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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 3  |  Page : 466-470
Effect of vitamin E coated dialyzers on anticoagulation requirement in hemodialyzed children


Department of Pediatric Nephrology, Armand Trousseau Hospital, APHP, University Pierre et Marie Curie, Paris, France

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Date of Web Publication26-Apr-2010
 

   Abstract 

As hemodialysis (HD) requires extra corporal blood flow and the need for anti­coagulation, we evaluated the effect of vitamin E coated membranes (VIE) on the requirement of low molecular weight heparin (LMWH) in pediatric HD patients. Patients and methods: seven children and adolescents on regular hemodialysis were started on VIE and their LMWH dose was decreased every week. In order to monitor the requirement of LMWH we used a coagulation score to evaluate coagulation in the dialyzer, air trap and blood line. Other classical parameters (hemoglobin, erythropoietin dose, inflammatory markers) were monitored weekly while the pa­tients were on VIE dialyzers. LMWH dose during the 1st week was 110 IU/kg ± 18 (defined as 100%), in the 2nd week the dose was 77 IU/kg ± 12 (70%), in the 3 rd week the dose was 33 IU/kg ± 5 (30%), and in the 4 th week anticoagulation could be stopped in one patient, in the other six pa­tients further decrease was impossible given the increase of the clotting score. There was no in­crease in clotting score during week one and two. During week three (while on 30% of the initial LMWH dose) six patients showed mild to moderate clotting phenomena: mild coagulation phe­nomena in three patients and moderate clotting phenomena in three others. One patient did not show any clotting phenomena in week three and LMWH was totally stopped. In conclusion, use of VIE dialyzers may help to reduce the requirement of anticoagulation in pediatric HD patients reducing bleeding problems and simplify hemostasis after HD sessions.

How to cite this article:
Aoun B, Janssen-Lozinska Y, Ulinski T. Effect of vitamin E coated dialyzers on anticoagulation requirement in hemodialyzed children. Saudi J Kidney Dis Transpl 2010;21:466-70

How to cite this URL:
Aoun B, Janssen-Lozinska Y, Ulinski T. Effect of vitamin E coated dialyzers on anticoagulation requirement in hemodialyzed children. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Oct 24];21:466-70. Available from: https://www.sjkdt.org/text.asp?2010/21/3/466/62729

   Introduction Top


Hemodialysis (HD) requires extracorporeal blood flow and anticoagulants. Dialyzer clot­ting is a common factor underlying poor dialy­sis performance and may be responsible for difficulties in anemia management and exce­ssive EPO requirement. [1] In order to prevent clotting phenomena, anticoagulation is often increased exposing the patient to higher risk of hemorrhage and prolonged bleeding times of the arteriovenous fistula.

The plasma half life time of low molecular weight heparin (LMWH) is dependent on renal clearance. Thus, patients with renal failure are potentially at risk for bleeding as a result of impaired LMWH clearance and prolonged an­ticoagulant effects. [2] Despite the general avoi­dance of LMWH in HD patients, they are rou­tinely used to prevent thrombosis of the extra­corporeal dialysis circuit. [3],[4]

LMWH are not removed from the plasma du­ring hemodialysis [2] or continuous veno-venous hemofiltration. Thus, LMWH can accumulate during dialysis sessions and increase the risk for bleeding. It has been shown that the risk for hemorrhage in the HD population was in­creased by 10-fold. [5]

Strategies to decrease anticoagulation require­ment during HD sessions are therefore war­rented. VitabranE (VIE) is a polysulfone dialy­zer coated with vitamin E alpha-tocopherol. VIE consist of a polysulfone membrane graf­ted with liposoluble vitamin E on the blood side allowing direct free radical scavenging at the membrane site. [6] It has been suggested that vitamin E coated membranes may have poten­tially beneficial effects such as reduced micro­inflammation and oxidative stress [7] as well as improved stabilization of the erythrocyte mem­brane. [7] Recently it has been suggested that vitamin E coated membranes may decrease an­ticoagulation requirement during dialysis session. [9],[3],[10]

Since no studies in children have been per­formed so far to evaluate the effect of VIE on anticoagulation use or anemia, we undertook this pilot study in seven children undergoing HD


   Patients and Methods Top


We included in this prospective study all pa­tients from one single pediatric nephrology de­partment who were on chronic hemodialysis for three 4-hour sessions per week for more than six months. All patients underwent HD sessions with the use of high flux dialyzers adapted to patients' body surface area. We analyzed hemoglobin levels (Hb), C-reactive protein (CRP), procalcitonin (PCT), IL-6, as well as LMWH and EPO doses (darbepoetin alpha) immediately before, during, and after the switch to VIE dialyzer. All patients were dialyzed initially using high permeability mem­branes (FX 100, Fresenius, Germany). Dialysis machine in all patients was Gambro AK200S.

