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which can involve over 600 cumulative hours per year&#46; These include risk of bleeding and thrombotic complications &#40;which are not always correlated with over or under-dosing&#41;&#44; metabolic effects&#44; primarily dyslipidemia&#44; osteoporosis&#44; and effects on blood cells&#44; especially platelets&#46;<span class="elsevierStyleSup">1&#44;2</span></p><p class="elsevierStylePara">Since the 1980&#8217;s&#44; low molecular weight heparin &#40;LMWH&#41; has been incorporated into daily clinical practice as an alternative to conventional&#44; or unfractionated heparin &#40;UFH&#41;&#44; with the goal of improving efficacy and safety&#44; reducing the secondary side effects produced&#44; and facilitating patient management in terms of dosage adjustments and administration regimens&#46;<span class="elsevierStyleSup">3-5</span> Several different studies have shown that LMWH and UFH have similar levels of efficacy and safety&#46;<span class="elsevierStyleSup">6-7</span> As regards side effects&#44; studies have shown that LMWH produces a lower increase in plasma triglyceride levels<span class="elsevierStyleSup">8&#44;9</span> and lower incidences of thrombocytopoenia<span class="elsevierStyleSup">10</span> and osteoporosis<span class="elsevierStyleSup">11</span> than UFH&#46; The ease of administration&#44; higher cost&#44; persistence of anticoagulation activity several hours after the HD session&#44; risk of accumulation using high and frequent doses&#44; and the complexity of adjusting doses using laboratory control tests are also factors to take into account when prescribing LMWH over UFH&#46; Thus&#44; whereas the guidelines recommend using LMWH over UFH&#44;<span class="elsevierStyleSup">12</span> in current clinical practice&#44; there is no established consensus for prescribing one type of heparin or the other&#46;</p><p class="elsevierStylePara">In addition to the individualisation of the type and dose of heparin to be used&#44; other aspects of this treatment also lack standardised criteria&#44; such as system priming with or without heparin &#40;and if so&#44; the dose to be used&#41;&#44; the mode of administration&#44; and the prescription for anticoagulation based on the HD technique used&#46; For their part&#44; elderly age and cardiovascular comorbidity already necessitate oral anti-platelet and&#47;or anticoagulant treatment in an undetermined percentage of prevalent HD patients&#44; for which there are no general recommendations when considering prescribing anticoagulation therapy during an HD session&#46;</p><p class="elsevierStylePara">Given the heterogeneity of the possible variables&#44; approaching to this subject first involves defining the current situation in clinical practice&#44; that is to say&#44; document which methods are being applied in the various dialysis centres around the country&#46; For this reason&#44; the Task Force for Anticoagulation in Haemodialysis of the Spanish Society of Nephrology &#40;S&#46;E&#46;N&#46;&#44; for its initials in Spanish&#41; proposed a study based on surveys completed by all of the haemodialysis units in Spain&#44; with the objectives of&#44; firstly&#44; assessing which anticoagulation methods are being used in Spain&#44; secondly&#44; what criteria define which methods to use&#44; and finally&#44; which method is more commonly associated with bleeding and thrombotic complications&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Ours was a cross-sectional descriptive study based on two different types of surveys&#58; one survey for haemodialysis centres&#44; and another for patients&#46; The first survey was designed to evaluate the anticoagulation policies used at public and private HD centres&#46; The patient survey analysed individual anticoagulation data from a randomly chosen 10-patient sample from each centre&#46; The surveys were distributed and collected between May and September 2008&#46;</p><p class="elsevierStylePara">The survey for dialysis centres collected information on the type of heparin used&#44; dose and method of administration&#44; and circuit priming&#46; The survey also included a section on the criteria used for deciding whether to administer LMWH or UFH&#44; with the following possible responses&#58; 1&#41; medical criteria &#40;dyslipidemia&#44; thrombocytopenia&#44; etc&#46;&#41;&#46; 2&#41; Dosing&#46; 3&#41; Cost&#46; 4&#41; Dialysis technique&#46; 5&#41; Vascular access&#46; 6&#41; Other&#46; Finally&#44; we asked for information on the adjustment methods used for dosing UFH and LMWH&#46;</p><p class="elsevierStylePara">In addition to the questions regarding the anticoagulation methods used for each patient&#44; the patient survey included questions on diagnosis of diabetes&#44; haemoglobin levels&#44; vascular access type&#44; membrane type&#44; dialysis technique&#44; duration of HD sessions&#44; and pump flow&#46; We also asked if the patient was receiving additional anticoagulant and&#47;or anti-platelet treatment&#44; as well as whether any bleeding or thrombotic complications arose in the previous week&#46;</p><p class="elsevierStylePara">We performed all statistical analyses using SPSS statistical software&#44; version 15&#46;0&#46; We analysed qualitative variables using absolute frequencies and percentages&#44; while quantitative variables were assessed using mean&#44; standard deviation&#44; median&#44; minimum&#44; and maximum&#46; We applied tests of normality &#40;Kolmogorov-Smirnov&#41; and homoscedasticity &#40;Levene&#41; prior to applying parametric tests&#46; We compared more than 2 groups using one-way ANOVA tests for normally distributed continuous variables&#44; and Kruskal-Wallis tests for non-parametric variables&#46; For comparisons of group means&#44; we used Student&#8217;s t-tests in the case of normally distributed continuous variables&#44; and Mann-Whitney U-tests for non-parametric variables&#46; In the case of discreet variables&#44; we used chi-square or Fisher&#8217;s exact tests when necessary&#46; Following these comparisons&#44; we selected those variables with a <span class="elsevierStyleItalic">P</span>-value &#60;&#46;100 for use in a logistic regression model&#46; The level of statistical significance was set at 5&#37;&#46;</p><p class="elsevierStylePara">This study has been approved by the Spanish Society of Nephrology&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">For a better comprehension of the results obtained&#44; we have separated this section into two parts&#44; corresponding to the data obtained in the surveys for haemodialysis centres and the data for patient surveys&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Haemodialysis Centre Survey</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We compiled surveys from 89 haemodialysis centres throughout the country&#44; constituting 29&#37; of all such centres in Spain&#46; Of these&#44; 43 &#40;48&#46;3&#37;&#41; were public entities&#44; and 46 &#40;51&#46;7&#37;&#41; were private&#46; Of the 89 centres that responded to the survey&#44; only 2 were paediatric units&#44; and these were excluded from the general statistical analysis&#46; The remaining 87 centres corresponded to adult patients&#44; and at the moment the survey was taken&#44; these centres treated a total of 6093 patients&#46;</p><p class="elsevierStylePara">The data obtained from these 87 surveys are as follows&#58;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">1&#46; Type of Heparin</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The majority of the centres surveyed &#40;61&#59; 70&#46;2&#37;&#41; utilised both types of heparin&#44; 19 &#40;21&#46;8&#37;&#41; only administered LMWH&#44; and 7 &#40;8&#37;&#41; only used UFH&#46; Although there was a certain tendency to use LMWH to a greater extent at public centres than private ones&#44; this difference was not statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;073&#41;&#46; The types of LMWH available at the 80 centres were&#58; enoxaparin &#40;60&#37;&#41;&#44; bemiparin &#40;32&#46;6&#37;&#41;&#44; nadroparin &#40;21&#46;3&#37;&#41;&#44; dalteparin &#40;12&#46;5&#37;&#41;&#44; and tinzaparin &#40;11&#46;3&#37;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">2&#46; Criteria Used for LMWH</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">This was a multiple choice question&#44; and the percentages for each response were calculated for the 78 centres that responded &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">3&#46; Type of HD Priming</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">There is a wide variability in both the use of heparin priming and the dose used&#46; We can summarise that&#58;</p><p class="elsevierStylePara">-If UFH was used during HD &#40;68 centres&#41;&#44; the majority used UFH for priming &#40;86&#46;7&#37;&#41;&#44; 7&#46;4&#37; did not use heparin for priming&#44; and 5&#46;9&#37; did so with or without heparin depending on the patient&#46;</p><p class="elsevierStylePara">-If LMWH was used &#40;73 centres&#41;&#44; 21&#46;9&#37; of centres did not use heparin priming&#44; 71&#46;3&#37; did so with heparin&#44; and 6&#46;8&#37; either used or did not use heparin&#44; depending on the patient&#46;</p><p class="elsevierStylePara">The heparin dose used for priming ranged between 1000UI and 10&#160;000UI&#46; However&#44; regardless of the type of heparin used in the HD session&#44; the most commonly used dose was 5000UI &#40;66&#37; of centres when UFH was used&#44; and 67&#46;6&#37; of centres when LMWH was used&#41;&#44; followed by 2500UI &#40;17&#37; with UFH&#44; and 16&#46;2&#37; with LMWH&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">4&#46; Dosing</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The methods of administration employed for heparin doses are summarised in Figure 1&#46; Regardless of the method of administration for UFH throughout the HD session&#44; the majority of centres used an initial bolus &#40;92&#46;6&#37; when using a continuous dose&#44; 97&#46;6&#37; when using an intermittent dose&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">5&#46; Adjustment Methods for the Heparin Dose</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We received 85 responses for this section from the 87 surveys sent&#46; As such&#44; the percentages for this question were calculated over 85&#44; and the results are summarised in Table 2&#46; The general rule was that several factors were taken into account when adjusting the dose used&#46; This was a multiple choice question that allowed us to assess the possible combination of factors in this context&#46; Among these&#44; the most common combinations used were&#58; &#8220;weight &#43; coagulation of the dialyser&#47;lines &#43; bleeding after disconnect&#8221; in 30 centres &#40;35&#46;3&#37;&#41; and &#8220;coagulation of the dialyser&#47;lines &#43; bleeding after disconnect&#8221; in 17 centres &#40;20&#37;&#41;&#44; with all others being much less common&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patient Survey</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Of the 