| Abstract|| |
The administration of an anticoagulant is essential to prevent clotting of blood in the extra corporeal circuit during a hemodialysis (HD) session. Unfractionated heparin (UFH) has been used for this purpose over many decades with satisfactory results. However, UFH has many unwanted side effects such as risk of bleeding, thrombocytopenia, paradoxical thrombosis as well as disturbances of blood lipids. Over the last few years, low molecular weight heparin (LMWH.) has been introduced in medical practice. We performed this prospective study at the Jeddah Kidney Center, Jeddah, Saudi Arabia to evaluate the efficacy of LMWH. We compared the changes in lipid profile during the period of administration of LMWH with the changes observed during the administration of UFH. A total of 30 patients were involved in this prospective study. During the first part of the study, which was carried out for 12 weeks, all the study patients received UFH as anticoagulant during the HD sessions. During the second part of the study, which was conducted over the subsequent 12 weeks, the same patients were given LMWH as anticoagulant during the HD sessions. During the HD sessions using Tinzaparin, no significant problems were observed and HD was performed efficiently. The total cholesterol level was reduced during the administration of LMWH while the triglyceride levels showed a rise during this period. Our study suggests that LMWH is a safe and effective substitute for UFH for anticoagulation during HD sessions. Studies on larger cohorts and for longer periods of time are required to validate our observation.
|How to cite this article:|
Badawi L, Akeel N, Shaheen FA, Al Ahmadi S. Dose and Lipid Lowering Effect of Tinzaparin Sodium: A Single Center Experience. Saudi J Kidney Dis Transpl 2005;16:161-5
|How to cite this URL:|
Badawi L, Akeel N, Shaheen FA, Al Ahmadi S. Dose and Lipid Lowering Effect of Tinzaparin Sodium: A Single Center Experience. Saudi J Kidney Dis Transpl [serial online] 2005 [cited 2022 Aug 12];16:161-5. Available from: https://www.sjkdt.org/text.asp?2005/16/2/161/32935
| Introduction|| |
The administration of an anticoagulant is essential to prevent clotting of blood in the extra corporeal circuit during a hemodialysis (HD) session. Unfractionated heparin (UFH) has been used for this purpose over many decades with satisfactory results. However, UFH has many unwanted side effects such as risk of bleeding, ,, thrombocytopenia and paradoxical thrombosis. , Disturbances of blood lipids is another important side effect of UFH. Lipo-protein lipase, which is released from the endothelium is important for the metabolism of lipids like very low density lipoprotein (VLDL). UFH stimulates release of lipoprotein lipase and frequent use of this drug during HD leads to lipoprotein lipase depletion in the endothelium. , Also, prolonged use of UFH. over many months can lead to osteoporosis, spontaneous fractures  and alopecia. 
Over the last few years, low molecular weight heparin (LMWH.) has been introduced in medical practice. Since then, many studies have been conducted to determine the appropriate dose as well as the efficacy of LMWH in the prevention of clotting during HD.  A study conducted for over six months involving 70 patients on HD undergoing about 4000 dialysis procedures, concluded that the use of LMWH is safe and effective. 
We performed this prospective study at the Jeddah Kidney Center, Jeddah, Saudi Arabia to evaluate the efficacy of LMWH [Tinzaparin Sod by LEO Pharma] as an alternative anticoagulant during HD. We observed the changes in lipid profile during the period of administration of LMWH with the changes observed during the administration of UFH. We have also reviewed the results of some other studies with the use of LMWH.
| Patients and Methods|| |
A total of 30 patients were involved in this prospective study. They were treated with regular HD, administered thrice weekly, for end-stage renal disease. The dialysis was aimed at attaining a KT/V of 1.2 to 1.3. All the patients had their HD through an arterio-venous fistula. There were 15 males and 15 females with an average age of 37.7 years. The average body weight was 60.9 kg. The patients were on HD for a mean period of 3 ½ years (7 months to 8 years).