LMWH dose required for hemodialysis ses­sion before the use of vitamin E coated dialy­zers was defined as 100%. During the first week all patients were switched to vitamin E coated membranes (VIE dialyzers, Asahi Ku­raray Kasei Medical, Japan) with an equivalent membrane surface and maintained on the same dose of LMWH. On the second week the dose of LMWH was decreased to 70% of the initial dose without changes of other HD parameters. On the third week the LMWH dose was de­creased to 30% of the initial dose and totally stopped on the fourth week. In case of mo­derate clotting phenomena no further decrease of LMWH dose was performed. In case of severe clotting phenomena the study was inter­rupted and the initial LMWH dose used for the next session.

Dialyzer clotting score

During each HD session, blood lines, air traps and dialyzers were analyzed. We used a sco­ring system for semiquantitative description of the clotting activation in the dialyzer from 1 to 4 after each HD session: 1-no blood trace, clear color, 2-rare blood traces, 3-moderate blood traces, 4-severe blood coagulation. The presence of blood clots in air traps and blood lines was analyzed. Mild clotting phenomena were defined as dialyzer score ≤ 3, without blood clots in air trap or blood lines.

Presence of small blood clots in air trap or blood lines or dialyzer score > 3 were con­sidered as moderate, and bigger blood clots in air trap or precocious interruption of HD ses­sion caused by clotting problems as severe clot­ting phenomena.

Coagulation parameter analysis

All patients were analyzed for coagulation parameters (protein C, protein S, antithrombin III, mutation of factor V, mutation of factor II, fibrinogen, MTHFR mutations).

History of thromboembolic events was recor­ded for each patient.


   Statistical Analysis Top


Statistical analysis was performed using sig­ma-stat (version 3.5). Data were summarized as mean ± standard error of the mean (SEM) for normally distributed data and as median and range for data that were not normally dis­tributed. P-values < 0.05 were considered sta­tistically significant.


   Results Top


Seven children on regular HD were included. Median patient age was 15 years (range 12­17); LMWH was used for anticoagulation du­ring HD in all patients. Patient characteristics, including prothrombotic factors and main dia­lysis parameters are summarized in [Table 1]. Dialyzer clotting scores of all patients over the study period are given in [Table 2]. Before star­ting the patients on VIE and during the 1st week of VIE, mean LMWH dose was 110 IU/kg ± 18 (100%), on the 2 nd week 77 IU/kg ± 12 (70%); on the 3 rd week 33 IU/kg ± 5 (30%), and on the 4 th week the anticoagulation was stopped in one patient. In the other six patients further decrease was not performed as increased clotting phenomena were noted [Table 2]. Therefore, in these six patients week four was conducted with the same anticoagulation as week three. No patient showed severe inter­dialytic clotting phenomena

There was no increase in clotting score du­ring week one and two. During week three (while on 30% of the initial LMWH dose) six patients showed mild to moderate clotting phe­nomena: mild coagulation phenomena in three patients and moderate clotting phenomena in three others. One patient did not show any clotting phenomena in week three and LMWH was totally stopped. In week four he was dia­lyzed without LMWH, but filter clotting score increased from one to three in all three ses­sions during week four whereas no other clot­ting phenomenon was noticed in this patient.

Hemoglobin levels before (13.5 g/dL ± 0.7), during (14 g/dL ± 0.8) and one month after (12 g/dL ± 2) the use of VIE, were not signifi­cantly different. EPO dose was (0.5 μg/kg ± 0.3) before, (0.4 μg/g ± 0.2) during, and (0.38 μg/kg ± 0.19) one month after the use of VIE dialyzers. CRP, PCT, and IL-6 remained in the low normal range during the whole study for all patients.

