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Araştırma Makalesi
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B12 vitamin eksikliği olan kişilerin tam kan, ortalama trombosit hacmi (MPV) ve nötrofil-lenfosit oranlarının (NLR) değerlendirilmesi

Yıl 2022, Cilt: 7 Sayı: 2, 30 - 35, 31.05.2022

Adem Durmaz

https://doi.org/10.22391/fppc.1032712

Öz

Giriş: B12 vitamin eksikliğinin; kan tetkiklerine, ortalama trombosit hacmine (MPV) ve inflamasyon markerlarından nötrofil-lenfosit oranına (NLR) etkilerinin araştırılması amaçlanmıştır.

Yöntem: Çalışmamız 375 hasta üzerinde yapılmıştır. B12’si düşük (<130 pg/dL) saptanan 170 hasta deney grubu olarak, B12 düzeyleri normal olan 205 kişide kontrol grubu olarak kabul edilmiştir. Bu iki grup arasında beyaz kan hücreleri (WBC), trombosit sayısı (Plt), hemoglobin (Hgb), ortalama eritrosit hacmi (MCV), MPV, nötrofil, lenfosit sayıları ve nötrofil-lenfosit oranları (NLR) incelenmiştir.

Bulgular: Yaş ortalaması B12 eksik grupta 48.45 ±17.497 yıl, kontrol grubunda ise 51.93 ±16.175 yıl idi. Eksik grupta B12vitamini ortalaması 101,41 ± 20,50 pg/mL (min-max; 37-130), kontrol grubunda ise 257,24 ± 88,13 pg/mL (min-max; 131-498) idi. WBC, Hgb, Plt, nötrofil, lenfosit, MVC, MPV ve NLR arasında istatiksel açıdan anlamlı bir fark olmadığı gözlendi.

Sonuç: Çalışmamızda B12 eksikliği ile kan tetkikleri arasında anlamlı bir ilişki bulamadık. Önceki çalışmalarda B12 eksikliğinde MPV değerlerinin etkilendiğine dair bilgiler bulunmaktadır. Yaptığımız çalışmada da B12 eksikliği ile MPV ve NLR arasında anlamlı bir ilişkinin olmadığını saptadık (p>0,05). B12 eksikliğinin, düzeyi ve süresi uzadıkça nasıl değişiklikler gözlenebileceği ve özellikle de bu vitamin eksikliğinin aterojenik olaylara olan etkileri hakkında yapılacak yeni çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

