JUSTICE KOFI BOAKYE-APPIAH 2751108

TOPICAL HEPARIN IN BURNS MANAGEMENT

Heparin belongs to a family of polyanionic polysaccharides called glycosaminoglycans (GAGs). The structure of GAGs is described in terms of their prevalent repeating disaccharide sequences, which consist of alternating uronic acid and amino sugar residues. Heparin is a highly sulfated polysaccharide composed of hexuronic acid and D-glucosamine residues joined by glycosidic linkages.1 Heparin is a polydisperse compound with a molecular weight ranging from 3,000 to 30,000 Da (Daltons) (mean weight, approximately 15,000 Da). Commercial heparin, or unfractionated heparin (UFH), is isolated from mammalian tissues rich in mast cells. Heparin acts as an anticoagulant by activating antithrombin and accelerating the rate at which antithrombin inactivates clotting enzymes, particularly thrombin (factor IIa) and factor Xa. UFH also enhances the inhibition of factor IXa, factor XIa, and factor VIIa bound to tissue factor by antithrombin. Heparin binds to antithrombin through a high affinity pentasaccharide, which is present on about one-third of heparin molecules. Binding of heparin to antithrombin via its unique pentasaccharide sequence causes a conformational change in the reactive center loop of antithrombin that accelerates its interaction with factor Xa, but not with thrombin. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and antithrombin. This bridging effect requires a heparin chain that contains at least 18 saccharides. By inactivating thrombin, heparin not only prevents fibrin formation, but also inhibits thrombin-induced activation of platelets and factors V and VIII.2 Besides binding to antithrombin, heparin also binds to a wide range of other proteins via electrostatic interactions. These proteins include heparin cofactor II, receptors, and growth factors. The relative strength of binding depends on the sulfation pattern, charge density, and molecular weight. A burn is a type of injury to flesh caused by heat, electricity, chemicals, light, radiation or friction.It is a coagulatve necrosis of the skin and sometimes,its underlying tissues. Most burns affect only the skin (epidermal tissue and dermis). Rarely, deeper tissues, such as muscle, bone, and blood vessels can also be injured. Burns may be treated with first aid, in an out-of-hospital setting, or may require more specialised treatment such as those available at specialised burn centers.

Managing burn injuries properly is important because they are common, painful and can result in disfiguring and disabling scarring, amputation of affected parts or death in severe cases. Complications such as shock, infection, multiple organ dysfunction syndrome, electrolyte imbalance and respiratory distress may occur. The treatment of burns may include the removal of dead tissue (debridement), applying dressings to the wound, fluid resuscitation, administering antibiotics, and skin grafting. While large burns can be fatal, modern treatments developed in the last 60 years have significantly improved the prognosis of such burns, especially in children and young adults.In the United States, approximately 4 out of every 100 people to suffer burns will die from their injuries. The majority of these fatalities occur either at the scene or on the way to hospital Burns are difficult to treat, wounds with complex local and systemic pathology and high mortality, that often heal slowly with scars and contractures. Glycosaminoglycans (GAGs) have been used in parenteral and topical application studies. These studies have uncovered anticoagulative, antiinflammatory and neoangiogenic properties, which may stimulate tissue repair and reepithelializing effects. The endogenous GAGs utilized in treating burns are heparin, dermatan sulfate, heparan sulfate, keratin sulfate, chondroitin-4- and chondroitin-6-sulfate, and hyaluronic acid. Heparin, the most sulfated and acidic GAG, has been used parenterally, topically, by inhalation, in pellet, and in bioengineered membranes. Heparin relieved pain, inhibited clotting and inflammation, restored blood flow, and enhanced healing. Heparin effects that improved and reduced burn care were time, dose, pH, site, source and duration related in studies. Potential adverse effects with heparin use are bleeding, thrombocytopenia and allergy. Heparin preserved lung and improved function. Heparin preserved intestinal integrity and reduced bacterial translocation. Collagen restoration was enhanced. The healed skin was smooth. Heparin reduced needs for pain medicine, topical antibiotics, resuscitation fluids, blood, water baths, debridement, surgery and grafts. Cost of treatments were reduced. Although not as yet fully substantiated, topical heparin therapy of burns may be a useful addition to the range of available treatments for burn wounds. Starting in 1963, the American Dr. MJ Saliba conceived and tested the hypothesis that larger than anti-coagulating doses of heparin administered both topically and parenterally should be effective in treating burned humans, because the pathology involved more than coagulating aspects, and the burns were directly accessible on the burn surface outside of the body, and indirectly accessible from inside the burned persons body. The first studies published in the United States by Saliba without controls12,13 and the later ones with coworkers14-17with controls14,17and without controls15,16 reported good clinical results, and uncovered multiple additional heparin properties and effects. The heparin was added prior to any burn-related surgery. Dr. Saliba reported the multiple beneficial effects of heparin from initial relief of pain, through the shortened enhanced healing with adequately restored tissues, into the final smooth skin consistently void of scars and contractures that resulted from continued topical administration of heparin in diminishing doses. There were no deaths.

Dr. Saliba then presented the studies, and worked as a heparin therapy consultant and coauthor in new studies with burn specialists in other countries. Dr. Saliba reported multiple beneficial heparin effects in addition to the anticoagulating - namely therapeutic antiinflammatory, neoangiogenic revascularizing, tissue restoring and regulating, and epithelializing effects. He was the first to describe neoangiogensis in ischemic tissues produced with heparin use; and the first to report the consistent smooth new skin usually void of scars and contracture that results with continued use of topically applied heparin in diminishing doses into final healing. Some heparin mechanisms were not initially stated because they were not known. In later burn and non-burn studies, researchers uncovered and documented the mechanisms by which heparin produced the effects. Saliba and coworkers treated over 1100 children and adults, from ages under 1 year to over age 82 years. He founded the Saliba Burns, Wounds, and Skin Problems Institute and the Saliba Burns Institute (SBI) Division. Dr. Saliba worked with associated doctors in multiple burn centers in several dozen countries. Up to 2009, the benefits of adding heparin were documented in over 32,500 seriously burned patients in countries worldwide. The studies were reported in burn journals and presented in international burn meetings, conferences, symposiums and congresses. Doctors in various countries reported reduced costs of 50-90% in patients treated with heparin prior-to-surgery, compared to the previous costs in similarly burned and treated patient without heparin. Saliba stated: "Heparin consistently relieves burn pain and other signs of inflammation. No pain medicines are needed and none, worldwide, have been used as a rule. Initial burn size is usually maximum size and thereafter the size and severity decreases. Fluid resuscitation needs are reduced to a half of usually. With the minimal swelling and reduced edema, escarotomy and fasciotomy incisions to relieve pressure in tissues are rarely needed. Blood loss is nil. Transfusions are uncommon. Revascularization and restored blood flow are regular features. Enhanced healing in approximately one-third usual time with smooth skin void of scars and contractures is the common result. With heparin added, medical and surgical procedures are reduced and simplified. The pathophysiology of thermal burn injuries involves: (1) sluggish blood flow with coagulation and infarction sequellae; (2) cascading tissue destructive inflammation; (3) destruction of blood vessels and deficient restoration of blood flow; (4) delayed and deficient restoration of collagen, smooth muscle cells, and dermal cells in the burn granulation tissue that results in (5) delayed and imperfect production and regulation in the epithelialization phase of new skin cells that results in new skin often marred by scars and contractures.

Heparin is precise therapy for these pathological features of burns. Heparin's multiple therapeutic effects precisely matched and favorably altered, stopped, reversed, corrected the multiple pathological features of burn. The documented multiple therapeutic heparin effects are: (1) Anticoagulating; (2) Anti-inflammatory; (3) Neoangiogenic-blood flow restoring; (4) Collagen, smooth muscle cell and dermal cell tissue restoring and regulating; and, (5) Re-epithelializing effects. Heparin use first, when not contraindicated, is compatible with other therapeutic treatments, including surgery. The surgery is slightly delayed, in lesser quantity, under more favorable conditions that improve results, including more successful skin grafts. Use of heparin results in many benefits to the patient, doctors, nurses, ancillary therapists, and relatives, in a humane manner at greatly reduced costs which have been affordable in countries worldwide, including the economically underdeveloped ones. Heparin is ideal for use in a single burned person or in the many persons simultaneously burned in the thermal disasters that are now commonly occurring in Peace, War, and Acts of Terrorism. Heparin sprayed on the burn surfaces and placed in blisters would promptly relieve the pain and initiate therapy at the site of a thermal disaster, as an emergency cost-effective treatment, for which there currently is no other suitable and workable therapy.