Ivo Jelicic

The individually optimized bolus dose of nadroparin is safe and effective in diabetic and nondiabetic patients with bleeding risk on hemodialysis

The risk of bleeding is a well‐known complication in patients on hemodialysis (HD). The aim of this prospective study was to determine the lowest single bolus dose of low–molecular‐weight heparin nadroparin for safe and effective HD in patients with a bleeding risk. Forty HD patients were divided into 4 subgroups with 10 participants (diabetics with and without a bleeding risk, nondiabetics with and without a bleeding risk). The actual starting bolus dose was decreased by 25% after the initial 4 weeks, further decreased by 25% of the starting dose after 4 weeks, and changed due to extracorporeal circuit clotting in the last 4 weeks. The parameters of coagulation were measured at the beginning, after 2 and 4 h of HD sessions. A significant reduction of nadroparin (first vs. last HD session) was observed in: diabetics with a bleeding risk (49.66 ± 12.33 vs. 28.78 ± 9.60 IU/kg/HD; P<0.001), diabetics without a bleeding risk (50.70 ± 15.23 vs. 33.95 ± 16.97 IU/kg/HD; P<0.001), and nondiabetics with a bleeding risk (61.25 ± 18.68 vs. 32.96 ± 10.06 IU/kg/HD; P<0.001). Altogether, the reduction of the nadroparin dose in these groups was 42.05%; 33.04%, and 46.19%, respectively. Although anti‐Xa at hour 4 at the end of the study was <0.4 IU/mL in our diabetic and nondiabetic patients without a risk of bleeding, serious clottings in the extracorporeal circuit and vascular access thromboses were not found. This study demonstrated for the first time that individually optimized doses of nadroparin are sufficient for safe and effective HD in patients with a bleeding risk.

Spleen rupture associated with septic emboli and endocarditis in a hemodialysis patient.

We present an uremic patient on chronic hemodialysis with splenic septic emboli associated with active infective endocarditis and anaerobic bacteremia complicated by ruptured spleen. A 62-year-old female patient was admitted because of fever and pain in the left upper abdomen and swelling and hematoma around the left brachiocephalic arteriovenous fistula. Transthoracic echocardiography revealed mobile hyperechoic mass (vegetation) on the anterior mitral valve. Abdominal ultrasound scan showed multiple hypoechoic lesions of the enlarged spleen, described as possible necroses or abscesses, and computed tomography showed low-density inhomogeneous lesions in the enlarged spleen with large perisplenic hematoma, with spleen rupture. Blood culture revealed anaerobic Gram-negative bacilli (Bacteroides spp.), ampicillin resistant. This is the first report of splenic rupture associated with anaerobic bacteremia and splenic septic emboli in a uremic patient on chronic hemodialysis. Splenic septic emboli with abscess/infarction in hemodialysis patients are a rare disorder but could be a consequence of dialysis access site infection and might predispose to splenic rupture. Ultrasound scan of abdomen is fast, inexpensive and easy to perform. As mortality is high, early surgical intervention on vascular access is mandatory.

Potential beneficial effects of low molecular weight heparin on cognitive impairment in elderly patients on haemodialysis

Vascular cognitive impairment or mixed vascular cognitive impairment and Alzheimer’s disease (AD) appear to be much more common in elderly patients than AD alone. Furthermore, vascular dementia (VaD) and AD are more prevalent in elderly patients receiving haemodialysis (HD), leading to a loss of independence and a poor quality of life. Hypotensive episodes in patients receiving HD contribute to vascular changes in the brain, with consequent progression of VaD and AD.The use of the lowest individually optimized bolus dose of low molecular weight heparin (LMWH) during HD, with fewer hypotensive episodes during and between HD procedures, may exert a sparing effect on changes in microvascular circulation and decrease the incidence of VaD and AD. We believe that long-term use of LMWH, with its direct effect on amyloid β protein (Aβ) in the blood and on Aβ accumulation in the brain and indirect effects on prevention of complement activation, may delay the progression of cognitive impairment in patients receiving HD.There is a need for a robustly designed, prospective trial to evaluate the effects of long-term treatment with LMWH on mild cognitive impairment, VaD and AD in elderly patients receiving maintenance HD.

