—— Fse area artic, ———— Cost-Effectiveness Analysis of Pharmacotherapy for Hematemesis- Melena Treatment in Hospitalized Patients with Hepatic Cirrhosis Doddy de Quelje’, Amelia Lorensia™*, Li ‘Feouly of Pharmacy Su aya University, J. Naogel Jaya Selotan No, 188, Surabaya, Indones "Ad asada Uneaan Wetan asp 0 Lmlaan Wein Nn 40-24 Surabay “Corresponding vine. mal amela lores na Widnarta!, Sugiarto Widjaja® arral.co™ Abstract ACKGROCND: Aut ical snore tnd effective for the pulticnt but also is costetfective in order (0 atain improvement of the p t's quality oF Tie, ‘Therefore, pharmacoeconomie evaluation especially CEA (costeffectiveness analysis), whieh compares costs and consequences of drug ther aimed to evaluate the therapeutic y. is needed, This study was METHODS: A total of 42 patien's and vitamin K-transamin were studied retrospectively sceiving vitamin K us’ medical records im 2 yours snd analyzed with costeffectiveness wrid and ACER (average cost effectiveness ratio) hased! on ChildTureotte-Pugh Score RESULT vitamin K in patients with Child-Tuscotte-Pugh Score osteflectiveness grid Was dominant For A. ACER analysis showed a lower score for vitamin K in all pationts included Child-Turcotte Pugh Seon classification, There was a0 significant difference in duration of cessation oF bleeding treatment in patieats with vitamin K compared with vitamin K-tronsarin in patients with Child-Turcotte Pui Sense A and B, while significant difference was found im patients with Childe Pugh Score C Turco’ Abstrak ATAR BELAKANG: Pendaralian arises I akut merupakan komplikasi sirosis yang. dapat rengacam ia, Hal ini merupakian toga farmasis umuk memastikan terap! dan pelayanan kefarmasion yang tidal hanya sma bagi pasien teva juga mempuayai biaya uje ii kualita hidup pasien. Oleh Karena itu, evalusi furmakockonomi yang efektit yang ber n untuk memper lerutama CEA (costeffectiveness analysis) yang mem bandlingkn biaya chan konsekwensi dar terapi hematemesis - melena pada pasien sirosis hepatik METODE: Total dari 42 pasien yan K dan vitamin K-transamia diteliti secara retrospektif dati roku modi sclums 2 tahun, dan dianalisis dengan east effectiveness grid dan ACER (average cost-effectiveness ratio) berdasarkan Child-Turcotte-Pugh Seore HASIL: Cast-fecsivencss iva dominant untuk vitamin K paki pasien dengan Chile Turconte-Pugh Score A. Analisis ACER menuajukian nila! yang lebih seaduh pada vitamin K pada seraust pasien fl menunjuskan melipati klasilikasi Child-Tavvotte-Pugh Seore, Tidak sd perbedaan bermakna untuk durasi dari penghestian terapi pendarahan pada pasion dengan vitamin K dibandingkan dengan vitamin Ketransantia pada pasien dengen Childe Turcotte-Pugh Score dan B, secara signifikan ada pada px Pugh Score C sedangkan perbedaan jon dengan Child-Tarcote- 53‘The Indonesian Biomedical Journal CONCLUSIONS: Vitamin K appeared t0 be more eost- effective as compared with vitamin K-transamia in all patients. The use of vitamin K had greater bese than ‘he coribination with transamin in all patients and Child- Turcotte-Pugh score classification, and thus should ae eonsideredas a primary therapy. Therelore, transantin addition as an altemative therapy for hepatic patients with hemater shioald be considered. KEYWORDS: is hepatic cirrhosis, hemattemesis-melena, vitamin K, CEA, Cost-Bileetiveness Anal) Invlomes Biomed 1.2013; 5 (1): 53-62 KESIMPULAN: Vitamin K cerbukti lebih efektf iays ibandingkan dengan vitamin K-transarnin pada semua pasien. Penggunaan vitamin K memiliki keuntungan yang eb besar didandingkan dengan xombinasi dari transamin vada semua pasien dan Klasitikasi Child-Turene. Pugh Seore, dan seharusnya dijadikan sebsgel terapi utsuna, Kemudiaa, penambahan terapi alleenatif pada pasien sirasis hepatik