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      Lipoprotein lipase responds similarly to tinzaparin as to conventional heparin during hemodialysis

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          Abstract

          Background

          Low molecular weight (LMW) heparins are used for anticoagulation during hemodialysis (HD). Studies in animals have shown that LMW-heparins release lipoprotein lipase (LPL) as efficiently as unfractionated (UF) heparin, but are less able to retard hepatic uptake of the lipase. This raises a concern that the LPL system may become exhausted by LMW-heparin in patients on HD. We have explored this in the setting of clinical HD.

          Methods

          Twenty patients on chronic hemodialysis were switched from a primed infusion of UF-heparin to a single bolus of tinzaparin. There were long term follow up of variables for the estimation of dialysis efficacy as well as of the LPL release during dialysis and the subsequent impact on the triglycerides.

          Results

          The LPL activity in blood was higher on tinzaparin at 40 but lower at 180 minutes during HD. These values did not change during the 6 month study period. There were significant correlations between the LPL activities in individual patients at the beginning and end of the 6 month study period and between the activities on UF-heparin and on tinzaparin, indicating that tissue LPL was not being exhausted. Triglycerides were higher during the HD-session with tinzaparin than UF-heparin. The plasma lipid/lipoprotein levels did not change during the 6 month study period, nor during a 2-year follow up after the switch from UF-heparin to tinzaparin. Urea reduction rate and Kt/V were reduced by 4 and 7% after 6 months with tinzaparin.

          Conclusion

          Our data demonstrate that repeated HD with UF-heparin or tinzaparin does not exhaust the LPL-system.

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          Most cited references36

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          A single bolus of a low molecular weight heparin to patients on haemodialysis depletes lipoprotein lipase stores and retards triglyceride clearing.

          Gunilla Olivecrona, Thomas Olivecrona, Birgit Näsström … (2005)
          Low molecular weight heparins (LMWH) are increasingly used during haemodialysis (HD) to prevent clotting in the extracorporeal devices. It has been suggested that LMWH release endothelial-bound lipoprotein lipase (LPL) less efficiently than unfractionated heparin (UFH) does and thereby cause less disturbance of lipid metabolism. Evidence from in vitro studies and from animal experiments indicate, however, that both types of heparin preparations have the same ability to release endothelial LPL, but LMWH are less effective in preventing uptake and degradation of LPL in the liver. Model studies in humans indicate that LMWH cause as much depletion of LPL stores and impaired lipolysis of triglyceride (TG)-rich lipoproteins as UFH does. Two anticoagulant regimes based on present clinical practice were compared in nine HD patients. UFH was administered as a primed infusion, whereas the LMWH (dalteparin) was given only as a single bolus pre-dialysis. Blood was sampled regularly for LPL activity and TG. LPL activity in blood was significantly lower during the dialysis with dalteparin. To explore the remaining activity at the endothelium, a bolus of UFH was given after 3 h of dialysis. The bolus brought out about the same amount of LPL, regardless of whether UFH or dalteparin had been used during dialysis. The increase in TG was significantly higher during dialysis with dalteparin. This study indicates that a single bolus of dalteparin pre-dialysis interferes with the LPL system as much as, or more than an infusion of UFH does.
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            Low-molecular-weight heparin in patients with renal insufficiency.

            Pirmin Schmid, Edgar G. Fischer, Walter A. Wuillemin (2009)
            Low-molecular-weight heparins (LMWH) have been shown to be safer, more effective and more convenient than unfractionated heparin (UFH) in many clinical situations. However, their use is limited in patients with renal insufficiency (RI) due to bioaccumulation. The literature is critically reviewed and known pharmacokinetic properties are summarised. An approach to using LMWH in patients with RI is proposed on the basis of currently available evidence. Pharmacokinetic data of commonly used LMWH and of UFH are summarised in respect of RI. Most data are known on enoxaparin. A dose reduction is recommended in patients with severe RI. Limited data on dalteparin and tinzaparin suggest that there is less bioaccumulation. However, further studies are needed, in respect of long-term use and clinical end-points in particular.There are no data on certoparin and only very limited data on nadroparin. A detailed approach is suggested for the use of LMWH in patients with severe RI. Briefly: (1) before using LMWH, evaluate the patient's renal function, ist expected course, imminent interventions, and general bleeding risk; (2) prefer LMWH to UFH in view of better efficacy and lower bleeding risk in general; (3) however, prefer i.v. UFH to s.c. LMWH if a patient is unstable, is awaiting emergency interventions, or has a high bleeding risk, since UFH can be stopped more quickly due to i.v. administration, has a shorter half-life time, and can be effectively antagonised; (4) prefer a well documented LMWH; use established dosing schemes; (5) monitor LMWH with peak anti-Xa levels in patients with severe RI regularly, and adjust dose to be in target range; (6) do not use LMWH in patients with severe RI if there is no possibility of measuring anti-Xa levels. LMWH may be considered for patients with severe RI. However, experience, judicious choice and careful monitoring of patients with severe RI treated with LMWH are necessary.
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              Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis.

              L Lit, R Cheung, Samuel Lai … (2001)
              The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMC Nephrol
                Title: BMC Nephrology
                Publisher: BioMed Central
                ISSN (Electronic): 1471-2369
                Publication date Collection: 2010
                Publication date (Electronic): 6 December 2010
                Volume: 11
                Page: 33
                Affiliations
                [1 ]Department of Internal Medicine, County Hospital in Östersund, SE-83131 Östersund, Sweden
                [2 ]Department of Internal Medicine, University Hospital, SE-90185, Umeå, Sweden
                [3 ]Department of Medical Biosciences, University of Umeå, SE-90187 Umeå, Sweden
                Article
                Publisher ID: 1471-2369-11-33
                DOI: 10.1186/1471-2369-11-33
                PMC ID: 3004894
                PubMed ID: 21129229
                SO-VID: 271cd8cb-9560-4452-b7b8-ce1448423450
                Copyright © Copyright ©2010 Mahmood et al; licensee BioMed Central Ltd.
                License:

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

                History
                Date received : 28 April 2010
                Date accepted : 6 December 2010
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Nephrology
                Data availability:
                ScienceOpen disciplines: Nephrology

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