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1 병원약사회지 (2015), 제 32 권제 3 호 J. Kor. Soc. Health-Syst. Pharm., Vol. 32, No. 3, 221 ~ 233 (2015) 회원학술보고 암환자의항응고약물치료에있어서항응고약물상담 (Anticoagulation service, ACS) 효과평가 박효주, 전혜영, 장혜경, 인용원, 이영미삼성서울병원약제부 Evaluation of Effectiveness on Anticoagulation Therapy with Pharmacist-managed Anticoagulation Service in Patients with Cancer Park Hyo Joo, Jeon Hye Young, Jang Hye Kyung, In Yong Won, Lee Young Mee Department of Pharmacy, Samsung Medical Center Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, Korea, , Korea Abstract : Thromboembolic events such as deep vein thrombosis(dvt) and pulmonary thromboembolism(pte) are common among patients with cancer as a consequence of cancer- and treatmentrelated factors and have an effect on prognosis. Also, these events are the second most frequent cause of death in cancer patients. In 2008, Samsung Medical Center started the Anticoagulation service(acs) which is a pharmacistmanaged anticoagulation service for cancer patients taking warfarin. The purpose of this study is to evaluate the effectiveness of ACS in patients with cancer. 투고일자 ; 심사완료일자 ; 게재확정일자 교신저자박효주 Tel: hyojoo.park@samsung.com

2 JKSHP, VOL.32, NO.3 (2015) In this retrospective study, patients were first time warfarin users at Samsung Medical Center from March 31, 2010 to March 31, Each patient was followed up for 6 months after taking warfarin for at least 3 months. Patients were divided into two groups: ACS group(n=61) and non-acs group (n=23). This study analyzed the baseline characteristics, warfarin indications, cancer types, contributing factors then compared anticoagulation control. The most common cancer type was lung cancer: 40.98%(n=25) of the ACS group and 65.22%(n=15) of the non-acs group. The most common indications for warfarin in both groups were PTE or DVT. The ACS group spent significantly more time in the therapeutic range(ttr, 25.24±24.13% vs 47.43± 22.20%, p>0.001), as well as in the expanded therapeutic range(ttr within±0.2 units, 39.89±29.81% vs 65.40±22.67%, p=0.001). The percentage of time in the extreme range(inr <1.5 or >4.0) was 37.8 ±35.4% vs 20.5±19.5%(p=0.09). The interval of INR monitoring was 24.2±11.2 days vs 13.0±4.6 days (p<0.001). There was no major bleeding in both groups. The incidence of minor bleeding was 0.926/person-year in the ACS group and 0.815/person-year in the non-acs group. These findings suggest that ACS group