harus diperimbangkan KATA KUNCI: CEA, Cost Effectiveness Analysis sirosis hepatik, hemaitemesis-melena, vitamin K, Indones Biomed J, 2013; 5 (1): 53-62 Introduction Th In patien metabolism elimination of drugs may be disturbed (1). liver is @ major site of metabolism of various drugs. with liver disease the liver capacity. for Ciethosis oft liver (hepatic cisthosis) is one of iver diseases that is chronic, isveversible, and caus ss high mortality(2), and this occupies the twellth leading cause of death in the United States (3). Hepatic cirrhosis is a diffuse process characterized by fibrosis and changes abaormel nodule structure (4), AS a resale, se the normal liver struewre 10 formed due to injury or long-term liver disease, and it causes the liver to fail its normal funetions such as protein synthesis, cleaning process of the blood, resistance 10) infection, digesting foods, and energy storage (5). The degree of severity of the liver disease can be divided into three categories with Child-Turcotte-Pugh Score, Child- Turcotte-Pugh Classiticationis @ system used to classify the deg in hepatic cirrhosis patients (6.7) ‘of liver damage or development of liver disease Table 1. Child-Turcotte-Pugh Score Ascites None Encephalopathy None Bilirubin (mgicl} <20 ‘Alourin (mai) 235 Prothrombin time (seconds, increased) 1-3 Slight Moderatelsevere Siightimoderate Moderatelsevere 23 >3.0 2835 <28 468 >60 58 A 7 B 10415 c Martin & Friedman, 2008 (8) 54There are some complications of cirrhosis. such hepatic encephalopatay (1 syndrome, SBP (spontaneous bacterial peritonitis), amd esophageal varices (3). Fifty percent of patients with alcoholic cirrhosis will develop esophageal varices after into years. About 25-35% patients with civhosis and large as ascites, |. hepatorenal rs alter being diagnosed, snd 70-80% paticw esophageal varices will experience variceal haemorthage. Acute variceal haemorrhage is a complication af cisthosis which has life threatening impact ( | und cls as a major cause of death in cirrhosis patients (8). The portal pressure due to increased resistance to blood low to the liver is largely due to the distortion of the liver structure 10 fibrous tissue and regenerative nodules and intra hepatic active vasoconstriction by 20%-30% of the increased intra hepatic resistance, and a decrease in endogenous production of nitric oxide (9) (One of the funesions of the liver isto produce several clotting factors (including prothcombia and fibrinogen) as well as to produce bile sults that are necessary for ¢gastrojatestinal absorption of vitamin K, which is needed jon factor (10). Deticieney in vitamin cause blood clotting disorders, to cause the patients (0 Dl On the other hene acidTXA), which agent, bas proven useful for controlling ble, duce coagula transamin is an_antifibrinolytic conditions, especially is more favorablein mall superticia lesions such as gastric erosion an in esophageal varices (1D), and proves to provide cost effectiveness in cizchosis ). Neff er al. had examined the economic impact of s used for prophylaxis and treatment of cirrhosis-related complications, and found it necessary *0 slated evaluate the costs and complications of eirthosis cisthosis (13), CEA is used in acconlance t the study objectives and outcome, relationship between cost which in this case is clinical outcorne, and CEA isan important instrument in setting priorities for strategic planning of therapy. By measuring and comparing cost ‘version. efficient lationship the fusure and consequences could be assessed and the resources needed in ‘coud he estimated (1) os: estivenes Analysis af Henistemess-Melena Teatnent io Cashoss Methods ‘This study was a mon-experimental researeh and used the retrospective approach, Dat