Differences in epidermal thickness and expression of apoptosis regulatory proteins in the skin of patients with chronic renal failure and pruritus

Chronic renal failure is often associated with skin itching (pruritus) in dialysis patients. In order to investigate the possible causes of pruritus, the epidermis of the thigh of 12 dialysis patients and 4 controls from patients without renal disease were examined. The sections of the epidermis were measured and immunohistochemically analyzed using antibodies to Bcl-2, Bax, caspase-3 proteins and TUNEL method. While the mean thickness of normal epidermis was 53 μm, in dialysis patients it ranged between 23 and 34 μm during the 3-5 year period on dialysis. Compared to normal skin, the fine balance between the Bcl-2 and Bax proteins did not greatly change in the epidermis of dialysis patients during the three years of dialysis. Following five-year dialysis, the epidermis displayed increased Bax and decreased Bcl-2 expression in the basal and intermediate epidermal layers, as well as the presence of apoptotic cells (TUNEL and caspase-3 positive) both in the superficial and intermediate epidermal layers. Our study demonstrated the predominant expression of cell death Bax proteins over cell survival Bcl-2 proteins, and apoptotic cells in the deeper layers of the epidermis in patients on long-term dialysis. We speculate that the thinning of the epidermis might be associated with the appearance of dead cells in the deeper epidermal layers, while the changed internal milieu of epidermal cells could possibly affect the intra-epidermal nerve endings thus leading to the sensation of pruritus.

What Are the Lowest Doses of Low Molecular Weight Heparin for Effective and Safe Hemodialysis in Different Subgroups of Patients

Dear Editor, Patients on hemodialysis (HD) are prone to two opposing hemostatic processes: a bleeding tendency and a hypercoagulable state. Bleeding episodes in patients on HD are common due to their underlying uremic state, age and concomitant diseases (diabetes, bleeding disorder, vascular diseases) (1). They may benefit from the possibility of using less systemic anticoagulation during HD (2,3). Regional anticoagulation with citrate has been developed for use as an alternative to unfractionated heparin, particularly in patients with a high risk of bleeding. But, for HD patients not at risk of bleeding, low molecular weight heparin (LMWH) provides a simple anticoagulation regimen. Prolonged use of citrate anticoagulation is complicated by concerns with calcium homeostasis and the development of metabolic alkalosis (4). A dialysate using low-dose citric acid instead of acetic acid as the acidifying agent may allow a heparin-free or reduced heparin dose dialysis. An improvement in the efficiency of dialysis, as demonstrated by a significantly higher eKt/V urea, was an unanticipated side benefit and might be explained by less dialyzer clotting from the dual anticoagulation effects of Ca chelation by citrate and heparin. The much higher cost of citrate dialysate currently makes this an unattractive option for regular use (5). The aim of our study was to find out what are the lowest single bolus doses of LMWH nadroparin calcium (Fraxiparine, Glaxo Welcome Production, Notre Dame de Bondeville, France) for the safe and effective HD in different subgroups of patients due to age, gender, diabetes and bleeding risk. The actual starting bolus dose of nadroparin (HD1 nadroparin), which was used in our Center for a minimum of 2 months according to the manufacturer’s recommendation (with only some “minor” bleedings from vascular access after HD, and very rare “major”gastrointestinal bleedings), was decreased twice by 25%: after the initial 4 weeks (HD2 nadroparin), and again after an additional 4 weeks (HD3 nadroparin). The maintenance period was 4 weeks (HD4 nadroparin) during which time this dose was adjusted due to clotting of the extracorporeal circuit. All 40 patients (age 64.93 ± 12.34 years) on intermittent HD for 61.63 ± 53.97 months, were included in this 12-week long study, 38 patients completed the study, two were transplanted, and none died. The nadroparin doses at the beginning and at the end of the study (HD1 vs. HD4) were: 53.19 ± 15.18 vs. 33.84 ± 12.64 IU/kg/HD; P < 0.001 (the reduction 36%). We investigated two subgroups of patients due to age: 25 patients >65 (mean 72.88 ± 5.26 years); and 15 patients <65 (mean 51.67 ± 8.68 years) undergoing intermittent HD for 52.60 ± 51.50, and 76.67 ± 56.39 months (respectively).The doses of nadroparin (HD1 vs. HD4) in patients >65 years were: 48.60 ± 10.45 vs. 31.34 ± 12.02 IU/kg/HD; P < 0.005, and patients <65 years: 60.84 ± 18.82 vs. 38.64 ± 12.88 IU/kg/HD; P < 0.001 (the reductions were 35.52% and 36.49%, respectively). Due to gender, we investigated subgroups of 22 male (mean age 63.36 ± 12.06 years) and 18 female patients (mean age 66.83 ± 12.75 years) undergoing intermittent HD for 53.82 ± 52.70, and 71.17 ± 55.48 months (respectively). The individually optimized bolus doses of nadroparin (HD1 vs. HD4) in male patients were: 53.04 ± 15.60 vs. 34.50 ± 12.80 IU/kg/ HD; P < 0.005, and in female patients were: 51.67 ± 14.70 vs. 32.93 ± 12.78 IU/kg/HD; P < 0.005 (the reductions were 35% and 36.27%, respectively). We also investigated four subgroups with 10 patients due to diabetes and bleeding risk (Table 1). A safe and significant reduction of nadroparin (HD1 vs. HD4) was observed in: diabetics with bleeding risk (49.66 ± 12.33 vs. 28.78 ± 9.60 IU/kg/HD; P < 0.001), diabetics without bleeding risk (50.70 ± 15.23 vs. 33.95 ± 16.97 IU/kg/HD; P < 0.001), and non-diabetics with bleeding risk (61.25 ± 18.68 vs. 32.96 ± 10.06 IU/kg/HD; P < 0.001). All together, the reductions of nadroparin dose in these groups were: 42.05%; 33.04% and 46.19%, respectively. The lowest reduction was in non-diabetics without bleeding risk: 12.03% (47.45 ± 10.87 vs. 41.75 ± 10.91 IU/kg/HD; P = 0.484) (6,7). bs_bs_banner