Among the three patients with moderate clot­ting increase during the decrease of the LM­WH dose, one patient had a heterozygote mu­tation of the MTHFR. Another one had a low protein C level. The 3 rd patient had atypical he­molytic uremic syndrome secondary to Factor H deficiency, and medical history of repeated thrombosis in his AVF and central venous catheter.


   Discussion Top


The results of our study suggest that the use of VIE dialyzers may allow a decrease of anti­coagulation during the HD session in some children and adolecents on chronic HD. In three of the seven patients a decrease by 70% of the initial LMWH dose led to significant coagulation in the hemodialysis circuit, but these patients had underlying disorders related to a higher risk for blood clotting.

In patients without intrinsic risk factors for coagulation, we decreased LMWH dose by 70% before experiencing a certain degree of coagu­lation in the dialyzer. Those with risk for coa­gulation needed a higher dose of LMWH, but we were able to decrease the dose by 30% be­fore starting to experience coagulation in the dialyzer. Further, it is known that in patients with prothrombotic risk factors LMWH re­quirement is generally higher than in normal subjects.

A controlled study design would have been of interest; unfortunately in a pediatric hemo­dialysis center, patient number is relatively small. Further, differences in age, body mass index, and underlying disorders make a mat­ched control group very difficult. Moreover, all hemodialyzed children are on a transplan­tation waiting list and the period on HD before transplantation is relatively short compared to adults, making a cross over study very difficult.

Studies on adult patients have demonstrated that the use of vitamin E coated dialyzers helps to reduce clotting problems in high risk pa­tients. [13] These authors have shown that throm­bembolic events can be reduced in high risk patients and anticoagulation can be decreased in patients without prothrombotic risk factors.

One important goal in the treatment of chil­dren and adolescents with ESRD is that social life remains as 'normal' as possible. Social ac­tivities and sport contribute to psychological stability and well-being. Physical activity ex­poses hemodialysis patients to potential trau­ma and hemorrhage. [14] However, hemorrhage in HD patients on LMWH remains relatively rare. [15] Nevertheless, a risk reduction for hemo­rrhage may increase physical activity, which is considered as an important protective factor for cardiovascular disease.

Others have reported a beneficial effect of vi­tamin E coated membranes on intra- and inter­dialytic complications. [16] In our study, two of the seven included patients have reported less thirst and less fatigue after the dialysis session. Due to the small sample size we cannot draw confident conclusions and a lager trial in chil­dren may help in supporting our conclusions. Patients' hemoglobin levels did not change significantly. This result is difficult to interpret due to the very short period on VIE dialyzers. The VIE dialyzer consists of a basis in poly­sulfone (known for its excellent biocompati­bility) associated to polyvinylpyrrolidone to increase the diffusive properties and a vitamin E coating with antioxidant properties. Oxygen free radicals may play a pathogenic role in some hemodialysis related complications. [16] The VIE dialyzer, in addition to anti-oxidant pro­perties, has improved biocompatibility charac­teristics due to its design aimed at limiting blood-membrane interaction. In our pediatric HD patients inflammation markers were low on standard polysulfone dialyzers and remai­ned low on VIEs. [17] Therefore, reduced inflam­mation cannot be assumed to be responsible for the noticed benefits. [18] Another hypothesis could be that current inflammation markers, such as CRP, PCT and IL-6 are not sensitive enough to monitor inflammation in pediatric HD patients.

Both coagulation within the circuit and he­morrhage can result in HD related anemia.[19] In adults a positive effect of VIE on hemoglobin levels was shown previously. [1]

We did not find any effect of VIE dialyzers on anemia or EPO requirement, but our obser­vation period was too short to interpret such a negative result. Thus, longer prospective con­trolled studies with more subtle inflammation markers on a larger patient number are war­ranted to confirm our results.

In conclusion, the use of VIE dialyzers may help to reduce the requirement of anticoagula­tion in pediatric HD patients. This might reduce bleeding problems and simplify hemostasis after HD sessions.