were obtained from adult sats’ medica] records which had major diagnosed hosis cases that lad been hospitalized im Adi Husada Usdaan Welas Hospital, Surabaya, Indonest 1010.49 Deveraber 201 rom January In this suudy, the method used was CEA (Coste effectiveness analysis). Iherapeutie cost and consequences of therapy were measured and compared, Research Variables Dependent variables in this study were cost (cast of vitamin K and combination of vitamin K-transamin) and clinical outcome (duration of eessation of bleeding). Independert variables inthis study were type of teatment sand Chit reotte-Pugh score. Population and Sample Population in this stacy s all the hospitalizec! hepatic cirrhosis patients with hematemesis-melena at Adi Husada 2010 10 December 2011, Samples in ihis sidy were hepatic eihosis pa Undaan Wetan Hospital, from Janu with hematemesisemelena who met the criteria andl had been hospitalized at Adi Husada Undaan Wetan Hospital Jamary 200 10 December 2011 grouped based on their degree of liver disease with Child fon ations. were Turcoite-Pugh score, ‘The number of samples was calculated based on formaac(15) N= pq (ucudd N= sini sample noanber p= potcentige epotion in frst poption seoup = percentue proportion in second popultion soup = degree of confidence coefficient ff confidence (example 95 ar 995) = estimate percemlige errs possibility oft number fF sinple deserimination (aboot 0.1 400,5) esti level Calculation of saraple’s number in this study’ N= pag. (Za sub)? =0,5 40,5 x (1,9610,2)2 = 24 patients “Thus, the mumber of samples needed in each intervention group was 6 pationss 55The Indonesian Biomedical Journal Inclusion and Exclusion Criteria Inclusion criteria in this study were hepatic circhosis patients with hematemesis-melena, adult age > 16 years (6), and patients u of vitamin Katransarnin, Exclusion criteria were patienss sf with vitamin K or combination who went home before the bleeding stopped, had not improved their clinica! qurcome, or died: patients who had not recovered from bleeding; patients with another kind of disease like hepatoma, or used anotlser medication (for example oral vitamin K of oral transamin), which could interfere the treatment studi incomplete patient's medical record including diagnoses or clinical ourcomes, { and outcome relationship; Data Analysis Te Data obtained Were analyzed with statistical method. First the normality of data was examined, then parametric fest ike Anovat one way, independent Test, ancl pooled Test or non-parametric like Kruskal Wallis and Mann Waitney L test were used to know the difference in duration oF treatment until the bleeding stopped and the costs, Degree of significance used for the tests was 0.05 used was SPSS 17.0, Besides, conclusions were also male using cosieffectiveness grid and ACER ealeulation, and the statistical progra Caleulation of ACER (average cost-effectiveness ratio) io (ACER) was, ACER = The average cost-eilectiveness calculated hased on the following formuks costeffectiveness, Results fectiveness was caleulated hased on the percentage of ulative duration of t 21 t0 1 cay in all patients andl i patients ‘nC until improvement was less than or eq with Child-Turcatte-Pagh $ uration of treatment to improve less than or equal to 3 days in patients with Child-Turcotte- C. Pugh Score Based ‘on the effectiveness of therapy. in patients with Child “Pugh Score A found that vitamin K was more effective than vitamin K-e sore A and B, 2s well ay the reo ‘iveness transamin although the difference was rather sigh, in all patients and patients Hectiveness minK. was only ealeulated based on with Child-Turcotte-Pugh Seore B and the of vitamin Karansamin was greater than vis While the cost ol the average cost of