The original kidney disease was chronic glomerulonephritis (CGN) in eight patients, chronic pyelonephritis (CPN) and diabetic nephropathy (DN) in two patients each and CPN with nephrolithiasis in one patient. The original kidney disease could not be identified in 17 patients.
Patients with bleeding disorders, clotting tendency and those on oral anticoagulants were not recruited. During the first part of the study, which was carried out for 12 weeks, all the study patients received UFH as anticoagulant during the HD sessions. A total of 4000 to 5000 units of UFH were given during each session of HD. The heparin was stopped 30 to 60 minutes prior to the termination of HD.
During the second part of the study, which was conducted over the subsequent 12 weeks, the same patients were given LMWH as anticoagulant during the HD sessions (Innohep/ Tinzaparin sod. Vial 10,000 iu/ml-vial 2ml). A bolus dose of 2500 units of anti Xa [TinzaparinLEO] was given into the arterial line before starting HD. The efficacy of anticoagulation was monitored by frequent visual inspection of the dialyzers, bubble chambers and tubings for any signs of clot formation. After the end of each HD session, the dialyzers and tubings were inspected again to exclude the presence of clots.
Observation for bleeding was carried out by watching needle puncture sites for any oozing of blood after applying pressure for the usual duration by the nurse (10-15 mins). Patients were requested to report the appearance of any hematoma, epistaxis, gingival bleeding, hematemesis or malena.
Since Anti Xa activity test was not available in our service, we did not include it in this study. Baseline investigations performed prior to the start of this study included hemoglobin (Hb), white blood cell (WBC) count, platelet count, partial thromboplastin time (PTT), blood urea nitrogen (BUN), serum creatinine (Cr), calcium (Ca), sodium (Na), potassium (K), glucose, total cholesterol, triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL). These investigations were repeated every four weeks during the study period.
| Results|| |
[Table - 1] shows the mean values of the investigations performed during treatment with UFH and LMWH in the study patients.
During the HD sessions using Tinzaparin, no significant problems were observed and HD was performed efficiently following the single bolus dose given at the start of the HD session. No additional doses were required during the procedure and close observation of the dialyzer and tubings during, and after completion of each HD session, did not show any clot formation. We found that 2500 iu of LMWH was appropriate for the majority of the patients (27/30). In two patients, the dose was reduced by 500 units; one patient reported that he had gingival bleeding after brushing few hours after HD and the other developed persistent oozing of blood from the needle puncture site. In the third patient, heparin was stopped due to development of minor intracerebral hemorrhage following an episode of hypertension.
During the part of the study when the patients were on UFH, clotting in the dialyzer was observed in three different patients. The dialyzer was changed each time. There were no bleeding episodes reported.
On review of the blood investigations, which were performed at the start of the study and every four weeks thereafter, no change was noticed in the WBC count and Hb level while platelets were slightly reduced when patients were on Tinzaparin.
The values of BUN, creatinine, Ca, Na, K, ALT and AST showed no difference in the two parts of the study. The total cholesterol level was reduced during the administration of LMWH with the mean value being 145 mg/dl compared to 175 mg/dl during the period of UFH usage. The triglyceride levels showed a rise during LMWH administration. The mean value was 153.8 mg/dl while on LMWH compared to 129.5 mg/dl while on UFH.
No significant changes were observed in the levels of HDL and LDL during the two parts of the study. Three female patients reported an increase in hair fall during the administration of LMWH although we noticed no significant alopecia.
| Discussion|| |
Over decades, UFH has been in use as a standard anticoagulant in extra-corporeal circulation during many procedures in medical practice. Hemodialysis is one of the commonest such procedures. Long term use of UFH for HD carries the risk of adverse effects. Since the advent of LMWH, many centers have reported the beneficial effect of this drug.  The need for nearly half the dose compared to UFH and a single bolus administration are two interesting features of LMWH. 
The dose of low LMWH (Tinzaparin) used in our study was between 2000 and 2500 units. There was no need to give higher doses as used in a study conducted by Elisaf, et al who used 2500-5000 units anti Xa during a HD session. 