patients managed by pharmacists achieved significantly better INR control compared to non-acs group patients as measured by the patients INR values over time. These values remained in the therapeutic and expanded range. Based on the results of this study, collaborative practice using pharmacists and physicians may be an effective model for anticoagulation management for cancer patients. [Key words] ACS(Anticoagulation Service), Warfarin, Cancer 연구배경및목적 Warfarin은경구용항응고제로정맥성혈전색전증의예방및치료, 심방세동환자의뇌졸중예방등에쓰이며 1) vitamin K antagonist로 vitamin K dependent coagulation protein인 factor II, VII, IX, X의활성을억제하여항응고효과를나타낸다. Warfarin 의효과는 INR(International Normalized Ratio) 을통해나타내며안전하고효과적인치료를위해서는이를치료영역내로유지하는것이중요하다. 2),3) INR이 치료범위아래로내려갈경우혈전색전증이발생할수있고, INR이치료범위보다높아질경우출혈부작용의빈도가높아지며, 특히 INR 4.0 이상이될경우뇌출혈의위험이현저하게증가한다. 4)-6) Warfarin의약효는병용약물과의상호작용, vitamin K 흡수의변화, warfarin 약물동태에영향을줄수있는동반질환등다양한요인들의영향을받을수있다. 특히암환자에서는식생활의변화, 병행하는항암화학요법등의여러가지요인들에의해 INR 변동폭이비암환자보다크고 7) warfarin으로치료하는동

3 박효주 : 암환자의항응고약물치료에있어서항응고약물상담 (Anticoagulation service, ACS) 효과평가 안암이아닌환자에비해 3배에서 6배높은출혈위험성을가진다. 8) 따라서 INR에영향을미치는요소들을고려하여주의깊은모니터링을통한용량조절이필요하다. DVT(Deep Vein Thrombosis), PTE(Pulmonary Thromboembolism) 는암환자에서가장흔하게나타나는혈전색전성질환이며이를포함한혈전색전성질환은암환자의사망원인중두번째로높은비율을차지하고있다. 9)-11) 또한암환자가아닌경우와비교했을때더높은발생위험을가지므로 11),12) 예방및치료가보다주의깊게요구된다. 암환자에서는혈전색전성질환발생의위험성이약 4배이상증가하며, 항암약물치료를받는경우약 6.5배가증가한다는연구결과가있다. 7) 이에기반하여삼성서울병원에서는 2008년 7월부터암병원혈액종양내과에서 warfarin을복용하는환자들을대상으로항응고약물상담업무 (anticoagulation service, ACS) 를확대시행하고있다. Saul N. Meingart 등 13) 은암환자중 warfarin으로항응고치료를한환자를대상으로, anticoagulation management service(ams) 가제공되었을때와그렇지않은경우로나누어그효과를비교평가하였다. 삼성서울병원에서는 Warfarin을복용하는암환자를대상으로약사에의해약물상담이진행되고있지만이에대한평가및현황파악은아직이루어진바없다. 따라서본연구에서는 warfarin을복용하는암환자의특성을파악하고약사에의한항응고약물상담군과비상담군의비교를통해항응고약물치료현황및항응고약물상담효과를평가하고자하였다. 연구방법 1. 용어의정의 연 (year) 단위로표현한기간이며, 이를사용하여환자들의분석기간을모두반영하였다. (2) 출혈부작용발생률 14) 분석기간중출혈부작용의발생횟수출혈부작용발생률 = Person-year (3) Major bleeding 치명적이고사망을초래할수있는두개내출혈 (intracranial hemorrhage), 경막하출혈 (subdural hemorrhage), 복막후출혈 (retroperitoneal hemorrhage) 혹은 hemoglobin 2 g/l 이상의감소, 수혈이나입원이필요한정도의출혈로정의하였다. 15) (4) Minor bleeding 멍 (bruise), 코피 (epistaxis), 반출혈 (ecchymosis), 잇몸출혈 (gingival bleeding), 결막출혈 (conjunctival hemorrhage), 미세혈뇨 (microscopic hematuria) 등 major bleeding을제외한모든출혈로정의하였다. 2. 연구대상및기간 (1) 연구대상 2010년 5월 31일부터 2013년 5월 31일까지삼성서울병원혈액종양내과에서 warfarin 복용을시작한 18 세이상의환자중 NCCN(National Comprehensive Cancer Network) guideline 16) 에서VTE의최소치료기간으로권고하는 3개월이상 warfarin을복용한환자 207명을대상으로하였다. 본연구에서사용된용어의의미및정의는다음과같다. (1) Person-year 14) 해당군에포함된환자들의분석기간을모두합하여, (2) 제외기준다음사항에해당하는경우는연구대상에서제외하였다. 1 타병원에서 warfarin 복용을시작하거나연구기간내에타병원조절이력이있는환자