the therapeutic use of visamin K andl ant 10 vitamin K-transemin based on the length of trea get better. The higher the severity of liver eitrhosis, the Jonger the (reatment will take and therefore contributes lo the increasing suber of drups used to Stop bleeding he used drug and will ultimately feet the cost of Based on calculation with ACER, it showed that vitarain K was more costetfective than vitamin Ketransamia in all patients es well as pationss with Child-Turcotte-Pagh Score A. Band C. Table 2. Cost-Effectiveness Grid for CEA HIGHER Effectiveness of Alierative A Relative lo Aleraive B fouat LOWER (dominant) ' sistrage off) + Atbitary - Htrade-off) : (dominates) ‘Skropnek, 2008 (17). 56Acie test Lime difference of improving the seatment fof the samples using parametric and nonparametric methods of analysis showed a significant difference ' 0.05) i comparison to the longer signilicance (ou treatment improved in patients with Child Tarcote-Pugh Seore A, B, and C (Table 4), Comparison of the lengths Of Gime of treatment to improve in patents with vitamin K therapy in patients with Child-Tureotte-Pugh Seore A-and B were not significant, while comparison of the Child-Tureotte-Pugh Score A and C with Band C showed nces. ‘Tise duration lengths al reatment significant dite tw improve therapy is patice’s with vitamin K-wransamin in patients with Child-Turcatte-Pugh Score A and B were Table 3. Patient Cos etveness Analysis of Heratemesi- Mek not signiticant, while in comparison the Cl Pugh Score A and C with B and © it showed Jifferences (ce ~ 0,05). The reselt of the Child-Tureotie- Pugh Score, duration of weatment to improve the ‘comparison hetween patients using vitamin K ad vitamin Keuaasamin was not significant at the Child-Tureotte Pugh Score A andl B, while the Child-Turcotie-Pagh Score C results were significant (= 0,05), Based on the cost uf the use of vitamin K only and vitamin K-transamin in the study samples, the result was a significant difierence in iparisen with the eost of treatment using vitamin K and vitamin K-tsansamain liver eisthosis in patients with Child “Turcotte-Pugh Seore A. B. and C (Table 6). its characteristics Gonder, male 28 (69.05) 759,85) 14 (03:39) air) 9207 Gonder, female 13 (90,85) 5 88,5) “88r) 6102.85) 0.188 Age, years sarzeiaat 9.08 = 940 548 215.46 earozi3ss — o05r ‘Autor eysolc pressure, mg 124.62 (10467-18267) 11°69 (101 67-162,67) 122( 1026-1968) 122.96 (102.56-157) 0612 Arteral @asiclc pressure, whg 67.67 (64-89) 536 (98.67-89) 09.67 (6009.77.53) 93404848) 0.541 Therapy Vitamin k 1811280) 7152.85) 5195.38), oqzas) aaa itamin KTransomin 2a (51.8) 6 (48,75) 1016867) Bisrts gor cost Vitamin (IDR) 128% (ear) 5.55010) s*.400(@.924) ——22,2007.020) 9.000 5.55010) +1400 (3.924) -22.200/7.020) 9.054 558010) ‘1.400 924) -22.200(7.020) 0.000 91 Vitamin KeTramsamin (DR) 2643 (81.773) 44975 (5737) 54.970 (26.954) BEET (BA.A7G) 0.033 AABIS(I9031) 598102694) BIB BAA) 9.519 4a375 (S737) 54870 (26984) 8B7BT. ATTA) — 0.025 0.082 Hospltalzation duration 614) 64 5@-8) weit) 9.000 6c) 5st) asi 0.790 eta 50-14) 85(14) 0.000 9,000 Duration cf vestment to biees stances 1.5 (1-8) +18) 4408) 28(8) 0000 Tr) 1416) 25(5) ana o) 1418) ze) 000 9.003 Duration ef treatment 4114) Tin) 002 Tan) 0873 Tit) 9.004 9.095, (Data are presented as n (1). moan = standard devialon, or median (range). Signftean aiference fps 0.08, 37‘The Indonesian Biomedical Journal Table 4, Patients characteristics in Child-Turcotte-Pugh-Scre A, B, and C Gonder, male 3 (42,86) 416687) 0.705 Gender. female 4 (67.14) 2 (33.33), 0414 Age, years, 64 # 10.50 53,33 £260 0.034 Aerial systolic pressure, mmHg 130,33 (101,87-140,58) 114.9 (101,86-162,87) 0.860 ‘torial diastole pressure, mmHg 62,67 (58,67-75,22), 74,17 (61,71-91,12) 0.077 Hospitalzed curation 439) 43-8) +000 Duration of treatment to blees stopped 1 (tet) + (1-2) 0.280 Duration of treatment 3(17) 3.5 (2-6) oat Cost 5.550 (0) 44,975 (18.737) 0,001 Gender, male 4 (99) 10 (700) 0.109 Gender. female + (20) 010) Age. yeers: 5222108 57,22 1297 0.323 Aerial systolic pressure, mmHg 109,87 (102,5-149.3) 129,59 (108,33-157) 0.179 ‘Aerial diastole pressure, mig 656 (62.97-69,6) 74,46 (60-84.8) 0,061 Hospitelzation duration 6 (5-10) 5 (3-8) 107 Duration of treaiment to bles stopped 2 (1-3) 4 (1-3) 0.103 Duration of treatment 6 (5-9) 25 (2-6) 0.907 Cost 11.100 (8.924) 53.970 (26.954) 9,001 Gonder, male 3 (50) 5 (62.5) 0.480 Gender, female 3 (60) 387.5) *,000 Age, years, 62,67 = 19,45 64,62 £8.23, o.g01 Atrial systolic pressure, mmHg 109,88 (102,56-132.5) 129,31 (10,14-139,7") 9,022 ‘Aerial diastolc pressure, mmHg 61,47 (54,99-78.36) 72,1 (60,17-8043) on Hospitalzed duration 11 (8-14) 85 (4-13) 0.134 Duration of treaiment to bleed stopped 45 (25) 251-3) o.o10 Duration of treatment 10 (7-14) 55 (7.9) 0.07 Cost 22.200 (7.020) 86.737 (34.170) 0.002 Data ae presentec! as (7s), mean + slandard deviation, or mein (range). Sgnfcant ailrence tp $0,05 58.(Cos: tieiveaes Analysis of Homomasi-Melens Trem ia Coss Table 5. ACER in all patients Toial Cosi to treat all palienis, DR 12641 IDR 62,643, Effectiveness 44.44% cure rate 58.33% cure rate ACER IDR 12.6410.44 = JOR 28,731 IDR 62,6430.58 = [DR 108,006 Table 6. ACER in patients with Child-Turcotte-Pugh-Score A, 8, and C A Total Cost io troat all pationts IDR 5.580 IDR 44,975 Efectiveness 100% cure rate 83.39% cure rate ACER OR 6.850 = JOR 5,550 IR 44.975 = [DR 4.186 1 0.83 B ‘Total Cost to treat all patents 1OR “1,700 JOR 53,970 Effectiveness 20% cure vate 70% cure vale ACER IDR 411,100 = IDR 55,500 IDR 52,970 = [DR 77.200 0.20 070 c Total Cost to treat all patients IDR 22.200 [OR 88,737 Effectiveness: 33.89% cure rate 100% cure rate ACER lpm 22,200 - Ion 67.272 (BR a8. 297 = IDR 96,797 ‘The design of this study was retrospective study Discussion using medical records of patiens who had history of hepatic cirthosis or patients with hepatic cirrhosis with Ani at Adi Husade Undaan Wetan trematemesis Surabaya Hospital, The main objective of ths study was 1 clinical phacmacy is 10 ensure good therapeutic to assess she eosiclfectiveness of therapy with vitamin K outcome and pharmaceutical ng One of the important pharmacist’s responsibilii re which must no! only compared to combination of vitamin K-transamtin u be safe and effective, but also have a high value from — CEA method with the aid of cost-effectiveness grid and economic and humanistic aspects. The implementation ACER value of pharmacy-economic research is very. important in In this research, the cause of the incident of pharmaceutical ear Ia fast phatmacy profession Would pematemesis-melena ‘its not confirmed, PVT is essed not succeed in thei role to provide pharmaceutical carey increased hepatic resistance in cis, reselling in without pharmaco-economic knowledge (17). Therefore. deterioration inthe portal venous outflow, vascular miero pharmaco-economie evaluation The CEA sehich compares. thrombosis secondaty to vases ischemia amd infarction cost and effcctiveness of therapy’ is needed (19). The may lead to the heatt, With the loss of liver tissue cost of Transamin is higher than the cost of viarin K, (parenchyimal extinction) being replaced by fibrotic iste and to krow whother addition of Transamin in vitamin Qo), ‘The incuent is most commonly caused y porta K monotherapy is needed in clinical practice, c0si vein tivorshoxis PV") that can contibate to significant effectiveness evilaton is eased morbidity and mortality. Cir evi 89The Indonesian Biomedical Journal should