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FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA

Year 2017, Volume: 18 Issue: 1, 13 - 18, 17.01.2017
https://doi.org/10.18229/kocatepetip.341653

Abstract

ÖZ
AMAÇ: Antiembolik ajanlar ortopedi ve travmatoloji kliniklerinde özellikle artroplasti, tümör ve travma cerrahilerinde embolizm problemlerini azaltmak için rutin olarak kullanılmaktadır. Fondaparinuks’un kırık iyileşmesi üzerine etkisi belirsizdir. Bu çalışmanın amacı sıçan modeli kullanarak fondaparinuksun kırık iyileşmesi üzerine etkisinin incelenmesi ve enoksaparinin etkisi ile karşılaştırılmasıdır.
GEREÇ VE YÖNTEM: 64 adet Wistar-Albino sekiz gruba randomize olarak ayrıldı. Genel anestezi altında sol femur kapalı standart kırıkları oluşturuldu. Kontrol grupları (A, B), heparin grupları (C, D), enoksaparin grupları (E, F), ve fondaparinuks grupları (G, H), sırasıyla izotonik NaCl (1cc/gün), heparin (1000 anti Xa IU/kg/gün), enoksaparin (100 anti Xa IU/kg/gün) ve fondaparinuks (0.2mg/kg/gün) olacak şekilde 14 gün süre ile uygulandı. A, C, E, G gruplarındaki sıçanlar postoperatif 14. günün, B, D, F, H gruplarındakiler ise 28. günün sonunda sakrifiye edildiler. Tüm femurların radyolojik incelemesi standart ön-arka ve yan grafiler kullanılarak Goldberg sınıflamasına göre yapıldı. Histolojik inceleme ise Huo histolojik iyileşme sınıflamasına göre yapıldı. Bu çalışmanın istatiksel analizleri GraphPad Prisma V.3 paket programı kullanılarak yapıldı. Sonuçlarda anlamlılık p<0.05 düzeyi olarak belirlendi.
BULGULAR: Radyolojik incelemede, ikinci ve dördüncü hafta sonundaki sonuçlar incelendiğinde, gruplar arasında istatiksel olarak anlamlı fark saptanmadı. Histolojik incelemede ise heparin almış olan H grubundaki iyileşme sonuçları diğer gruplarla karşılaştırıldığında istatiksel olarak anlamlı şekilde kötü olarak saptandı. Diğer gruplar arasında histolojik açıdan, heparin grubu hariç, istatiksel olarak anlamlı bir fark saptanmadı. Ayrıca histolojik ve radyolojik olarak fondaparinuks ve enoksaparin grupları arasında kırık iyileşmesi üzerine etkileri arasında istatiksel olarak anlamlı fark saptanmadı (p>0.05).
SONUÇ: Çalışmamızda fondaparinuksun enoksaparin ile karşılaştırıldığında kırık iyileşmesi üzerine herhangi ekstra olumlu etkisini saptamadık. Fondaparinuks uygulamasının kırık iyileşmesi üzerine negatif bir etkisi saptanmamış olması nedeniyle travma vakalarında embolizm problemlerini önlemede kullanılabileceği kanaatindeyiz

