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Lower plasma levels of lipoprotein lipase after infusion of low molecular weight heparin than after administration of conventional heparin indicate more rapid catabolism of the enzyme
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
2003 (English)In: Journal of Laboratory and Clinical Medicine, ISSN 0022-2143, E-ISSN 1532-6543, Vol. 142, no 2, 90-99 p.Article in journal (Refereed) Published
Abstract [en]

The functional pool of lipoprotein lipase (LPL) is anchored to heparan sulfate at the vascular endothelium. Injection of heparin releases the enzyme into the circulating blood. Animal experiments have shown that the enzyme is then extracted and degraded by the liver. Low molecular weight (LMW) heparin preparations are widely used in the clinic and are supposed to release less LPL. In this study, we infused a LMW heparin into healthy volunteers for 8 hours. The peak of LPL activity was only about 30% and the subsequent plateau of LPL activity only about 40% compared with those seen with conventional heparin. When a bolus of heparin was given after 4 hours' infusion of LMW or conventional heparin, only relatively small, and similar, amounts of LPL entered plasma. This suggests that the difference between LMW and conventional heparin lay in the ability to retain LPL in the circulating blood, not in the ability to release the lipase. Triglycerides (TGs) decreased when the heparin infusion was started, as expected from the high circulating LPL activities. After 1 to 2 hours, TG levels increased again, and after 8 hours they were about twice as high as before the heparin infusion. This indicates that the amount of LPL available for lipoprotein metabolism had become critically low in relation to TG transport rates. This study indicates that LMW heparin compared with conventional heparin causes as much or more depletion of LPL and subsequent impairment of TG clearing.

Place, publisher, year, edition, pages
2003. Vol. 142, no 2, 90-99 p.
Keyword [en]
APTT, activated partial thromboplastin time, AUC, area under the curve, BMI, body-mass index, HDL, high-density lipoprotein, HL, hepatic lipase, LDL, low-density lipoprotein, LML, low molecular weight, LPL, lipoprotein lipase, TG, triglyceride
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-4170DOI: 10.1016/S0022-2143(03)00059-3PubMedID: 12960955OAI: diva2:143158
Available from: 2004-10-27 Created: 2004-10-27 Last updated: 2010-08-11Bibliographically approved
In thesis
1. Lipoprotein lipase in hemodialysis patients and healthy controls: effects of heparin
Open this publication in new window or tab >>Lipoprotein lipase in hemodialysis patients and healthy controls: effects of heparin
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mortality from cardiovascular disease in patients on chronic hemodialysis (HD) is 10 to 20 times greater than in the general population. One major risk factor is renal dyslipidemia, characterised by an impaired catabolism of triglyceride (TG)-rich lipoproteins with accumulation of atherogenic remnant particles. A contributing factor may be derangement of the lipoprotein lipase (LPL) system, the major lipase in the catabolism of TG-rich lipoproteins. The functional pool of LPL is located at vascular surfaces, and is released by heparin into the circulating blood and extracted and degraded by the liver. Unfractionated heparin (UFH) is commonly used during dialysis to avoid clotting in the extracorporeal devices, but is increasingly replaced by various low molecular weight heparin (LMWH) preparations. Plasma LPL activity is usually lower after injection of LMWH which is therefore said to release less LPL and cause less disturbance of lipoprotein metabolism than UFH. However, animal studies have revealed that LMWH is as efficient as UFH in releasing LPL but is less efficient in retarding hepatic uptake. The aim of this study was to explore the effects of UFH and a LMWH (dalteparin) on LPL activity and TG concentrations in HD-patients compared with healthy controls, matched for age and gender. A disturbed LPL system might contribute to an impaired lipoprotein metabolism, and hence, an aggravated cardiovascular condition.

An 8-hour primed infusion of UFH to controls gave rise to an initial peak of LPL activity within 30 minutes. The activity then dropped by almost 80% over the next two hours and levelled off to a plateau that corresponded to 15% of the peak level. When UFH was infused to HD-patients the curve for LPL activity resembled that for controls, but was reduced by 50% during the peak, while the plateau activities were comparable. The interpretation was that the functional pool, represented by the initial peak, was impaired in HD-patients, while the production of lipase molecules, reflected by the plateau, was only marginally reduced. During the peak of LPL activity TG decreased in both groups, but less in HD-patients, as was expected from the lower circulating lipase activity. During the plateau phase with low lipase activity, TG increased towards and beyond baseline values.

When dalteparin was infused, the same pattern of plasma LPL activity was observed, although remarkably reduced. In controls the peak was only 30% and the subsequent plateau 40% compared with the activities during the UFH infusion. A bolus of UFH given when the LPL activity had levelled off to a plateau brought out about the same amount of activity, regardless of whether dalteparin or UFH had been infused. The conclusion was that both heparin preparations had reduced endothelial LPL to a similar extent, but that dalteparin less efficiently retarded the hepatic uptake of the enzyme. As a consequence to this, TG tended to reach higher levels after the dalteparin infusion. The LPL activities were further reduced in HD-patients during infusion with dalteparin, the peak was only 27% and the plateau 35% compared with the activities when UFH was infused. There was no decrease in TG, but rather a continuous increase, suggesting a profound depletion of functional LPL.

In another study in HD-patients, two anticoagulation regimes based on present clinical practice were compared, and the doses were adjusted to the respective manufacturers recommendation. UFH was administered as a primed infusion, whereas dalteparin was given only as a single bolus pre-dialysis, not followed by an infusion. The results were in line with those in the experimental studies and indicate that also in the clinical setting LMWH interferes with the LPL system as least as much as an infusion of UFH does, and temporarily impairs lipolysis of TG. This interference might, in consequence, contribute to an aggravated cardiovascular condition in HD-patients.

65 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 921
dalteparin, dialysis, lipoprotein metabolism, LMWH, LPL, triglycerides, UFH, uremia
Research subject
Medical and Physiological Chemistry
urn:nbn:se:umu:diva-340 (URN)91-7305-742-8 (ISBN)
Public defence
2004-11-12, E04, 6E, 13:00
Available from: 2004-10-27 Created: 2004-10-27 Last updated: 2010-08-11Bibliographically approved

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Näsström, BirgitStegmayr, Bernd GOlivecrona, GunillaOlivecrona, Thomas
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