B12 vitamini eksikliği ortalama trombosit hacmi nötrofil lenfosit

Kaynakça

  • 1. Turkish Hematology Society, (2011) "Vitamin B12 deficiency diagnosis and treatment guide". Available at: https://thd.org.tr/thddata/books/94/bolum-i-b12-vitamini-eksikligi-tani-ve-tedavikilavuzu.pdf , Date of Access: 04.12.2021
  • 2. Sanderson SM, Gao X, Dai Z, Locasale JW. Methionine metabolism in health and cancer: a nexus of diet and precision medicine. Nat Rev Cancer. 2019;19(11):625-37. https://doi.org/10.1038/s41568-019-0187-8
  • 3. Imbard A, Benoist JF, Blom HJ. Neural tube defects, folic acid and methylation. Int J Environ Res Public Health. 2013;10(9):4352-89. https://doi.org/10.3390/ijerph10094352
  • 4. Pawlak R, Parrott SJ, Raj S, Cullum-Dugan D, Lucus D. How prevalent is vitamin B(12) deficiency among vegetarians? Nutr Rev. 2013;71(2):110-7. https://doi.org/10.1111/nure.12001
  • 5. Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ 2014;349:g5226. https://doi.org/10.1136/bmj.g5226
  • 6. Derin S, Koseoglu S, Sahin C, Sahan M. Effect of vitamin B12 deficiency on olfactory function. Int Forum Allergy Rhinol. 2016;6(10):1051-5. https://doi.org/10.1002/alr.21790
  • 7. Devalia V, Hamilton MS, Molloy AM. British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. https://doi.org/10.1111/bjh.12959
  • 8. Quadros EV. Advances in the understanding of cobalamin assimilation and metabolism. Br J Haematol. 2010;148(2):195-204. https://doi.org/10.1111/j.1365-2141.2009.07937.x
  • 9. Sobczyńska-Malefora A, Gorska R, Pelisser M, Ruwona P, Witchlow B, Harrington DJ. An audit of holotranscobalamin ("Active" B12) and methylmalonic acid assays for the assessment of vitamin B12 status: application in a mixed patient population. Clin Biochem. 2014;47(1-2):82-6. https://doi.org/10.1016/j.clinbiochem.2013.08.006
  • 10. Valente E, Scott JM, Ueland PM, Cunningham C, Casey M, Molloy AM. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly. Clin Chem. 2011;57(6):856-63. https://doi.org/10.1373/clinchem.2010.158154
  • 11. Coban E, Ozdogan M, Yazicioglu G, Akcit F. The mean platelet volume in patients with obesity. Int J Clin Pract. 2005;59(8):981-2. https://doi.org/10.1111/j.1742-1241.2005.00500.x
  • 12. Kisacik B, Tufan A, Kalyoncu U, Karadag O, Akdogan A, Ozturk MA, et al. Mean platelet volume (MPV) as an inflammatory marker in ankylosing spondylitis and rheumatoid arthritis. Joint Bone Spine. 2008;75(3):291-4. https://doi.org/10.1016/j.jbspin.2007.06.016
  • 13. Jilma B, Blann A, Pernerstorfer T, Stohlawetz P, Eichler HG, Vondrovec B, et al. Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin. Am J Respir Crit Care Med. 1999;159(3):857-63. https://doi.org/10.1164/ajrccm.159.3.9805087
  • 14. Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5-14.
  • 15. Duffy BK, Gurm HS, Rajagopal V, Gupta R, Ellis SG, Bhatt DL. Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol. 2006;97(7):993-6. https://doi.org/10.1016/j.amjcard.2005.10.034
  • 16. Tsujimura A, Kawamura N, Ichimura T, Honda K, Ishiko O, Ogita S. Telomerase activity in needle biopsied uterine myoma-like tumors: differential diagnosis between uterine sarcomas and leiomyomas. Int J Oncol. 2002;20(2):361-5. https://doi.org/10.3892/ijo.20.2.361
  • 17. Aydın I, Agilli M, Aydin F.N, Gulcan Kurt Y, Cayci T, Tas A, et al. Using neutrophil-lymphocyte ratio as a regulatory marker in hypertensive patients. Med J SDU. 2015;57: 414-8. https://doi.org/10.5455/gulhane.166398
  • 18. Kwok T, Cheng G, Woo J, Lai WK, Pang CP. Independent effect of vitamin B12 deficiency on hematological status in older Chinese vegetarian women. Am J Hematol. 2002;70(3):186-90. https://doi.org/10.1002/ajh.10134
  • 19. Abuhandan M, Gumus H, Solmaz A, Guzel B. Assessment of mean platelet volume in patients deficiency vitamin B12. J Harran Univ Med Fac 2014;11(3):253-6.
  • 20. Zhou L, Lin S, Zhang F, Ma Y, Fu Z, Gong Y, et al. The correlation between RDW, MPV and weight indices after metabolic surgery in patients with obesity and DM/IGR: follow-up observation at 12 months. Diabetes Ther. 2020;11(10):2269-81. https://doi.org/10.1007/s13300-020-00897-9
  • 21. Toplak H, Wascher TC. Influence of weight reduction on platelet volume: different effects of a hypocaloric diet and a very low calorie diet. Eur J Clin Invest. 1994;24(11):778-80. https://doi.org/10.1111/j.1365-2362.1994.tb01076.x
  • 22. Thompson CB, Diaz DD, Quinn PG, Lapins M, Kurtz SR, Valeri CR. The role of anticoagulation in the measurement of platelet volumes. Am J Clin Pathol. 1983;80(3):327-32. https://doi.org/10.1093/ajcp/80.3.327
  • 23. Korniluk A, Koper-Lenkiewicz OM, Kamińska J, Kemona H, Dymicka-Piekarska V. Mean platelet volume (MPV): new perspectives for an old marker in the course and prognosis of inflammatory conditions. Mediators Inflamm. 2019;2019:9213074. https://doi.org/10.1155/2019/9213074
  • 24. Beyan C, Beyan E. Mean platelet volume and vitamin D deficiency may not be related in diabetic patients. Ann Endocrinol (Paris). 2015;76(1):75-6. https://doi.org/10.1016/j.ando.2014.11.002
  • 25. Noris P, Melazzini F, Balduini CL. New roles for mean platelet volume measurement in the clinical practice? Platelets, 2016:27(7):607-12. https://doi.org/10.1080/09537104.2016.1224828
  • 26. Lippi G, Pavesi F, Pipitone S. Evaluation of mean platelet volume with four haematological analyzers: harmonization is still an unresolved issue. Blood Coagul Fibrinolysis. 2015;26:235-7. https://doi.org/10.1097/MBC.0000000000000220
  • 27. Ittermann T, Feig MA, Petersmann A, Radke D, Greinacher A, Völzke H, et al. Mean platelet volume is more important than age for defining reference intervals of platelet counts. PLoS One. 2019;14(3):e0213658. https://doi.org/10.1371/journal.pone.0213658
  • 28. Beyan A, Beyan E. The mean platelet volume in patients with ankylosing spondylitis. Cukurova Med J 2017;42(2):404-5. https://doi.org/10.17826/cutf.323176
  • 29. Seo YJ, Jeong JH, Choi JY, Moon IS. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio: novel markers for diagnosis and prognosis in patients with idiopathic sudden sensorineural hearing loss. Dis Markers. 2014;2014:702807. https://doi.org/10.1155/2014/702807
  • 30. Mertoglu C, Gunay M. Neutrophil-Lymphocyte ratio and Platelet-Lymphocyte ratio as useful predictive markers of prediabetes and diabetes mellitus. Diabetes Metab Syndr. 2017;11(Suppl 1):127-31. https://doi.org/10.1016/j.dsx.2016.12.021
  • 31. Yildirim Bas F, Arslan B. The association between the neutrophil lymphocyte ratio and vitamin D levels. Turk J Fam Med Prim Care. 2018; 12(2): 88-91. https://doi.org/10.21763/tjfmpc.432455
  • 32. Sezgin Y. Approach to Vitamin B12 Deficiency. Konuralp Med J. 2019;11(3):482-8. https://doi.org/10.18521/ktd.591971

Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency

Yıl 2022, Cilt: 7 Sayı: 2, 30 - 35, 31.05.2022

Adem Durmaz

https://doi.org/10.22391/fppc.1032712

Öz

Introduction: It was aimed to investigate the effects of vitamin B12 deficiency on blood tests, mean platelet volume (MPV), and neutrophil-lymphocyte ratio (NLR), which is one of the inflammation markers.

Methods: Our study is a case-control study of 375 patients. 170 patients with low B12 (<130 pg/dL) were accepted as the experimental group, and 205 individuals with normal B12 levels were accepted as the control group. Between these two groups, white blood cells (WBC), platelet count (Plt), hemoglobin (Hgb), mean erythrocyte volume (Mean Corpuscular Volume-MCV), mean platelet volume (Mean Platelet Volume-MPV), neutrophil, lymphocyte counts, and neutrophil -lymphocyte ratios (NLR) were examined.

Results: The mean age was 48.45 ±17.497 years in the B12 deficient group and 51.93 ±16.175 years in the control group. The mean of vitamin B12 in the deficient group was 101.41 ± 20.50 pg/mL (min-max 37-130), while it was 257.24 ± 88.13 pg/mL (131–498) in the control group. It was observed that there was no statistically significant difference between WBC, Hgb, Plt, neutrophil, lymphocyte, MVC, MPV and NLR values.

Conclusion: In our study, we could not find a significant relationship between B12 deficiency and blood tests. In previous studies, there has been information that MPV values are affected by B12 deficiency. In our study, we found that there was no significant relationship between B12 deficiency and MPV or NLR (p > 0.05). There is a need for new studies on how B12 deficiency will change as the degree and duration of B12 deficiency increases, especially its effect on atherogenic events. 