4 JKSHP, VOL.32, NO.3 (2015) 2 Warfarin 복용기간이 3개월미만인환자 3 Warfarin 복용중본원에서 follow up이중단된환자 4 항응고약물비상담군으로분류된환자중입원시 warfarin 복용시작후외래치료로전환시항응고약물상담군에포함된환자 5 혈액종양내과가아닌다른과에서 warfarin 조절한환자 6 기타 ( 비암환자, INR을측정하지않은환자, 18 세미만인환자 ) 3. 연구방법대상환자들의전자의무기록 (Electronic medical record, EMR) 과항응고약물상담환자전자차트를후향적인방법으로분석하였다. 분석은 warfarin 복용시작일기준으로 INR 변동이심한처음 1개월은연구기간에서제외 13) 하였으며이후 6개월간의데이터를분석하였다. 환자군은외래치료를기반으로, ACS에의뢰하여 warfarin 복용을한 ACS 상담군과 ACS에의뢰하지않고복용한 ACS 비상담군으로나누어조사를진행하였다. 간격을조사하였다. (3) 출혈부작용평가연구기간중대상환자에게나타난출혈부작용을 major bleeding과 minor bleeding으로나누어평가하였다. (4) 통계학적분석 SPSS version 22.0을사용하여, 연속형변수의경우 independent t-test 또는 Mann-Whitney analysis 를, 범주형변수의경우 Pearson chi-squared test 또는 Fisher test를시행하였다. 각항목은 p value가 0.05 미만일때유의성이있는것으로평가하였다. 4. 피험자보호본연구는피험자의안전보호에관한대책등을포함한연구계획을삼성서울병원기관윤리심의위원회 (Institutional Review Board, IRB) 로부터승인 (IRB No ) 받았으며, 후향적관찰연구로서피험자동의는생략하였다. (1) 조사내용 연구결과 대상환자의성별, 나이, 암종류, warfarin 적응증, 항암치료종류와 warfarin 약효에영향을줄수있는환자영양상태, 컨디션, 병용약물등의항목을설정 12),17)-22) 하여조사하였다. (2) Warfarin 사용평가 Warfarin의항응고효과는 INR로나타냈다. 환자의 base INR, target INR을조사하였고 Rosendaal 등에의해기술된선형보간법 23) 을사용하여 target INR 로유지된일수의백분율, expanded range(target INR±0.2 units), 그리고치료효과가없거나출혈위험이있는 extreme range(inr < 1.5 or INR > 4.0) 에서 INR이유지된일수의백분율, 24) INR 모니터링시행 1. 대상환자군의특성 2010년 5월 31일부터 2013년 5월 31일까지삼성서울병원혈액종양내과에서 warfarin 복용을시작하여 3개월이상의항응고약물치료가필요한 18세이상의환자 207명중제외기준에해당하는타병원에서 warfarin 복용을시작하거나연구기간내에타병원조절이력이있는환자 45명, Warfarin 복용기간이 3 개월미만인환자 24명, Warfarin 복용중본원에서 follow up이중단된환자 12명, 항응고약물비상담군으로분류된환자중입원시 warfarin 복용시작후외래치료로전환시항응고약물상담군에포함된환자 37명, 혈액종양내과가아닌다른과에서 warfarin 조절한환자 2명, 비암환자 1명, INR을측정하지않은

5 박효주 : 암환자의항응고약물치료에있어서항응고약물상담 (Anticoagulation service, ACS) 효과평가 Table 1. Patients Characteristics - Baseline Characteristics Non ACS group (n=23) ACS group (n=61) p-value Age(yr) (mean±sd) 62.57± ±11.25 NS Gender(No.of patients(%)) Male 17 (73.9) 33 (54.1) NS Female 6 (26.1) 28 (45.9) Cancer diagnosis (No.of patients(%)) Lung Cancer 15 (65.2) 25 (41.0) Lymphoma 2 (8.7) 7 (11.5) Hematologic malignancy 1 (4.3) 2 (3.3) Thymus cancer 1 (4.3) 1 (1.6) Breast cancer 0 (0) 5 (8.2) NS Multiple myeloma 0 (0) 5 (8.2) Genitourinary cancer 4 (17.4) 1 (1.6) Others 0 (0) 15 (24.6) Colon cancer 0 3 Esophageal cnacer 0 1 Galbladder cancer 0 2 Liver cell carcinoma 0 1 Pancreatic cancer 0 1 Parotid gland cancer 0 1 Rectal cancer 