89 centres that responded to our surveys&#44; 80 provided patient data&#44; with a total of 770 patients surveyed&#46; The general statistical analysis did not include 12 patients &#40;10 due to non-compliance with the full range of questions asked at one centre&#44; and 2 who were paediatric patients&#41;&#46; In this manner&#44; a total of 758 adult patients were included in the analysis from 78 different dialysis centres&#44; of which 34 &#40;43&#46;6&#37;&#41; were public and 44 &#40;56&#46;4&#37;&#41; were private&#46; The most important characteristics of these patients are summarised in Table 3&#46;</p><p class="elsevierStylePara">The most relevant data obtained in the patient survey can be summarised as&#58;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">1&#46; Anticoagulation in the Study Population</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We obtained data on 733 patients&#44; of which 323 &#40;44&#46;1&#37;&#41; received treatment with UFH&#44; 378 &#40;51&#46;5&#37;&#41; with LMWH&#44; and 32 &#40;4&#46;4&#37;&#41; received no anticoagulation during dialysis&#46; At public centres&#44; 64&#46;2&#37; of patients received LMWH&#44; whereas 46&#46;1&#37; of patients received this type of heparin at private centres &#40;statistically significant difference&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46;</p><p class="elsevierStylePara">The heparin dose was quantified in 291 patients&#44; 186 of which received UFH and 105 received LMWH&#46; The mean dose of UFH was 2988 &#40;1706&#41; UI &#40;range&#58; 500-9500UI&#44; median&#58; 3000UI&#41; and the mean dose of LMWH was 3598 &#40;1601&#41; UI &#40;range&#58; 1000-8000UI&#44; median&#58; 3500UI&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">2&#46; Anticoagulation According to Patient Characteristics</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Upon analysis of patient characteristics based on the type of heparin used&#44; we observed no differences in terms of sex or prevalence of diabetes&#46; However&#44; patients that received LMWH tended to be younger&#44; and had lower haemoglobin levels &#40;Table 3&#41;&#46; There were no differences in the heparin doses prescribed &#40;for both UFH and LMWH&#41; in terms of age&#44; sex&#44; haemoglobin levels&#44; or diagnosis of diabetes&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">3&#46; Anticoagulation According to Vascular Access</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The distribution of vascular access types in the 758 patients that responded to this part of the survey was&#58; autologous arteriovenous fistula &#40;AVF&#41;&#58; 68&#46;5&#37;&#44; prosthesis&#58; 7&#46;8&#37;&#44; and catheter&#58; 23&#46;7&#37;&#46; There were no differences in terms of the distribution of the different types of vascular access between public and private centres&#46; In patients with AVF&#44; LMWH was utilised more frequently &#40;56&#37; vs 44&#37;&#41; whereas patients with prostheses were administered UFH more frequently &#40;62&#37; vs 38&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;048&#41;&#46; In patients with a catheter&#44; the rates of using the two types of heparin were similar&#46;</p><p class="elsevierStylePara">There were no differences in terms of the heparin doses prescribed &#40;whether for UFH or LMWH&#41; based on the type of vascular access used&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">4&#46; Anticoagulation According to the Technique and Membrane Type Used for Dialysis</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The dialysis technique used was recorded for 757 patients&#44; of which 413 &#40;54&#46;6&#37;&#41; received high-flux HD&#44; 249 &#40;32&#46;9&#37;&#41; received low-flux HD&#44; and 95 &#40;12&#46;5&#37;&#41; received on-line haemodiafiltration &#40;OL-HDF&#41;&#46; At public centres&#44; the distribution was&#58; high-flux HD&#58; 47&#46;5&#37;&#44; low-flux HD&#58; 30&#46;7&#37;&#44; and OL-HDF&#58; 21&#46;7&#37;&#44; whereas at private centres&#44; the distribution was 59&#46;8&#37;&#44; 34&#46;5&#37;&#44; and 5&#46;7&#37;&#44; respectively &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;001&#41;&#46;</p><p class="elsevierStylePara">The distribution of the type of heparin used according to the dialysis technique used is represented in Figure 2&#46;</p><p class="elsevierStylePara">The types of membranes used for dialysis were&#58; cellulose&#58; 6&#46;1&#37;&#44; polysulfone&#58; 59&#46;5&#37;&#44; polyethersulfone&#58; 12&#46;2&#37;&#44; polyamide&#58; 15&#46;8&#37;&#44; AN69&#58; 3&#46;7&#37;&#44; and other&#58; 2&#46;7&#37;&#46; We observed no significant differences in terms of the type of membrane used between public and private centres&#46; There were also no significant differences in the type of heparin administered &#40;UFH vs LMWH&#41; based on membrane type&#46;</p><p class="elsevierStylePara">The heparin doses prescribed were similar regardless of the HD technique or membrane type used&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">5&#46; Anticoagulation According to Time on Dialysis and Pump Flow</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The mean duration of HD sessions was 231 &#40;26&#41; minutes &#40;range&#58; 120-310 minutes&#41;&#44; with the most common duration of sessions being 4&#58;00-4&#58;30 hours &#40;n&#61;440&#59; 59&#46;2&#37;&#41;&#44; followed by the interval of 3&#58;30-4&#58;00 hours &#40;n&#61;172&#59; 23&#46;1&#37;&#41;&#44; and &#62;4&#58;30 hours &#40;n&#61;63&#59; 8&#46;4&#37;&#41;&#46; There was no correlation between the type of heparin used and the duration of the HD session&#46; As was expected&#44; the dose of heparin prescribed was significantly lower in patients with shorter dialysis sessions &#40;less than 4 hours&#41; as compared to sessions lasting &#62;4 hours&#44; both when employing UFH &#40;2443&#177;1246UI vs 3264&#177;1804UI&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;003&#41; and LMWH &#40;2828&#177;1234UI vs 3870&#177;1630UI&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;002&#41;&#46;</p><p class="elsevierStylePara">Mean blood pump flow was 346 &#40;47&#41; ml&#47;min &#40;range&#58; 150-500ml&#47;min&#41;&#46; Pump flow was significantly higher in the group that received UFH as compared to the group that received LMWH &#40;351&#177;42ml&#47;min vs 339&#177;51ml&#47;min&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;001&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">6&#46; Anticoagulation in Haemodialysis and Anti-platelet and&#47;or Anticoagulant Treatment</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We acquired survey responses regarding anti-platelet and&#47;or oral anticoagulant treatment from 727 patients&#46; Of these&#44; 331 &#40;45&#46;5&#37;&#41; received anti-platelets&#44; 134 &#40;18&#46;4&#37;&#41; received oral anticoagulants&#44; and 36 &#40;5&#37;&#41; received both&#46; Overall&#44; 425 &#40;58&#46;5&#37;&#41; received some type of anti-platelet and&#47;or anticoagulant treatment&#46;</p><p class="elsevierStylePara">The majority of patients that received oral anticoagulant treatment &#40;n&#61;115&#59; 85&#46;8&#37;&#41; also required heparin during HD&#46; LMWH was used somewhat more frequently in these cases&#44; although this difference was not statistically significant &#40;LMWH&#58; 56&#46;4&#37;&#59; UFH&#58; 43&#46;6&#37;&#41;&#46; The UFH dose prescribed in patients that also received coumarin-type drugs was lower than in those that did not &#40;2279&#177;1499UI vs 3105&#177;1721UI&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;012&#41;&#44; whereas no significant differences were observed in the doses prescribed for LMWH &#40;3913&#177;1768UI vs 3439&#177;1486UI&#44; respectively&#41;&#46;</p><p class="elsevierStylePara">As regards priming&#44; 77&#46;9&#37; of patients that received oral anticoagulants underwent heparin priming&#44; with doses similar to those of other patients&#46;</p><p class="elsevierStylePara">Patients receiving anti-platelet treatment had no differences from others in terms of the dose of heparin prescribed&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">7&#46; Anticoagulation and Bleeding Complications</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Of the 743 patients analysed in this section&#44; 33 &#40;4&#46;4&#37;&#41; had experienced some type of bleeding complication within the previous week of filling out the survey&#46; We observed no correlations between bleeding complications and age&#44; sex&#44; diabetes&#44; or anti-platelet treatment&#46; Patients with bleeding complications had significantly lower haemoglobin levels than patients that did not &#40;10&#46;9&#177;1&#46;4g&#47;dl vs 12&#46;1&#177;1&#46;2g&#47;dl&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#44; and received oral anticoagulation therapy more frequently &#40;Figure 3&#41;&#46; If we eliminate patients that received oral anticoagulants from the analysis&#44; no significant differences were present in terms of the number of bleeding complications between patients receiving UFH and those receiving LMWH &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;078&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">8&#46; Anticoagulation and Thrombotic Complications </span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Thrombotic complications in the week prior to taking the survey were reported in 14 of the 737 patients analysed &#40;1&#46;9&#37;&#41;&#44; with a greater frequency of occurrence in patients that received LMWH &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;003&#41;&#46; There were no significant differences in the dose of heparin prescribed&#44; whether UFH or LMWH&#44; between patients that experienced thrombotic complications and those that did not&#46;</p><p class="elsevierStylePara">Finally&#44; of the 2 paediatric centres asked to participate&#44; 1 provided the surveys for 2 patients&#46; Both received LMWH &#40;enoxaparin&#41;&#44; with heparin priming and high-flux HD using polysulfone&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Firstly&#44; we would like to point out that both surveys can be considered valid for the analysis of our objectives&#46; The number of centres&#44; the geographic distribution of the various autonomous communities in Spain&#44; the inclusion of both public and private centres&#44; and the number of patients treated all lend strength to the haemodialysis centre survey&#46; The patient survey was bolstered by the random selection of patients&#44; lending similar characteristics to our sample as in other recent studies such as the Dopps III&#44; which was considered representative of the adult Spanish population on dialysis&#46;<span class="elsevierStyleSup">13</span> As such&#44; the mean age&#44; sex distribution&#44; proportion of diabetic patients&#44; mean haemoglobin values&#44; and distribution of the different types of vascular accesses used are comparable between these studies&#46;<span class="elsevierStyleSup">13</span></p><p class="elsevierStylePara">The primary objectives of our study were to assess the anticoagulation methods employed in Spain