be screened for varices and ther anti coagulated with low-molecular-seipl ppacin for at least a 6-month period. Newer evidence suggests that prophylactic anti- coagulation in patients with cirthosis may have « role in clinical ma with decreased invidenee oF PVT and improved survival 21) in Table sed on Chilé-Turcort ‘The patients characteristics ean be se while patients characteristics Pa significant difference if p = 0,05. In this study, these was up with a number of samples less than 6. and it was Child-Turcotte-Pugh score B group using vitwmin K with just 5 subjects, ‘This was de to the limitation of hepatic classification ean be seen in ‘Table 4. P value indicates cirrhosis patients with hematemesis-melena, This research compared the cost and effectiveness of therapy based om the desree of severity of the liver damage. The difference of liver severity will take effect fn therapeutic effectiveness, "The higher the liver damage, the lower the therapeutic effectiveness, dus to decreese of ation factor symthesis (1,22), and if these is any hepatocellular disease or if the liver cell couldn’t synthesize blood coagulation factor, vitamin K ake eft (23) Pugh Score, there is anotiver ver function for c is woulda’ given to patie Beside Child-Tureon instrument used to classify the severity of the liver damage, which is a newer method called MELD (model of ead liver disease}. ‘There are some benefits of MELD. ike 20 subjective assessment like Child-Turcotte-P score (uscites. hepatic encephalopathy). but hepatologists snerally do not vse MELD because not all Inboratories use INR (intemnationalized ratio) whieh is one of MELD components as coagulation marker in hepatic cirshosis patient, and there is no clear value limitation on MELD. Besides that, MELD scor needs calculation, therefore quick an simple measurement couldn't be applied (24) In Indonesia, the biggest risk factor as the cause oof hepatic cimthosis progression of hepatitis C and B Infections followed by hemochromatosis (25) rat than alcohol, because of the dillerence between the amount oF aleghol consumed by people in westem countries than The development of Hepatitis C lo hepatic cirshosis usually take years or decades, with average of 20 years (26). Most of hepatic cisthosis patients are elderly people. usually in the range of 52-69 years old due to hepatic cirrhosis éevelopment which takes years or decades, From this study it is knowa that hepatic citchosis symptoms appears averagely at the age of SI years and culminates at the range of 32-69 yer people in Indonesia. In this study bleeding mostly stopped! at the frst day after medication, although the pat st had bled for days botore hospitalized, ‘his is in accordance with Literature 60 that claims when vitamin K is given parenterally ProthrombinTime (PT) may need 12 t0 24 hours to normal although improvement may happen in 1 to 2 touts (27), whereas transamin has t! = 2 hoors(28),Therefore, itis ‘most likely that patient’ leeding could he stopped at the first day of treatment Antiibrinolytic therapy has been shown to be wsefial nr controlling bleeding in some conditions, especially nr patients with sastric erosion and also it. esophageal varices. Antilibrinolytic effect is not associated with due to the aproved systemie fibrinolysis, but re: nihibition of local fibrinolysis in gastroduodenal mecoss (ranexamie acid) in bean option, but there (10), Therefore, the use of transam audition to tne use of vilamin K 110 sufficient evidence supporting a recommendation on the use of tranesamal acid in the tearment of estroimestinal bleedin Re, cid is a useful tre and bleeding from varives (7). gardless ofthe fact there is zn evidence that rmexamic tment for refractory bleeding due t gastric antral