0 2 Sarcoma 0 2 Stomach cancer 0 2 Warfarin- indication (No.of patients(%)) PTE / DVT 19 (82.6) 56 (91.8) p=0.011 Others (Infarction, Catheter related thrombus 등 ) 4 (17.4) 5 (8.2) Warfarin days (mean±sd) ± ±57.62 NS Anticancer therapy (No.of patients(%)) Chemotherapy 12 (52.2) 36 (59) Radiotherapy 1 (4.3) 0 (0) CCRT 8 (34.8) 14 (23.0) NS CCRT + Surgery 1 (4.3) 0 (0) No treatment 1 (4.3) 11 (18.0) *NS: Not Significant / CCRT(Combined Chemotherapy and Radiation Therapy)

6 JKSHP, VOL.32, NO.3 (2015) Table 2. Patients Characteristics - Contributing factors Non ACS group (n=23) ACS group (n=61) Nutrition (No.of patients(%)) Poor oral intake 2 (8.7) 14 (23.0) Herbal, Diet (Vit K) 2 (8.7) 21 (34.4) Condition (No.of patients(%)) Diarrhea 2 (8.7) 5 (8.2) Fever 0 (0) 0 (0) Nausea,vomiting 1 (4.3) 4 (6.6) Mucositis 1 (4.3) 2 (3.3) Stomatitis 0 (0) 1 (1.6) Drug interaction (Table 3) Anticancer medications Others Table 3. Patients Characteristics - Contributing factors - Drug interaction Non ACS group ACS group Anticancer medications * Afatinib 2 0 Bleomycin 1 0 Busulfan 0 1 Capecitabine 1 0 Carboplatin 5 6 Cisplatin 0 19 Corticosteroid (Chemotherapy) 2 10 Crizotinib 2 1 Cyclophosphamide 3 5 Docetaxel 6 0 Doxorubicin 3 4 Erlotinib 3 1 Etoposide 2 6 Fluorouracil 3 0 Geftinib 6 3 Gemcitabine

7 박효주 : 암환자의항응고약물치료에있어서항응고약물상담 (Anticoagulation service, ACS) 효과평가 Non ACS group ACS group Hydroxyurea 0 1 Ifosfamide 0 6 Irinotecan 5 3 Letrozole 1 0 Melphalan 0 2 Methotrexate 1 1 Oxaliplatin 3 0 Paclitaxel 4 2 Rituximab 2 1 Sorafenib 1 0 Tegafur 2 0 Thiotepa 1 0 Vinblastine 0 1 Vincristine 3 2 Vinorelbine 4 1 Other medications ** Antifungal - fluconazole 0 2 Antibacterial - sulfamethoxazole/trimethoprim,ciprofloxacin 1 5 Analgesic - acetaminophen,naproxen,tramadol 7 11 Hormone - megesterol,levothyroxine,methimazole 4 7 Steroid - dexamethasone,prednisolone,methylprednisolone 3 24 Others - cimetidine, centrum, rosuvastatin, propafenone 1 4 *Lexicomp Vit K Antagonist/Antineoplastic Agents Interaction, J Oncol Pharm Pract.2013 Sep;19(3): **Micromedex, Managing Oral Anticoagulation Therapy: clinical and operational guidelines 환자 1명, 18세미만인환자 1명, 총 123명을제외하고최종적으로항응고약물상담군 61명, 비상담군 23명의환자를대상으로연구를진행하였다. 대상환자의특징은 Table 1과같다. 항응고약물비상담군평균나이는 62.57±11.89세, 상담군평균나이는 59.44±11.25세였다. 비상담군성별은남자 17명 (73.9%) 과여자 6명 (26.1%), 상담군은남자 33명 (54.1%) 과여자 28명 (45.9%) 이었다. 암종은폐암이비상담군에서 15명 (65.2%), 상담군 25명 (41.0%) 으로다수를차지하였다. Warfarin 치료의적응증으로는 PTE, DVT 가비상담군에서 19명 (82.6%), 상담군에서 56명 (91.8%) 으로대부분을차지하였다. Warfarin 복용분석일수의평균은비상담군 ±40.61일, 상담군 ±57.62일이었다. 병행중인항암치료는항암화학요법단독이비상담군 12명 (52.2%), 상담군 36명 (59.0%) 으로가장많았다. Warfarin 약효에영향을줄수있는요인으로는환자의영양상태, 건강식품및한약병용, vitamin K 섭취변화그리고그밖에환자의영양상태및 warfarin의대사에영향을줄수있는 diarrhea, fever, mucositis 등의증상들도있었