and what criteria they are based on&#46; The near-50&#37; distribution of the two types of heparin&#44; despite the guideline recommendations that favour LMWH&#44;<span class="elsevierStyleSup">12</span> indicate that&#44; in clinical practice&#44; there are additional criteria taken into account&#46; Based on the type of data compiled&#44; we cannot completely verify the reason for the lower frequency with which LMWH is used at private centres&#44; even though availability was similar&#46; The issue of costs could be an important factor&#59; however&#44; only 10&#37; of centres indicated that cost was taken into account when deciding upon treatment&#46; Whereas the greater costs of LMWH limited its use in the past&#44; this currently does not appear to be an important limiting factor&#44; with other criteria taking precedent in deciding upon whether to prescribe this drug&#46;<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">The risk of bleeding is the primary secondary side effect of anticoagulation therapy in HD&#46; In our study&#44; there was no association between bleeding complications and the type of heparin administered&#44; which confirms previous observations that indicated a similar level of safety for both UFH and LMWH&#46;<span class="elsevierStyleSup">6&#44;7</span> We are not aware of the reason for the greater frequency of thrombotic complications observed in the group receiving LMWH&#46; The possible reasons include a lower efficacy of this drug&#44; inferior dosage adjustment&#44; or the fact that LMWH was prescribed more frequently in complex patients with a greater tendency towards coagulability&#46;</p><p class="elsevierStylePara">Medical criteria&#44; followed by ease of administration&#44; were the most commonly reported reasons for indicating LMWH&#46; In addition to bleeding and thrombotic phenomena&#44; dyslipidaemia&#44;<span class="elsevierStyleSup">14</span> osteoporosis&#44;<span class="elsevierStyleSup">15</span> and thrombocytopoenia<span class="elsevierStyleSup">16-19</span> are the most common side effects observed in the use of heparin in HD patients&#44; and were surely considered within the medical criteria used to decide upon the prescription of LMWH in the patients included in our study&#46; Several studies have demonstrated a lower increase in triglyceride levels in HD patients with LMWH than in those receiving UFH&#44;<span class="elsevierStyleSup">8&#44;9&#44;14&#44;20&#44;21</span> although other studies did not corroborate with these findings&#46;<span class="elsevierStyleSup">22-24</span> On the other hand&#44; in patients without renal failure receiving prolonged treatment&#44; the risk of developing osteoporosis is lower when utilising LMWH instead of UFH&#46;<span class="elsevierStyleSup">15&#44;25&#44;26</span> In HD&#44; LMWH has also been reported to cause osteoporosis at a lower rate than UFH&#44;<span class="elsevierStyleSup">11&#44;27</span> although no studies have clearly confirmed this phenomenon&#46; Finally&#44; in the population without renal failure&#44; the incidence of thrombocytopenia induced by type II heparin is lower with LMWH than UFH&#44;<span class="elsevierStyleSup">28&#44;29</span> which has also been described in patients on HD&#46;<span class="elsevierStyleSup">10</span></p><p class="elsevierStylePara">Both the survey for HD centres and the patient survey revealed that the type of vascular access was the third most common indication for employing LMWH&#46; Although one study did show that the permeability of vascular accesses improves with the use of LMWH&#44;<span class="elsevierStyleSup">30</span> to our knowledge&#44; there are no studies that have shown any advantages from using a certain type of heparin over another when using autologous AVF or prosthesis&#46;</p><p class="elsevierStylePara">The dialysis technique used was also one of the criteria employed for deciding whether to administer LMWH&#44; which was prescribed at a greater rate than UFH in OL-HDF&#46; On the other hand&#44; the dose of LMWH was not significantly different when comparing between OL-HDF&#44; low-flux HD&#44; and high-flux HD&#46; These data appear to contradict our understanding of the pharmacokinetics of LMWH during HD sessions&#46; Several studies have shown that anti-Xa activity is significantly reduced in high-flux HD and convective techniques&#44; as a consequence of the elimination of LMWH through the dialysate&#47;ultrafiltrate&#46; McMahon et al&#46; showed that the anti-Xa activity in high-flux HD was lower than in low-flux HD when using the same dose of enoxaparin&#46;<span class="elsevierStyleSup">31</span> Using continuous HD techniques&#44; Isla et al&#46; demonstrated significant enoxaparin losses in the ultrafiltrate&#47;dialysate&#46;<span class="elsevierStyleSup">32 </span>Another study showed that anti-Xa activity at the end of the HD session was significantly lower on OL-HDF than low-flux HD&#46;<span class="elsevierStyleSup">33</span> In any case&#44; LMWH losses in dialysate are higher at the start of an HD session when administering boluses through the arterial branch of the HD system&#46;<span class="elsevierStyleSup">10</span> For these reasons&#44; in high-flux HD and even more so in HF and HDF techniques&#44; some authors recommend administering LMWH at the start of the HD session in the venous branch of the extracorporeal blood circuit&#44;<span class="elsevierStyleSup">10</span> or to administer it 3-4 minutes before starting dialysis&#46;<span class="elsevierStyleSup">34</span> In our study&#44; we did not analyse what type of administration was used &#40;arterial or venous branch&#41; or the moment of administration&#44; since these questions were not included in the surveys&#46;</p><p class="elsevierStylePara">As regards the type of material used in HD&#44; platelet activation and coagulation varies according to the membrane used&#44; such that the following sequence can be established based on these properties&#58; unmodified cellulose membranes &#62; unmodified AN69 &#62; polysulfone &#62; polyamide&#46;<span class="elsevierStyleSup">35</span> In our study&#44; we observed that the type of membrane used was not correlated with the type of heparin or dosage used in normal clinical practice&#46; However&#44; we must keep in mind that the majority of these patients were treated using synthetic membranes&#44; primarily polysulfones&#47;polyethersulfones&#46;</p><p class="elsevierStylePara">It is interesting to point out that in patients receiving LMWH&#44; the pump flow was significantly lower than in patients receiving UFH&#46; Given that pump flow is directly related to heparin dose&#44; these results should be interpreted taking into account that&#44; given a higher risk of coagulation from a lower pump flow&#44; LMWH tends to be used&#44; probably with the goal of increasing efficacy&#44; which would partly explain the greater incidence of thrombotic phenomena observed in this group&#46;</p><p class="elsevierStylePara">Diabetes did not affect the use of heparin&#44; neither type nor dose&#44; which is in accordance with the current clinical mind-set that has rejected the antiquated and unproven idea that heparinisation in dialysis could increase the risk of ocular bleeding complications in these patients&#44; which could worsen the prognosis of diabetic retinopathy&#46;</p><p class="elsevierStylePara">The majority of dialyser producers recommend dialyser and circuit priming with saline solution and UFH&#44; with the generally accepted standard dose of 5000UI&#44; regardless of which type of heparin will be used in the HD session&#46;<span class="elsevierStyleSup">36</span> However&#44; in clinical practice&#44; a significant percentage of HD centres in Spain do not employ heparin priming&#44; especially when LMWH is used as an anticoagulant&#46; Some next generation HD machines allow for priming with the dialysate fluid itself&#44; removing the need for heparin&#44; which reduces costs and simplifies the procedure&#46; In the survey for HD centres&#44; the dose used for heparin priming varied widely&#44; which implies great heterogeneity in the anticoagulation practices within our country&#46;</p><p class="elsevierStylePara">The surveys clearly show that dosing adjustments are for the most part made through trial and error&#44; and that methods for measuring coagulation states in patients are rarely used&#46; Due to the design of the survey&#44; we do not know the reason for which 5&#46;9&#37; of centres determined an anti-Xa factor for adjusting LMWH dose&#46; One of the possible indications is pre-HD measurements in patients with a daily dialysis regimen&#44; where there is an evident risk of accumulation&#46;<span class="elsevierStyleSup">35</span></p><p class="elsevierStylePara">In our study&#44; we observed that over half of all patients on HD were also receiving treatment with oral anticoagulants and&#47;or anti-platelets&#46; Few previous studies have analysed this factor in prevalent HD patients&#46; In the DOPPS study&#44; approximately 30&#37; of patients on dialysis took aspirin&#46;<span class="elsevierStyleSup">37</span> In another analysis from one single centre&#44; 25&#37; of patients were receiving oral anticoagulants&#46;<span class="elsevierStyleSup">38</span> An American study involving 41&#160;425 incident patients on HD showed that 8&#46;3&#37; received warfarin&#44; 10&#37; clopidogrel&#44; and 30&#46;4&#37; aspirin&#44; and that the risk of death and hospitalisation from bleeding was greater in patients that received warfarin and clopidogrel&#44; but not aspirin&#46;<span class="elsevierStyleSup">39</span> Elliott et al&#46;&#44;<span class="elsevierStyleSup">40</span> in a systematic review of 28 publications&#44; concluded that warfarin doubled the risk of severe bleeding in HD patients&#46; These results coincide in part with our own&#44; where there was a correlation between the appearance of bleeding complications and treatment with oral anticoagulants&#44; and not with anti-platelets&#44; although we do not know what proportion of patients were receiving aspirin or other anti-platelets&#46;</p><p class="elsevierStylePara">The results from our surveys show that the majority of patients receiving oral anticoagulants required heparin during the dialysis session&#44; which coincides with previous observations&#46;<span class="elsevierStyleSup">41</span> With this in mind&#44; we can make the general inference that oral anticoagulation is insufficient for preventing system coagulations in HD&#46; Even so&#44; our study produced the striking result that&#44; while patients with oral anticoagulation had UFH prescriptions that were adjusted to lower amounts&#44; this did not occur when LMWH was used&#44; and these doses were not different between the two groups of patients&#46;</p><p class="elsevierStylePara">As a final conclusion&#44; there is a lack of general accordance in terms of which aspects are important for anticoagulation in patients on HD&#44; such as which type of heparin to use &#40;UFH vs LMWH&#41;&#44; the type of administration for UFH &#40;continuous or intermittent&#41;&#44; the use of heparin