Anahtar Kelimeler

Vitamin B12 deficiency Mean Platelet Volume neutrophils lymphocytes

Kaynakça

  • 1. Turkish Hematology Society, (2011) "Vitamin B12 deficiency diagnosis and treatment guide". Available at: https://thd.org.tr/thddata/books/94/bolum-i-b12-vitamini-eksikligi-tani-ve-tedavikilavuzu.pdf , Date of Access: 04.12.2021
  • 2. Sanderson SM, Gao X, Dai Z, Locasale JW. Methionine metabolism in health and cancer: a nexus of diet and precision medicine. Nat Rev Cancer. 2019;19(11):625-37. https://doi.org/10.1038/s41568-019-0187-8
  • 3. Imbard A, Benoist JF, Blom HJ. Neural tube defects, folic acid and methylation. Int J Environ Res Public Health. 2013;10(9):4352-89. https://doi.org/10.3390/ijerph10094352
  • 4. Pawlak R, Parrott SJ, Raj S, Cullum-Dugan D, Lucus D. How prevalent is vitamin B(12) deficiency among vegetarians? Nutr Rev. 2013;71(2):110-7. https://doi.org/10.1111/nure.12001
  • 5. Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ 2014;349:g5226. https://doi.org/10.1136/bmj.g5226
  • 6. Derin S, Koseoglu S, Sahin C, Sahan M. Effect of vitamin B12 deficiency on olfactory function. Int Forum Allergy Rhinol. 2016;6(10):1051-5. https://doi.org/10.1002/alr.21790
  • 7. Devalia V, Hamilton MS, Molloy AM. British Committee for Standards in Haematology. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. https://doi.org/10.1111/bjh.12959
  • 8. Quadros EV. Advances in the understanding of cobalamin assimilation and metabolism. Br J Haematol. 2010;148(2):195-204. https://doi.org/10.1111/j.1365-2141.2009.07937.x
  • 9. Sobczyńska-Malefora A, Gorska R, Pelisser M, Ruwona P, Witchlow B, Harrington DJ. An audit of holotranscobalamin ("Active" B12) and methylmalonic acid assays for the assessment of vitamin B12 status: application in a mixed patient population. Clin Biochem. 2014;47(1-2):82-6. https://doi.org/10.1016/j.clinbiochem.2013.08.006
  • 10. Valente E, Scott JM, Ueland PM, Cunningham C, Casey M, Molloy AM. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly. Clin Chem. 2011;57(6):856-63. https://doi.org/10.1373/clinchem.2010.158154
  • 11. Coban E, Ozdogan M, Yazicioglu G, Akcit F. The mean platelet volume in patients with obesity. Int J Clin Pract. 2005;59(8):981-2. https://doi.org/10.1111/j.1742-1241.2005.00500.x
  • 12. Kisacik B, Tufan A, Kalyoncu U, Karadag O, Akdogan A, Ozturk MA, et al. Mean platelet volume (MPV) as an inflammatory marker in ankylosing spondylitis and rheumatoid arthritis. Joint Bone Spine. 2008;75(3):291-4. https://doi.org/10.1016/j.jbspin.2007.06.016
  • 13. Jilma B, Blann A, Pernerstorfer T, Stohlawetz P, Eichler HG, Vondrovec B, et al. Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin. Am J Respir Crit Care Med. 1999;159(3):857-63. https://doi.org/10.1164/ajrccm.159.3.9805087
  • 14. Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5-14.
  • 15. Duffy BK, Gurm HS, Rajagopal V, Gupta R, Ellis SG, Bhatt DL. Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol. 2006;97(7):993-6. https://doi.org/10.1016/j.amjcard.2005.10.034
  • 16. Tsujimura A, Kawamura N, Ichimura T, Honda K, Ishiko O, Ogita S. Telomerase activity in needle biopsied uterine myoma-like tumors: differential diagnosis between uterine sarcomas and leiomyomas. Int J Oncol. 2002;20(2):361-5. https://doi.org/10.3892/ijo.20.2.361
  • 17. Aydın I, Agilli M, Aydin F.N, Gulcan Kurt Y, Cayci T, Tas A, et al. Using neutrophil-lymphocyte ratio as a regulatory marker in hypertensive patients. Med J SDU. 2015;57: 414-8. https://doi.org/10.5455/gulhane.166398
  • 18. Kwok T, Cheng G, Woo J, Lai WK, Pang CP. Independent effect of vitamin B12 deficiency on hematological status in older Chinese vegetarian women. Am J Hematol. 2002;70(3):186-90. https://doi.org/10.1002/ajh.10134
  • 19. Abuhandan M, Gumus H, Solmaz A, Guzel B. Assessment of mean platelet volume in patients deficiency vitamin B12. J Harran Univ Med Fac 2014;11(3):253-6.
  • 20. Zhou L, Lin S, Zhang F, Ma Y, Fu Z, Gong Y, et al. The correlation between RDW, MPV and weight indices after metabolic surgery in patients with obesity and DM/IGR: follow-up observation at 12 months. Diabetes Ther. 2020;11(10):2269-81. https://doi.org/10.1007/s13300-020-00897-9
  • 21. Toplak H, Wascher TC. Influence of weight reduction on platelet volume: different effects of a hypocaloric diet and a very low calorie diet. Eur J Clin Invest. 1994;24(11):778-80. https://doi.org/10.1111/j.1365-2362.1994.tb01076.x
  • 22. Thompson CB, Diaz DD, Quinn PG, Lapins M, Kurtz SR, Valeri CR. The role of anticoagulation in the measurement of platelet volumes. Am J Clin Pathol. 1983;80(3):327-32. https://doi.org/10.1093/ajcp/80.3.327
  • 23. Korniluk A, Koper-Lenkiewicz OM, Kamińska J, Kemona H, Dymicka-Piekarska V. Mean platelet volume (MPV): new perspectives for an old marker in the course and prognosis of inflammatory conditions. Mediators Inflamm. 2019;2019:9213074. https://doi.org/10.1155/2019/9213074
  • 24. Beyan C, Beyan E. Mean platelet volume and vitamin D deficiency may not be related in diabetic patients. Ann Endocrinol (Paris). 2015;76(1):75-6. https://doi.org/10.1016/j.ando.2014.11.002
  • 25. Noris P, Melazzini F, Balduini CL. New roles for mean platelet volume measurement in the clinical practice? Platelets, 2016:27(7):607-12. https://doi.org/10.1080/09537104.2016.1224828
  • 26. Lippi G, Pavesi F, Pipitone S. Evaluation of mean platelet volume with four haematological analyzers: harmonization is still an unresolved issue. Blood Coagul Fibrinolysis. 2015;26:235-7. https://doi.org/10.1097/MBC.0000000000000220
  • 27. Ittermann T, Feig MA, Petersmann A, Radke D, Greinacher A, Völzke H, et al. Mean platelet volume is more important than age for defining reference intervals of platelet counts. PLoS One. 2019;14(3):e0213658. https://doi.org/10.1371/journal.pone.0213658
  • 28. Beyan A, Beyan E. The mean platelet volume in patients with ankylosing spondylitis. Cukurova Med J 2017;42(2):404-5. https://doi.org/10.17826/cutf.323176
  • 29. Seo YJ, Jeong JH, Choi JY, Moon IS. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio: novel markers for diagnosis and prognosis in patients with idiopathic sudden sensorineural hearing loss. Dis Markers. 2014;2014:702807. https://doi.org/10.1155/2014/702807
  • 30. Mertoglu C, Gunay M. Neutrophil-Lymphocyte ratio and Platelet-Lymphocyte ratio as useful predictive markers of prediabetes and diabetes mellitus. Diabetes Metab Syndr. 2017;11(Suppl 1):127-31. https://doi.org/10.1016/j.dsx.2016.12.021
  • 31. Yildirim Bas F, Arslan B. The association between the neutrophil lymphocyte ratio and vitamin D levels. Turk J Fam Med Prim Care. 2018; 12(2): 88-91. https://doi.org/10.21763/tjfmpc.432455
  • 32. Sezgin Y. Approach to Vitamin B12 Deficiency. Konuralp Med J. 2019;11(3):482-8. https://doi.org/10.18521/ktd.591971
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları
Bölüm Araştırma Makalesi (Original Article)
Yazarlar