8 JKSHP, VOL.32, NO.3 (2015) Table 4. Analysis of Base INR and Target INR Non ACS group(n=23) ACS group(n=61) Base INR (mean±sd) 1.010± ±0.083 측정하지않음 (No. of patients) 5 1 Target INR (No.of patients) 설정된기준없음 * * NCCN guideline 에서암환자의 VTE 치료시권고기준인 으로설정하여분석 16) Percentage of Days (mean±sd) Non ACS group(n=23) ACS group(n=61) Therapeutic range 25.24± ±22.20 Expanded range (±0.2) 39.89± ±22.67 * Mann-Whitney test ** T-test Fig. 1 Comparing the percentage of time in therapeutic range (TTR) and expanded range (TTR within ±0.2 units) 다. 이에대해분석하였다 (Table 2). 항암치료제와기타약물중 warfarin 약효를높이거나낮추는약물을선정하여해당하는약물을병용한이력을조사하였다 (Table 3). 2. Warfarin 사용평가 Base INR 평균은비상담군 1.01±0.08, 상담군 1.03 ±0.08이고이중비상담군에서 5명, 상담군에서 1명은 base INR을측정하지않았다. 비상담군의경우 target INR에대한기록이부재하여 NCCN Ver guideline에서암환자의 VTE 치료시권고기준인 으로설정하여분석하였고상담군에서는 인경우가 39명으로가장많았다 (Table 4). Warfarin 치료기간동안목표치료범위안에서 INR이유지된일수의백분율평균은 ACS 비상담군

9 박효주 : 암환자의항응고약물치료에있어서항응고약물상담 (Anticoagulation service, ACS) 효과평가 Percentage of Days (mean±sd) ACS 비의뢰 (n=23) ACS 의뢰 (n=61) Extreme range (<1.5 or >4.0) 37.8± ±19.5 * Mann-Whitney test Fig. 2 Comparing the percentage of time in extreme range (INR <1.5 or >4.0) 총복용일 / 총모니터링횟수 Non ACS group(n=23) ACS group(n=61) 모니터링간격 (mean±sd) 24.2± ±4.6 * Mann-Whitney test Fig. 3 Interval of INR monitoring 25.24±24.13%, ACS 상담군 47.43±22.20% (p<0.001) 이었다. Expanded range(target INR± 0.2) 에서는각각 39.89±29.81%, 65.40±22.67% (p=0.001) 로나타났다 (Fig. 1). Extreme range (INR <1.5 or >4.0) 에서는비상담군 37.8±35.4%, 상담군 20.5±19.5%(p=0.09) 로조사되었다 (Fig. 2). Warfarin 복용기간동안시행된 INR 모니터링시행 간격의분석결과비상담군에서는평균 24.2±11.2일에한번모니터링을시행하였고, 상담군에서는 13.0± 4.6일 (p<0.001) 을간격으로시행하였다 (Fig. 3). 3. 출혈부작용발현비교연구기간중대상환자에서 major bleeding은관찰

10 JKSHP, VOL.32, NO.3 (2015) Table 5. Bleeding events Type of bleeding Non ACS group (n=23) ACS group (n=61) p-value Major bleeding ( 건 ) Minor bleeding ( 건 ) 8 24 출혈부작용발생률 0.815/person-year 0.926/person-year NS 되지않았다. 그러나 minor bleeding은 ACS 비상담군에서총 8건이발생하였으며, 상담군에서총 24 건이발생하였다. 출혈부작용발생률은각각 0.815/person-year, 0.926/person-year(p=0.756) 으로비상담군에서더높았다 (Table 5). 고찰암환자에서혈전색전성질환은암환자가아닌경우와비교했을때더높은발생위험을가지고, 사망원인중두번째로높은비율을차지할정도로암환자의치료예후에영향을줄수있는요인이다. 따라서혈전색전증의예방및치료는암환자들에게중요하다. 