and doses for priming&#44; the methods for adjusting dosage&#44; and the type of heparin to use based on the dialysis technique&#46; As such&#44; there is a notorious disparity in the criteria used in general daily practice for prescribing anticoagulation treatment in patients on HD&#44; which necessitates a review of the results produced at each centre and on the national level&#44; and possibly the creation of a guideline for anticoagulation in haemodialysis&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">ACKNOWLEDGEMENTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The task force received the valuable collaboration of Laboratorios Farmac&#233;uticos Rovi S&#46;A&#46;&#44; who provided consistent technical support in the structuring and the surveys&#8217; printing&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of Interest</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara">The authors have no conflicts of interest to declare&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27371&#95;en&#95;t1&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27371_en_t1_11106i.jpg" alt="HD centre survey&#46; Criteria for the use of LMWH vs UFH"></img></a></p><p class="elsevierStylePara">Table 1&#46; HD centre survey&#46; Criteria for the use of LMWH vs UFH</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27372&#95;en&#95;t2&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27372_en_t2_11106i.jpg" alt="HD centre survey&#46; Dose adjustment methods"></img></a></p><p class="elsevierStylePara">Table 2&#46; HD centre survey&#46; Dose adjustment methods</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27374&#95;en&#95;t3&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27374_en_t3_11106i.jpg" alt="Patient survey&#46; Baseline characteristics&#46; Type of heparin administered according to age&#44; sex&#44; diabetes&#44; and haemoglobin levels"></img></a></p><p class="elsevierStylePara">Table 3&#46; Patient survey&#46; Baseline characteristics&#46; Type of heparin administered according to age&#44; sex&#44; diabetes&#44; and haemoglobin levels</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27375&#95;en&#95;f1&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27375_en_f1_11106i.jpg" alt="HD centre survey&#46; Heparin dosing"></img></a></p><p class="elsevierStylePara">Figure 1&#46; HD centre survey&#46; Heparin dosing</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27376&#95;en&#95;f211106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27376_en_f211106i.jpg" alt="Patient survey&#46; Type of heparin administered according to the haemodialysis technique employed"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Patient survey&#46; Type of heparin administered according to the haemodialysis technique employed</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27377&#95;en&#95;f3&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27377_en_f3_11106i.jpg" alt="Patient survey&#46; Treatment with oral anticoagulants in patients with and without bleeding complications in the previous week"></img></a></p><p class="elsevierStylePara">Figure 3&#46; Patient survey&#46; Treatment with oral anticoagulants in patients with and without bleeding complications in the previous week</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Objetivos&#58;</span> Los objetivos del presente trabajo fueron conocer qu&#233; m&#233;todos de anticoagulaci&#243;n se emplean en la pr&#225;ctica habitual en los pacientes en hemodi&#225;lisis &#40;HD&#41; en Espa&#241;a&#44; de qu&#233; criterios dependen y las complicaciones derivadas de su uso&#46; <span class="elsevierStyleBold">Material y m&#233;todos</span><span class="elsevierStyleBold">&#58;</span> Es un estudio de dise&#241;o transversal basado en dos tipos de encuestas&#44; una de centros y otra de pacientes&#46; La primera fue contestada por 87 unidades de HD de adultos que inclu&#237;an 6&#46;093 pacientes&#44; y 2 unidades pedi&#225;tricas&#59; 43 centros &#40;48&#44;3&#37;&#41; eran de titularidad p&#250;blica y 46 &#40;51&#44;7&#37;&#41;&#44; privada&#47;concertada&#46; En la encuesta de pacientes se analizaban 758 pacientes elegidos al azar de manera aleatoria en 78 unidades de HD&#46; <span class="elsevierStyleBold">Resultados&#58;</span> A&#41; <span class="elsevierStyleItalic">Encuesta de centros</span>&#58; La mayor&#237;a de los centros de adultos &#40;n &#61; 61&#44; 70&#44;2&#37;&#41; dispon&#237;an tanto de heparina de bajo peso molecular &#40;HBPM&#41; como de heparina no fraccionada &#40;HNF&#41;&#44; 19 &#40;21&#44;8&#37;&#41; s&#243;lo emplean HBPM y 7 &#40;8&#37;&#41; utilizaban exclusivamente HNF&#46; Las criterios m&#225;s frecuentes para el empleo de HBPM fueron indicaciones m&#233;dicas &#40;83&#44;3&#37; de los centros&#41; y la comodidad en la administraci&#243;n &#40;29&#44;5&#37;&#41;&#46; Los m&#233;todos m&#225;s empleados para el ajuste de la dosis eran la coagulaci&#243;n del circuito &#40;88&#44;2&#37; de los centros&#41;&#44; el sangrado del acceso vascular tras la desconexi&#243;n &#40;75&#44;3&#37;&#41; y el peso del paciente &#40;57&#44;6&#37;&#41;&#46; B&#41; <span class="elsevierStyleItalic">Encuesta de pacientes</span>&#58; La distribuci&#243;n del tipo de heparina empleada fue&#58; 44&#44;1&#37; HNF&#44; 51&#44;5&#37; HBPM y 4&#44;4&#37; di&#225;lisis sin heparina&#46; La HBPM se utiliza m&#225;s frecuentemente en los centros p&#250;blicos &#40;64&#44;2&#37; de los pacientes&#41; que en los privados&#47;concertados &#40;46&#44;1&#37;&#41; &#40;p &#60; 0&#44;001&#41;&#46;<span class="elsevierStyleBold"> </span>La HBPM se utilizaba con mayor frecuencia en la hemodiafiltraci&#243;n en l&#237;nea que en la HD de alto flujo &#40;p &#60; 0&#44;001&#41;&#46; Un 45&#44;5&#37; de los pacientes recib&#237;an antiagregantes&#44; un 18&#44;4&#37; anticoagulantes orales y un 5&#37; ambos<span class="elsevierStyleBold">&#46;</span><span class="elsevierStyleBold"> </span>El<span class="elsevierStyleBold"> </span>4&#44;4&#37; de los pacientes tuvo complicaciones hemorr&#225;gicas en la &#250;ltima semana y el 1&#44;9&#37; complicaciones tromb&#243;ticas&#46; Las complicaciones hemorr&#225;gicas fueron m&#225;s frecuentes en los pacientes que tomaban anticoagulantes orales &#40;p &#61; 0&#44;01&#41;&#46; No hab&#237;a asociaci&#243;n entre el tipo de heparina y las complicaciones hemorr&#225;gicas&#46; <span class="elsevierStyleBold">Conclusiones&#58; </span>Se puede concluir que existe una gran disparidad de criterios en la prescripci&#243;n de la anticoagulaci&#243;n en HD&#46; Es aconsejable revisar los resultados propios y externos&#44; y posiblemente crear una gu&#237;a de anticoagulaci&#243;n en hemodi&#225;lisis&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Objectives&#58;</span> This study&#8217;s objectives were to determine which anticoagulation methods are commonly used in patients who are undergoing haemodialysis &#40;HD&#41; in Spain&#44; on what criteria do they depend&#44; and the consequences arising from their use&#46; <span class="elsevierStyleBold">Material and Method&#58; </span>Ours was a cross-sectional study based on two types of surveys&#58; a &#34;HD Centre Survey&#34; and a &#34;Patient Survey&#34;&#46; The first survey was answered by 87 adult HD units serving a total of 6093 patients&#44; as well as 2 paediatric units&#46; Among these units&#44; 48&#46;3&#37; were part of the public health system and the remaining 51&#46;7&#37; units were part of the private health system&#46; The patient survey analysed 758 patients who were chosen at random from among the aforementioned 78 HD units&#46; <span class="elsevierStyleBold">Results&#58;</span> A&#41; <span class="elsevierStyleItalic">HD <span class="elsevierStyleItalic">Centre Survey</span></span>&#58; The majority of adult HD units &#40;n&#61;61&#44; 70&#46;2&#37;&#41; used both kinds of heparin&#44; 19 of them &#40;21&#46;8&#37;&#41; only used LMWH and 7 of them &#40;8&#37;&#41; only used UFH&#46; The most frequently applied criteria for the use of LMWH were medical indications &#40;83&#46;3&#37; of HD units&#41; and ease of administration &#40;29&#46;5&#37;&#41;&#46; The most frequently used methods for adjusting the dosage were clotting of the circuit &#40;88&#46;2&#37; of units&#41;&#44; bleeding of the vascular access after disconnection &#40;75&#46;3&#37;&#41;&#44; and patient weight &#40;57&#46;6&#37;&#41;&#46; B&#41; <span class="elsevierStyleItalic">Patient Survey</span>&#58; The distribution of the types of heparin used was&#58; UFH&#58; 44&#46;1&#37;&#44; LMWH&#58; 51&#46;5&#37;&#44; and dialysis without heparin in 4&#46;4&#37; of patients&#46; LMWH was more frequently used in public medical centres &#40;64&#46;2&#37; of patients&#41; than in private medical centres &#40;46&#46;1&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; LMWH was more frequently used in on-line haemodiafiltration &#40;HF&#41; than in high-flux HD &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; Antiplatelet agents were given to 45&#46;5&#37; of patients&#44; oral anticoagulants to 18&#46;4&#37; of patients&#44; and both to 5&#37; of patients&#46; Additionally&#44; 4&#46;4&#37; of patients had suffered bleeding complications during the previous week&#44; and 1&#46;9&#37; of patients suffered thrombotic complications&#46; Bleeding complications were more frequent in patients with oral anticoagulants &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;001&#41;&#44; although there was no association between the type of heparin and the occurrence of bleeding or thrombotic complications&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> We are able to conclude that there is a great amount of disparity in the criteria used for the medical prescription of anticoagulation in HD&#46; It is advisable that each HD unit revise their own results as well as those from other centres&#44; and possibly to create an Anticoagulation Guide in Haemodialysis&#46;</p>"
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Spanish study of anticoagulation in haemodialysis
Estudio español sobre anticoagulación en hemodiálisis
Grupo de Estudio Español sobre Anticoagulación en Hemodiálisis, José A. Herrero Calvob, José A. Herrero-Calvoc, Emilio González Parrad, Emilio González-Parrae, Rafael Pérez Garcíaf, Rafael Pérez-Garcíag, Fernando Tornero Molinah, Fernando Tornero-Molinai
b Nefrología, Hospital Clínico San Carlos, Madrid, Spain,
c Servicio de Nefrología, Hospital Clínico San Carlos, Madrid,
d Nefrología, Fundación Jiménez Díaz, Madrid, Spain,
e Servicio de Nefrología, Fundación Jiménez Díaz, Madrid,
f Nefrología, Hospital Infanta Leonor, Madrid, Spain,
g Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid,
h Nefrología, Hospital del Sureste, Madrid, Spain,
i Servicio de Nefrología, Hospital del Sureste, Madrid,
