Effects of Clopidogrel and Low-Molecular-Weight Heparin on Viability of Random Skin Flaps in Rats

The transfer of tissue via skin flap, which generally remains connected (via pedicle) to the donor area, is widely used in all areas of reconstructive surgery to close cutaneous defects.1–3 However, flap necrosis is still a threat, with serious consequences for the patient. Several publications are nowdevoted to techniques for enhancing flap viability. Flap necrosis may be intrinsic or extrinsic in nature. Although systemic conditions (infection, arteriosclerosis, hypotension, and malnutrition) and local dynamics (compression, tension, and pedicle twists) are among the many extrinsic influences, inadequate circulation is the only known intrinsic factor.4,5 Hence, any means of improving arterial supply and venous flow to prevent ischemic necrosis and promote surgical success are welcomed adjuncts. Several studies have confirmed that the blood supply to tissues is improved by anticoagulants. Heparin, aspirin, and clopidogrel are the most common agents in this regard. Lowmolecular-weight heparins (LMWHs) are a new class of synthetic anticoagulants that are often used to treat ischemic heart disease and myocardial infarction or to serve as thromboembolic prophylaxis in various surgical contexts. LMWHs bind to and potentiate antithrombin III, specifically inhibiting factor Xa in the coagulation cascade. Other anticoagulants, including standard heparin, are less precise, binding various clotting factors.6–8 According to the literature, use of heparin to salvage ischemic pedicles has met with inconsistent results. Intravenous heparin at various doses in a rabbit model significantly improved pedicle circulation and survival, even if administered 6 hours after surgery.7 However, a constant infusion of heparin failed to improve survival of random flaps in a pig model.9 Other related studies include work by Shalom et al,10