Journals / Adıyaman Üniversitesi Sağlık Bilimleri Dergisi / 2016 / Cilt: 2 Sayı: 3

COMPARISON OF RIVAROXABAN AND DIFFERENT ANTICOAGULANTS ON BONE UNION IN A RAT MODEL

RİVAROKSABAN VE FARKLI ANTİKOAGÜLANLARIN KIRIK KAYNAMASI ÜZERİNE ETKİLERİNİN BİR RAT MODELİNDE KARŞILAŞTIRILMASI

Pages
310–322
Publication Date
2016-12-15
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Rivaroxaban may represent a viable alternative to other anti-thrombotic agents owing to its oral administration, no requirement for therapeutic monitoring, and better patient tolerability.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Thromboembolic complications due to immobilization in the treatment of lower extremity fractures are the leading problems in treatment.
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Key Findings & Data:Methods : In our study, 60 rats of the same number of Sprague-Dawley rats were divided into 4 groups.
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Conclusion & Impact:Rivaroxaban may represent a viable alternative to other anti-thrombotic agents owing to its oral administration, no requirement for therapeutic monitoring, and better patient tolerability.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Kemik iyileşmesi · Rivaroksaban · Enoksaparin

Abstract

Objective: Thromboembolic complications due to immobilization in the treatment of lower extremity fractures are the leading problems in treatment. This study was undertaken to examine the effect of a number of different anti-embolic agents, i.e. enoxaparin, fondaparinux, and rivaroxaban, on bone healing in an experimental rat model. Methods : In our study, 60 rats of the same number of Sprague-Dawley rats were divided into 4 groups. Group 1 received 1 cc saline solution subcutaneously, group 2 fondaparinux 1 mg / kg subcutaneously, group 3 rivaroxaban 3 mg / kg oral gavage and group 4 enoxaparin 100 anti Xa IU / kg subcutaneously once daily for 2 weeks.All groups were sacrificed at 4 weeks and biochemical, radiographic and histopathologic evaluations of fractured calluses in acute and subacute periods were evaluated. Results: A high inter-rater agreement was found for clinical assessments for the presence of pathological macroscopic mobility in the fracture line. Complete fusion was significantly lower among rats in Group 4 as compared to Groups, 1, 2, and 3. Group 2 had complete fusion. Radiological assessment scores in Group 1 were significantly lower as compared to those in Groups 2 and 3 . Also, Group 4 had significantly lower radiological scores than Group 2. Histopathological assessments showed no statistically significant differences between the study groups, although scores in Groups 2 and 3 were numerically higher. Conclusion: In this study, enoxaparin, rivaroxaban, and fondaparinux, demonstrated no adverse impacts on bone healing. Rivaroxaban may represent a viable alternative to other anti-thrombotic agents owing to its oral administration, no requirement for therapeutic monitoring, and better patient tolerability.

