Epoetin omega for treatment of anemia in maintenance hemodialysis patients

After the synthesis of epoetins alpha and -beta, a third molecule of recombinant human erythropoietin (rHuEPO) was synthesized and was named epoetin-omega. The molecule of epoetin-omega is a sialoglycoprotein with smaller amounts of O-bound sugars, less acidic and with different hydrophylity than the other 2 epoetins. The purpose of the study was to assess the efficacy, safety and clinical tolerance of epoetin-omega for treatment of renal anemia. In an open-label, uncontrolled prospective clinical study, 22 end-stage renal disease patients (9 male and 13 female) were followed for 6 months. They all had a hemoglobin (Hb) value below 85 g/l, and were on regular hemodialysis therapy 3 times a week, 4 hours per session. The initial weekly dose of epoetin-omega was 90 units per kg of body weight (b.w.) divided in 3 equal portions and administered subcutaneously after each dialysis session. After correction of the hemoglobin, the dose of rHuEPO was individualized to keep Hb within target limits of 100-120 g/l. To follow efficacy and safety, a number of clinical and laboratory parameters were monitored. All patients responded well to the therapy with corrected hemoglobin after the 10th week of the study. The mean dose of epoetin-omega during the correction period never exceeded 100 U/kg b.w. per week. The average maintenance dose of rHuEPO was 50-60 U/kg b.w. per week. Iron was, where needed, supplied intravenously. We noted no change in serum urea. creatinine, phosphorus, and heparin dose per dialysis session. The prothrombin time improved during the study. Serum albumin increased. No change was observed in urea reduction ratio (URR), body weight and mean arterial pressure. One serious adverse event was noted: worsening of hypertension in 1 patient, with the development of hypertensive encephalopathy and severe headache. rHuEPO treatment was stopped. The blood pressure was effectively controlled by reducting her body weight by 5%. Thereafter, rHuEPO therapy was resumed with good blood pressure control. We could conclude that recombinant human erythropoietin-omega was an efficient and safe therapeutic agent for the treatment of renal anemia.     

Carnitine action on red blood cell osmotic resistance in hemodialysis patients

Low red blood cell osmotic resistance (RBCOR) in dialysis patients aggravates anemia and raises EPO needs. We studied RBCOR in 30 stable patients (22 M, 8 F), dialyzed for more than one year, with no systemic illness, blood transfusions, recent infection or treatment by ACE inhibitors. Nineteen were on EPO. Cuprophane dialysis membranes were used in 21, synthetic in the remaining nine. RBCOR was low in 13 patients and these patients received L-carnitine, 20 mg/kg IV, post dialysis, for one year (A); 17 with normal RBCOR served as untreated controls (B). We investigated the relations between RBCOR and membrane material, time on HD (THD), weekly dialysis duration (WHDT), serum total carnitine (TC), acyl carnitine (AC), free carnitine (FC) and AC/FC in all patients, before and after carnitine supplementation. RBCOR changes under carnitine treatment were evaluated. Age, sex, primary renal disease, THD, EPO dose, hematology and biochemistry were similar in treated patients and controls. Patients in group A (dialysed with cuprophane) had lower RBCOR than group B, (dialysed with synthetic and cuprophane membranes) (0.473 +/- 0.02 vs. 0.420 +/- 0.02, P < 0.001). RBCOR remained stable under carnitine in group A, but became abnormally low in controls (especially in 10/17 patients). RBCOR was significantly higher than the pretreatment values in 5/13 group A patients (month 0-M0: 0.48 +/- 0.02, M12: 0.45, +/- 0.02, P < 0.05). Carnitine levels, similar in both groups before treatment, remained stable in group A, but dropped in group B (TC: 52.1 +/- 9.6/31.1 +/- 21.2, FC: 33.1 +/- 8.3/15.6 +/- 19.2 micromol/L, P < 0.002). Patients with shorter WHDT (< or = 12 vs. > 12 h) had higher FC levels (36 +/- 6.9 vs. 30 +/- 6 micromol/L, P < 0.03). Low RBCOR is frequent in stable dialyzed patients. It is related to dialysis membranes and is aggravated by time on hemodialysis. Serum carnitine levels depend on weekly dialysis time and on carnitine supplementation, that normalizes osmotic resistance in some dialysis patients.     

Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients

The objective of this study was to quantitate the improvement in exercise capacity produced in anemic chronic hemodialysis (HD) patients after correction of their anemia with recombinant human erythropoietin (rHuEPO). The maximal exercise capacity and quadriceps strength of 19 anemic HD patients was tested before and after correction of the anemia with rHuEPO. A progressive work exercise protocol (PWET) on a cycle ergometer was used to compare measurements of maximal oxygen uptake (VO2max), maximal heart rate, and subjective assessment of fatigue during the test. Measurements of quadriceps strength were performed before the cycle ergometer studies. At baseline, all patients had reduced VO2max (15.3 +/- 5.4 mL/kg/min) and maximal exercise heart rates (138.5 +/- 23.9 beats/min). rHuEPO increased the mean hematocrit from 21.2% to 35%, and this was associated with a 17% increase (P less than 0.0005) in the VO2max. At any specified work load, rHuEPO treatment decreased heart rate, minute ventilation, and the subjective perception of fatigue. Both isometric and isokinetic measurements of quadriceps strength were improved following administration of rHuEPO. The maximal exercise heart rate was decreased in comparison to the baseline measurements (P less than 0.04), suggesting that in contrast to normal subjects, HD patients stop exercise before oxygen transport limitations are reached. In this unselected group of chronic HD patients, rHuEPO produced clinically significant improvements in both aerobic exercise capacity and isometric and isokinetic quadriceps strength. The improvement in aerobic capacity was substantially less than would have been expected from the correction of a comparable degree of anemia in non-HD patients. None of the 19 treated patients attained the exercise performance level predicted for a sedentary normal subject.     

Propofol enhances red cell antioxidant capacity in swine and humans

Purpose  To determine the effect of an anaesthetic with antioxidant potential, propofol, on red blood cell (RBC) antioxidant enzyme activities and RBC susceptibility to peroxidative challenge. Methods  Propofol was administered by intravenous bolus (2.5 mg·kg⁻¹) and continuous infusion (36 and 72 ml·hr⁻¹ in nine swine; 216 ml·hr⁻¹ in two swine), to achieve serum concentrations between 5 and 30μg·ml⁻¹ for two hours at each rate. Arterial blood sampling was at 0,10, 30, 60, and 120 min for each rate of infusion, for measurement of plasma propofol concentration, activities of plasma and RBC Superoxide dismutase, glutathione peroxidase, gluthathione reductase, RBC catalase, and RBC malondialdehyde (MDA) formation in response to exvivo oxidative challenge with t-butyl hydrogen peroxide (tBHP; 1.5mM). Antioxidant mechanisms were determined byin vitro study of MDA formation, GSH depletion, and oxidation of haemoglobin to methaemoglobin in human erythrocytes exposed to propofol 0–75 μM. The antioxidant potential of propofol was compared with that of alpha-tocopherol utilising the reaction with 2,4,6-tripyridyl-s-triazine (TPTZ). Results  Propofol had no effect on plasma or RBC antioxidant enzyme activities. It inhibited RBC MDA production over the range of 0–20 μg·ml⁻¹ (y = −18.683x + 85.431 ; R² = 0.8174). Effective propofol concentrations for 25% and 50% reductions in MDA levels were 7–12 and 12–20 μg·ml⁻¹, respectively. Propofol has a similar effect on human erythrocytesin vitro (R₂ = 0.98). Conclusion  Propofol antagonises the effects of forced peroxidation of red cells at anaesthetic and sub-anaesthetic concentrations in swine. Its actions include scavenging of oxygen derived free radicals in a tocopherol-like manner.

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Résumé Objectif  Déterminer l’effet d’un agent anesthésique possédant un potentiel antioxydant, le propofol, sur l’activité d’un enzyme antioxydant des globules rouges (GR) et sur la susceptibilité des GR à une provocation peroxydative. Méthodes  Le propofol a été administré en bolus intraveineux (2,5 mg·kg⁻¹) et en infusions continues (36 et 72 ml·h⁻¹ chez 9 porcs; 216 ml·h⁻¹ chez 2 porcs) pour obtenir des concentrations sériques entre 5 et 30 μg·ml⁻¹ durant deux heures à chaque vitesse d’infusion. Des prélèvements sanguins par voie artérielle ont été réalisés à 0, 10, 30, 60 et 120 min. pour chaque vitesse d’infusion; on a mesuré la concentration de propofol, l’activité de la superoxyde dismutase du plasma et des GR, de la peroxydase du glutathion, de la réductase du glutathion, de la catalase du GR, ainsi que de la formation dans le GR de la malondialdehyde (MDA) en réponse à une provocation oxydative exvivo avec le peroxyde d’hydrogène t-butylique (tBHP, 1,5 mM). Les mécanismes antioxydants ont été déterminés par l’étudein vitro de la formation de MDA, de la déplétion de GSH ainsi que de l’oxydation de l’hémoglobine en methémoglobine dans des GR humains exposés au propofol 0–75 μM. Le potentiel antioxydant du propofol a été comparé à celui de l’alpha-tocophérol en utilisant la réaction avec le 2,4,6-tripyridyl-s-triazine (TPTZ). Résultats  Le propofol n’a pas eu d’effet sur l’activité de l’enzyme antioxydant du plasma ou des GR. Il a inhibé la production de MDA par les GR pour tout le spectre de 0–20 μg·ml⁻¹ (y = −18.683x + 85.431 ; R² = 0,8174). Les concentrations de propofol efficaces pour obtenir une réduction des taux de MDA de 25 et de 50% étaient respectivement de 7–12 et de 12–20 μg·ml⁻¹. Le propofol a un effet analogue sur les globules rouges humainsin vitro (R₂ = 0,98). Conclusion  Le propofol, à des concentrations anesthésiques et subanesthésiques chez le porc, antagonise les effets d’une peroxydation forcée des globules rouges. Son mode d’action comporte l’épuration des radicaux libres provoqués par l’oxygène comme le fait le tocophérol.

