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      Low Molecular Weight Heparin in Hemodialysis Patients with a Bleeding Tendency


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          Efficacy and safety of a low-molecular-weight heparin (LMWH) were studied in 33 stable maintenance hemodialysis patients who had a bleeding tendency on unfractionated heparin. The optimal dose of LMWH for each patient was titrated before the study; the mean total LMWH dosage was 1,152 ± 574 IU. No major bleeding or clot formation was noted in a total of 2,470 hemodialysis sessions during 6 months of LMWH administration. The mean value of plasma anti-factor Xa (anti-Xa) activity increased from 0.05 ± 0.03 IU/ml before dialysis to 0.34 ± 0.28 IU/ml after 2 h of dialysis and returned to 0.15 ± 0.09 IU/ml after 4 h of dialysis; the mean activated partial thromboplastin time was 26.1 ± 4.4 s before dialysis, 30.7 ± 9.5 s (an 18% increase) after 2 h of dialysis, and 26.2 ± 4.4 s after 4 h of dialysis. No significant change in serum antithrombin levels was noted throughout the whole study period. We conclude that a low dosage of LMWH is safe and effective in hemodialysis patients who have a risk of bleeding with unfractionated heparin. Serum anti-Xa activity is better than activated partial thromboplastin time and antithrombin in assessing the optimal dose of LMWH. A plasma anti-Xa activity of 0.37 IU/ml after 2 h of hemodialysis may represent an optimal dosage of LMWH for most patients.

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          Low-density lipoproteins and risk for coronary artery disease.

          Based on the established relation between low-density lipoprotein (LDL) cholesterol and coronary artery disease (CAD), the treatment guidelines of the US National Cholesterol Education Program (NCEP) focus on LDL cholesterol reduction for primary and secondary prevention of CAD events. Abundant clinical trial evidence supports the importance of LDL cholesterol-lowering in decreasing CAD risk, both in angiographic trials, which measure CAD progression, and in trials with morbidity and mortality endpoints. The LDL cholesterol targets in the guidelines remain important treatment goals, and ongoing trials should answer questions of whether further reduction in LDL cholesterol will provide much additional benefit. Even in trials of statin therapy, in which substantial reductions of LDL cholesterol have been obtained, statins decrease (by 23-37%) but do not entirely eliminate events, suggesting that lipid parameters besides LDL cholesterol, such as high-density lipoprotein (HDL) cholesterol, triglyceride, lipoprotein(a), and LDL particle size and susceptibility to oxidation, as well as other risk factors, influence CAD risk. Unfortunately, at present, the majority of high-risk patients are not receiving either diet or drug therapy. Systematic screening to identify high-risk patients and methodical follow-up to implement diet, lifestyle modification, and drug therapy to lower LDL cholesterol, as provided for in the NCEP guidelines, should lead to significant benefits in the prevention of CAD events.
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            Dose titration study of tinzaparin, a low molecular weight heparin, in patients on chronic hemodialysis.

            The minimal necessary dose of Innohep (IH) (MNDI) (Innohep [tinzaparin], Leo Pharmaceutical Corp., Ballerup, Denmark) was examined in 40 patients switched from conventional heparin ([CH], Leo Pharmaceutical Corp.) to IH and in 13 patients already treated with IH. Clotting in the venous chamber and in the dialyzer was evaluated on a 4 point scale by visual inspection. IH was administrated as a bolus injection into the arterial side of the dialyzer at the beginning of dialysis sessions. The initial dose of IH was 50% of the total dose of CH used before the study (in respective IU). According to clotting in the venous chamber or dialyzer, the dose of IH was titrated by stepwise changes of 500 IU to the lowest possible dose until 3 subsequent dialysis sessions without clotting were obtained. The total dose of CH (bolus and infusion) before switching was 6,162 +/- 2,100 IU. The bleeding time from the cannulation site after dialysis, in 24 patients with A-V fistulas, was 7.1 +/- 2.8 min(triplicates). Eight patients were excluded before achieving the MNDI, 3 due to bleeding not clearly related to heparinization (1 due to gingival bleeding, 1 to epistaxis, and 1 to sugillations), 1 due to alopecia, 2 due to a need of more than 10,000 IU of IH, and 2 patients due to cessation of treatment resulting from anxiety. After switching over, the MNDI amounted to 66 +/- 26% in respective IU. The conversion IH/CH ratio correlated significantly to the blood flow rate and the type of dialyzer. When compared on 3 subsequent sessions before and after switching to IH, no differences were found in the bleeding time after decannulation and in clotting in the venous chamber while dialyzer clotting fell on the visual scale from an average of 0.36 to 0.19 (p < 0.01). No total clot formation was observed during the study. The MNDI correlated positively to the body weight, blood flow rate, and time on dialysis (with the respective coefficients of correlation of r being 0.58, 0.44, and 0.30, p < 0.05) and was also influenced by the type of dialyzer. The average MNDIs for the Hemoflow-FS hollow-fiber (Fresenius, Bad Homburg, Germany), Lundia PRO plate (Gambro, Lund, Sweden), and Polyflux hollow fiber (Gambro) were 2,571, 3,727, and 5,020 IU (p < 0.01, ANOVA). In patients on chronic hemodialysis, IH given as a bolus of 4,250 IU effectively prevented extracorporeal clotting during dialysis, similarly to CH. However, a considerable individual variation in MNDIs not related to the need for CH was observed, and this necessitates individual dosage adjustments to obtain the optimal prevention of clotting with minimal bleeding risk.

              Author and article information

              S. Karger AG
              December 2000
              01 December 2000
              : 86
              : 4
              : 499-501
              aDivision of Nephrology, Department of Medicine, and bDepartment of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, cDepartment of Pharmacology, National Yang-Ming University, Taipei, and dNational Taipei College of Nursing, Taipei, Taiwan
              45840 Nephron 2000;86:499–501
              © 2000 S. Karger AG, Basel

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              Page count
              Tables: 1, References: 8, Pages: 3
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              Short Communication

              Cardiovascular Medicine,Nephrology
              Low molecular weight heparin,Hemodialysis,Antithrombin,Anti-factor Xa activity,Synthetic membrane


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