Ankaferd® Kanama Durdurucunun Beyin Parankiminde Hemostatik Etkisi: Deneysel Çalışma
Year 2022,
Volume: 6 Issue: 1, 31 - 37, 28.04.2022
Emrah Egemen
,
Ümit Akın Dere
,
Başak Ünver Koluman
,
Yücel Doğruel
Ahmet Koluman
,
Batuhan Bakırarar
,
Nazlı Çil
,
Esin Avcı
,
Emine Tural
,
Fatih Yakar
Abstract
Amaç: Hemostaz, ameliyatın başarısı için hayati bir aşamadır. Düşük maliyetli ve güvenilir bir ajan olan Ankaferd kanama durdurucu (AKD)
pek çok ameliyatta kullanılmasına rağmen henüz kafa içi bölgede kullanıma sunulmamıştır. Bu çalışma, AKD’nun sitotoksik etkilerini ve
memeli beyin parankimasında güvenlik profilini ortaya çıkarmayı amaçlamaktadır.
Gereç ve Yöntemler: 30 Wistar Albino sıçan, 10 sıçandan oluşan üç gruba ayrıldı. Beyin parankim hasarına bağlı kanamalarda grup 1’de
salin, grup 2’de %50 seyreltilmiş AKD ve grup 3’te %100 AKD ile hemostaz sağlandı. Ameliyat öncesi ve sakrifiye edilirken alınan kan
örneklerinde ürotensin, Antitrombin III (AT3) ve fibrinojen çalışıldı. Ayrıca sıçanların sakrifiye edilmesinden sonra histolojik inceleme yapıldı
ve yaralanma skorları değerlendirildi.
Bulgular: Ameliyat öncesi alınan kan örneklerinde grup 2 ve 3’teki fibrinojen düzeyleri grup 1’e göre anlamlı derecede yüksekti. Her üç
grupta da ameliyat öncesi döneme kıyasla sakrifikasyon sırasında ürotensin’de önemli bir artış vardı. (p=0,005) Grup 2’de hafif yaralanma,
grup 3’te hafif yaralanma ve grup 1’de ciddi yaralanma istatistiksel olarak anlamlı derecede yüksekti. (p=0.005) Bu sonuçlar %50 seyreltilmiş
AKD kullanımının güvenli olduğunu göstermektedir.
Sonuç: Memeli beyin parankiminde ilk kez kullanılan AKD, sıçanlarda güvenli olarak değerlendirildi. Hemostatik matriks ajanlarla
karşılaştırıldığında, güvenlik ve etkinliğe ek olarak, düşük maliyeti gelecekte klinik kullanımını artırabilir.
Supporting Institution
Pamukkale Üniverstesi Bilimsel Araştırma Projesi Koordinatörlüğü Hızlı Destek Projesi
Project Number
2020HZDP016
References
- 1. Garber A, Jang S. Novel therapeutic strategies in the
management of non-variceal upper gastrointestinal bleeding.
Clin Endos 2016;49:421-424.
- 2. Göker H, Haznedaroğlu IC, Erçetin S, Kirazlı S, Akman
U, Öztürk Y, Fırat HC. Haemostatic actions of the folkloric
medicinal plant extract Ankaferd Blood Stopper. J Int Med Res
2008;36:163-170.
- 3. Emrah K, Ali AH, Utku O, Murat K, Kenan S, Deniz B. Efficacy
of tranexamic acid on blood loss in thoracolumbar spinal fusion
surgery. J Coll Physicians Surg Pak 2021;31(12):1449-1454.
- 4. Keskin E, Aydın HA, Kalaycı M, Işık E, Özgen U, Şimşek
K, Baklacı D, Gökçe M. The histopathological effects of
reabsorbable polyethylene glycol hydrogel (Coseal) on epidural
fibrosis in an experimental postlaminectomy model in rats. Turk
J Med Sci 2021;51(3):1512-1520.
- 5. Kamamoto D, Kanazawa T, Ishihara E, Yanagisawa K, Tomita
H, Ueda R, Jinzaki M, Yoshida K, Toda M. Efficacy of a topical
gelatin-thrombin hemostatic matrix, FLOSEAL®, in intracranial
tumor resection. Surg Neurol Int 2020;11:16.
- 6. Dinçol ME, Özbaş H, Yılmaz B, Ersev H, Gökyay S, Olgaç
V. Effect of the plant-based hemostatic agent Ankaferd
Blood Stopper VR on the biocompatibility of mineral trioxide
aggregate. BMC Oral Health 2016;16:111.