The Influence of Decreased Low-Molecular-Weight Heparin Nadroparin Dose on Diastolic Blood Pressure in Patients on Hemodialysis

The aim of present study was to assess the impact of decreasing single bolus dose of nadroparin on blood pressure in patients on hemodialysis (HD). Forty HD patients were included in this study. The bolus dose of nadroparin was decreased twice by 25%; this lower dose was maintained for last 4 weeks, during which the dose was adjusted. There were no significant differences between the first and the last predialysis: systolic blood pressure ([pre-SBP]; 131.05 ± 25.58 vs 125.92 ± 25.49 mm Hg; P = .133), diastolic blood pressure ([pre-DBP]; 73.82 ± 11.82 vs 72.89 ± 9.13 mm Hg; P = .653), and pulse pressure ([pre-PP]; 57.24 ± 20.39 vs 53.03 ± 21.20 mm Hg; P = .121). We found correlation between delta nadroparin and pre-DBP in the last HD (rho = 0.310; P = .031) but not between delta nadroparin and pre-SBP and pre-PP values. This is the first report of influence of nadroparin dose lowering on pre-DBP in HD patients.

BLOOD PRESSURE VARIABILITY DURING HAEMODIALYSIS SESSION IMPAIRED COGNITIVE AND MOTOR FUNCTIONS IN URAEMIC PATIENTS: PP.8.330

