LOW-MOLECULAR-WEIGHT HEPARINS AND HEPARINOIDS AND THEIR USE IN ACUTE OR PROGRESSING ISCHEMIC STROKE

Thrombotic or thromboembolic occlusion of a cerebral artery is the most common pathophysiologic mechanism of acute ischemic stroke. An antithrombotic agent would therefore appear to be an ideal medication for treatment of this condition. Heparin is an effective anticoagulant, but it has poor bioavailability and effects on thrombin and platelets that predispose it to life-threatening complications such as hemorrhage and thrombocytopenia. Low-molecular-weight (LMW) heparins have better bioavailability, a higher anti-Xa:anti-IIa ratio, and less effect on platelets than heparin; yet their heterogeneity has hampered their proper investigation in clinical trials and it has not yet been proven that they exhibit less tendency toward hemorrhage and thrombocytopenia than conventional heparin. The LMW heparinoid, Org 10172, is superior to standard heparin in terms of its bioavailability, anti-Xa:anti-IIa ratio, and lack of effect on platelets. It is less likely than heparin and many LMW heparins to induce thrombocytopenia. Like the various heparins, Org 10172 exhibits dose-dependent hemorrhagic tendencies, yet preliminary studies have found doses that are safe for use in patients with acute ischemic stroke. These studies also suggest that Org 10172 may improve outcome and lessen mortality in this population. A prospective, randomized, double-blind, controlled trial is needed to establish the potential efficacy of Org 10172 in patients who suffer acute or progressing ischemic stroke.