- 7. Uğur A, Saraç N, Çankal DA, Özle M. The antioxidant and
antimutagenic activities of Ankaferd blood stopper, a natural
hemostatic agent used in dentistry. Turk J Med Sci 2016;46:657-
663.
- 8. Uzun O, Erkan L, Haznedaroğlu IC. Effective management
of hemoptysis via endobronchial application of Ankaferd
hemostat. Arch Bronconeumol 2014;50:407-409.
- 9. Atalay H, Atalay A, Doğan OF. Local use of ankaferd blood
clotter in emergent beating heart coronary artery bypass
grafting. Open Cardiovasc Med J 2015;9:18-25.
- 10. Ergenoğlu MU, Yerebakan H, Küçükaksu DS. A new practical
alternative for the control of sternal bleeding during cardiac
surgery: Ankaferd Blood Stopper. Heart Surgery Forum
2010;13(6):379-380.
- 11. Kurt M, Önal I, Akdoğan M, Kekilli M, Arhan M, Sayılır A, Öztaş
E, Haznedaroğlu I. Ankaferd Blood Stopper for controlling
gastrointestinal bleeding due to distinct benign lesions
refractory to conventional antihemorrhagic measures. Can J
Gastroenterol 2010;24:380-384.
- 12. Heller SJ, Tokar JL, Nguyen MT, Haluszka O, Weinberg DS.
Management of bleeding GI tumors. Gastrointest Endosc
2010;72:817-824.
- 13. Istanbulluoğlu MO, Kaynar M, Ciçek T, Koşan M, Öztürk B,
Özkardeş H. A new hemostatic agent (Ankaferd Blood Stopper
(VR) in tubeless percutaneous nephrolithotomy: A prospective
randomised study. J Endourol 2013;27:1126-1130.
- 14. Yalçınkaya FR, Kerem M, Güven EO, Gökçe A, Davarcı M.
The effect of ankaferd to stop bleeding in experimental partial
nephrectomy. Bratisl Lek Listy 2011;112:676-678.
- 15. Huri E, Akgül T, Ayyıldız A, Germiyanoğlu C. Hemostasis in
retropubic radical prostatectomy with Ankaferd Blood Stopper:
a case report. Kaohsiung J Med Sci 2009;25:445-447.
- 16. Teker AM, Korkut AY, Gedikli O, Kahya V. Prospective,
controlled clinical trial of Ankaferd Blood Stopper in children
undergoing tonsillectomy. Int J Pediatr Otorhinolaryngol
2009;73:1742-1745.
- 17. Meriç Teker A, Korkut AY, Kahya V, Gedikli O. Prospective,
randomised, controlled clinical trial of Ankaferd Blood
Stopper in patients with acute anterior epistaxis. Eur Arch
Otorhinolaryngol 2010;267:1377-1381.
- 18. Vezeau PJ. Topical hemostatic agents: What the oral and
maxillofacial surgeon needs to know. Oral Maxillofac Surg Clin
North Am 2016;28:523-532.
- 19. İşler SC, Demircan S, Çakarer S, Çebi Z, Keskin C, Soluk
M, Yüzbaşıoğlu E. Effects of folk medicinal plant extract
ankaferd blood stopper on early bone healing. J Appl Oral Sci
2010;18:409-414.
- 20. Yang Z, Aderemi OA, Zhao Q, Edsall PR, Simovic MO, Lund
BJ, Espinoza MD, Woodson AM, Li Y, Cancio LC. Early
Complement and Fibrinolytic Activation in a Rat Model of Blast-
Induced Multi-Organ Damage. Mil Med 2019;184: 282-290.
- 21. Erdoğan H, Kelten B, Tunçdemir M, Erturkuner SP, Uzun H,
Karaoğlan A. Hemostasis vs epidural fibrosis? A comparative
study on an experimental rat model of laminectomy. Neurol
Neurochir Pol 2016;50(5):323-30.
- 22. Yılmaz M, Gülabi D, Güçlü B, Kaya I, Başak K, Baş A. The
effect of Ankaferd Blood Stopper? on epidural fibrosis after
laminectomy in rats: An experimental study. Turk Neurosurg
2017;27(1):114-118.
- 23. Kuruoğlu E, Önger ME, Marangoz AH, Kocacan SE, Çokluk
C, Kaplan S. Postlaminectomy bone and scar formations
in presence of Ankaferd Blood Stopper and Bitter Melon
(Momordica Charantia): An experimental study. Turk Neurosurg
2017;27(3):441-446.