Adem Durmaz 0000-0001-5890-3622

Yayımlanma Tarihi 31 Mayıs 2022
Gönderilme Tarihi 5 Aralık 2021
Kabul Tarihi 24 Mayıs 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 7 Sayı: 2

Kaynak Göster

APA Durmaz, A. (2022). Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency. Family Practice and Palliative Care, 7(2), 30-35. https://doi.org/10.22391/fppc.1032712
AMA Durmaz A. Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency. Fam Pract Palliat Care. Mayıs 2022;7(2):30-35. doi:10.22391/fppc.1032712
Chicago Durmaz, Adem. “Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency”. Family Practice and Palliative Care 7, sy. 2 (Mayıs 2022): 30-35. https://doi.org/10.22391/fppc.1032712.
EndNote Durmaz A (01 Mayıs 2022) Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency. Family Practice and Palliative Care 7 2 30–35.
IEEE A. Durmaz, “Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency”, Fam Pract Palliat Care, c. 7, sy. 2, ss. 30–35, 2022, doi: 10.22391/fppc.1032712.
ISNAD Durmaz, Adem. “Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency”. Family Practice and Palliative Care 7/2 (Mayıs2022), 30-35. https://doi.org/10.22391/fppc.1032712.
JAMA Durmaz A. Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency. Fam Pract Palliat Care. 2022;7:30–35.
MLA Durmaz, Adem. “Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency”. Family Practice and Palliative Care, c. 7, sy. 2, 2022, ss. 30-35, doi:10.22391/fppc.1032712.
Vancouver Durmaz A. Evaluation of whole blood, mean platelet volume (MPV) and neutrophil-lymphocyte ratios (NLR) in people with B12 vitamin deficiency. Fam Pract Palliat Care. 2022;7(2):30-5.
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Family Practice and Palliative Care      ISSN 2458-8865       E-ISSN 2459-1505