AL Azhar University- Gaza Deanship of Postgraduate Studies Faculty of Pharmacy Pharmaceutical Sciences program Prevalence of anemia among hemodialysis patients treated with recombinant human erythropoietin (rhEPO) in Gaza Strip Submitted by: Tasneem Basem Shaban Supervisors: Dr. Amin T. Hamed Dr. Marwan A. Arafat Assoc. Professor of Pharmacology PhD in Nephrology Faculty of Pharmacy Al Shiffa Hospital Al- Azhar University- Gaza A thesis submitted for master degree in Pharmaceutical Sciences Gaza, 2016 i ii ا ا ا (٥٩ :مﺎﻌﻧﻷا) iii DECLARATION I, the undersigned hereby, declare that the thesis titled: Prevalence of anemia among hemodialysis patient treated with recombinant human erythropoietin (rhEPO) in Gaza Strip. Is my own research work and the work provided in this thesis, unless otherwise referenced, is the researcher’s own work, and has never been submitted elsewhere for any other degree qualification nor for any academic titles, nor for any other academic or publishing institutions. I, hereto, affirm that I will be completely responsible in academic and legal terms if this work proves the opposite. Student’s name: Tasneem Basem Sha’ban Signature: Date: iv Dedication To my beloved parents, for the sacrifices that they had made For their endless love Support and encouragement. To my beloved husband and son who helped me to accomplish this thesis and for their patience and understanding. To my brothers and sister for their great efforts and help. v Acknowledgement This research would not have been possible without the support of many people. I would like to express my deepest gratitude and appreciation to my supervisors, Dr. Amin T. Hamed and Dr. Marwan A. Arafat who were abundantly helpful and offered me invaluable assistance, continuous support, encouragement and guidance that led to the emergence of this work in its current form. My gratitude and thanks to Al- Azhar University- Gaza, Palestine. My thanks and appreciation goes to my teachers in Faculty of Pharmacy for their encouragement and assistance. Deep thanks and respects for my friends at Faculty of Pharmacy Al- Azhar University- Gaza and my friends at Al- Shifa hospital for their high cooperation and support. Thanks and respects for my colleagues and all hemodialysis staff at Al- Shifa hospital, Shohadaa Al Aqsa hospital and Nasir hospital for their high cooperation. I would like to thank Dr. Nibal Al Shawwa and my colleagues in the pharmacy department at Al Shifa hospital, especially in the internal and central pharmacies for their help and support. Also, I would like to thank all the patients for their approval to participate in this study, without their help, this study could not be accomplished. Lastly, I offer my regards and blessings to all of those who supported me in any respect during the completion of this thesis. vi Prevalence of anemia among hemodialysis patients treated with recombinant human erythropoietin (rhEPO) in Gaza Strip Abstract (English) Background: Anemia is a major complication of chronic kidney disease (CKD), it is common in all stages but is more pronounced at the end stage renal disease (ESRD). Anemia in CKD has multifactorial etiology. However, erythropoietin deficiency is the most significant cause of anemia in ESRD. Despite use of recombinant human erythropoietin (rhEPO), anemia is a frequent finding in hemodialysis patients in Gaza Strip Objectives: The present study was undertaken to assess the prevalence of anemia among patients on regular hemodialysis treated with recombinant human erythropoietin (rhEPO) in Gaza Strip; to determine the dose of rhEPO; to identify iron status of hemodialysis patient; and to study some of the modifiable factors that affect anemia and response to rhEPO as vascular access type; compliance to hemodialysis sessions; hospitalization and albumin level as indicator for inflammation and malnutrition. Methodology: To achieve this purpose, seventy four hemodialysis patients from both genders aged between 18-60 years, diagnosed as an ESRD on hemodialysis for more than two years and treated with rhEPO at Al Shifaa hospital, Shohadaa Al Aqsa hospital and Nasir hospital, Gaza Strip-Palestine, were enrolled in this retrospective, cross sectional study, in the period between Jan 2013 to Dec 2014. A questionnaire interview was used to collect the different socio-demographic factors as, age, gender, other comorbidities, duration and number of hemodialysis sessions/week. Data concerning the medical history as, primary cause of ESRD, exact time for initiation hemodialysis, hospitalization and laboratory tests as hemoglobin (Hb), platelet count, serum albumin, transferrin saturation, serum iron, calcium, vii phosphate and alkaline phosphatase, were collected by reviewing the medical record of each patient. Results: Anemia is a major finding among hemodialysis patients in Gaza Strip, Most hemodialysis patients (85%) had mean Hb values below 11.0 g/dl, mean differences of hemoglobin values decreased throughout the study period with statistically significant value, the mean dose of erythropoietin used was 5702±71 IU/week (93.34 ±33.7 IU/kg/week). There was a variability in response to erythropoietin among HD patients, transferrin saturation increased throughout the study period with statistically significant value, 62% of hemodialysis patients had transferrin saturation more than 20% and there was a statistically significant decrease in the mean albumin level during the study period. Factors that may contribute to progression of anemia among HD patients in Gaza Strip include, unstable supply of rhEPO, dependence on central venous catheters to maintain regular hemodialysis, increase hospitalization rate among HD patients, 37% of patients dialyzed less than four hours, 63% had albumin level less than normal (3.5g\dl), and 52% of patients had hyperphosphatemia. Conclusions & Recommendations: The prevalence of anemia is high in HD patients in Gaza Strip. Anemia management needs more attention, rhEPO should be continuously available for HD patients, and its cost must be weighed against the cost of anemia complication, strategies