 
   References Top

1.Cruz DN, De Cal M, Garzotto F, et al. Effect of vitamin E-coated dialysis membranes on anemia in patients with chronic kidney disease: an Italian multicenter study. Int J Artif Organs 2008;31:545-52.  Back to cited text no. 1  [PUBMED]    
2.Lim W, Cook DJ, Crowther MA. Safety and efficacy of low molecular weight heparins for hemodialysis in patients with end-stage renal failure: a meta-analysis of randomized trials. J Am Soc Nephrol 2004;15:3192-206.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Mandolfo S, Bucci R, Imbasciati E. Vitamin E­coated membrane dialyzer and beta2-micro­globulin removal. Artif Organs 2003;27: 1123-­7.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Schneiter S, Huynh-Do U, Heizmann M. Bleeding complication due to accumulation of low-molecular-weight heparin in a patient with renal insufficiency. Praxis (Bern 1994) 2007; 96:733-7.  Back to cited text no. 4      
5.Davenport A. Practical guidance for dialyzing a hemodialysis patient following acute brain injury. Hemodial Int 2008;12:307-12.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Satoh M, Yamasaki Y, Nagake Y, et al. Oxi­dative stress is reduced by the long-term use of vitamin E-coated dialysis filters. Kidney Int 2001;59:1943-50.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Morimoto H, Nakao K, Fukuoka K, et al. Long­term use of vitamin E-coated polysulfone mem­brane reduces oxidative stress markers in hae­modialysis patients. Nephrol Dial Transplant 2005;20:2775-82.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Uzum A, Toprak O, Gumustas MK, et al. Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis. J Nephrol 2006;19:739-45.  Back to cited text no. 8  [PUBMED]    
9.Cruz DN, de Cal M, Ronco C. Oxidative stress and anemia in chronic hemodialysis: the pro­mise of bioreactive membranes. Contrib Nephrol 2008;161:89-98.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]  
10.Girndt M, Lengler S, Kaul H, et al. Prospective crossover trial of the influence of vitamin E­coated dialyzer membranes on T-cell activa­tion and cytokine induction. Am J Kidney Dis 2000;35:95-104.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Usalan C, Erdem Y, Altun B, et al. Protein Z levels in haemodialysis patients. Int Urol Nephrol 1999;31:541-5.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Nampoory MR, Das KC, Johny KV, et al. Hyper coagulability: A serious problem in pa­tients with ESRD on maintenance hemodia­lysis, and its correction after kidney transplan­tation. Am J Kidney Dis 2003;42:797-805.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Huraib S, Tanimu D, Shaheen F, et al. Effect of vitamin-E-modified dialysers on dialyser clotting, erythropoietin and heparin dosage: a comparative crossover study. Am J Nephrol 2000;20:364-8.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]  
14.Boccardo P, Remuzzi G, Galbusera M. Platelet dysfunction in renal failure. Semin Thromb Hemost 2004;30:579-89.  Back to cited text no. 14  [PUBMED]    
15.Gouin-Thibault I, Pautas E, Siguret V. Safety profile of different low-molecular weight he­parins used at therapeutic dose. Drug Saf 2005; 28:333-49.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]  
16.Tanimu D, Huraib S, Shaheen FA, et al. The Effect of Vitamin E-Modified Dialyzers on Acute Intra-dialytic Symptoms: A Comparative Crossover Study. Saudi J Kidney Dis Transpl 2000;11:543-7.  Back to cited text no. 16  [PUBMED]  Medknow Journal  
17.Sasaki M. Development of vitamin E-modified polysulfone membrane dialyzers. J Artif Organs 2006;9:50-60.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Calo LA, Naso A, Pagnin E, et al. Vitamin E­coated dialyzers reduce oxidative stress related proteins and markers in hemodialysis-a molecular biological approach. Clin Nephrol 2004;62:355-61.  Back to cited text no. 18      
19.Zachee P, Vermylen J, Boogaerts MA. Hema­tologic aspects of end-stage renal failure. Ann Hematol 1994;69:33-40.  Back to cited text no. 19      

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Correspondence Address:
Tim Ulinski
Department of Pediatric Nephrology and INSERM U515, Hospital Armand Trousseau, AP-HP, University Paris VI 26, Avenue du Docteur Netter 75571 Paris
France
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    Tables

  [Table 1], [Table 2]

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