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          "en" => "HD centre survey&#46; Criteria for the use of LMWH vs UFH"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In haemodialysis &#40;HD&#41;&#44; a common issue arises in the form of coagulation of the extra-corporeal blood circuit&#44; which must be prevented&#44; normally by administering heparin&#46; The objective is to use the lowest possible dose of anticoagulant so as to maintain the dialyser and venous chamber free from blood cell debris&#46; Another objective is to be able to quickly achieve haemostasis at the vascular access points after the session&#46; In general&#44; the doses applied tend to be lower than the necessary amount for complete anticoagulation&#44; although these doses vary widely between patients&#44; and depend on both patient and HD characteristics&#46;<span class="elsevierStyleSup">1&#44;2</span> On the other hand&#44; insufficient anticoagulation therapy can decrease the effectiveness of dialysis to purify the blood&#46;<span class="elsevierStyleSup">1&#44;2</span></p><p class="elsevierStylePara">Several different issues can arise from applying repeated and intermittent heparin to patients on HD programmes&#44; which can involve over 600 cumulative hours per year&#46; These include risk of bleeding and thrombotic complications &#40;which are not always correlated with over or under-dosing&#41;&#44; metabolic effects&#44; primarily dyslipidemia&#44; osteoporosis&#44; and effects on blood cells&#44; especially platelets&#46;<span class="elsevierStyleSup">1&#44;2</span></p><p class="elsevierStylePara">Since the 1980&#8217;s&#44; low molecular weight heparin &#40;LMWH&#41; has been incorporated into daily clinical practice as an alternative to conventional&#44; or unfractionated heparin &#40;UFH&#41;&#44; with the goal of improving efficacy and safety&#44; reducing the secondary side effects produced&#44; and facilitating patient management in terms of dosage adjustments and administration regimens&#46;<span class="elsevierStyleSup">3-5</span> Several different studies have shown that LMWH and UFH have similar levels of efficacy and safety&#46;<span class="elsevierStyleSup">6-7</span> As regards side effects&#44; studies have shown that LMWH produces a lower increase in plasma triglyceride levels<span class="elsevierStyleSup">8&#44;9</span> and lower incidences of thrombocytopoenia<span class="elsevierStyleSup">10</span> and osteoporosis<span class="elsevierStyleSup">11</span> than UFH&#46; The ease of administration&#44; higher cost&#44; persistence of anticoagulation activity several hours after the HD session&#44; risk of accumulation using high and frequent doses&#44; and the complexity of adjusting doses using laboratory control tests are also factors to take into account when prescribing LMWH over UFH&#46; Thus&#44; whereas the guidelines recommend using LMWH over UFH&#44;<span class="elsevierStyleSup">12</span> in current clinical practice&#44; there is no established consensus for prescribing one type of heparin or the other&#46;</p><p class="elsevierStylePara">In addition to the individualisation of the type and dose of heparin to be used&#44; other aspects of this treatment also lack standardised criteria&#44; such as system priming with or without heparin &#40;and if so&#44; the dose to be used&#41;&#44; the mode of administration&#44; and the prescription for anticoagulation based on the HD technique used&#46; For their part&#44; elderly age and cardiovascular comorbidity already necessitate oral anti-platelet and&#47;or anticoagulant treatment in an undetermined percentage of prevalent HD patients&#44; for which there are no general recommendations when considering prescribing anticoagulation therapy during an HD session&#46;</p><p class="elsevierStylePara">Given the heterogeneity of the possible variables&#44; approaching to this subject first involves defining the current situation in clinical practice&#44; that is to say&#44; document which methods are being applied in the various dialysis centres around the country&#46; For this reason&#44; the Task Force for Anticoagulation in Haemodialysis of the Spanish Society of Nephrology &#40;S&#46;E&#46;N&#46;&#44; for its initials in Spanish&#41; proposed a study based on surveys completed by all of the haemodialysis units in Spain&#44; with the objectives of&#44; firstly&#44; assessing which anticoagulation methods are being used in Spain&#44; secondly&#44; what criteria define which methods to use&#44; and finally&#44; which method is more commonly associated with bleeding and thrombotic complications&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Ours was a cross-sectional descriptive study based on two different types of surveys&#58; one survey for haemodialysis centres&#44; and another for patients&#46; The first survey was designed to evaluate the anticoagulation policies used at public and private HD centres&#46; The patient survey analysed individual anticoagulation data from a randomly chosen 10-patient sample from each centre&#46; The surveys were distributed and collected between May and September 2008&#46;</p><p class="elsevierStylePara">The survey for dialysis centres collected information on the type of heparin used&#44; dose and method of administration&#44; and circuit priming&#46; The survey also included a section on the criteria used for deciding whether to administer LMWH or UFH&#44; with the following possible responses&#58; 1&#41; medical criteria &#40;dyslipidemia&#44; thrombocytopenia&#44; etc&#46;&#41;&#46; 2&#41; Dosing&#46; 3&#41; Cost&#46; 4&#41; Dialysis technique&#46; 5&#41; Vascular access&#46; 6&#41; Other&#46; Finally&#44; we asked for information on the adjustment methods used for dosing UFH and LMWH&#46;</p><p class="elsevierStylePara">In addition to the questions regarding the anticoagulation methods used for each patient&#44; the patient survey included questions on diagnosis of diabetes&#44; haemoglobin levels&#44; vascular access type&#44; membrane type&#44; dialysis technique&#44; duration of HD sessions&#44; and pump flow&#46; We also asked if the patient was receiving additional anticoagulant and&#47;or anti-platelet treatment&#44; as well as whether any bleeding or thrombotic complications arose in the previous week&#46;</p><p class="elsevierStylePara">We performed all statistical analyses using SPSS statistical software&#44; version 15&#46;0&#46; We analysed qualitative variables using absolute frequencies and percentages&#44; while quantitative variables were assessed using mean&#44; standard deviation&#44; median&#44; minimum&#44; and maximum&#46; We applied tests of normality &#40;Kolmogorov-Smirnov&#41; and homoscedasticity &#40;Levene&#41; prior to applying parametric tests&#46; We compared more than 2 groups using one-way ANOVA tests for normally distributed continuous variables&#44; and Kruskal-Wallis tests for non-parametric variables&#46; For comparisons of group means&#44; we used Student&#8217;s t-tests in the case of normally distributed continuous variables&#44; and Mann-Whitney U-tests for non-parametric variables&#46; In the case of discreet variables&#44; we used chi-square or Fisher&#8217;s exact tests when necessary&#46; Following these comparisons&#44; we selected those variables with a <span class="elsevierStyleItalic">P</span>-value &#60;&#46;100 for use in a logistic regression model&#46; The level of statistical significance was set at 5&#37;&#46;</p><p class="elsevierStylePara">This study has been approved by the Spanish Society of Nephrology&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">For a better comprehension of the results obtained&#44; we have separated this section into two parts&#44; corresponding to the data obtained in the surveys for haemodialysis centres and the data for patient surveys&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Haemodialysis Centre Survey</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We compiled surveys from 89 haemodialysis centres throughout the country&#44; constituting 29&#37; of all such centres in Spain&#46; Of these&#44; 43 &#40;48&#46;3&#37;&#41; were public entities&#44; and 46 &#40;51&#46;7&#37;&#41; were private&#46; Of the 89 centres that responded to the survey&#44; only 2 were paediatric units&#44; and these were excluded from the general statistical analysis&#46; The remaining 87 centres corresponded to adult patients&#44; and at the moment the survey was taken&#44; these centres treated a total of 6093 patients&#46;</p><p class="elsevierStylePara">The data obtained from these 87 surveys are as follows&#58;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">1&#46; Type of Heparin</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The majority of the centres surveyed &#40;61&#59; 70&#46;2&#37;&#41; utilised both types of heparin&#44; 19 &#40;21&#46;8&#37;&#41; only administered LMWH&#44; and 7 &#40;8&#37;&#41; only used UFH&#46; Although there was a certain tendency to use LMWH to a greater extent at public centres than private ones&#44; this difference was not statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;073&#41;&#46; The types of LMWH available at the 80 centres were&#58; enoxaparin &#40;60&#37;&#41;&#44; bemiparin &#40;32&#46;6&#37;&#41;&#44; nadroparin &#40;21&#46;3&#37;&#41;&#44; dalteparin &#40;12&#46;5&#37;&#41;&#44; and tinzaparin &#40;11&#46;3&#37;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">2&#46; Criteria Used for LMWH</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">This was a multiple choice question&#44; and the percentages for each response were calculated for the 78 centres that responded &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">3&#46; Type of HD Priming</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">There is a wide variability in both the use of heparin priming and the dose used&#46; We can summarise that&#58;</p><p class="elsevierStylePara">-If UFH was used during HD &#40;68 centres&#41;&#44; the majority used UFH for priming &#40;86&#46;7&#37;&#41;&#44; 7&#46;4&#37; did not use heparin for priming&#44; and 5&#46;9&#37; did so with or without heparin depending on the patient&#46;</p><p class="elsevierStylePara">-If LMWH was used &#40;73 centres&#41;&#44; 21&#46;9&#37; of centres did not use heparin priming&#44; 71&#46;3&#37; did so with heparin&#44; and 6&#46;8&#37; either used or did not use heparin&#44; depending on the patient&#46;</p><p class="elsevierStylePara">The heparin dose used for priming ranged between 1000UI and 10&#160;000UI&#46; However&#44; regardless of the type of heparin used in the HD session&#44; the most commonly used dose was 5000UI &#40;66&#37; of centres when UFH was used&#44; and 67&#46;6&#37; of centres when LMWH was used&#41;&#44; followed by 2500UI &#40;17&#37; with UFH&#44; and 16&#46;2&#37; with LMWH&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">4&#46; Dosing</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The methods of administration employed for heparin doses are summarised in Figure 1&#46; Regardless of the method of administration for UFH throughout the HD session&#44; the majority of centres used an initial bolus &#40;92&#46;6&#37; when using a continuous dose&#44; 97&#46;6&#37; when using an intermittent dose&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">5&#46; Adjustment Methods for the Heparin Dose</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We received 85 responses for this section from the 87 surveys sent&#46; As