References

  • Marsland D, Mears SC, Kates SL. Venous thromboembolic prophylaxis for hip fractures. Osteoporos Int 2010; 21: 593-604.
  • Shackford SR, Davis JW, Hollingsworth-Fridlund P, et al. Venous thromboembolism in major trauma. Am J Surg 1990; 159:365– 369.
  • Leclerc JR, Geerts WH, Desjardins L, et al. Prevention of deep vein thrombosis after major knee surgery– a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Haemost 1992; 67: 417- 423.
  • Lindner T, Cockbain AJ, El Masry MA, et al. The effect of anticoagulant pharmacotherapy on fracture healing. Expert Opin Pharmacother 2008; 9(7):1169–1187.
  • Palmer AJ, Koppenhagen K, Kirchhof B, et al. Efficacy and safety of low molecular weight heparin, unfractionated heparin and warfarin for thromboembolism prophylaxis in orthopedic surgery: A meta-analysis of randomized clinical trials. Haemostasis 1997; 27: 75– 84.
  • Shaughnessy SG, Young E, Deschamps P, et al. The effects of low molecular weight and standard heparin on calcium loss from fetal rat calvaria. Blood 1995; 15:86 (4): 1368-1373.
  • Muir JM, Andrew M, Hirsh J, et al. Histomorphometric analysis of the effects of standard heparin on trabecular bone in vivo. Blood 1996; 15: 88 (4): 1314-1320.
  • Street JT, McGrath M, O’Regan K, et al. Thromboprophylaxis using a low molecular weight heparin delays fracture repair. Clin Orthop2000; 381: 278-289.
  • Matziolis G, Perka C, Disch A, et al. Effects of fondaparinux compared with dalteparin, enoxaparin and unfractionated heparin on human osteoblasts. Calcif Tissue Int. 2003; 73(4): 370-379.
  • Hanschin AE, Trentz OA, Hoerstrup SP, et al. Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro. Br J Surg. 2005; 92 (2): 177-183.
  • Demirtas A, Azboy I, Bulut M, et al. Investigation of the effects of Enoxaparin, Fondaparinux and Rivaroxaban used in thromboembolism prophylaxis on fracture healing in rats. Eur Rev Med Pharmacol Sci. 2013; Jul (14): 1850-1856.
  • Say F, Iltar S, Alemdaroglu KB, et al. The effect of various types of low molecular weight heparins on fracture healing. Thromb Res 2013; 131(3):114-119.
  • Bonnarens F, Einhorn TA. Production of a standard closed fracture in laboratory animal bone. J Orthop Res 1984; 2(1): 97-101.
  • Folwarczna J, Janiec W, Gawor M, et al. Effects of enoxaparin on histomorphometric parameters of bones in rats. Pol J Pharmacol 2004; 56(4):451-457.
  • Schlitt A, Buerke M, Hauroeder B, et al. Fondaparinux and enoxaparin in comparison to unfractionated heparin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model. Thromb Haemost; 2003; 90:245-251.
  • Chung LT, Holton HL, Silverman PR. The effect of fondaparinux versus enoxaparin in the survival of a congested skin flap in a rabbit model. Ann Plast Surg 2006; 56: 312-15.
  • Olanders K, Börjesson A, Zhao X, et al. Effects of anticoagulant treatment on intestinal ischaemia and reperfusion injury in rats. Acta Anaesthesiol Scand 2005; 49: 517-524.
  • Folwarczna J, Janiec W, Sliwinski L. Effects of heparin and low-molecular weight heparin on bone mechanical properties in rats. Thromb Haemost. 2004; 92 (5): 940-946.
  • Goldberg VM, Powell A, Shaffer JW, et al. Bone grafting: role of histocompatibility in transplantation. J Orthop Res 1985; 3:389-404.
  • Huo MH, Troiano NW, Pelker RR, et al. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res 1991; 9:383-390.
  • Douketis JD, Ginsberg JS, Burrows RF, et al. The effects of long-term heparin therapy during pregnancy on bone density. A prospective matched cohort study. Thromb Haemost.1996; 75(2): 254-257.
  • Von Mandach U, Aebersold F, Huch R, et al. Short-term low-dose heparin plus bedrest impairs bone metabolism in pregnant women. Eur J Obstet Gynecol Reprod Biol 2003; 10; 106(1): 25-30.
  • Simmons HA, Raisz LG. Effects of acid and basic fibroblast growth factor and heparin on rezorption of cultured fetal rat long bones. J Bone Miner Res 1991; 6 (12):1301-1305.
  • Chigot P, De Gennes C, Samama MM. Osteoporosis induced either by unfractionated heparin or low molecular weight heparin. J Mal Vasc 1996; 21(3): 121-125.
  • Barbour DA, Kick SD, Steiner JF, et al. A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 1994; 170(3): 862-869.
  • Kock HJ, Werther S, Uhlenkott H, et al. Influence of unfractionated and low molecular weight heparin on bone healing: an animal model. Unfallchirurg 2002; 105 (9): 791-796.
  • Hak DJ, Stewart RL, Hazelwood SJ. Effect of low molecular weight heparin on fracture healing in a stabilized rat femur fracture model. J Orthop Res 2006; 24(4): 645-652.
  • Muir JM, Hirsh J, Weitz JI, et al. A histomorphometric comparison of the effects of heparin and low-molecular weight heparin on cancellous bone in rats. Blood 1997;1; 89(9): 3236-3242.
  • Rajgopal R, Bear M, Butcher MK, et al. The effect of heparin and low molecular weight heparins on bone. Thromb Res 2008; 122 (3): 293-298.
  • Casele HL, Laifer SA. Prospective evaluation of bone density in pregnant women receiving the low molecular weight heparin enoxaparin sodium. J Matern Fetal Med 2000; 9(2): 122-125.
  • Walenga MJ, Jeske P W, Bara L, et al. Biochemical and pharmacologic rationale for the development of a synthetic heparin pentasaccharide Thromb Res 1997; 86:1:1-36.
Year 2017, Volume: 18 Issue: 1, 13 - 18, 17.01.2017
https://doi.org/10.18229/kocatepetip.341653