Introduction: Change in cognitive and motor function is one of the well known consequence of the end stage renal disease (ESRD). Little is known about influence of blood pressure during haemodialysis (HD) session on cognitive and motor functions. The aim of the study was to determinate whether blood pressure during HD session may impair cognitive and motor functions in HD patients. Subjects: In study were included 42 participants (14 females, 28 males) aged 54,36 ± 11,20 years (range 34–80) on chronic HD regimen 6,14 ± 3,97 years. The mean HD dose calculated as Kt/V was 1,32 ± 0,24. The systolic and diastolic arterial pressure were measured on the beginning and at the end of observed HD session. The pulse pressure (PP) and mean arterial pressure (MAP) were calculated, and differences between PP and MAP on the beginning and at the end of the HD were calculated (delta PP and delta MAP). Cognitive and motor abilities were investigated using a test of convergent thinking (test 11) from the Complex Reactiometer Drenovac (CRD) system. Results of the cognitive and motor abilities were given as total time of test solving in seconds (TT). Cognitive and motor parameters were calculated one hour before and one hour after the same HD session. Results: The differences between groups of subjects with delta PP>=8 mmHg and delta PP < 8 mmHg were found in preHD 11TT (207,54 ± 66,61 vs. 175,99 ± 43,94; p = 0,049) and postHD 11TT (183,01 ± 69,96 vs. 147,40 ± 36,33; p = 0,032). The subjects with predialysis systolic pressure >140 mmHg have significant differences in preHD 11TT compared with subjects with predialysis systolic pressure <140 mmHg, (215,74 ± 61,09 vs. 178,16 ± 54,24; p = 0,024). There was significant correlation between preHD 11TT and delta PP (Spearmans rho = 0,276; p = 0,047). Conclusion: Significant influence of arterial pressure on cognitive and motor functions in HD population was demonstrated. The intradialytic HD instability with variation between pre- and post HD blood pressure values is important factor in cognitive and motor functions deterioration.

High ANTI-PF4/Heparin Antibodies Titer and Thromboses Due to Infection 9 Months After Cessation of Heparin in Hemodialyzed Patient With Heparin-Induced Thrombocytopenia: LONG LASTING ANTI-PF4/HEPARIN ANTIBODIES

Superficialization of an AVF as second stage procedure by means of flap elevation (1) and open lipectomy (2), have been shown to be effective yet invasive options to prepare the cephalic vein for needling in obese patients. Previous attempts of minimally invasive procedures, such as ultrasoundguided liposuction (3), were shown to be associated with wound necrosis and large hematomas. Therefore, based on endoscopic surgery for hernia repair and following the technique of endoscopic basilic vein transposition (4), we developed a superficialization technique to obtain AVF function that allows visual control of the vein during the entire procedure. This minimizes the risk of vein injury and allows identifying other anatomical structures such as superficial fascia and tributaries. Endoscopic surgery for superficialization and closing of tributaries over a deep lying AVF has not been previously described. The novel technique renders revision and superficialization safer, as it reduces the risk of vein injury without prolonging the procedure. Furthermore, this minimally invasive technique avoids long skin scars, and provides excellent functional and aesthetic results.

INFLUENCE OF NADROPARIN DECREASING ON BLOOD PRESSURE IN HAEMODIALYSED PATIENTS: PP.26.57

Introduction: Patients receiving chronic haemodialysis (HD), especially diabetics, have an increased risk of arterial hypertension and cardiovascular morbidity. Previous studies were described hypotensive effect of systemic heparin administration. The aim of this study was to assess the impact of decreasing single bolus dose of low molecular weight heparin (LMWH) nadroparin on blood pressure among patients on HD. Design and Method: Forty patients (18 females), 20 diabetics, mean age 64,93 ± 12,34 years (range 36–84) undergoing intermittent HD for 62,63 ± 53,97 months (range 5–196) were included in this 12-weeks long prospective study. The recommended nadroparin bolus dose was decreased by 25% after 4 weeks, again by 25% after 8 weeks, and maintained 50% lower doses for 4 weeks. The blood pressure was measured at the beginning of each HD. The efficacy and safety of LMWH were assessed by dialysis system clotting and the dose of LMWH was respectively changed. Results: Overall, there was difference between the first and the last LMWH dose but not between the first and the last predialysis blood pressure parameters (Table 1.). In the subgroup of diabetics the differences in the first and the last predialysis systolic and PP were found (Table 2.). Conclusion: This trial demonstrated the influence of lowering nadroparin doses on blood pressure in HD patients. The significant decreasing of LMWH level led to paradoxally decreasing in systolic and pulse pressure only in diabetics on chronic haemodialysis. Figure 1. No caption available.