암환자의경우병의진행과정에서나타날수있는 oncogenesis, angiogenesis 등으로인해혈전의생성과정에관여하는요소들에영향을미쳐혈전을유발할수있다. 암의병기, 위치, 항암치료, 환자의영양상태와컨디션등이위험요소가될수있다. 암종별로혈전색전성질환발생위험도를보면위암과췌장암이혈전색전성질환발생에대해가장높은위험성을가지며폐암, 림프종등이그다음으로높은위험성을가진다. 25),26) 본연구는혈액종양내과환자를대상으로진행하였다. 대상환자중혈전생성위험이높은암종인소화기계암환자의비율이낮았고대상환자의대다수가폐암환자 (ACS 비상담군 65.2%, ACS 상담군 41.0%) 였다. 또한대부분 PTE, DVT를적응증 (ACS 비상담군 82.6%, ACS 상담군 91.8%) 으로 warfarin을복용하였다. 암환자들은질환및항암치료부작용등으로영양상태가불량하고위장관부작용, 발열등 warfarin 의약효를높일수있는요인에취약하다. 또한 warfarin을복용하는암환자들에서는, 항암치료뿐만아니라다양한약물치료가병행되며실제분석한결과 warfarin과상호작용을유발할수있는약물을병용하는경우가많았다 (Table 3). 본연구에서는환자별로병용한약물이매우다양하고중복해서복용한경우가많아각각의약물별로 warfarin 약효에대한영향정도를평가하지는못하였다. Warfarin 약효평가측면에서는 warfarin 치료기간동안목표하는치료범위안에서 INR이유지된일수의백분율평균 (ACS 비상담군 25.24%, ACS 상담군 47.43%, p<0.001) 과 expanded range에서유지된백분율평균 (ACS 비상담군 39.89%, ACS 상담군 65.40%, p=0.001) 모두 ACS 상담군에서더높게나타나통계적으로유의한차이가있었다. 이전의연구 13) 에서암환자를대상으로 warfarin 치료시항응고약물상담이병행된경우, 상담이진행되지않은경우와비교했을때본논문에서처럼더높은치료효과를나타냈다 (AMS 비상담군 46.1%, AMS 상담군 56.5%, p=0.55). 치료효과가적거나출혈부작용이증가할수있는 extreme range에서 INR이유지된기간의백분율은 ACS 비상담군에서더높게나타났다 (ACS 비상담군 37.8%, ACS 상담군 20.5%, p=0.09). 이를통해항응고약물상담실의중재에의해적절한항응고효과조절이이루어졌음을확인할수있었다. 또한 INR 모니터링측면에서, ACS 상담군에서보다잦은빈도 (ACS 비상담군 24.2일 / 회, ACS 상담군 13.0일 / 회 ) 로모니터링을시행하고있음을확인하였다. 조사기간동안 major bleeding은발생하지않았고 minor bleeding의발생빈도는 ACS 비상담군 0.815/personyear, ACS 상담군 0.926/person-year(p=0.756) 으로 ACS 상담군이더높게나타났으며통계적으로유의한차이는없었다. ACS 비상담군의경우출혈부작용을기록하는형식은따로없었기때문에의사가남긴진료 EMR에의존하여조사하였다. ACS 상담군의경

11 박효주 : 암환자의항응고약물치료에있어서항응고약물상담 (Anticoagulation service, ACS) 효과평가 우매환자상담시부작용발생여부를확인하여약사가기록하는항응고약물상담전자차트를참고하여조사하였다. ACS 비상담군의경우전산기록이충분하지않고, ACS 상담군의경우보다잦은모니터링과부작용상담기록으로인해, 통계적으로유의하지는않지만더높은부작용발생률을나타내는데영향이있었을것으로판단된다. 이를통해항응고약물상담의효과를평가했을때, ACS를통해 warfarin을복용하는경우약효에영향을줄수있는다양한요인들을파악하여용량조절에반영하고지속적인모니터링을함으로써 warfarin 약효를보다효과적으로치료범위내로유지할수있음을확인하였다. 본연구는후향적 (retrospective) 조사방법으로진행되었으며, 항응고효과에영향을끼칠수있는요인들을설정하여현황을파악하였으나그요인각각의 warfarin 약효에대한영향은파악할수없었다. 우선 contributing factor 중병용약물의경우, 여러약물을중복하여복용한경우가많았고 INR test 시행간격이일정하지않으며각약물을병용한기간동안의 INR 변화를알수없었다. 따라서해당약물의 warfarin 약효에대한영향을정확하게파악하는데어려움이있었다. 또한후향적으로기록에의존한연구이기때문에환자영양상태, diarrhea, fever 등의요인에대해서도발생횟수및심각한정도등자세한정보가부족하였고발생기간동안의 INR 변화를알수없었기때문에각각의요소와의분석을할수없는제한점이있었다. 따라서본연구는위의요인들이항응고효과에영향을미칠수있다는것을가정하고, 암환자에서항응고약물상담효과를평가한것이다. 이를보완하기위해서는전향적인방법으로연구가이루어질필요가있을것으로사료된다. 또한대상환자군의규모가충분히크지않고전산기록부족으로인해제한적분석이이루어졌다는한계점이있었다. 그러나본연구는혈액종양내과에서항응고약물치료중인암환자의특성과약물치료효과를 INR 조절및출혈부작용발현등을통해파악할수있었고, ACS를통해 Warfarin 치료를하는암환자들과 ACS 에의뢰하지않고치료를하는암환자와의항응고약물상담효과를비교평가할수있었다는데의의가있다. 