Abstract

References

  • Marsland D, Mears SC, Kates SL. Venous thromboembolic prophylaxis for hip fractures. Osteoporos Int 2010; 21: 593-604.
  • Shackford SR, Davis JW, Hollingsworth-Fridlund P, et al. Venous thromboembolism in major trauma. Am J Surg 1990; 159:365– 369.
  • Leclerc JR, Geerts WH, Desjardins L, et al. Prevention of deep vein thrombosis after major knee surgery– a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Haemost 1992; 67: 417- 423.
  • Lindner T, Cockbain AJ, El Masry MA, et al. The effect of anticoagulant pharmacotherapy on fracture healing. Expert Opin Pharmacother 2008; 9(7):1169–1187.
  • Palmer AJ, Koppenhagen K, Kirchhof B, et al. Efficacy and safety of low molecular weight heparin, unfractionated heparin and warfarin for thromboembolism prophylaxis in orthopedic surgery: A meta-analysis of randomized clinical trials. Haemostasis 1997; 27: 75– 84.
  • Shaughnessy SG, Young E, Deschamps P, et al. The effects of low molecular weight and standard heparin on calcium loss from fetal rat calvaria. Blood 1995; 15:86 (4): 1368-1373.
  • Muir JM, Andrew M, Hirsh J, et al. Histomorphometric analysis of the effects of standard heparin on trabecular bone in vivo. Blood 1996; 15: 88 (4): 1314-1320.
  • Street JT, McGrath M, O’Regan K, et al. Thromboprophylaxis using a low molecular weight heparin delays fracture repair. Clin Orthop2000; 381: 278-289.
  • Matziolis G, Perka C, Disch A, et al. Effects of fondaparinux compared with dalteparin, enoxaparin and unfractionated heparin on human osteoblasts. Calcif Tissue Int. 2003; 73(4): 370-379.
  • Hanschin AE, Trentz OA, Hoerstrup SP, et al. Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra) on human osteoblasts in vitro. Br J Surg. 2005; 92 (2): 177-183.
  • Demirtas A, Azboy I, Bulut M, et al. Investigation of the effects of Enoxaparin, Fondaparinux and Rivaroxaban used in thromboembolism prophylaxis on fracture healing in rats. Eur Rev Med Pharmacol Sci. 2013; Jul (14): 1850-1856.
  • Say F, Iltar S, Alemdaroglu KB, et al. The effect of various types of low molecular weight heparins on fracture healing. Thromb Res 2013; 131(3):114-119.
  • Bonnarens F, Einhorn TA. Production of a standard closed fracture in laboratory animal bone. J Orthop Res 1984; 2(1): 97-101.
  • Folwarczna J, Janiec W, Gawor M, et al. Effects of enoxaparin on histomorphometric parameters of bones in rats. Pol J Pharmacol 2004; 56(4):451-457.
  • Schlitt A, Buerke M, Hauroeder B, et al. Fondaparinux and enoxaparin in comparison to unfractionated heparin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model. Thromb Haemost; 2003; 90:245-251.
  • Chung LT, Holton HL, Silverman PR. The effect of fondaparinux versus enoxaparin in the survival of a congested skin flap in a rabbit model. Ann Plast Surg 2006; 56: 312-15.
  • Olanders K, Börjesson A, Zhao X, et al. Effects of anticoagulant treatment on intestinal ischaemia and reperfusion injury in rats. Acta Anaesthesiol Scand 2005; 49: 517-524.
  • Folwarczna J, Janiec W, Sliwinski L. Effects of heparin and low-molecular weight heparin on bone mechanical properties in rats. Thromb Haemost. 2004; 92 (5): 940-946.
  • Goldberg VM, Powell A, Shaffer JW, et al. Bone grafting: role of histocompatibility in transplantation. J Orthop Res 1985; 3:389-404.
  • Huo MH, Troiano NW, Pelker RR, et al. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res 1991; 9:383-390.
  • Douketis JD, Ginsberg JS, Burrows RF, et al. The effects of long-term heparin therapy during pregnancy on bone density. A prospective matched cohort study. Thromb Haemost.1996; 75(2): 254-257.
  • Von Mandach U, Aebersold F, Huch R, et al. Short-term low-dose heparin plus bedrest impairs bone metabolism in pregnant women. Eur J Obstet Gynecol Reprod Biol 2003; 10; 106(1): 25-30.
  • Simmons HA, Raisz LG. Effects of acid and basic fibroblast growth factor and heparin on rezorption of cultured fetal rat long bones. J Bone Miner Res 1991; 6 (12):1301-1305.
  • Chigot P, De Gennes C, Samama MM. Osteoporosis induced either by unfractionated heparin or low molecular weight heparin. J Mal Vasc 1996; 21(3): 121-125.
  • Barbour DA, Kick SD, Steiner JF, et al. A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 1994; 170(3): 862-869.
  • Kock HJ, Werther S, Uhlenkott H, et al. Influence of unfractionated and low molecular weight heparin on bone healing: an animal model. Unfallchirurg 2002; 105 (9): 791-796.
  • Hak DJ, Stewart RL, Hazelwood SJ. Effect of low molecular weight heparin on fracture healing in a stabilized rat femur fracture model. J Orthop Res 2006; 24(4): 645-652.
  • Muir JM, Hirsh J, Weitz JI, et al. A histomorphometric comparison of the effects of heparin and low-molecular weight heparin on cancellous bone in rats. Blood 1997;1; 89(9): 3236-3242.
  • Rajgopal R, Bear M, Butcher MK, et al. The effect of heparin and low molecular weight heparins on bone. Thromb Res 2008; 122 (3): 293-298.
  • Casele HL, Laifer SA. Prospective evaluation of bone density in pregnant women receiving the low molecular weight heparin enoxaparin sodium. J Matern Fetal Med 2000; 9(2): 122-125.
  • Walenga MJ, Jeske P W, Bara L, et al. Biochemical and pharmacologic rationale for the development of a synthetic heparin pentasaccharide Thromb Res 1997; 86:1:1-36.
There are 31 citations in total.

