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.

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.

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.

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.

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.

Bedside Risk-Scoring Model for Prediction of 30 days’ Mortality in Patients with Cirrhosis Underwent Endoscopic Band Ligation for Acute Variceal Bleeding

( Jung Hee Kim ),( Se Woo Park ),( Jang Han Jung ),( Jae Gun Park ),( Chang Suk Bang ),( Ji Won Park ),( Da Hae Park ),( Jin Lee ),( Dong Hee Koh ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Acute variceal bleeding is a fatal complication for cirrhotic patients and endoscopic band ligation (EVL) is recommended for treatment. But there are sporadic data for mortality in patients underwent EVL of acute variceal bleeding. We developed a novel bed-side scoring model to predict 30 days’ mortality for cirrhotic patients who underwent EVL of acute variceal bleeding. Methods: From a Cox-regression model for 30 days’ mortality, variables were developed among baseline characteristics, history of complication, the presence of hepatocellular carcinoma, ascites and endoscopic finding from the derivation cohort (n=1372) underwent EVL for acute variceal bleeding. The model’s prognostic performance was compared with CTP and MELD score and assessed in validation cohort. (n=200). Results: Among 1372 patients, rebleeding or death within 5 days was observed in 51 patients (3.7%) and 72 patients (5.2%), respectively. The validation cohort showed more aggressive clinical outcome than derivation cohort in term of endoscopic active bleeding, shock at presentation and treatment failure.From a multivariate Cox-regression model, four objective variables (the presence of HCC, CTP class (A/B vs. C), the shock at presentation and the history of hepatic encephalopathy) were developed and scored to generate an 11-point risk prediction model. The scoring model was able to stratify patient 30 days’ mortality as low (4.25%), medium (20.9%) and high (42.3%) risk group. (P<0.001) The time-dependent area under receiver-operating characteristics curves (AUROCs) for 30days mortality were higher in risk prediction model than CPT score. (derivation cohort: 0.79 vs 0.73, validation cohort:0.82 vs 0.75, P<0.001). Even in the group of same MELD (<15 or ≥15), new scoring model also stratified 30 days’ mortality to three groups with statistically significant in derivation and validation cohort. Conclusions: New simplified scoring system was useful in estimating 30days mortality for patients who underwent EVL for acute variceal bleeding. This score can be useful in planning and guiding further strategies after EVL which warrants prospective validation.

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.

The Use of Nafamostat Mesilate as an Anticoagulant during Continuous Renal Replacement Therapy for Children with a High Risk of Bleeding

이상택,조희연,Lee, Sang Taek,Cho, Heeyeon Korean Society of Pediatric Nephrology 2014 Childhood kidney diseases Vol.18 No.2

Purpose: Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has been investigated as an anticoagulant for adult patients with a high risk of bleeding, who need chronic renal replacement therapy (CRRT). However, little is known about the use of NM as an anticoagulant in pediatric CRRT. The aim of this study was to evaluate the ideal dosage, efficacy, and safety of NM in pediatric CRRT. Methods: We conducted a retrospective study of 40 pediatric patients who had undergone at least 24 h of venovenous CRRTs between January 2011 and October 2013. We divided the patients according to risk of bleeding. Those at high risk received no anticoagulation (group 1) or NM as an anticoagulant (group 2), while those at low risk received heparin (group 3). Results: Forty patients (25 male and 15 female; mean age, $8.2{\pm}6.6$ years) were enrolled. The mean duration of CRRT was 13.0 days, and the survival rate was 57.5%. The mean hemofilter lifespan was 39.3 h in group 1 and 11.3 h in group 3. In group 2, hemofilter lifespan was extended from 7.5 h to 27.4 h after the use of NM (P =0.001). The mean hemofilter lifespan with NM was greater than with heparin (P =0.018). No patient experienced a major bleeding event during treatment with NM. Conclusion: NM may be a good alternative anticoagulant in pediatric patients with a high risk of bleeding requiring CRRT, and is not associated with bleeding complications. 목적: Nafamostat mesilate는 출혈성 경향이 있는 성인 환자에서 지속적 신대체 요법시 항응고제로 사용되고 있지만 소아에서의 경험은 잘 알려지지 않았다. 본 연구는 출혈 성향이 높은 소아에서 지속적 신대체 요법을 시행하는 경우에 항응고제로서 Nafamostat mesilate의 용량, 효과, 및 안전성에 대하여 알아보기 위해 수행하였다. 방법: 2011년 1월부터 2013년 10월까지 최소 24시간이상 지속적신대체요법을 받은 40명의 소아환자들을 대상으로 하여 의무기록을 후향적으로 분석하였다. 환자들은 출혈 위험군(그룹 1: 항응고제 사용 안함, 그룹 2: 항응고제로 Nafamostat mesilate 사용)과 출혈 위험이 없는 군(그룹 3: 항응고제로 헤파린 사용)으로 분류하였다. 결과: 40명의 환자 중에서 남아는 25명 여아는 15명 이었으며 평균 나이는 $8.2{\pm}6.6$세 이었다. 지속적신대체요법의 평균 시간은 13일 이었다. 평균 혈액 필터 수명은 그룹 1에서는 39.3시간 이었고, 그룹 3에서는 11.3시간이었다. 그룹 2에서는 Nafamostat mesilate 사용 전에는 7.5시간 이었으나 Nafamostat mesilate 사용 후에는 27.4시간으로 연장되었으며 통계학적으로 유의하였다(P=0.001). 평균 혈액 필터 수명은 Nafamostat mesilate을 사용한 그룹에서는 헤파린을 사용한 그룹보다 통계적으로 의미 있게 연장되었다(P=0.018). Nafamostat mesilate 사용한 군에서 의미있는 출혈이 동반되지는 않았다. 결론: Nafamostat mesilate은 출혈 성향이 높은 소아에서 지속적 신대체 요법을 시행하는 경우에 헤파린을 대체해서 사용될 수 있는 항응고제로 생각된다.