- 24. Okumuş M, Yüksel KZ, Özbağ D, Çıralık H, Yılmaz Z,
Gümüşalan Y, Bakan V, Kalender AM. Medicinal plant extract
(Ankaferd Blood Stopper) application in deep tissue injuries in
rats: histopathological investigation of the effect on regional and
systemic tissues. Ulus Travma Acil Cerrahi Derg 2013;19(1):1-
7.
- 25. Beyazıt Y, Kurt M, Kekilli M, Göker H, Haznedaroğlu IC.
Evaluation of hemostatic effects of Ankaferd as an alternative
medicine. Alternative Medicine Review 2010;15(4):329-336.
- 26. Okay M, Öztürk Y, Haznedaroğlu IC. The Antithrombin
Effect of Ankaferd Hemostat (ABS) Is Related to the High
Iron Content of the Medicine. Clin Appl Thromb Hemost
2019;25:1076029618824416.
- 27. Özel Demiralp D, Haznedaroğlu İC, Akar N. Functional
proteomic analysis of Ankaferd® Blood Stopper. Turk J
Haematol 2010;27(2):70-77.
- 28. Luh HT, Huang AP, Yang SH, Chen CM, Cho DY, Chen CC,
Kuo LT, Li CH, Wang KC, Tseng WL, Hsing MT, Yang BS, Lai
DM, Tsai JC. Local hemostatic matrix for endoscope-assisted
removal of intracerebral hemorrhage is safe and effective. J
Formos Med Assoc 2018;117(1):63-70.
- 29. Ereth MH, Schaff M, Ericson EF, Wetjen NM, Nuttall GA, Oliver
WC Jr. Comparative safety and efficacy of topical hemostatic
agents in a rat neurosurgical model. Neurosurgery 2008;63(4
Suppl 2):369-372; discussion 372.
- 30. Fiss I, Danne M, Stendel R. Use of gelatin-thrombin matrix
hemostatic sealant in cranial neurosurgery. Neurol Med Chir
(Tokyo) 2007;47(10):462-467.
- 31. Gazzeri R, Galarza M, Conti C, De Bonis C. Incidence of
thromboembolic events after use of gelatin-thrombin-based
hemostatic matrix during intracranial tumor surgery. Neurosurg
Rev 2018;41(1):303-310.
- 32. Ho MY, Yang SH, Chen CM, Huang AP. Hemostatic thrombingelatin
matrix-related intracranial cyst formation. World
Neurosurg 2019;126:475-480.
- 33. Zeiler FA, Kaufmann AM, Silvaggio J. Thrombin hemostatic
matrix leading to acute cerebral edema and sterile fluid
collection formation post-tumor resection: Two cases. Acta
Neurochir (Wien) 2015;157(3):513-516.
The Haemostatic Effects of Ankaferd Blood Stopper® on Mammalian Brain Parenchyma: An Experimental Study
Year 2022,
Volume: 6 Issue: 1, 31 - 37, 28.04.2022
Emrah Egemen
,
Ümit Akın Dere
,
Başak Ünver Koluman
,
Yücel Doğruel
Ahmet Koluman
,
Batuhan Bakırarar
,
Nazlı Çil
,
Esin Avcı
,
Emine Tural
,
Fatih Yakar
Abstract
Aim: Haemostasis is a vital stage for the success of the surgery. Although Ankaferd Blood Stopper
(ABS), a low-cost and reliable agent, is used in many surgeries, it is not yet available for use in the
intracranial area. This study aims to reveal ABS’s cytotoxic effects and safety profile in mammalian
brain parenchyma.
Material and Methods: 30 Wistar Albino rats were divided into three groups consisting of 10 rats.
Haemostasis was achieved with saline in group 1, 50% diluted ABS in group 2, and 100% ABS in
group 3 in bleeding caused by damage to the brain parenchyma. Urotensin, Antithrombin III (AT3) and
fibrinogen were studied in blood samples taken before surgery and during sacrification. In addition, the
histologic examination was performed after the sacrification of rats and injury scores were assessed.
Results: Fibrinogen levels in groups 2 and 3 were significantly higher than group 1 in blood samples
taken before surgery. There was a significant increase in urotensin during sacrification compared to
the pre-surgical period in all three groups. (p=0.005) Slight injury in group 2, mild injury in group 3, and
severe injury in group 1 were statistically significantly higher. (p=0.005) These results indicate that the
use of 50% diluted ABS is safe.
Conclusion: ABS, used for the first time in the mammalian brain parenchyma, was evaluated as safe
in rats. Compared to haemostatic matrix agents, in addition to safety and efficacy, its low cost might
increase its clinical use in the future.
