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Investigation of the antiangiogenic behaviors of rivaroxaban and low molecular weight heparins

Yavuz, Celal; Caliskan, Ahmet; Karahan, Oguz; Yazici, Suleyman; Guclu, Orkut; Demirtas, Sinan; Mavitas, Binali

Blood Coagulation & Fibrinolysis: June 2014 - Volume 25 - Issue 4 - p 303–308
doi: 10.1097/MBC.0000000000000019

Antithrombotic agents play important roles in the prophylactic and therapeutic management of many cardiovascular disorders. Therefore, many researchers have focused on developing new strategies for anticoagulation. New oral anticoagulants and factor Xa inhibitors are products of such research. Although they are identified as advantageous, there are limited data available about their multisystemic interactions. Thus, the antiangiogenic behaviors of oral factor Xa inhibitors and low molecular weight heparins (LMWHs) were investigated in this study. The chick chorioallantoic membrane (CAM) model was designed to investigate the antiangiogenic potential of new oral factor Xa inhibitors (rivaroxaban) and LMWHs (enoxaparin sodium and tinzaparin sodium). Four different molar concentrations (10−4, 10−5, 10−6, and 10−7 μmol/l) were studied for each drug. Each concentration was studied on 20 fertilized eggs. Vessel structures were evaluated under a stereoscopic microscope, and vessel formation was scaled according to previous literature. Both enoxaparin and tinzaparin sodium have increased antiangiogenic efficacy on CAM in a dose-dependent manner. However, this increased efficacy did not reach significant levels (average score < 0.5). On the contrary, while rivaroxaban showed dose-dependent antiangiogenic properties similar to enoxaparin and tinzaparin, a significant average antiangiogenic score (0.7) was detected at 10−4 μmol/l concentrations. New oral anticoagulants seem to be more favorable. However, their safety for the cardiovascular system needs to be clarified through microsystem studies on, for example, angiogenesis.

Department of Cardiovascular Surgery, Medical School of Dicle University, Diyarbakir, Merkez, Turkey

Correspondence Oguz Karahan, MD, Medical School of Dicle University, Department of Cardiovascular Surgery, 21280, Diyarbakir, Turkey Tel: +0090 412 248 80 01 1108; fax: +0090 412 48 84 40; e-mail:

Received 13 July, 2013

Revised 26 September, 2013

Accepted 28 September, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins