Heparins: Mechanism of Action and Application in Acute Pancreatitis

Abstract

Introduction. Heparin is a glycosaminoglycan composed of chains of alternating d-glucosamine and uronic acid residues. Its major anticoagulant effect is attributed to a unique pentasaccharide structure. Heparin prevents coagulation after binding with a plasma antithrombin III. Antithrombin III is a protease inhibitor and complex heparin antithrombin III inhibits activity of thrombin, as well as neutralizes active forms of factors IX, X, XI and XII. However, the most important action of heparin is not inhibition of thrombin activity, but inhibition of thrombin creation, especially through accelerating the neutralization of factor Xa. In large concentration, heparin combined with antithrombin III also inhibits platelet aggregation. Aim. To analyze the mechanism of action of heparin and its application for the treatment of patients with acute pancreatitis. Materials and methods. Content analysis, method of system and comparative analysis, bibliosemantic method of study of actual scientific researches concerning the mechanism of action of heparin and its application for the treatment of patients with acute pancreatitis was used. Results. In various experimental and clinical studies, heparin has been found to exhibit the anti-inflammatory activity. Heparin has shown protective and therapeutic effect in patients suffering from a range of inflammatory diseases, including rheumatoid arthritis, bronchial asthma, allergy and ulcerative colitis. The heparin-antithrombin III complex significantly reduces the activity of trypsin and chymotrypsin. There are experimental and some clinical studies showing protective and therapeutic effect of heparin in the pancreas. Experimental data indicate that pretreatment with heparin inhibits the development of acute pancreatitis evoked by bile, taurocholate, cerulein, or pancreatic ischemia followed by reperfusion. There are also experimental studies showing therapeutic effect of heparin in the course of acute pancreatitis. Clinical reports concern mainly the role of heparin in the prevention of acute pancreatitis due to endoscopic retrograde cholangiopancreatography and treatment of acute pancreatitis evoked by hyperlipidemia. Conclusions. The administration of heparin enhances the effect of conventional treatment of severe acute pancreatitis, markedly decreases the incidence of encephalopathy and improves the survival rate in patients with this disease. Due to the anticoagulation and anti-inflammatory properties, accessibility, ease of use of low molecular weight heparins they can be included in the complex treatment of patients with severe pancreatitis, especially at an early stage of the disease, for the purpose of prevention and correction of organ dysfunction.

Keywords

• acute pancreatitis
• hemostasis
• heparin
• inflammation