Project Number
2020HZDP016
References
- 1. Garber A, Jang S. Novel therapeutic strategies in the
management of non-variceal upper gastrointestinal bleeding.
Clin Endos 2016;49:421-424.
- 2. Göker H, Haznedaroğlu IC, Erçetin S, Kirazlı S, Akman
U, Öztürk Y, Fırat HC. Haemostatic actions of the folkloric
medicinal plant extract Ankaferd Blood Stopper. J Int Med Res
2008;36:163-170.
- 3. Emrah K, Ali AH, Utku O, Murat K, Kenan S, Deniz B. Efficacy
of tranexamic acid on blood loss in thoracolumbar spinal fusion
surgery. J Coll Physicians Surg Pak 2021;31(12):1449-1454.
- 4. Keskin E, Aydın HA, Kalaycı M, Işık E, Özgen U, Şimşek
K, Baklacı D, Gökçe M. The histopathological effects of
reabsorbable polyethylene glycol hydrogel (Coseal) on epidural
fibrosis in an experimental postlaminectomy model in rats. Turk
J Med Sci 2021;51(3):1512-1520.
- 5. Kamamoto D, Kanazawa T, Ishihara E, Yanagisawa K, Tomita
H, Ueda R, Jinzaki M, Yoshida K, Toda M. Efficacy of a topical
gelatin-thrombin hemostatic matrix, FLOSEAL®, in intracranial
tumor resection. Surg Neurol Int 2020;11:16.
- 6. Dinçol ME, Özbaş H, Yılmaz B, Ersev H, Gökyay S, Olgaç
V. Effect of the plant-based hemostatic agent Ankaferd
Blood Stopper VR on the biocompatibility of mineral trioxide
aggregate. BMC Oral Health 2016;16:111.
- 7. Uğur A, Saraç N, Çankal DA, Özle M. The antioxidant and
antimutagenic activities of Ankaferd blood stopper, a natural
hemostatic agent used in dentistry. Turk J Med Sci 2016;46:657-
663.
- 8. Uzun O, Erkan L, Haznedaroğlu IC. Effective management
of hemoptysis via endobronchial application of Ankaferd
hemostat. Arch Bronconeumol 2014;50:407-409.
- 9. Atalay H, Atalay A, Doğan OF. Local use of ankaferd blood
clotter in emergent beating heart coronary artery bypass
grafting. Open Cardiovasc Med J 2015;9:18-25.
- 10. Ergenoğlu MU, Yerebakan H, Küçükaksu DS. A new practical
alternative for the control of sternal bleeding during cardiac
surgery: Ankaferd Blood Stopper. Heart Surgery Forum
2010;13(6):379-380.
- 11. Kurt M, Önal I, Akdoğan M, Kekilli M, Arhan M, Sayılır A, Öztaş
E, Haznedaroğlu I. Ankaferd Blood Stopper for controlling
gastrointestinal bleeding due to distinct benign lesions
refractory to conventional antihemorrhagic measures. Can J
Gastroenterol 2010;24:380-384.
- 12. Heller SJ, Tokar JL, Nguyen MT, Haluszka O, Weinberg DS.
Management of bleeding GI tumors. Gastrointest Endosc
2010;72:817-824.
- 13. Istanbulluoğlu MO, Kaynar M, Ciçek T, Koşan M, Öztürk B,
Özkardeş H. A new hemostatic agent (Ankaferd Blood Stopper
(VR) in tubeless percutaneous nephrolithotomy: A prospective
randomised study. J Endourol 2013;27:1126-1130.
- 14. Yalçınkaya FR, Kerem M, Güven EO, Gökçe A, Davarcı M.
The effect of ankaferd to stop bleeding in experimental partial
nephrectomy. Bratisl Lek Listy 2011;112:676-678.
- 15. Huri E, Akgül T, Ayyıldız A, Germiyanoğlu C. Hemostasis in
retropubic radical prostatectomy with Ankaferd Blood Stopper:
a case report. Kaohsiung J Med Sci 2009;25:445-447.
- 16. Teker AM, Korkut AY, Gedikli O, Kahya V. Prospective,
controlled clinical trial of Ankaferd Blood Stopper in children
undergoing tonsillectomy. Int J Pediatr Otorhinolaryngol
2009;73:1742-1745.
- 17. Meriç Teker A, Korkut AY, Kahya V, Gedikli O. Prospective,
randomised, controlled clinical trial of Ankaferd Blood
Stopper in patients with acute anterior epistaxis. Eur Arch
Otorhinolaryngol 2010;267:1377-1381.