Özet

Amaç: Alt ekstremite kırıklarının tedavisinde immobilizasyona bağlı tromboembolik olayları önlemek için antikoagulan profiklasisi kullanmak gerekmektedir. Biz bu çalışmada; deneysel bir sıçan kırık modelinde, faktör Xa’nın seçici olarak inhibisyon yapan rivaroksabanın ile kırık iyileşme süreci üzerine etkilerini,enoksaparin ve fondaparinuks ile kıyaslamayı amaçladık. Yöntem: Çalışmamızda 60 adet Sprague -Dawley cinsi eşit sayıda rat 4 guruba ayrıldı ve Grup 1’e (kontrol grubu) 1 cc salin solüsyonu subkutan, g rup 2’ye fondaparinuks 1 mg/kg dozunda subkutan, grup 3’e rivaroksaban 3 mg/kg dozunda oral gavaj yoluyla ve grup 4’e enoxaparin 100 anti Xa IU/kg dozunda subkutan olarak, 2 hafta boyunca günde tek doz uygulandı . Tüm gruplar 4. haftada sakrifiye edilerek kırık kallusları akut ve subakut dönemlerde biyomekanik, radyografik ve histopatolojik olarak değerlendirildi. Bulgular: Makroskopik patolojik hareket varlığı incelendiğinde, gözlemciler arasındaki uyum istatistiksel olarak anlamlı bulundu . Grup 4’ün tam füzyon istatistiksel olarak anlamlı derecede düşük bulundu ve grup 2’deki tüm sıçanlarda tam füzyon gözlendi. Radyolojik incelemede; Grup 1’in radyolojik değerlendirme skorları grup 2 ve grup 3’den istatistiksel olarak anlamlı derecede düşük bulundu, grup 4’ün radyolojik değerlendirme skorları grup 2’den istatistiksel olarak anlamlı derecede düşük bulundu. Histopatolojik sonuçlar değerlendirildiğinde, grup 2 ve grup 3’te skorlar daha yüksek olsa da, tüm grupların histopatolojik skorları arasında istatistiksel olarak anlamlı farklılık gözlenmedi. Sonuç: Çalışmamızda enoksaparin, rivaroksaban ve fondaparinuksun kırık iyileşmesi üzerine herhangi bir olumsuz etkisi görülmemiş olup aksine fondaparinuks ve rivaroksabanın bir miktar olumlu etkilesi olabileceği düşünülmüştür. Rivaroksaban; oral yolla kullanılabilmesi ve monitörizasyon gerektirmemesi nedeniyle, hastalar tarafından daha kolay tolere edilebileceği ve diğer antikoagulan ajanlara iyi bir alternatif olacağı kanaatindeyiz.

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Cite This Article

Gültekin, M. Z., Alagöz, E., Yüksel, S., Özsoy, Ş., Avcı, A., Güleç, M. A., Uğur, O. (2016). COMPARISON OF RIVAROXABAN AND DIFFERENT ANTICOAGULANTS ON BONE UNION IN A RAT MODEL. Adıyaman Üniversitesi Sağlık Bilimleri Dergisi, Cilt: 2 Sayı: 3, 310–322. https://doi.org/10.30569/adiyamansaglik.438883

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References (30)

