| Abstract|| |
Although unfractionated heparin (UFH) is the anticoagulant commonly used for hemodialysis (HD), low molecular weight heparin (LMWH) has been found to be equally efficacious. The aim of this study was to explore the safety and efficacy of a single bolus dose of the LMWH, enoxaparin. Thirty-eight patients on maintenance HD were randomly divided into two equal groups. The mean age and body-weight of the two groups were comparable. While one group received 1 mg/kg body-weight (the manufacturer's recommended dose) of enoxaparin for three dialysis sessions of three-hours duration each, the other group received a fixed dose of 40 mg for the same number of dialyses. For the next three dialysis sessions, these doses were exchanged between the groups. In all, a total of 228 HD sessions were monitored for clotting of blood lines/dialyzers and bleeding from vascular access and other sites. The rate of complications was compared with the historical data while UFH was being used for the same patients. In general, enoxaparin was associated with fewer episodes of bleeding and clotting. Our study confirms that LMWH is of comparable efficacy to UFH and probably a lesser than recommended dose is adequate for a three-hour HD session.
Keywords: Hemodialysis, Anticoagulant, Bolus dose, Unfractionated heparin, Low molecular weight heparin.
|How to cite this article:|
Al-Arrayed S, Seshadri R. Use of Low Molecular Weight Heparin for Hemodialysis: A Short-Term Study. Saudi J Kidney Dis Transpl 2002;13:146-50
|How to cite this URL:|
Al-Arrayed S, Seshadri R. Use of Low Molecular Weight Heparin for Hemodialysis: A Short-Term Study. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2019 Nov 22];13:146-50. Available from: http://www.sjkdt.org/text.asp?2002/13/2/146/33126
| Introduction|| |
Unfractionated heparin (UFH) has been the established anticoagulant for hemodialysis (HD) for several decades. However, in the past 15 years many reports on the use of low-molecular-weight heparin (LMWH) for anticoagulation in general, and for HD in particular, have been published. ,,,, It has been noted that LMWHs are associated with less bleeding complications and the anticoagulant effect is satisfactory for regular HD. ,,, Long-term efficacy and safety of LMWH have also been reported. ,,
The objective of our study was to explore the feasibility of a lower than recommended dose with a LMWH (enoxaparin) in HD patients.
| Patients and Methods|| |
Thirty-eight patients on regular HD were included in this study. All these subjects were on UFH (in a dose of 1000 I.U. as bolus, followed by 1000 I.U. infusion hourly during each session of HD) before the study. They were randomly divided into two equal groups A and B [Table - 1]. There were seven males and 12 females in group A and six males and 13 females in group B.
Mean age was 52.7 ± 26 years in group A and 56.5 ± 27 years in group B. Mean body weight was 61.6 ± 19.5 kg (group A) and 61.8 ± 20.5 kg (group B). Each subject received three-hour dialysis session, three times per week. The average duration on dialysis before the study was 20.4 months (range 1-52 months) in group A and 21.4 months (range 1-117 months) in group B.
All patients were dialyzed using new steamsterilized polysulfone membrane hollowfiber dialyzer (Fresenius) at an average blood flow rate of 175-225 ml/min using bicarbonate dialysate with a flow rate of 500 ml/min. The mean dose of erythropoietin was 3900 ± 2200 units per session for group A and 3600 ± 2000 units for group B. The cause of end-stage renal failure in the study patients is listed in [Table - 2]. The laboratory parameters of the two groups before starting the study are shown in [Table - 3]. Each group received two different doses of enoxaparin.
While one group received three dialysis sessions with the manufacturer's recommended dose of enoxaparin (i.e. 1 mg/kg body weight), the other group received the fixed dose of 40 mg for three consecutive dialysis sessions and these doses of enoxaparin were exchanged during the subsequent three dialysis sessions. The LMWH was given as a single bolus dose at the beginning of each HD session into the "arterial" line of the extra-corporeal circuit. A total of 228 sessions of dialysis were carried out in all. All the subjects were carefully observed for complications (bleeding, clotting and allergic reaction). Monitoring of the efficacy of anticoagulation was done by visual inspection of bloodlines and dialyzers for fibrin/clot formation. Tests for coagulation were not performed during or immediately after use of enoxaparin, as these are not altered significantly. , Anti-Xa activity could not be measured for want of laboratory facility. The incidence and duration of bleeding at the needle puncture site of arteriovenous fistulae and other sites (e.g. epistaxis and gum bleeding) were also recorded.
| Results|| |
The rate of complications noted during the study in comparison with the historical data while using UFH for the same groups of patients is shown in [Table - 4]. No subject experienced allergy to either form of heparin.
In general, complications were more frequent with UFH than with either regimen of LMWT. With UFH, bleeding occurred in eight of the 38 subjects (20.8%) and clots formed in seven of them (18.2%). Two patients experienced epistaxis and one patient had retinal bleeding.
With enoxaparin, clotting was noted in five of the 38 patients (13%) and each had one episode only. Bleeding occurred in five (13%). In group A, one episode each of bleeding occurred in two patients when the dose was 1 mg/kg. Four of the 38 patients (7.8%) had clotting with 40 mg and 2 (5.2%) had bleeding with the same dose.
None of the episodes of clotting was severe enough to warrant change of the dialyzer or bloodlines. None of the bleeding episodes on enoxaparin required blood transfusion and the bleeding could be controlled by venous compression at the site of arteriovenous fistula.
| Discussion|| |
Low molecular weight heparins are derived from unfractionated heparin by enzymatic or chemical hydrolysis. The mean molecular weight is 4000-6000 daltons in these fractions for effective anti-thrombotic activity.  Prevention of fibrin-clot formation in the extra-corporeal circuit during HD is the rationale for using an anticoagulant. This quality lies in the anti-Xa activity rather than anti-IIa (anti-thrombin) activity. Other advantages of LMWH are decreased tendency for both bleeding  and incidence of thrombocytopenia. 