should be put in place to improve patient adherence to erythropoiesis stimulating agents (ESAs), iron and dialysis, regular periodic monitoring of hemoglobin, iron status and renal function tests should be done for HD patients. Keywords: End Stage Renal Disease (ESRD), Hemodialysis, anemia, recombinant human erythropoietin (rhEPO), Gaza Strip. viii ﻲﻓ ﻊﻨﺼﻤﻟا يﺮﺸﺒﻟا ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا جﻼﻋ نﻮﻘﻠﺘﯾ ﻦﯾﺬﻟا يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ﻰﺿﺮﻣ ﻦﯿﺑ مﺪﻟا ﺮﻘﻓ رﺎﺸﺘﻧا ةﺰﻏ عﺎﻄﻗ ﺔﺳارﺪﻟا ﺺﺨﻠﻣ ﻊﯿﻤﺟ ﻲﻓ ﻊﺋﺎﺷ ﻮھو ،ﻦﻣﺰﻤﻟا يﻮﻠﻜﻟا رﻮﺼﻘﻟا ضﺮﻤﻟ ﺔﯿﺴﯿﺋﺮﻟا تﺎﻔﻋﺎﻀﻤﻟا ﺪﺣأ ﻮھ مﺪﻟا ﺮﻘﻓ :ﺔﻣﺪﻘﻤﻟا ،ةدﺪﻌﺘﻣ مﺪﻟا ﺮﻘﻓ بﺎﺒﺳأ .مﺪﻘﺘﻤﻟا يﻮﻠﻜﻟا رﻮﺼﻘﻟا ﻲﻓ ﺎﻋﻮﯿﺷ ﺮﺜﻛأ ﮫﻨﻜﻟ ،ﻦﻣﺰﻤﻟا يﻮﻠﻜﻟا رﻮﺼﻘﻟا ﻞﺣاﺮﻣ ﻰﺿﺮﻤﻟا ءﺎﻄﻋإ ﻚﻟﺬﻟ، ﮫﺼﻘﻧ ﻰﻟإ يدﺆﯾ ﺎﻤﻣ ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا نﻮﻣﺮھ ﻊﯿﻨﺼﺗ ﻲﻓ ﺔﯿﻠﻜﻟا ﻞﺸﻓ ﺎﮭﻤھأ ﻦﻜﻟ .ﻦﯿﺑﻮﻠﺟﻮﻤﯿﮭﻠﻟ لﻮﺒﻘﻣ ىﻮﺘﺴﻣ ﻰﻠﻋ ظﺎﻔﺤﻠﻟ ﺔﻟﺎﺤﻟا هﺬھ ﻲﻓ ﻲﺳﺎﺳأ ﻮھ ﻊﻨﺼﻤﻟا يﺮﺸﺒﻟا ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا .مﺪﻟا ﺮﻘﻓ ﻦﻣ نﻮﻧﺎﻌﯾ ﻰﺿﺮﻤﻟا ﻦﻣ ةﺮﯿﺒﻛ ﺔﺒﺴﻧ ﺖﻟاز ﺎﻣ ،ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا ماﺪﺨﺘﺳا ﻦﻣ ﻢﻏﺮﻟﺎﺑ ﻦﻜﻟو جﻼﻋ نﻮﻘﻠﺘﯾ ﻦﯾﺬﻟا يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ﻰﺿﺮﻣ ﻦﯿﺑ مﺪﻟا ﺮﻘﻓ رﺎﺸﺘﻧا ىﺪﻣ مﯾﯾﻘﺗﻟ ﺔﺳاردﻟا هذھ تﯾرﺟأ :فﺪﮭﻟا ىﻮﺘﺴﻣ ﻢﯿﯿﻘﺗ ،ﺎﮭﺘﯾﺎﻔﻛو ﺾﯾﺮﻤﻟا ﻰﻠﻋ ةﺎﻄﻌﻤﻟا ﺔﻋﺮﺠﻟا ﺮﯿﺛﺄﺗ ىﺪﻣ ﻢﯿﯿﻘﺗ ، ﻊﻨﺼﻤﻟا يﺮﺸﺒﻟا ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا ﻰﻠﻋ ﺮﺛﺆﺗ ﻲﺘﻟاو ﻞﯾﺪﻌﺘﻠﻟ ﺔﻠﺑﺎﻘﻟا ﻞﻣاﻮﻌﻟا ﻦﻣ ﺔﻋﻮﻤﺠﻣ ﺔﺳاردو ،ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا ﻰﻠﻋ هﺮﯿﺛﺄﺗو ﺪﯾﺪﺤﻟا تﺎﺴﻠﺠﺑ ﺾﯾﺮﻤﻟا ماﺰﺘﻟا ىﺪﻣ ،ﺔﻣﺪﺨﺘﺴﻤﻟا ﺔﯿﻧﺎﯾﺮﺸﻟا -ﺔﯾﺪﯾرﻮﻟا ﺔﻠﺻﻮﻟا عﻮﻧ :ﻞﺜﻣ جﻼﻌﻠﻟ ﻰﺿﺮﻤﻟا ﺔﺑﺎﺠﺘﺳا .ﻰﺿﺮﻤﻟا ءﻻﺆھ ﺪﻨﻋ مﻮﯿﺴﻟﺎﻜﻟاو ،تﺎﻔﺳﻮﻔﻟا ،ﻦﯿﻣﻮﯿﺒﻟﻻا ىﻮﺘﺴﻣ ،ﻞﯿﺴﻐﻟا حواﺮﺘﺗ ، مﺪﻘﺘﻤﻟا يﻮﻠﻜﻟا ﻞﺸﻔﻟﺎﺑ بﺎﺼﻣ ﺾﯾﺮﻣ نﻮﻌﺒﺳو ﺔﻌﺑرأ ،ضﺮﻐﻟا اﺬھ ﻖﯿﻘﺤﺘﻟ :ﺔﺳارﺪﻟا ﺔﯿﺠﮭﻨﻣ ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا جﻼﻋ اﻮﻘﻠﺗ و ﻞﻗﻷا ﻰﻠﻋ ﻦﯿﻣﺎﻌﻟ يﻮﻠﻜﻟا ﻞﯿﺴﻐﻠﻟ اﻮﻌﻀﺧ ،ﺎﻣﺎﻋ ٦٠-١٨ ﻦﯿﺑ ﻢھرﺎﻤﻋأ ﻰﻔﺸﺘﺴﻣ ﻲﻓ ٢٠١٤ ﺮﺒﻤﺴﯾد ﻰﻟإ ٢٠١٣ ﺮﯾﺎﻨﯾ ﻦﯿﺑ ﺎﻣ ةﺮﺘﻔﻟا ﻲﻓ ﻲﻌﺟر ﺮﺛﺄﺑ ﻢﮭﺘﺳارد ﻢﺗ ، ﻊﻨﺼﻤﻟا يﺮﺸﺒﻟا .