NSAIDs was evaluated by interview and H. pylori infection was confirmed by endoscopic biopsy specimens and CLO test in all cases. Results: The rates of duodenal ulcer were 62.5% in bleeding group and 50.5% in nonbleeding group (p<0.05). NSAIDs and H. pylori-infection didn't show a significant correlation with bleeding (p>0.05). However, CagA showed a positive correlation with the peptic ulcer bleeding, especially gastric ulcer bleeding (p<0.05). Conclusions: In peptic ulcer patients, duodenal ulcer is more prone to bleeding than gastric ulcer. Use of NSAIDs doesn't increase the risk of upper gastrointestinal bleeding. Location of ulcer and CagA positivity seem to be risk factors of upper gastrointestinal bleeding. (Kor J Gastroenterol 2000;35:178 - 185)

Optimal Dose of Edoxaban for Very Elderly Atrial Fibrillation Patients at High Risk of Bleeding: The LEDIOS Registry

Ju Youn Kim,Juwon Kim,Seung-Jung Park,Kyoung-Min Park,Sang-Jin Han,Dae Kyeong Kim,Yae Min Park,Sung Ho Lee,Jong Sung Park,Young Keun On The Korean Society of Cardiology 2024 Korean Circulation Journal Vol.54 No.2

Background and Objectives: Optimal anticoagulation in very elderly patients is challenging due to the high risk of anticoagulant-induced bleeding. The aim of this study was to assess outcomes of on-label reduced-dose edoxaban (30 mg) in very elderly patients who had additional risk factors for bleeding. Methods: This was a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of on-label reduced-dose edoxaban in atrial fibrillation (AF) patients 80 years of age or older and who had more than 1 risk factor for bleeding. Results: A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study, and 586 (23.9%) were 80 years of age or older with additional risk factors for bleeding. Major bleeding events occurred frequently among very elderly AF patients who had additional bleeding risk factors compared to other patients (unadjusted hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.16-4.02); however, there were no significant differences in stroke incidence (HR, 1.86; 95% CI, 0.98-3.55). There were no significant differences for either factor after adjusting for age and sex (adjusted HR, 1.65; 95% CI, 0.75-3.62 for major bleeding; adjusted HR, 1.13; 95% CI, 0.51-2.50 for stroke). Conclusions: In very elderly AF patients with comorbidities associated with greater risk of bleeding, the incidence of major bleeding events was significantly increased. In addition, risk of stroke showed tendency to increase in same population. Effective anticoagulation therapy might be important in these high-risk population, and close observation of bleeding events might also be required.

Optimal Dose of Edoxaban for Very Elderly Atrial Fibrillation Patients at High Risk of Bleeding: The LEDIOS Registry

Ju Youn Kim,Juwon Kim,Seung-Jung Park,Kyoung-Min Park,Sang-Jin Han,Dae Kyeong Kim,Yae Min Park,Sung Ho Lee,Jong Sung Park,Young Keun On 대한심장학회 2024 Korean Circulation Journal Vol.54 No.7

Background and Objectives: Optimal anticoagulation in very elderly patients is challenging due to the high risk of anticoagulant-induced bleeding. The aim of this study was to assess outcomes of on-label reduced-dose edoxaban (30 mg) in very elderly patients who had additional risk factors for bleeding. Methods: This was a multi-center, prospective, non-interventional observational study to evaluate the efficacy and safety of on-label reduced-dose edoxaban in atrial fibrillation (AF) patients 80 years of age or older and who had more than 1 risk factor for bleeding. Results: A total of 2448 patients (mean age 75.0±8.3 years, 801 [32.7%] males) was included in the present study, and 586 (23.9%) were 80 years of age or older with additional risk factors for bleeding. Major bleeding events occurred frequently among very elderly AF patients who had additional bleeding risk factors compared to other patients (unadjusted hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.16–4.02); however, there were no significant differences in stroke incidence (HR, 1.86; 95% CI, 0.98–3.55). There were no significant differences for either factor after adjusting for age and sex (adjusted HR, 1.65; 95% CI, 0.75–3.62 for major bleeding; adjusted HR, 1.13; 95% CI, 0.51–2.50 for stroke). Conclusions: In very elderly AF patients with comorbidities associated with greater risk of bleeding, the incidence of major bleeding events was significantly increased. In addition, risk of stroke showed tendency to increase in same population. Effective anticoagulation therapy might be important in these high-risk population, and close observation of bleeding events might also be required.

