Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review

Abstract

Background. Heparin, used clinically as an anticoagulant, also has anti-inflammatory properties. The purpose of this systematic review was to provide a comprehensive review regarding the efficacy and safety of heparin and its derivatives as anti-inflammatory agents. Methods. We searched the following databases up to March 2012: Pub Med, Scopus, Web of Science, Ovid, Elsevier, and Google Scholar using combination of Mesh terms. Randomized Clinical Trials (RCTs) and trials with quasi-experimental design in clinical setting published in English were included. Quality assessments of RCTs were performed using Jadad score and Consolidated Standards of Reporting Trials (CONSORT) checklist. Results. A total of 280 relevant studies were reviewed and 57 studies met the inclusion criteria. Among them 48 studies were RCTs. About 65% of articles had score of 3 and higher according to Jadad score. Twelve studies had a quality score > 40% according to CONSORT items. Asthma (n = 7), inflammatory bowel disease (n = 5), cardiopulmonary bypass (n = 8), and cataract surgery (n = 6) were the most studied disease condition. Forty studies use unfractionated heparin (UFH) for intervention; the remaining studies use low molecular weight heparin (LMWH). Conclusion. Despite the conflicting results, heparin seems to be a safe and effective anti-inflammatory agent; although it is shown that heparin can decrease the level of inflammatory biomarkers and improves patient conditions, still more data from larger rigorously designed studies are needed to support use of heparin as an anti-inflammatory agent in clinical setting. However, because of the association between inflammation, atherogenesis, thrombogenesis, and cell proliferation, heparin and related compounds with pleiotropic effects may have greater therapeutic efficacy than compounds acting against a single target.

Old and new applications of non-anticoagulant heparin

“…A recent systematic review with meta-analysis showed the beneficial effects of heparin treatment in asthmatic patients [13]. In normal subjects, heparin can inhibit reactive oxygen species (ROS) generation [14], supporting the observed cardiovascular protective effects, and also increases nitric oxide bioavailability through the release of vessel immobilized myeloperoxidase [15].…”

“…As recently reviewed [78] in other clinical trials there was no statistical difference in the primary outcome, showing a narrow spectrum of experimental activity compared to heparin. In another recent review with meta-analysis, heparin and derivatives showed positive effects in cataract surgery [13]. LMWHs compared with heparin, showed more benefit as nephro-and neuroprotective agents.…”

“…Experimental and clinical studies in patients with proteinuric glomerulonephritis showed benefit by oral treatment with sulodexide, a mixture of LMW heparin and dermatan sulfate in a Acute respiratory distress syndrome* [5,42] Allergic rhinitis [43] Antimalaric a [44] Antiphospholipid syndrome [45] Asthma and bronchial constriction [5,13] Cardioversion of atrial fibrillation [46] Cardiopathies [47] Chronic obstructive pulmonary diseases [5] Cystic fibrosis [18,48] Glomerulonephritis [26] Hyperlipemias [49] Inflammatory bowel diseases [5,29,50] Mucolytic agent (Inhaled) [51] Nervous system protection by radiation [52] Rheumatoid arthritis [5,53] Severe sepsis [54] Tissue repair and wound healing [5] Vasoprotection [55] a Heparin, inhibiting and reversing cytoadherence and rosetting of Plasmodium falciparium infected erythrocytes "in vitro". Tested from 1967 in severe malaria clinical trials, after some overall promising outcomes, were discontinued due to severe intracranial bleeding [44] 4:1 weight ratio [26].…”

Hyper-Homocysteinemia and other Inherited Thrombophilic Factors Inducing Retinal Vein Occlusion. The Employment of Novel Orals Anti-Coagulants is Possible?

“…Current guidelines recommend an initial treatment with Low Molecular Weight Heparins (LMWHs) [35]. These are useful for their additional properties, such as anti-angiogenic effect [36], anti-inflammatory and immunomodulatory properties [37][38][39]. Practically, if diagnosed within 15 days, LWMH must be administered for two first weeks.…”

Vnetje – skupni patogenetski dejavnik arterijske aterosklerotične in venske trombembolične bolezni

“…Toda znižanje vnetnih kazalcev v petih dneh po nastopu akutne VT bi lahko bilo tudi posledica vpliva heparina, s katerim so bolnike zdravili. Poskusi so namreč dokazali, da ima heparin protivnetno delovanje (33).…”