such&#44; the percentages for this question were calculated over 85&#44; and the results are summarised in Table 2&#46; The general rule was that several factors were taken into account when adjusting the dose used&#46; This was a multiple choice question that allowed us to assess the possible combination of factors in this context&#46; Among these&#44; the most common combinations used were&#58; &#8220;weight &#43; coagulation of the dialyser&#47;lines &#43; bleeding after disconnect&#8221; in 30 centres &#40;35&#46;3&#37;&#41; and &#8220;coagulation of the dialyser&#47;lines &#43; bleeding after disconnect&#8221; in 17 centres &#40;20&#37;&#41;&#44; with all others being much less common&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patient Survey</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Of the 89 centres that responded to our surveys&#44; 80 provided patient data&#44; with a total of 770 patients surveyed&#46; The general statistical analysis did not include 12 patients &#40;10 due to non-compliance with the full range of questions asked at one centre&#44; and 2 who were paediatric patients&#41;&#46; In this manner&#44; a total of 758 adult patients were included in the analysis from 78 different dialysis centres&#44; of which 34 &#40;43&#46;6&#37;&#41; were public and 44 &#40;56&#46;4&#37;&#41; were private&#46; The most important characteristics of these patients are summarised in Table 3&#46;</p><p class="elsevierStylePara">The most relevant data obtained in the patient survey can be summarised as&#58;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">1&#46; Anticoagulation in the Study Population</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We obtained data on 733 patients&#44; of which 323 &#40;44&#46;1&#37;&#41; received treatment with UFH&#44; 378 &#40;51&#46;5&#37;&#41; with LMWH&#44; and 32 &#40;4&#46;4&#37;&#41; received no anticoagulation during dialysis&#46; At public centres&#44; 64&#46;2&#37; of patients received LMWH&#44; whereas 46&#46;1&#37; of patients received this type of heparin at private centres &#40;statistically significant difference&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46;</p><p class="elsevierStylePara">The heparin dose was quantified in 291 patients&#44; 186 of which received UFH and 105 received LMWH&#46; The mean dose of UFH was 2988 &#40;1706&#41; UI &#40;range&#58; 500-9500UI&#44; median&#58; 3000UI&#41; and the mean dose of LMWH was 3598 &#40;1601&#41; UI &#40;range&#58; 1000-8000UI&#44; median&#58; 3500UI&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">2&#46; Anticoagulation According to Patient Characteristics</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Upon analysis of patient characteristics based on the type of heparin used&#44; we observed no differences in terms of sex or prevalence of diabetes&#46; However&#44; patients that received LMWH tended to be younger&#44; and had lower haemoglobin levels &#40;Table 3&#41;&#46; There were no differences in the heparin doses prescribed &#40;for both UFH and LMWH&#41; in terms of age&#44; sex&#44; haemoglobin levels&#44; or diagnosis of diabetes&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">3&#46; Anticoagulation According to Vascular Access</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The distribution of vascular access types in the 758 patients that responded to this part of the survey was&#58; autologous arteriovenous fistula &#40;AVF&#41;&#58; 68&#46;5&#37;&#44; prosthesis&#58; 7&#46;8&#37;&#44; and catheter&#58; 23&#46;7&#37;&#46; There were no differences in terms of the distribution of the different types of vascular access between public and private centres&#46; In patients with AVF&#44; LMWH was utilised more frequently &#40;56&#37; vs 44&#37;&#41; whereas patients with prostheses were administered UFH more frequently &#40;62&#37; vs 38&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;048&#41;&#46; In patients with a catheter&#44; the rates of using the two types of heparin were similar&#46;</p><p class="elsevierStylePara">There were no differences in terms of the heparin doses prescribed &#40;whether for UFH or LMWH&#41; based on the type of vascular access used&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">4&#46; Anticoagulation According to the Technique and Membrane Type Used for Dialysis</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The dialysis technique used was recorded for 757 patients&#44; of which 413 &#40;54&#46;6&#37;&#41; received high-flux HD&#44; 249 &#40;32&#46;9&#37;&#41; received low-flux HD&#44; and 95 &#40;12&#46;5&#37;&#41; received on-line haemodiafiltration &#40;OL-HDF&#41;&#46; At public centres&#44; the distribution was&#58; high-flux HD&#58; 47&#46;5&#37;&#44; low-flux HD&#58; 30&#46;7&#37;&#44; and OL-HDF&#58; 21&#46;7&#37;&#44; whereas at private centres&#44; the distribution was 59&#46;8&#37;&#44; 34&#46;5&#37;&#44; and 5&#46;7&#37;&#44; respectively &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;001&#41;&#46;</p><p class="elsevierStylePara">The distribution of the type of heparin used according to the dialysis technique used is represented in Figure 2&#46;</p><p class="elsevierStylePara">The types of membranes used for dialysis were&#58; cellulose&#58; 6&#46;1&#37;&#44; polysulfone&#58; 59&#46;5&#37;&#44; polyethersulfone&#58; 12&#46;2&#37;&#44; polyamide&#58; 15&#46;8&#37;&#44; AN69&#58; 3&#46;7&#37;&#44; and other&#58; 2&#46;7&#37;&#46; We observed no significant differences in terms of the type of membrane used between public and private centres&#46; There were also no significant differences in the type of heparin administered &#40;UFH vs LMWH&#41; based on membrane type&#46;</p><p class="elsevierStylePara">The heparin doses prescribed were similar regardless of the HD technique or membrane type used&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">5&#46; Anticoagulation According to Time on Dialysis and Pump Flow</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The mean duration of HD sessions was 231 &#40;26&#41; minutes &#40;range&#58; 120-310 minutes&#41;&#44; with the most common duration of sessions being 4&#58;00-4&#58;30 hours &#40;n&#61;440&#59; 59&#46;2&#37;&#41;&#44; followed by the interval of 3&#58;30-4&#58;00 hours &#40;n&#61;172&#59; 23&#46;1&#37;&#41;&#44; and &#62;4&#58;30 hours &#40;n&#61;63&#59; 8&#46;4&#37;&#41;&#46; There was no correlation between the type of heparin used and the duration of the HD session&#46; As was expected&#44; the dose of heparin prescribed was significantly lower in patients with shorter dialysis sessions &#40;less than 4 hours&#41; as compared to sessions lasting &#62;4 hours&#44; both when employing UFH &#40;2443&#177;1246UI vs 3264&#177;1804UI&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;003&#41; and LMWH &#40;2828&#177;1234UI vs 3870&#177;1630UI&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;002&#41;&#46;</p><p class="elsevierStylePara">Mean blood pump flow was 346 &#40;47&#41; ml&#47;min &#40;range&#58; 150-500ml&#47;min&#41;&#46; Pump flow was significantly higher in the group that received UFH as compared to the group that received LMWH &#40;351&#177;42ml&#47;min vs 339&#177;51ml&#47;min&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;001&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">6&#46; Anticoagulation in Haemodialysis and Anti-platelet and&#47;or Anticoagulant Treatment</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We acquired survey responses regarding anti-platelet and&#47;or oral anticoagulant treatment from 727 patients&#46; Of these&#44; 331 &#40;45&#46;5&#37;&#41; received anti-platelets&#44; 134 &#40;18&#46;4&#37;&#41; received oral anticoagulants&#44; and 36 &#40;5&#37;&#41; received both&#46; Overall&#44; 425 &#40;58&#46;5&#37;&#41; received some type of anti-platelet and&#47;or anticoagulant treatment&#46;</p><p class="elsevierStylePara">The majority of patients that received oral anticoagulant treatment &#40;n&#61;115&#59; 85&#46;8&#37;&#41; also required heparin during HD&#46; LMWH was used somewhat more frequently in these cases&#44; although this difference was not statistically significant &#40;LMWH&#58; 56&#46;4&#37;&#59; UFH&#58; 43&#46;6&#37;&#41;&#46; The UFH dose prescribed in patients that also received coumarin-type drugs was lower than in those that did not &#40;2279&#177;1499UI vs 3105&#177;1721UI&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;012&#41;&#44; whereas no significant differences were observed in the doses prescribed for LMWH &#40;3913&#177;1768UI vs 3439&#177;1486UI&#44; respectively&#41;&#46;</p><p class="elsevierStylePara">As regards priming&#44; 77&#46;9&#37; of patients that received oral anticoagulants underwent heparin priming&#44; with doses similar to those of other patients&#46;</p><p class="elsevierStylePara">Patients receiving anti-platelet treatment had no differences from others in terms of the dose of heparin prescribed&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">7&#46; Anticoagulation and Bleeding Complications</span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Of the 743 patients analysed in this section&#44; 33 &#40;4&#46;4&#37;&#41; had experienced some type of bleeding complication within the previous week of filling out the survey&#46; We observed no correlations between bleeding complications and age&#44; sex&#44; diabetes&#44; or anti-platelet treatment&#46; Patients with bleeding complications had significantly lower haemoglobin levels than patients that did not &#40;10&#46;9&#177;1&#46;4g&#47;dl vs 12&#46;1&#177;1&#46;2g&#47;dl&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#44; and received oral anticoagulation therapy more frequently &#40;Figure 3&#41;&#46; If we eliminate patients that received oral anticoagulants from the analysis&#44; no significant differences were present in terms of the number of bleeding complications between patients receiving UFH and those receiving LMWH &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;078&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleItalic"><span class="elsevierStyleBold">8&#46; Anticoagulation and Thrombotic Complications </span></span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Thrombotic complications in the week prior to taking the survey were reported in 14 of the 737 patients analysed &#40;1&#46;9&#37;&#41;&#44; with a greater frequency of occurrence in patients that received LMWH &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;003&#41;&#46; There were no significant differences in the dose of heparin prescribed&#44; whether UFH or LMWH&#44; between patients that experienced thrombotic complications and those that did not&#46;</p><p class="elsevierStylePara">Finally&#44; of the 2 paediatric centres asked to participate&#44; 1 provided the surveys for 2 patients&#46; Both received LMWH &#40;enoxaparin&#41;&#44; with heparin priming and high-flux HD using polysulfone&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Firstly&#44; we would like to point out that both surveys can be considered valid for the analysis of our objectives&#46; The number of centres&#44; the geographic distribution of the various