고령의 심방세동 환자의 Warfarin 치료 시, 출혈 발생률과 위험인자 분석

조현복,민경아,인용원,이영미,손기호 한국병원약사회 2011 병원약사회지 Vol.28 No.2

Atrial fibrillation is an independent risk factor for stroke, and oral anticoagulation therapy with warfarin is effective in the prevention of stroke in atrial fibrillation. It has been reported that the prevalence of atrial fibrillation increases with age, and numbers of elderly patients who take warfarin is also increasing. As a result, increasing rate of bleeding associated with warfarin in elderly patients has been reported in previous studies. This study was designed to evaluate the incidence rate of bleeding in relation to age, and the factor associated with bleeding. In this retrospective study, baseline characteristics, anticoagulant control (target INR of 2-3)and the incidence of bleeding were assessed in an elderly population (≥75 years) compared with a younger population (between 65 and 74 years). All patients were new warfarin users, attending anticoagulation service (ACS) at Samsung Medical Center from January 1, 2008 to August 31,2009. Each patient was followed up by 1 year after starting taking warfarin. A total of 155 patients were studied, and 100 patients in the younger group providing 83.1 person-years of follow-up and 55 patients in the elderly group providing 39.5 person-years of follow up. Between younger and elderly group, average of duration of INR within target range is 57.5% and 61.5% respectively, and there is no significant difference (p=0.269). No difference of incidence of minor bleedings was found between the elderly group and the elderly group(p=0.395). Major bleedings were developed 1 event in younger group and 2 events in the elderly group. Incidence rate of major bleeding in the elderly group was higher than the younger group in 4.21folds, but it was not statistically significant (95% CI, 0.38-46.4). 42.6% of all bleeding and 33.3%of major bleeding were developed in first 90 days after starting warfarin therapy. Male (p=0.031)was analyzed as a risk factor for bleeding associated with warfarin in the all 155 patient, and history of cancer was analyzed that had effect on the analyzing sex as a risk factor for bleeding. However, we couldn't find the risk factors of bleeding for the elderly group. These findings suggest that older age and early period of warfarin therapy were related to increasing of bleeding caused by warfarin, and needed much care for anticoagulation therapy. Further studies to analyse risk factors for bleeding and there results may be help provide better anticoagulation therapy to elderly atrial fibrillation patients for prevention of stroke.

고령자 상부위장관 출혈에 관한 임상적 고찰

김태두,주영은,김신묵,성종호,안영주,정용환,양대현,유종선,윤종만 全南大醫大 1993 전남의대학술지 Vol.30 No.1

Risk Factors for Post-Thyroidectomy Bleeding: an Analysis of 19,657 Cases from a Single Institution

Dawid Lee,Kyorim Back,Jun-Ho Choe,Jee Soo Kim,Jung-Han Kim 대한갑상선-내분비외과학회 2020 The Koreran journal of Endocrine Surgery Vol.20 No.4

Purpose Post-thyroidectomy bleeding (PTB) is rare but may be a life-threatening complication. This study investigated the incidence of and risk factors for postoperative bleeding after thyroid surgery. Methods The medical records of all patients who underwent thyroidectomy at Samsung Medical Center between November 1994 and July 2018 were reviewed retrospectively to identify any risk factors for PTB. Clinicopathological factors related to post-thyroidectomy bleeding were included in our analysis, and the association of potential risk factors with outcomes was tested by logistic regression analysis. Results Of 19,657 patients, PTB occurred in 132 (0.67%). In addition, 130 cases of PTB had emerged within 24 hours, while only 2 patients required re-operation after discharge. One patient expired due to hypoxic brain damage. A univariate analysis revealed that male sex (odds ratio [OR]=2.28, P<0.0001), chronic kidney disease (OR=5.26, P=0.02), the use of anti-hemorrhagic agents (OR=0.57, P=0.0017), and surgeon-specific factors (OR=3.4, P<0.0001) were significantly associated with PTB. However, upon multivariate analysis, only male sex (OR=2.34, P<0.0001) and surgeon-specific factors (OR=3.10, P<0.0001) were significant risk factors for PTB. Conclusion Male sex and surgeon-related factors significantly increased the risk of PTB. Since our study showed a tendency for PTB to increase within 24 hours of surgery, surgeons should look through whole surgical process or surgical techniques to minimize bleeding during the operation and conduct a close observation of all patients immediately after surgery.

