Year : 2010 | Volume
: 21 | Issue : 3 | Page : 466--470
Effect of vitamin E coated dialyzers on anticoagulation requirement in hemodialyzed children
Bilal Aoun, Yuliya Janssen-Lozinska, Tim Ulinski
Department of Pediatric Nephrology, Armand Trousseau Hospital, APHP, University Pierre et Marie Curie, Paris, France
Department of Pediatric Nephrology and INSERM U515, Hospital Armand Trousseau, AP-HP, University Paris VI 26, Avenue du Docteur Netter 75571 Paris
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;21:466-470
|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 Jul 15 ];21:466-470
Available from: http://www.sjkdt.org/text.asp?2010/21/3/466/62729
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.  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.  Despite the general avoidance of LMWH in HD patients, they are routinely used to prevent thrombosis of the extracorporeal dialysis circuit. ,
LMWH are not removed from the plasma during hemodialysis  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. 
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.  It has been suggested that vitamin E coated membranes may have potentially beneficial effects such as reduced microinflammation and oxidative stress  as well as improved stabilization of the erythrocyte membrane.  Recently it has been suggested that vitamin E coated membranes may decrease anticoagulation requirement during dialysis session. ,,
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
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 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 st 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.
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.  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.  However, hemorrhage in HD patients on LMWH remains relatively rare.  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.  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.  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.  Therefore, reduced inflammation cannot be assumed to be responsible for the noticed benefits.  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. In adults a positive effect of VIE on hemoglobin levels was shown previously. 
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.
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