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      Bovine and porcine heparins: different drugs with similar effects on human haemodialysis

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          Abstract

          Background

          Heparins from porcine and bovine intestinal mucosa differ in their structure and also in their effects on coagulation, thrombosis and bleeding. However, they are used as undistinguishable drugs.

          Methods

          We compared bovine and porcine intestinal heparin administered to patients undergoing a particular protocol of haemodialysis. We compared plasma concentrations of these two drugs and also evaluated how they affect patients and the dialyzer used.

          Results

          Compared with porcine heparin, bovine heparin achieved only 76% of the maximum plasma concentration as IU mL -1. This observation is consistent with the activities observed in the respective pharmaceutical preparations. When the plasma concentrations were expressed on weight basis, bovine heparin achieved a maximum concentration 1.5 fold higher than porcine heparin. The reduced anticoagulant activity and higher concentration, on weight basis, achieved in the plasma of patients under dialysis using bovine instead of porcine heparin did not affect significantly the patients or the dialyzer used. The heparin dose is still in a range, which confers security and safety to the patients.

          Discussion

          Despite no apparent difference between bovine and porcine intestinal heparins in the haemodialysis practice, these two types of heparins should be used as distinct drugs due to their differences in structure and biological effects.

          Conclusions

          The reduced anticoagulant activity achieved in the plasma of patients under dialysis using bovine instead of porcine heparin did not affect significantly the patients or the dialyzer.

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          Most cited references17

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          Use and safety of unfractionated heparin for anticoagulation during maintenance hemodialysis.

          Anticoagulation is essential to hemodialysis, and unfractionated heparin (UFH) is the most commonly used anticoagulant in the United States. However, there is no universally accepted standard for its administration in long-term hemodialysis. Dosage schedules vary and include weight-based protocols and low-dose protocols for those at high risk of bleeding, as well as regional anticoagulation with heparin and heparin-coated dialyzers. Adjustments are based largely on clinical signs of under- and overanticoagulation. Risks of UFH use include bleeding, heparin-induced thrombocytopenia, hypertriglyceridemia, anaphylaxis, and possibly bone mineral disease, hyperkalemia, and catheter-associated sepsis. Alternative anticoagulants include low-molecular-weight heparin, direct thrombin inhibitors, heparinoids, and citrate. Anticoagulant-free hemodialysis and peritoneal dialysis also are potential substitutes. However, some of these alternative treatments are not as available as or are more costly than UFH, are dependent on country and health care system, and present dosing challenges. When properly monitored, UFH is a relatively safe and economical choice for anticoagulation in long-term hemodialysis for most patients. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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            Characterization of unfractionated heparin: comparison of materials from the last 50 years.

            Physicochemical and anticoagulant characteristics of 27 samples from recent batches of commercially produced unfractionated heparin have been determined as part of the process of establishment of the 5th International Standard Unfractionated Heparin. They have been compared with current heparin standards (European Pharmacopoeia, United States Pharmacopoeia, Chinese), with the 4th International Standard Unfractionated Heparin. and with the three predecessor International Standards. The results indicate that the 4th International Standard Unfractionated Heparin, established in 1982, has significantly lower molecular weight and specific activity than recently produced heparin; this is also true of all preceding International Standard Heparins and of the United States Pharmacopoeial standard. The composition of commercial unfractionated heparin may therefore have changed over time; reasons for this are discussed.
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              Analysis of pharmaceutical heparins and potential contaminants using (1)H-NMR and PAGE.

              In 2008, heparin (active pharmaceutical ingredient, API) lots were associated with anaphylactoid-type reactions. Oversulfated chondroitin sulfate (OSCS), a semi-synthetic glycosaminoglycan (GAG), was identified as a contaminant and dermatan sulfate (DS) as an impurity. While DS has no known toxicity, OSCS was toxic leading to patient deaths. Heparins, prepared before these adverse reactions, needed to be screened for impurities and contaminants. Heparins were analyzed using high-field (1)H-NMR spectroscopy. Heparinoids were mixed with a pure heparin and analyzed by (1)H-NMR to assess the utility of (1)H-NMR for screening heparin adulterants. Sensitivity of heparinoids to deaminative cleavage, a method widely used to depolymerize heparin, was evaluated with polyacrylamide gel electrophoresis to detect impurities and contaminants, giving limits of detection (LOD) ranging from 0.1% to 5%. Most pharmaceutical heparins prepared between 1941 and 2008 showed no impurities or contaminants. Some contained DS, CS, and sodium acetate impurities. Heparin prepared in 2008 contained OSCS contaminant. Heparin adulterated with heparinoids showed additional peaks in their high-field (1)H-NMR spectra, clearly supporting NMR for monitoring of heparin API with an LOD of 0.5-10%. Most of these heparinoids were stable to nitrous acid treatment suggesting its utility for evaluating impurities and contaminants in heparin API. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association
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                Author and article information

                Journal
                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central
                1756-0500
                2013
                13 June 2013
                : 6
                : 230
                Affiliations
                [1 ]Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
                [2 ]Instituto de Bioquímica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
                [3 ]Divisão de Nefrologia, Departamento de Medicina Clínica, Universidade Federal Fluminense, Niterói, Brazil
                [4 ]Serviço de Nefrologia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
                Article
                1756-0500-6-230
                10.1186/1756-0500-6-230
                3688204
                23763719
                a46d598e-d662-4224-aa41-7dff334c2ebd
                Copyright ©2013 Tovar et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 October 2012
                : 7 June 2013
                Categories
                Research Article

                Medicine
                heparin,antithrombotic effects,haemodialysis
                Medicine
                heparin, antithrombotic effects, haemodialysis

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