간이식 환자의 출혈 경향과 치과적 고려 사항

박원서,백윤재,도레미,김기덕,정복영,방난심,윤희정,유태민,Park, Wonse,Baik, Yoon-Jae,Doh, Re-Mee,Kim, Kee-Deog,Jung, Bock-Young,Pang, Nan-Sim,Yun, Hee-Jung,You, Tae-Min 대한치과마취과학회 2012 Journal of Dental Anesthesia and Pain Medicine Vol.12 No.3

Background: The major goal of dental management before and after liver transplantation is the prevention of bacteremia from an oral source that could lead to systemic infection. However dental treatment in liver transplant patients have the risk of infection and bleeding. so it is needed special dental consideration. Methods: 42 liver transplant candidates who visited department of Advanced General Dentistry in Yonsei University College of dentistry from March 1, 2010 to February 29, 2012 were selected. The clinical data of those patients were analyzed; coagulation status such as PT, INR, aPTT, platelet count before and 6 months after liver transplantation, dental infectious foci, time interval between dental visit and operation date of liver transplantation. Results: Before liver transplant, the patient's PT and INR was prolonged, and the platelet count was lower than normal range. But 6 months later from liver transplantation, most of the figures turned into a normal range. The dental infection foci were chronic periodontitis, dental caries, chronic apical periodontitis, root rest et al but we did extraction of 6 root rest before liver transplantation and postponed other treatment after liver transplantation due to bleeding and infection risk of patients. Because of insufficient interval between dental visit and operation date, 64.3% of patients could not finish the dental treatment. Conclusions: The patients before liver transplantation have the risk of bleeding. The treatment of those patient should be removal of only factors that can cause dental infections after transplantation and other treatment must be postponed until the stable period of the transplant that patient's condition has improved.

Benefits of Thromboelastography and Thrombin Generation Assay for Bleeding Prediction in Patients With Thrombocytopenia or Hematologic Malignancies

김선영,구자윤,유현주,김지은,장선표,최수연,고영일,김인호,김현경 대한진단검사의학회 2017 Annals of Laboratory Medicine Vol.37 No.6

Background: Thromboelastography (TEG) provides comprehensive information on the whole blood clot formation phases, whereas thrombin generation assay (TGA) reveals the endogenous thrombin levels in plasma. We investigated the potential significance of TEG and TGA parameters for prediction of clinical bleeding in hematologic patients on the basis of the patient’s platelet levels. Methods: TEG and TGA were performed in 126 patients with thrombocytopenia or hematologic malignancies. The bleeding tendencies were stratified on the basis of the World Health Organization bleeding grade. Results: Maximum amplitude (MA) and clot formation in TEG and endogenous thrombin potential (ETP) in TGA showed significant associations with high bleeding grades (P=0.001 and P=0.011, respectively). In patients with platelet counts ≤10×109/L, low MA values were strongly associated with a high bleeding risk. For bleeding prediction, the area under the curve (AUC) of MA (0.857) and ETP (0.809) in patients with severe thrombocytopenia tended to be higher than that of platelets (0.740) in all patients. Patients with platelet counts ≤10×109/L displayed the highest AUC of the combined MA and ETP (0.929). Conclusions: Both TEG and TGA were considered to be good predictors of clinical bleeding in patients with severe thrombocytopenia. Combination of the ETP and MA values resulted in a more sensitive bleeding risk prediction in those with severe thrombocytopenia.