vascular ectasia in patients with cirrhosis 29, Comparative based on effectiveness pharmaco- economics reviews, caleulating the pereentage of py hematemesiy melenaped <1 day in all patients and in patients with ChildTurcotte-Pu ot until the bleeding that stopped < 3 days in Score € analyzed using cost-e“Teetiveness grid and perforined by cents wilh cimrhosis of the liver with Score A and B, as well as old teatme paticmts wi Data ACER. From th 2) it ean be seen that vitamin K has a dominant outcome Costeffectiveness inthe table grid (Table n patients with Child-Turcotte-Pugh Seure A and trade fof on all patiemss as well as patients with Child-Turcotte- Pagh Score B and C. Consider further follow up on the results of the trade oll'is using ACER. Krom the dominant nding ip the resuls, it ean be seen that tseatment with vitamin K have a lower ‘cost with higher effectiveness than vitamin K-transamia, so it ean be concluded that vitamin K is more cost-effective than vitamin K-tansamin, Based on the calculation of ACER (Table 5 ane 6), it showed the value of vitamin K ACER was smaller than the vitamin K-transamin, so it ean be concluded that vitarnin K is move costeffective than vitumin K-ransanin in all patients as well as in patients wish Child-Tureotte-? Score A. B, and C. There are some limitations of this study including that of the number of samples which was too small, because {was taken from | hospital even in 2 years, and that’s why the data were not homogenous and the distribution was not normal either. We recommend that in she future Siudies using more samples with a longer time spanThe Indone n Biomedical Journal 2 ei Yate nem tempt oan 2s seth TNE AGH mn ae es aia 2s! ila 62 © nao, canon dares Ga sg eked Shadsigeacd bile Aaa eet AS LeNea pars neaiated ttNboratey costs ce vor asehed Another limitation was that the outcome of treatment was duration observed only until the bleeding stopped other outcomes associated with bleeding such as PL (Prothrombin Time) was not observed, Prothrombin Time is 4 laboratory test needed to evalvate hlood cosgulation tate. Decrease of PT is an expected result from bleeding medication Conclusion Tae use of vitamin K therapy is more cost-effective he patients with liver cirthosis ane hematemesis-melena, acd than combination therapy of vitamin K-transamin inal in paiients with Child-Turvotie-Pugh seore A, B, and C. ‘This conclusion should be regarded with eausion due to its limitation andl farther researc is needed. Su prospective design so that the results obiained can be representative of the actual condition of the patient and ‘onfoundiag variables can be better controlled so as 10 obtain a good study of the relationship between risk factors and effeeis. In addition, the number of samples should stion is given for further research usin be enlarged in order to get more homogeneous dats andl normal distribution, other components of cost such as cost of hospital, doctor, ete, could he calculated, not only the cost of therapy vitamin K or vitariin K-iransamin, and the ‘oucome observed is not only of the duration of bleeding, bur also Prothromain Time, side effects, ane other facrors thas affect bleedin ‘Acknowledgements: ais researel way supported by the Research and Community Service Institution of the University of Surabaya (Lembaga Penelitan dan Pengabdian Kepada Masyaraet Ubaya), Surabaya, References 1, Kerwiard 8, Tan CK, Pengqunaan Obst pada Gargouar Hat. Tre Asia~ Ta CK Prayltra A extors, Faas IA Henan bengoostan Rasanel don Penosargeny Pinan Pasien, Surabaya: Flex iedia Kempirisda. 2003. 9.15 2, Soase JY. Timm EG, Strayand JJ, Porial Hypertension ard Gidsia Ir Bpia JT Tabet RL Yao GC. aclors Cos: 27. 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