결론암환자에서혈전색전성질환은암질환과관련하여또는항암치료의영향으로흔하게발생하여암환자의사망원인중높은비중으로차지하므로혈전색전증의예방및치료는암환자에있어중요하다. 이에근거하여삼성서울병원암병원항응고약물상담실에서는 2008년부터혈액종양내과에서의뢰되는 warfarin 복용환자를대상으로항응고약물상담을진행하고있다. 본연구에서는 ACS에의뢰하여 Warfarin을복용한암환자와 ACS에의뢰하지않고 warfarin을복용한암환자로나누어해당환자의특성과목표약효유지기간, 부작용발생빈도등을조사하여항응고약물상담효과를평가하고자연구를진행하였다. 연구결과, 약사에의해항응고약물상담을받은환자군의경우약효에영향을줄수있는다양한요인들을파악하고지속적인모니터링을함으로써 warfarin 약효가목표범위내로보다효과적으로유지되고있음을확인하였다. 따라서전문약사의자문및복약상담을통해보다많은환자가안전하고적절한치료효과를유지하기위해 ACS 의뢰를적극적으로고려해볼수있고, 의사와약사간의협력활동이필요할것으로사료된다. 참고문헌 1) Ansell J., Hirsh J., Dalen J., Bussey H., Anderson D., Poller L.: Jacobson A., Dylin D., Machar D., Managing Oral Anticoagulant Therapy, Chest, 119(1) suppl, 22S-38S (2001) 2) Ansell J., Hirsh J., Hylek E., Jacobson A., Crowther M., Palareti G.: American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. Jun 133(6 Suppl), 160S- 198S (2008) 3) Stephanie Young, Lisa Bishop, Laurie Twells, Carla Dillon, John Hawboldt, Patrick O'Shea: Comparison of pharmacist managed

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13 박효주 : 암환자의항응고약물치료에있어서항응고약물상담 (Anticoagulation service, ACS) 효과평가 ing in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am J Med. 87, (1989) 20) Palareti G., Legnani C., Lee A. et al.: A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy. Thromb Haemost. 84, (2000) 21) Wester J. P., de Valk H. W., Nieuwenhuis H. K. et al. : Risk factors for bleeding during treatment of acute venous thromboembolism. Thromb Haemost. 76, 682-8(1996) 22) White R. H., Beyth R. J., Zhou H., Romano P. S.: Major bleeding after hospitalization for deep-venous thrombosis. Am J Med. 107, (1999) 23) Rosendaal F. R., Cannegieter S. C., van der Meer F. J., Briet E.: A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost, 69, (1993) 24) Wilson S. J. et al.: Comparing the quality of oral anticoagulant management by anticoagulation clinics and by family physicians: a randomized controlled trial. Canadian Medical Association or its licensors, 19, 169(4), (2003) 25) Pathophysiol Haemost Thromb: 35(1-2), (2006) 26) Alok A. Khorana, Nicole M. Kuderer, Eva Culakova, Gary H. Lyman and Charles W. Francis.: Development and validation of a predictive model for chemotherapy-associated thrombosis. 111, (2008)

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052~063ÇÐ¼úº¸°í5¹Ú¼±¹Ì 병원약사회지 (203), 제 30 권제 호 J. Kor. Soc. Health-Syst. Pharm., Vol. 30, No., 52 ~ 63 (203) 회원학술보고 Warfarin 과 Propafenone 병용시용량조절기준설정 삼성서울병원약제부 Proposal for Warfarin Dosage Guideline during Warfarin-Propafenone