Details

Subjects Health Care Administration
Journal Section Articles
Authors

Ahmet Şükrü Mercan This is me

Bahattin Kerem Aydın This is me

Mehmet Nuri Konya

Hakan Sofu

Ertan Yılmaz This is me

Vedat Şahin

Publication Date January 17, 2017
Acceptance Date May 13, 2016
Published in Issue Year 2017 Volume: 18 Issue: 1

Cite

APA Mercan, A. Ş., Aydın, B. K., Konya, M. N., Sofu, H., et al. (2017). FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA. Kocatepe Tıp Dergisi, 18(1), 13-18. https://doi.org/10.18229/kocatepetip.341653
AMA Mercan AŞ, Aydın BK, Konya MN, Sofu H, Yılmaz E, Şahin V. FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA. KTD. January 2017;18(1):13-18. doi:10.18229/kocatepetip.341653
Chicago Mercan, Ahmet Şükrü, Bahattin Kerem Aydın, Mehmet Nuri Konya, Hakan Sofu, Ertan Yılmaz, and Vedat Şahin. “FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA”. Kocatepe Tıp Dergisi 18, no. 1 (January 2017): 13-18. https://doi.org/10.18229/kocatepetip.341653.
EndNote Mercan AŞ, Aydın BK, Konya MN, Sofu H, Yılmaz E, Şahin V (January 1, 2017) FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA. Kocatepe Tıp Dergisi 18 1 13–18.
IEEE A. Ş. Mercan, B. K. Aydın, M. N. Konya, H. Sofu, E. Yılmaz, and V. Şahin, “FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA”, KTD, vol. 18, no. 1, pp. 13–18, 2017, doi: 10.18229/kocatepetip.341653.
ISNAD Mercan, Ahmet Şükrü et al. “FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA”. Kocatepe Tıp Dergisi 18/1 (January 2017), 13-18. https://doi.org/10.18229/kocatepetip.341653.
JAMA Mercan AŞ, Aydın BK, Konya MN, Sofu H, Yılmaz E, Şahin V. FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA. KTD. 2017;18:13–18.
MLA Mercan, Ahmet Şükrü et al. “FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA”. Kocatepe Tıp Dergisi, vol. 18, no. 1, 2017, pp. 13-18, doi:10.18229/kocatepetip.341653.
Vancouver Mercan AŞ, Aydın BK, Konya MN, Sofu H, Yılmaz E, Şahin V. FONDAPARİNUKSUN KIRIK İYİLEŞMESİNE GERÇEKTEN POZİTİF ETKİSİ VAR MIDIR? SIÇANLAR ÜZERİNDE YAPILAN DENEYSEL BİR ÇALIŞMA. KTD. 2017;18(1):13-8.

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