autonomous communities in Spain&#44; the inclusion of both public and private centres&#44; and the number of patients treated all lend strength to the haemodialysis centre survey&#46; The patient survey was bolstered by the random selection of patients&#44; lending similar characteristics to our sample as in other recent studies such as the Dopps III&#44; which was considered representative of the adult Spanish population on dialysis&#46;<span class="elsevierStyleSup">13</span> As such&#44; the mean age&#44; sex distribution&#44; proportion of diabetic patients&#44; mean haemoglobin values&#44; and distribution of the different types of vascular accesses used are comparable between these studies&#46;<span class="elsevierStyleSup">13</span></p><p class="elsevierStylePara">The primary objectives of our study were to assess the anticoagulation methods employed in Spain and what criteria they are based on&#46; The near-50&#37; distribution of the two types of heparin&#44; despite the guideline recommendations that favour LMWH&#44;<span class="elsevierStyleSup">12</span> indicate that&#44; in clinical practice&#44; there are additional criteria taken into account&#46; Based on the type of data compiled&#44; we cannot completely verify the reason for the lower frequency with which LMWH is used at private centres&#44; even though availability was similar&#46; The issue of costs could be an important factor&#59; however&#44; only 10&#37; of centres indicated that cost was taken into account when deciding upon treatment&#46; Whereas the greater costs of LMWH limited its use in the past&#44; this currently does not appear to be an important limiting factor&#44; with other criteria taking precedent in deciding upon whether to prescribe this drug&#46;<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">The risk of bleeding is the primary secondary side effect of anticoagulation therapy in HD&#46; In our study&#44; there was no association between bleeding complications and the type of heparin administered&#44; which confirms previous observations that indicated a similar level of safety for both UFH and LMWH&#46;<span class="elsevierStyleSup">6&#44;7</span> We are not aware of the reason for the greater frequency of thrombotic complications observed in the group receiving LMWH&#46; The possible reasons include a lower efficacy of this drug&#44; inferior dosage adjustment&#44; or the fact that LMWH was prescribed more frequently in complex patients with a greater tendency towards coagulability&#46;</p><p class="elsevierStylePara">Medical criteria&#44; followed by ease of administration&#44; were the most commonly reported reasons for indicating LMWH&#46; In addition to bleeding and thrombotic phenomena&#44; dyslipidaemia&#44;<span class="elsevierStyleSup">14</span> osteoporosis&#44;<span class="elsevierStyleSup">15</span> and thrombocytopoenia<span class="elsevierStyleSup">16-19</span> are the most common side effects observed in the use of heparin in HD patients&#44; and were surely considered within the medical criteria used to decide upon the prescription of LMWH in the patients included in our study&#46; Several studies have demonstrated a lower increase in triglyceride levels in HD patients with LMWH than in those receiving UFH&#44;<span class="elsevierStyleSup">8&#44;9&#44;14&#44;20&#44;21</span> although other studies did not corroborate with these findings&#46;<span class="elsevierStyleSup">22-24</span> On the other hand&#44; in patients without renal failure receiving prolonged treatment&#44; the risk of developing osteoporosis is lower when utilising LMWH instead of UFH&#46;<span class="elsevierStyleSup">15&#44;25&#44;26</span> In HD&#44; LMWH has also been reported to cause osteoporosis at a lower rate than UFH&#44;<span class="elsevierStyleSup">11&#44;27</span> although no studies have clearly confirmed this phenomenon&#46; Finally&#44; in the population without renal failure&#44; the incidence of thrombocytopenia induced by type II heparin is lower with LMWH than UFH&#44;<span class="elsevierStyleSup">28&#44;29</span> which has also been described in patients on HD&#46;<span class="elsevierStyleSup">10</span></p><p class="elsevierStylePara">Both the survey for HD centres and the patient survey revealed that the type of vascular access was the third most common indication for employing LMWH&#46; Although one study did show that the permeability of vascular accesses improves with the use of LMWH&#44;<span class="elsevierStyleSup">30</span> to our knowledge&#44; there are no studies that have shown any advantages from using a certain type of heparin over another when using autologous AVF or prosthesis&#46;</p><p class="elsevierStylePara">The dialysis technique used was also one of the criteria employed for deciding whether to administer LMWH&#44; which was prescribed at a greater rate than UFH in OL-HDF&#46; On the other hand&#44; the dose of LMWH was not significantly different when comparing between OL-HDF&#44; low-flux HD&#44; and high-flux HD&#46; These data appear to contradict our understanding of the pharmacokinetics of LMWH during HD sessions&#46; Several studies have shown that anti-Xa activity is significantly reduced in high-flux HD and convective techniques&#44; as a consequence of the elimination of LMWH through the dialysate&#47;ultrafiltrate&#46; McMahon et al&#46; showed that the anti-Xa activity in high-flux HD was lower than in low-flux HD when using the same dose of enoxaparin&#46;<span class="elsevierStyleSup">31</span> Using continuous HD techniques&#44; Isla et al&#46; demonstrated significant enoxaparin losses in the ultrafiltrate&#47;dialysate&#46;<span class="elsevierStyleSup">32 </span>Another study showed that anti-Xa activity at the end of the HD session was significantly lower on OL-HDF than low-flux HD&#46;<span class="elsevierStyleSup">33</span> In any case&#44; LMWH losses in dialysate are higher at the start of an HD session when administering boluses through the arterial branch of the HD system&#46;<span class="elsevierStyleSup">10</span> For these reasons&#44; in high-flux HD and even more so in HF and HDF techniques&#44; some authors recommend administering LMWH at the start of the HD session in the venous branch of the extracorporeal blood circuit&#44;<span class="elsevierStyleSup">10</span> or to administer it 3-4 minutes before starting dialysis&#46;<span class="elsevierStyleSup">34</span> In our study&#44; we did not analyse what type of administration was used &#40;arterial or venous branch&#41; or the moment of administration&#44; since these questions were not included in the surveys&#46;</p><p class="elsevierStylePara">As regards the type of material used in HD&#44; platelet activation and coagulation varies according to the membrane used&#44; such that the following sequence can be established based on these properties&#58; unmodified cellulose membranes &#62; unmodified AN69 &#62; polysulfone &#62; polyamide&#46;<span class="elsevierStyleSup">35</span> In our study&#44; we observed that the type of membrane used was not correlated with the type of heparin or dosage used in normal clinical practice&#46; However&#44; we must keep in mind that the majority of these patients were treated using synthetic membranes&#44; primarily polysulfones&#47;polyethersulfones&#46;</p><p class="elsevierStylePara">It is interesting to point out that in patients receiving LMWH&#44; the pump flow was significantly lower than in patients receiving UFH&#46; Given that pump flow is directly related to heparin dose&#44; these results should be interpreted taking into account that&#44; given a higher risk of coagulation from a lower pump flow&#44; LMWH tends to be used&#44; probably with the goal of increasing efficacy&#44; which would partly explain the greater incidence of thrombotic phenomena observed in this group&#46;</p><p class="elsevierStylePara">Diabetes did not affect the use of heparin&#44; neither type nor dose&#44; which is in accordance with the current clinical mind-set that has rejected the antiquated and unproven idea that heparinisation in dialysis could increase the risk of ocular bleeding complications in these patients&#44; which could worsen the prognosis of diabetic retinopathy&#46;</p><p class="elsevierStylePara">The majority of dialyser producers recommend dialyser and circuit priming with saline solution and UFH&#44; with the generally accepted standard dose of 5000UI&#44; regardless of which type of heparin will be used in the HD session&#46;<span class="elsevierStyleSup">36</span> However&#44; in clinical practice&#44; a significant percentage of HD centres in Spain do not employ heparin priming&#44; especially when LMWH is used as an anticoagulant&#46; Some next generation HD machines allow for priming with the dialysate fluid itself&#44; removing the need for heparin&#44; which reduces costs and simplifies the procedure&#46; In the survey for HD centres&#44; the dose used for heparin priming varied widely&#44; which implies great heterogeneity in the anticoagulation practices within our country&#46;</p><p class="elsevierStylePara">The surveys clearly show that dosing adjustments are for the most part made through trial and error&#44; and that methods for measuring coagulation states in patients are rarely used&#46; Due to the design of the survey&#44; we do not know the reason for which 5&#46;9&#37; of centres determined an anti-Xa factor for adjusting LMWH dose&#46; One of the possible indications is pre-HD measurements in patients with a daily dialysis regimen&#44; where there is an evident risk of accumulation&#46;<span class="elsevierStyleSup">35</span></p><p class="elsevierStylePara">In our study&#44; we observed that over half of all patients on HD were also receiving treatment with oral anticoagulants and&#47;or anti-platelets&#46; Few previous studies have analysed this factor in prevalent HD patients&#46; In the DOPPS study&#44; approximately 30&#37; of patients on dialysis took aspirin&#46;<span class="elsevierStyleSup">37</span> In another analysis from one single centre&#44; 25&#37; of patients were receiving oral anticoagulants&#46;<span class="elsevierStyleSup">38</span> An American study involving 41&#160;425 incident patients on HD showed that 8&#46;3&#37; received warfarin&#44; 10&#37; clopidogrel&#44; and 30&#46;4&#37; aspirin&#44; and that the risk of death and hospitalisation from bleeding was greater in patients that received warfarin and clopidogrel&#44; but not aspirin&#46;<span class="elsevierStyleSup">39</span> Elliott et al&#46;&#44;<span class="elsevierStyleSup">40</span> in a systematic review of 28 publications&#44; concluded that warfarin doubled the risk of severe bleeding in HD patients&#46; These results coincide in part with our own&#44; where there was a correlation between the appearance of bleeding complications and treatment with oral anticoagulants&#44; and not with anti-platelets&#44; although we do not know what proportion of patients were receiving aspirin or other anti-platelets&#46;</p><p class="elsevierStylePara">The results from our surveys show that the majority of patients receiving oral anticoagulants required heparin during the dialysis session&#44; which coincides with previous observations&#46;<span class="elsevierStyleSup">41</span> With this in mind&#44; we can make the general inference that oral anticoagulation is insufficient for preventing system coagulations in HD&#46; Even so&#44; our study produced the striking result that&#44; while patients with oral anticoagulation had UFH prescriptions that were adjusted to lower amounts&#44; this did not occur when LMWH was used&#44; and these doses were not different between the two groups of patients&#46;</p><p class="elsevierStylePara">As a final conclusion&#44; there is a lack of general accordance in terms of which aspects are important for anticoagulation in patients on HD&#44; such as which type of heparin to use &#40;UFH vs LMWH&#41;&#44; the type of administration for UFH &#40;continuous or intermittent&#41;&#44; the use of heparin and doses for priming&#44; the methods for adjusting dosage&#44; and the type of heparin to use based on the dialysis technique&#46; As such&#44; there is a notorious disparity in the criteria used in general daily practice for prescribing anticoagulation treatment in patients on HD&#44; which necessitates a review of the results produced at each centre and on the national level&#44; and possibly the creation of a guideline for anticoagulation in haemodialysis&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">ACKNOWLEDGEMENTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The task force received the valuable collaboration of Laboratorios Farmac&#233;uticos Rovi S&#46;A&#46;&#44; who provided consistent technical support in the structuring and the surveys&#8217; printing&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of Interest</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara">The authors have no conflicts of interest to declare&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27371&#95;en&#95;t1&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27371_en_t1_11106i.jpg" alt="HD centre survey&#46; Criteria for the use of LMWH vs UFH"></img></a></p><p class="elsevierStylePara">Table 1&#46; HD centre survey&#46; Criteria for the use of LMWH vs UFH</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27372&#95;en&#95;t2&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27372_en_t2_11106i.jpg" alt="HD centre survey&#46; Dose adjustment methods"></img></a></p><p class="elsevierStylePara">Table 2&#46; HD centre survey&#46; Dose adjustment methods</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27374&#95;en&#95;t3&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27374_en_t3_11106i.jpg" alt="Patient survey&#46; Baseline characteristics&#46; Type of heparin administered according to age&#44; sex&#44; diabetes&#44; and haemoglobin levels"></img></a></p><p class="elsevierStylePara">Table 3&#46; Patient survey&#46; Baseline characteristics&#46; Type of heparin administered according to age&#44; sex&#44; diabetes&#44; and haemoglobin levels</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27375&#95;en&#95;f1&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27375_en_f1_11106i.jpg" alt="HD centre survey&#46; Heparin dosing"></img></a></p><p class="elsevierStylePara">Figure 1&#46; HD centre survey&#46; Heparin dosing</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27376&#95;en&#95;f211106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27376_en_f211106i.jpg" alt="Patient survey&#46; Type of heparin administered according to the haemodialysis technique employed"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Patient survey&#46; Type of heparin administered according to the haemodialysis technique employed</p><p class="elsevierStylePara"><a href="grande&#47;11106&#95;16025&#95;27377&#95;en&#95;f3&#95;11106i&#46;jpg" class="elsevierStyleCrossRefs"><img src="11106_16025_27377_en_f3_11106i.jpg" alt="Patient survey&#46; Treatment with oral anticoagulants in patients with and without bleeding complications in the previous week"></img></a></p><p class="elsevierStylePara">Figure 3&#46; Patient survey&#46; Treatment with oral anticoagulants in patients with and without bleeding complications in the previous week</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Objetivos&#58;</span> Los objetivos del presente trabajo fueron conocer qu&#233; m&#233;todos de anticoagulaci&#243;n se emplean en la pr&#225;ctica habitual en los pacientes en hemodi&#225;lisis &#40;HD&#41; en Espa&#241;a&#44; de qu&#233; criterios dependen y las complicaciones derivadas de su uso&#46; <span class="elsevierStyleBold">Material y m&#233;todos</span><span class="elsevierStyleBold">&#58;</span> Es un estudio de dise&#241;o transversal basado en dos tipos de encuestas&#44; una de centros y otra de pacientes&#46; La primera fue contestada por 87 unidades de HD de adultos que inclu&#237;an 6&#46;093 pacientes&#44; y 2 unidades pedi&#225;tricas&#59; 43 centros &#40;48&#44;3&#37;&#41; eran de titularidad p&#250;blica y 46 &#40;51&#44;7&#37;&#41;&#44; privada&#47;concertada&#46; En la encuesta de pacientes se analizaban 758 pacientes elegidos al azar de manera aleatoria en 78 unidades de HD&#46; <span class="elsevierStyleBold">Resultados&#58;</span> A&#41; <span class="elsevierStyleItalic">Encuesta de centros</span>&#58; La mayor&#237;a de los centros de adultos &#40;n &#61; 61&#44; 70&#44;2&#37;&#41; dispon&#237;an tanto de heparina de bajo peso molecular &#40;HBPM&#41; como de heparina no fraccionada &#40;HNF&#41;&#44; 19 &#40;21&#44;8&#37;&#41; s&#243;lo emplean HBPM y 7 &#40;8&#37;&#41; utilizaban exclusivamente HNF&#46; Las criterios m&#225;s frecuentes para el empleo de HBPM fueron indicaciones m&#233;dicas &#40;83&#44;3&#37; de los centros&#41; y la comodidad en la administraci&#243;n &#40;29&#44;5&#37;&#41;&#46; Los m&#233;todos m&#225;s empleados para el ajuste de la dosis eran la coagulaci&#243;n del circuito &#40;88&#44;2&#37; de los centros&#41;&#44; el sangrado del acceso vascular tras la desconexi&#243;n &#40;75&#44;3&#37;&#41; y el peso del paciente &#40;57&#44;6&#37;&#41;&#46; B&#41; <span class="elsevierStyleItalic">Encuesta de pacientes</span>&#58; La distribuci&#243;n del tipo de heparina empleada fue&#58; 44&#44;1&#37; HNF&#44; 51&#44;5&#37; HBPM y 4&#44;4&#37; di&#225;lisis sin heparina&#46; La HBPM se utiliza m&#225;s frecuentemente en los centros p&#250;blicos &#40;64&#44;2&#37; de los pacientes&#41; que en los privados&#47;concertados &#40;46&#44;1&#37;&#41; &#40;p &#60; 0&#44;001&#41;&#46;<span class="elsevierStyleBold"> </span>La HBPM se utilizaba con mayor frecuencia en la hemodiafiltraci&#243;n en l&#237;nea que en la HD de alto flujo &#40;p &#60; 0&#44;001&#41;&#46; Un 45&#44;5&#37; de los pacientes recib&#237;an antiagregantes&#44; un 18&#44;4&#37; anticoagulantes orales y un 5&#37; ambos<span class="elsevierStyleBold">&#46;</span><span class="elsevierStyleBold"> </span>El<span class="elsevierStyleBold"> </span>4&#44;4&#37; de los pacientes tuvo complicaciones hemorr&#225;gicas en la &#250;ltima semana y el 1&#44;9&#37; complicaciones tromb&#243;ticas&#46; Las complicaciones hemorr&#225;gicas fueron m&#225;s frecuentes en los pacientes que tomaban anticoagulantes orales &#40;p &#61; 0&#44;01&#41;&#46; No hab&#237;a asociaci&#243;n entre el tipo de heparina y las complicaciones hemorr&#225;gicas&#46; <span class="elsevierStyleBold">Conclusiones&#58; </span>Se puede concluir que existe una gran disparidad de criterios en la prescripci&#243;n de la anticoagulaci&#243;n en HD&#46; Es aconsejable revisar los resultados propios y externos&#44; y posiblemente crear una gu&#237;a de anticoagulaci&#243;n en hemodi&#225;lisis&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Objectives&#58;</span> This study&#8217;s objectives were to determine which anticoagulation methods are commonly used in patients who are undergoing haemodialysis &#40;HD&#41; in Spain&#44; on what criteria do they depend&#44; and the consequences arising from their use&#46; <span class="elsevierStyleBold">Material and Method&#58; </span>Ours was a cross-sectional study based on two types of surveys&#58; a &#34;HD Centre Survey&#34; and a &#34;Patient Survey&#34;&#46; The first survey was answered by 87 adult HD units serving a total of 6093 patients&#44; as well as 2 paediatric units&#46; Among these units&#44; 48&#46;3&#37; were part of the public health system and the remaining 51&#46;7&#37; units were part of the private health system&#46; The patient survey analysed 758 patients who were chosen at random from among the aforementioned 78 HD units&#46; <span class="elsevierStyleBold">Results&#58;</span> A&#41; <span class="elsevierStyleItalic">HD <span class="elsevierStyleItalic">Centre Survey</span></span>&#58; The majority of adult HD units &#40;n&#61;61&#44; 70&#46;2&#37;&#41; used both kinds of heparin&#44; 19 of them &#40;21&#46;8&#37;&#41; only used LMWH and 7 of them &#40;8&#37;&#41; only used UFH&#46; The most frequently applied criteria for the use of LMWH were medical indications &#40;83&#46;3&#37; of HD units&#41; and ease of administration &#40;29&#46;5&#37;&#41;&#46; The most frequently used methods for adjusting the dosage were clotting of the circuit &#40;88&#46;2&#37; of units&#41;&#44; bleeding of the vascular access after disconnection &#40;75&#46;3&#37;&#41;&#44; and patient weight &#40;57&#46;6&#37;&#41;&#46; B&#41; <span class="elsevierStyleItalic">Patient Survey</span>&#58; The distribution of the types of heparin used was&#58; UFH&#58; 44&#46;1&#37;&#44; LMWH&#58; 51&#46;5&#37;&#44; and dialysis without heparin in 4&#46;4&#37; of patients&#46; LMWH was more frequently used in public medical centres &#40;64&#46;2&#37; of patients&#41; than in private medical centres &#40;46&#46;1&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; LMWH was more frequently used in on-line haemodiafiltration &#40;HF&#41; than in high-flux HD &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; Antiplatelet agents were given to 45&#46;5&#37; of patients&#44; oral anticoagulants to 18&#46;4&#37; of patients&#44; and both to 5&#37; of patients&#46; Additionally&#44; 4&#46;4&#37; of patients had suffered bleeding complications during the previous week&#44; and 1&#46;9&#37; of patients suffered thrombotic complications&#46; Bleeding complications were more frequent in patients with oral anticoagulants &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;001&#41;&#44; although there was no association between the type of heparin and the occurrence of bleeding or thrombotic complications&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> We are able to conclude that there is a great amount of disparity in the criteria used for the medical prescription of anticoagulation in HD&#46; It is advisable that each HD unit revise their own results as well as those from other centres&#44; and possibly to create an Anticoagulation Guide in Haemodialysis&#46;</p>"
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ISSN: 20132514
Original language: English
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Idiomas
Nefrología (English Edition)
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¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?