Enoxaparin, with a mean molecular weight of 4000 daltons has 98 I.U./mg of anti-Xa activity and 25 I.U./mg of anti-IIa activity, and is well suited for use during HD. 
The lowest effective single bolus dosage for a 4-hour HD reported for the LMWH, nadroparin, is 125 anti-Xa UIC/kg. ,
LMWHs have been effectively used both as a single bolus dose, ,,, and as a continuous infusion ,, during HD.
In this short-term study of enoxaparin in 228 HD sessions for 38 patients, it was found that the anticoagulant efficacy and the incidence of complications (clotting/bleeding) were comparable to UFH. The LMWH may be superior to UFH because of its effectiveness as a single bolus dose requiring no infusion pump, its long biological half-life and as it rarely requires anticoagulant monitoring.
Interestingly, in this study it was noted that 40 mg of enoxaparin (lower than recommended dose) was adequate to provide anticoagulation for a three-hour dialysis session. This is possibly because of the high anti-Xa activity. But, individualization of the dose of enoxaparin is often required in patients with clotting/bleeding tendency.
In conclusion, LMWH as a single bolus dose is a safe and effective alternative to UFH for anticoagulation during HD. Larger group and long-term studies are required to assess the efficacy and safety of the smaller bolus dose (40 mg) of enoxaparin.
| Acknowledgement|| |
The authors wish to thank the nursing staff of the artificial kidney unit for their care of patients and enthusiastic participation in this study. Thanks are also due to Ms RhonePoulenc for the generous supply of enoxaparin.
| References|| |
|1.||Schrader J, Valentine R, Tonnis HJ, et al. Low molecular weight heparin in hemo dialysis and hemofiltration patients. Kidney Int 1985;28:823-9. |
|2.||Ljunberg B. A low molecular weight fraction as an anticoagulant during hemo-dialysis. Clinical Nephrol 1985;24:15-20. Anastassisdes EG, Lane OA, Flynn A, Curtis JC. Preliminary evaluation of repeated use of a low molecular weight heparin in hemodialysis for chronic renal failure. Proc Euro Dial Transplant 1985;22:329-33. |
|3.||Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992;79:1-17. [PUBMED] [FULLTEXT]|
|4.||Holmer E, Soderberg K, Bergqvist D, Lindahl K. Heparin and its low molecular weight derivatives: anticoagulant and antithrombotic properties. Haemostasis 1986; 16(Suppl 2):1-7. |
|5.||Borm JJ, Krediet R, Sturk A, Ten Cate JW. Heparin versus low molecular weight heparin K 2165 in chronic haemodialysis patients: a randomized crossover study. Haemostasis 1986;16(Suppl 2):59-68. [PUBMED] |
|6.||Schrader J, Stibbe W, Armstrong VW, et al. Comparison of low molecular weight heparin to standard heparin in hemodialysis/ hemofiltration. Kidney Int 1988;33:890-6. [PUBMED] |
|7.||Schrader J, Stibbe W, Kandt M, et al. Low molecular weight heparin versus standard heparin: a long-term study in hemodialysis and hemofiltration patients. ASAIO Trans 1990;36:28-32. |
|8.||Grau E, Siguenza F, Maduell F, et al. Low molecular weight heparin (CY-216) versus unfractionated heparin in chronic hemodialysis. Nephron 1992;62:13-7. |
|9.||Nurmohamed MT, Ten Cate J, Stevens P, Hoek JA, Lins RL, Ten Cate JW. Longterm efficacy and safety of a low molecular weight heparin in chronic hemodialysis patients. ASAIO Trans 1991;37:M459-61. [PUBMED] |
|10.||Bambauer R, Rucker S, Weber U, Kohler M. Comparison of low molecular weight heparin and standard heparin in hemodialysis. ASAIO Trans 1990;36:M646-9. |
|11.||Holmer E, Mattson C, Nilsson S. Anticoagulant and antithrombotic effects of heparin and low molecular weight heparin fragments in rabbits. Thromb Res 1982;25: 475-85. |
|12.||Hirsh J. In vivo effects of low molecular weight heparin on experimental thrombosis and bleeding. Haemostasis 1986;16:82-6. [PUBMED] |
|13.||Hirsh J. Low molecular weight heparin. Blood 1992;79:1-17. |
|14.||Warkentin TE, Levine MN, Hirsh J, et al. Heparin induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330-5. [PUBMED] [FULLTEXT]|
|15.||Barrowcliffe TW. Low molecular weight heparin(s). Br J Haematol 1995;90:1-7. [PUBMED] |
|16.||Lai KN, Wang AY, Ho K, et al. Use of low-dose low molecular weight heparin in hemodialysis. Am J Kidney Dis 1996;28: 721-6. [PUBMED] |
|17.||Lai KN, Ho K, Li M, Szeto CC. Use of single dose low molecular weight heparin in long hemodialysis. Int J Artif Organs 1998;21:196-200. [PUBMED] |
|18.||Koutsikos D, Fourtounas C, Kapetanaki A, et al. A cross-over study of a new low molecular weight heparin in hemodialysis. Int J Artif Organs 1996;19:467-71. [PUBMED] |
Department of Nephrology, Salmaniya Medical Complex, P.O. Box 12, Manama
[Table - 1], [Table - 2], [Table - 3], [Table - 4]