We did not notice any clotting episodes or major bleeding with the use of Tinzaparin. Similar efficacy of Tinzaparin was also seen in many other studies  where 62 patients were studied while under Tinzaparin as anticoagulant during HD.
The analysis of serum lipid values for all the patients showed no significant difference during the use of UFH and LMWH. This was shown on comparison of cholesterol values between the start and the end of the study using LMWH and UFH, [Table - 2]. Other studies using LMWH have also shown similar favorable results regarding lipid profile. ,,,,,,,, Our study suggests that LMWH is a safe and effective substitute for UFH for anticoagulation during HD sessions. Studies on larger cohorts and for longer periods of time are required to validate our observation.
| References|| |
|1.||Cecil Text Book of Medicine, Page 120-1. |
|2.||Integrated Pharmacology, Curtis, Sutter, Waker, Hoffman Page 208. |
|3.||Harrisons Principles of Internal Medicine Page 744. |
|4.||Basic and Clinical Pharmacology. Bertram G.K. Atzung. Page 409. |
|5.||Teraoka J, Matsui N, Nakagawa S, Takeuchi J. The Role of heparin in the changes of lipid patterns during a single Hemodialysis. Clin Nephrol 1982;17:96-9. [PUBMED] |
|6.||Nurmohamed MT, ten Cate J, Stevens P, Hoek JA, Lins RL, ten Cate JW. Long term efficacy and safety of low molecular weight heparin in chronic hemodialysis patients. A comparison with standard heparin. ASAIO Trans 1991;37:M459-61. |
|7.||Simpson HK, Baird J, Allison M, et al. Long-term use of the low molecular weight heparin tinzaparin in hemodialysis. Haemostasis 1996;26(2):90-7. |
|8.||Egfjord M, Rosenlund L, Hedegaard B, et al. Dose titration study of tinzaparin, a low molecular weight heparin, in patients on chronic hemodialysis. Artif Organs 1998;22(8):633-7. |
|9.||Elisaf MS, Germanos NP, Bairaktari HT, Pappas MB, Koulouridis EI, Siamopoulos KC. Effects of conventional vs. low molecular weight heparin on lipid profile in hemodialysis patients. Am J Nephrol 1997;17 (2):153-7. |
|10.||Wiemer J, Scherberich JE. When lipids increase in dialysis: the role of heparin! Standard heparin increases, low molecular weight heparin lowers triglycerides. MMW Fortschr Med 1999;141(43):29-32. |
|11.||Schmitt Y, Scheider H. Low-molecularweight heparin (LMWH): influence on blood lipids in patients on chronic haemodialysis. Nephrol Dialysis Transplant 1993;8(5):438-42. |
|12.||Maurin N, Kierdorf H. A low molecular weight heparin in hemodialysis. Klin Wochenschr 1988;15:66(6):246-9. |
|13.||Akiba T, Tachibana K, Ozawa K, et al. Long-term use of low molecular weight heparin ameliorates hyperlipidemia in patients on hemodialysis. ASAIO J 1992;38(3): M326-30 |
|14.||Lai KN, Ho K, Cheung RC, et al. Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis. Int J Artif Organs 2001;24(7):447-55 |
|15.||Leu JG, Liou HH, Wu SC, Yang WC, Huang TP. Low molecular weight heparin in diabetic and nondiabetic hypercholesterolemic patients receiving long-term hemodialysis. J Formos Med Assoc 1998;97(1): 49-54. |
|16.||Kronenberg F, Konig P, Lhotta K, Steinmetz A, Dieplinger H. Low molecular weight heparin does not necessarily reduce lipids and lipoproteins in hemodialysis patients. Clin Nephrol 1995;43(6):399-404. |
|17.||Kronenberg F, Konig P, Neyer U, et al. Influence of various heparin preparations on lipoproteins in hemodialysis patients: a multicentre study. Thromb Haemost 1995; 74(4):1025-8. |
Faissal AM Shaheen
Saudi Center for Organ Transplantation, P.O. Box 27049, Riyadh 11417
Source of Support: None, Conflict of Interest: None
[Table - 1], [Table - 2]