  1. Shackford SR, Davis JW, Hollingsworth-Fridlund P, Brewer NS, Hoyt DB, Mackersie RC. Venous thromboembolism in major trauma. Am J Surg 1990;159:365–9.
  2. 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: 417–23.
  3. Erli H, Melchert M, Rüger M. The effect of low-dosed unfractioned and low-molecular-weight heparins on bone healing in vivo. Internet J Orthop Surg 2006;3(Number 2)
  4. Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin HL, Raschke R, et al. Heparin and low-molecular-weightheparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 2001;119(S1):64–94.
  5. Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia. Prog Hemost Thromb 1991;10:1–34.
  6. Monreal M, Olive A, Lafoz E, Del Rio L. Heparins, coumarin, and bone density. Lancet 1991;338(8768):706.
  7. Lindner T, Cockbain AJ, El Masry MA, et al. The effect of anticoagulant pharmacotherapy on fracture healing. Expert Opin Pharmacother 2008;9(7):1169–87.
  8. Palmer AJ, Koppenhagen K, Kirchhof B, Weber U, Bergemann R. 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.
  9. Turpie AG. Fondaparinux: a factor Xa inhibitor for antithrombotic therapy. Expert Opin Pharmacother 2004;5(6):1373–84.
  10. Yen SH, Lin PC, Kuo FC, Wang JW. Thromboprophylaxis after minimally invasive total knee arthroplasty: A comparison of rivaroxaban and enoxaparin. Biomed J. 2014;37(4):199-204.
  11. Kearon C. Duration of venous thromboembolism prophylaxis after surgery. Chest 2003;124(Suppl.):386–92.
  12. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: american college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(6_suppl):381–453.
  13. Aurégan JC, Coyle RM, Danoff JR, Burky RE, Akelina Y, Rosenwasser MP. The rat model of femur fracture for bone and mineral research: An improved description of expected comminution, quantity of soft callus and incidence of complications. Bone Joint Res. 2013;2(8):149-54.
  14. Akman S, Gögüs A, Şener N, Bilgiç B, Aksoy B, Seçkin F. Effect of diclofenac sodium on union of tibial fractures in rats. Adv Ther 2002;19(3):119–25.
  15. Goldberg VM, Powell A, Shaffer JW, Zika J, Bos GD, Heiple KG. Bone grafting: role of histocompatibility in transplantation. J Orthop Res. 1985;3(4):389-404.
  16. Huo MH, Troiano NW. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic and histomorphometric parameters in rats. J Orthop Res. 1991;9(3):383-90.
  17. Demirtaş A, Azboy I, Bulut M, Uçar BY, Alabalik U, Necmioğlu NS. Investigation of the effects of Enoxaparin, Fondaparinux, and Rivaroxaban used in thromboembolism prophylaxis on fracture healing in rats: Eur Rev Med Pharmacol Sci. 2013;17:1850-6.
  18. Matzsch T, Bergqvist D, Hedner U, Nilsson B, Ostergaard P. Heparininduced osteoporosis in rats. Thromb Haemost. 1986;56(3):293-4.
  19. Say F, İltar S, Alemdaroğlu KB, Özel İ, Aydoğan NH, Gönültaş M. The effect of various types low molecular weight heparins on fracture healing; Thromb Res. 2013;131(3):114-9
  20. Street JT, McGrath M, O'Regan K, Wakai A, McGuinness A, Redmond HP. Thromboprophylaxis using a low molecular weight heparin delays fracture repair. Clin Orthop Relat Res 2000;381:278–89
  21. Shaughnessy SG, Young E, Deschamps P, Hirsh J. The effectss of low molecular weight and Standard heparin on calcium loss from fetal rat calvariae. Blood 1995;86:1368-73.
  22. Muir JM, Andrew M, Hirsh J, Weitz JI, Young E, Deschamps P, Shaughnessy SG. Histomorphometric analysis of the effects of standard heparin on trabecular bone in vivo. Blood 1996;88:1314-20.
  23. Petilla V, Leinonen P, Markkola A, Hiilesmaa V, Kaaja R. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost 2002;87:182-6.
  24. Street J, Wang JH, Redmond HP. Vascular endothelial growth factor in human fracture hematoma does not confer angiogenic capability in vitro. Surg Forum 1999;50:527–9.
  25. Walenga MJ, Jeske PW, Bara L, Samama MM, Fareed J. Biochemical and pharmacologic rationale for the development of a synthetic heparin pentasaccharide. Thromb Res 1997;86:1-36.
  26. Hawkins D, Evans J. Minimising the risk of heparininduced osteoporosis during pregnancy. Expert Opin Drug Saf 2005;4:583-90.
  27. Fusaro M, Crepaldi G, Maggis, D’angelo A, Calo L, Miozzo D, Fornasieri A, Gallieni M. Bleeding, vertebral fractures and vascular calcifications in patients treated with warfarin: hope for lower risks with alternative therapies. Curr Vasc Pharmacol 2011;9:763-9.
  28. Borris LC. Rivaroxaban and dabigatran etexilate: two new oral anticoagulants for extended postoperative prevention of venous thromboembolism after elective total hip arthroplasty. Arch Orthop Trauma Surg 2010;130:583-9.
  29. Turun S, Banghua L, Yuan Y, Zhenhui L, Ying N, Jin C. A systematic review of Rivaroxaban versus Enoxaparin in the prevention of venous thromboembolism after hip or knee replacement. Thromb Res 2011;127:525-34.
  30. Fusaro M, Crepaldi G, Maggis, D’angelo A, Calo L, Miozzo D, Fornasieri A, Gallieni M. Bleeding, vertebral fractures and vascular calcifications in patients treated with warfarin: hope for lower risks with alternative therapies. Curr Vasc Pharmacol 2011;9:763-9.