- 18. Vezeau PJ. Topical hemostatic agents: What the oral and
maxillofacial surgeon needs to know. Oral Maxillofac Surg Clin
North Am 2016;28:523-532.
- 19. İşler SC, Demircan S, Çakarer S, Çebi Z, Keskin C, Soluk
M, Yüzbaşıoğlu E. Effects of folk medicinal plant extract
ankaferd blood stopper on early bone healing. J Appl Oral Sci
2010;18:409-414.
- 20. Yang Z, Aderemi OA, Zhao Q, Edsall PR, Simovic MO, Lund
BJ, Espinoza MD, Woodson AM, Li Y, Cancio LC. Early
Complement and Fibrinolytic Activation in a Rat Model of Blast-
Induced Multi-Organ Damage. Mil Med 2019;184: 282-290.
- 21. Erdoğan H, Kelten B, Tunçdemir M, Erturkuner SP, Uzun H,
Karaoğlan A. Hemostasis vs epidural fibrosis? A comparative
study on an experimental rat model of laminectomy. Neurol
Neurochir Pol 2016;50(5):323-30.
- 22. Yılmaz M, Gülabi D, Güçlü B, Kaya I, Başak K, Baş A. The
effect of Ankaferd Blood Stopper? on epidural fibrosis after
laminectomy in rats: An experimental study. Turk Neurosurg
2017;27(1):114-118.
- 23. Kuruoğlu E, Önger ME, Marangoz AH, Kocacan SE, Çokluk
C, Kaplan S. Postlaminectomy bone and scar formations
in presence of Ankaferd Blood Stopper and Bitter Melon
(Momordica Charantia): An experimental study. Turk Neurosurg
2017;27(3):441-446.
- 24. Okumuş M, Yüksel KZ, Özbağ D, Çıralık H, Yılmaz Z,
Gümüşalan Y, Bakan V, Kalender AM. Medicinal plant extract
(Ankaferd Blood Stopper) application in deep tissue injuries in
rats: histopathological investigation of the effect on regional and
systemic tissues. Ulus Travma Acil Cerrahi Derg 2013;19(1):1-
7.
- 25. Beyazıt Y, Kurt M, Kekilli M, Göker H, Haznedaroğlu IC.
Evaluation of hemostatic effects of Ankaferd as an alternative
medicine. Alternative Medicine Review 2010;15(4):329-336.
- 26. Okay M, Öztürk Y, Haznedaroğlu IC. The Antithrombin
Effect of Ankaferd Hemostat (ABS) Is Related to the High
Iron Content of the Medicine. Clin Appl Thromb Hemost
2019;25:1076029618824416.
- 27. Özel Demiralp D, Haznedaroğlu İC, Akar N. Functional
proteomic analysis of Ankaferd® Blood Stopper. Turk J
Haematol 2010;27(2):70-77.
- 28. Luh HT, Huang AP, Yang SH, Chen CM, Cho DY, Chen CC,
Kuo LT, Li CH, Wang KC, Tseng WL, Hsing MT, Yang BS, Lai
DM, Tsai JC. Local hemostatic matrix for endoscope-assisted
removal of intracerebral hemorrhage is safe and effective. J
Formos Med Assoc 2018;117(1):63-70.
- 29. Ereth MH, Schaff M, Ericson EF, Wetjen NM, Nuttall GA, Oliver
WC Jr. Comparative safety and efficacy of topical hemostatic
agents in a rat neurosurgical model. Neurosurgery 2008;63(4
Suppl 2):369-372; discussion 372.
- 30. Fiss I, Danne M, Stendel R. Use of gelatin-thrombin matrix
hemostatic sealant in cranial neurosurgery. Neurol Med Chir
(Tokyo) 2007;47(10):462-467.
- 31. Gazzeri R, Galarza M, Conti C, De Bonis C. Incidence of
thromboembolic events after use of gelatin-thrombin-based
hemostatic matrix during intracranial tumor surgery. Neurosurg
Rev 2018;41(1):303-310.
- 32. Ho MY, Yang SH, Chen CM, Huang AP. Hemostatic thrombingelatin
matrix-related intracranial cyst formation. World
Neurosurg 2019;126:475-480.
- 33. Zeiler FA, Kaufmann AM, Silvaggio J. Thrombin hemostatic
matrix leading to acute cerebral edema and sterile fluid
collection formation post-tumor resection: Two cases. Acta
Neurochir (Wien) 2015;157(3):513-516.