ﻦﯿﻄﺴﻠﻓ /ةﺰﻏ عﺎﻄﻗ ،ﺮﺻﺎﻧ ﻰﻔﺸﺘﺴﻣو ﻰﺼﻗﻷا ءاﺪﮭﺷ ﻰﻔﺸﺘﺴﻣ ،ءﺎﻔﺸﻟا ،ﻞﻤﻌﻟا ﺔﻌﯿﺒط ،ﺲﻨﺠﻟا ،ﺮﻤﻌﻟا :ﻞﺜﻣ ﺔﯿﻧﺎﻜﺴﻟاو ﺔﯿﻋﺎﻤﺘﺟﻻا ﻞﻣاﻮﻌﻟا ﻊﻤﺠﻟ نﺎﯿﺒﺘﺳا ماﺪﺨﺘﺳﺎﺑ ﻚﻟذ ﻢﺗ ﺪﻗو ﺐﺒﺴﻟا :ﻞﺜﻣ ﺾﯾﺮﻤﻠﻟ ﻲﺒﻄﻟا ﺦﯾرﺎﺘﻟﺎﺑ ﺔﻘﻠﻌﺘﻤﻟا تﺎﻧﺎﯿﺒﻟا ﺎﻣأ .ىﺮﺧﻵا ضاﺮﻣﻷا و ﻲﻤﯿﻠﻌﺘﻟا ىﻮﺘﺴﻤﻟا ﺢﺋﺎﻔﺼﻟا ،ﻦﯿﺑﻮﻠﺟﻮﻤﯿﮭﻟا ﻞﺜﻣ ﺔﯾﺮﺒﺨﻤﻟا تﺎﺻﻮﺤﻔﻟاو ،يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ءﺪﺑ ﺖﻗوو ،يﻮﻠﻜﻟا ﻞﺸﻔﻠﻟ ﻲﺴﯿﺋﺮﻟا .ﺾﯾﺮﻣ ﻞﻜﻟ ﻲﺒﻄﻟا ﻞﺠﺴﻟا ﺔﻌﺟاﺮﻤﺑ ﺖﻌﻤﺟ ﺪﻘﻓ تﺎﻔﺳﻮﻔﻟاو مﻮﯿﺴﻟﺎﻜﻟا، ﻦﯿﻣﻮﺒﻟﻷا ،ﺔﯾﻮﻣﺪﻟا ﻞﯿﺴﻐﻟا ﻰﺿﺮﻣ ﻢﻈﻌﻣ ،ةﺰﻏ عﺎﻄﻗ ﻲﻓ ﻰﻠﻜﻟا ﻞﯿﺴﻏ ﻰﺿﺮﻣ ﻦﯿﺑ ﺔﻈﺣﻼﻣ ﺔﺠﯿﺘﻧ ﻮھ مﺪﻟا ﺮﻘﻓ :ﺞﺋﺎﺘﻨﻟا لﻼﺧ ﻦﯿﺑﻮﻠﺟﻮﻤﯿﮭﻠﻟ قوﺮﻔﻟا ﻂﺳﻮﺘﻣ ﺾﻔﺨﻧا ،لد/ج ١١ ﻦﻣ ﻞﻗأ ﻢﮭﯾﺪﻟ ﻦﯿﺑﻮﻠﺟﻮﻤﯿﮭﻟا نﺎﻛ (٪٨٥) يﻮﻠﻜﻟا ةﺪﺣو ٧١ ± ٥٧٠٢ ﺖﻧﺎﻛ ﺔﻣﺪﺨﺘﺴﻤﻟا ﻦﯿﺘﯾﻮﺑوﺮﺜﯾرﻹا ﺔﻋﺮﺟ ، ﺔﯿﺋﺎﺼﺣإ ﺔﻟﻻد تاذ ﺔﻤﯿﻘﺑ ﺔﺳارﺪﻟا ةﺮﺘﻓ ﻰﺿﺮﻣ ﺔﺑﺎﺠﺘﺳا ﻲﻓ توﺎﻔﺗ كﺎﻨھ نﺎﻛ ،(عﻮﺒﺳأ / ﻢﺠﻛ / ﺔﯿﻟود ةﺪﺣو ٣٣.٧ ± ٩٣.٣٤) عﻮﺒﺳﻷا/ﺔﯿﻟود ،ﺔﯿﺋﺎﺼﺣإ ﺔﻟﻻد تاذ ﺔﻤﯿﻘﺑ ﺔﺳارﺪﻟا ةﺮﺘﻓ لﻼﺧ ﺪﯾﺪﺤﻟا ﻊﺒﺸﺗ ﺔﻤﯿﻗ تداز ، ﻦﯿﺘﯾﻮﺑوﺮﺜﯾرﻺﻠﻟ يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ﺔﻤﯿﻘﺑ ضﺎﻔﺨﻧا ﺎﻀﯾا ﺔﺳارﺪﻟا تﺮﮭظا ،٪٢٠ ﻦﻣ ﺮﺜﻛأ ﻢﮭﯾﺪﻟ ﺪﯾﺪﺤﻟا ﻊﺒﺸﺗ ﺔﺒﺴﻧ ﺖﻧﺎﻛ ﻰﺿﺮﻤﻟا ﻦﻣ %٦٢ .ﺔﺳارﺪﻟا ةﺮﺘﻓ لﻼﺧ ﻰﺿﺮﻤﻟا ﺪﻨﻋ ﻦﯿﻣﻮﺒﻟﻷا ىﻮﺘﺴﻣ ﻲﻓ ﺔﯿﺋﺎﺼﺣإ ﺔﻟﻻد تاذ ix ﻲﻓ يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ﻰﺿﺮﻣ ﻦﯿﺑ مﺪﻟا ﺮﻘﻓ رﻮﻄﺗ ﻲﻓ ﻢﮭﺴﺗ ﻞﻣاﻮﻌﻟا ﻦﻣ ﺪﯾﺪﻌﻟا نأ ﻰﻟإ ﺔﺳارﺪﻟا ﺖﻠﺻﻮﺗ ﻰﻠﻋ ظﺎﻔﺤﻠﻟ ﺔﯾﺰﻛﺮﻤﻟا ﺔﯾﺪﯾرﻮﻟا ةﺮﻄﺴﻘﻟا ﻰﻠﻋ دﺎﻤﺘﻋﻻا ،ﻢﻈﻨﻣو ﻢﺋاد ﻞﻜﺸﺑ ءاوﺪﻟا ﺮﻓﻮﺗ مﺪﻌﻛ ،ةﺰﻏ عﺎﻄﻗ ﻦﻣ ةﺮﯿﺒﻛ ﺔﺒﺴﻧ ،يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ﻰﺿﺮﻤﻟ ﻰﻔﺸﺘﺴﻤﻟا لﻮﺧد لﺪﻌﻣ ةدﺎﯾز ،يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ﺔﯾراﺮﻤﺘﺳا ﻲﻓ ةدﺎﯾز ﻢﮭﯾﺪﻟ نﺎﻛ ﻰﺿﺮﻤﻟا ﻦﻣ 52% و ﻦﯿﻣﻮﯿﺒﻟﻻا ىﻮﺘﺴﻣ ﻲﻓ ضﺎﻔﺨﻧا ﻢﮭﯾﺪﻟ نﺎﻛ (%٦٣) ﻰﺿﺮﻤﻟا .تﺎﻔﺳﻮﻔﻟا ىﻮﺘﺴﻣ ةﺎﻋﺪﻣ اﺬھو ،ةﺰﻏ عﺎﻄﻗ ﻲﻓ يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ﻰﺿﺮﻣ ىﺪﻟ ﻊﻔﺗﺮﻣ مﺪﻟا ﺮﻘﻓ رﺎﺸﺘﻧا لﺪﻌﻣ :تﺎﯿﺻﻮﺘﻟا و ﺞﺋﺎﺘﻨﻟا ، ﻰﺿﺮﻤﻟا ءﻻﺆﮭﻟ راﺮﻤﺘﺳﺎﺑ ﻊﻨﺼﻤﻟا يﺮﺸﺒﻟا ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا ﺮﯿﻓﻮﺗ ﺚﯿﺣ ﻦﻣ ﻦﯿﻟوﺆﺴﻤﻟا ﻞﺒﻗ ﻦﻣ مﺎﻤﺘھﻼﻟ ﻢﻈﺘﻨﻣ و يرود ﻢﯿﯿﻘﺗ ﻞﻤﻋو ، جﻼﻌﻟﺎﺑ ﺾﯾﺮﻤﻟا ماﺰﺘﻟا ﻦﯿﺴﺤﺘﻟ ﺔﻣزﻼﻟا تﺎﯿﺠﯿﺗاﺮﺘﺳﻻا ﻊﺿﻮﻟ ﻲﻌﺴﻟاو . ﻰﻠﻜﻟا ﻒﺋﺎظوو ﺪﯾﺪﺤﻟا ،ﻦﯿﺑﻮﻠﺟﻮﻤﯿﮭﻠﻟ ،مﺪﻟا ﺮﻘﻓ ،ﻊﻨﺼﻤﻟا يﺮﺸﺒﻟا ﻦﯿﺗﻮﯿﺑوﺮﺜﯾرﻻا ، يﻮﻠﻜﻟا ﻞﯿﺴﻐﻟا ،مﺪﻘﺘﻤﻟا يﻮﻠﻜﻟا رﻮﺼﻘﻟا :ﺔﯿﺣﺎﺘﻔﻣ تﺎﻤﻠﻛ .ةﺰﻏ عﺎﻄﻗ x
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