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Supported in part by a research grant from Zeneca Pharma Inc (Canada Ltd.).

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Presented at the 71st Clinical and Scientific Congress of the International Anesthesia Research Society, March 14–18,1997 San Francisco, Ca, USA.     

Cellulose acetate membrane improves some aspects of red blood cell function in haemodialysis patients

The present study was designed to evaluate the influence of two haemodialysis membranes of different biocompatibility on red blood cell function. Twelve patients were studied in two consecutive dialyses, with cuprophan and cellulose acetate. Blood was extracted at 0, 20 and 180 min after the beginning of the haemodialysis session and general haematological parameters, osmotic fragility, deformability, methaemoglobin concentration and malonyldialdehyde (MDA) red blood cell content were determined. Osmotic fragility improved with both membranes, but this improvement was more marked with cellulose acetate. MDA red blood cell content showed a tendency to increase after 3 h with cuprophan (114 +/- 11% of the basal value), whereas it tended to decrease with cellulose acetate (92 +/- 12%), the differences between the two groups being statistically significant. These results suggest that red cell function may improve by changing the characteristics of haemodialysis membranes. This phenomenon could be related to a better biocompatibility.     

Anti-N-like and anti-Form red cell antibodies in chronic hemodialysis patients

Allogeneic red blood cell (RBC) transfusions and the use of reusable dialyzers sterilized with formaldehyde can lead to RBC alloimmunization in chronic hemodialysis patients. The formed RBC alloantibodies have been implicated in immediate kidney allograft failure and decreased RBC survival observed in these patients. Using indirect antiglobulin test, direct antiglobulin test (DAT), and direct Polibrene test (DPT), we detected an RBC alloimmunization rate of 17.2% (11/64) in transfused hemodialysis patients, and found the presence of anti-N-like and anti-Form antibodies in 5 (5.7%) and 53 (60.9%) individuals, respectively. The sensitivity rate of the DPT was significantly higher than that of the DAT in detecting anti-Form, but the DAT showed a higher specificity rate compared with the DPT. We conclude that patients treated with reusable dialyzers sterilized with formaldehyde may develop specific RBC alloantibodies that could increase the potential risk of hemolysis, decrease survival of RBCs, and increase the need of blood supply.     

Tissue antioxidant capacity during anesthesia: propofol enhances in vivo red cell and tissue antioxidant capacity in a rat model.

The effects of anesthesia on ischemia-reperfusion injury are of considerable scientific and clinical interest. We examined the effects of propofol (known to possess antioxidant activity) and halothane (devoid of antioxidant activity in vitro) on tissue and red blood cell (RBC) antioxidant capacity. Adult male Wistar rats were anesthetized with halothane 0.5%-1.0% (n = 7), propofol 500 microg x kg(-1) x min(-1) with halothane 0.25%-0.5% (small-dose propofol; n = 9), or propofol 2000 microg x kg(-1) x min(-1) (large-dose propofol; n = 8) for 45 min. Blood and tissue samples of liver, kidney, heart, and lung were then harvested for in vitro exposure to a peroxidizing agent. Red cell malondialdehyde and tissue thiobarbituric acid reactive substances were determined spectrophotometrically. Antioxidant capacities of blood and tissues in the Large-Dose Propofol group, and of blood and all tissues except lung in the Small-Dose Propofol group, were increased significantly compared with halothane (P < 0.003). The increases in tissue antioxidant capacities varied in their magnitude: RBC > liver > kidney > heart > lung. There was a high correlation between changes in RBC susceptibility to oxidative damage and corresponding changes in tissues. These findings demonstrate that large-dose propofol significantly enhances tissue antioxidant capacity, and RBC antioxidant capacity can serve as a functional measure of tissue activity, in vivo. IMPLICATIONS: We designed this study to investigate the antioxidant effects of propofol in various tissues in a rat model. Pretreatment of animals with propofol led to a reduction in the susceptibility to an in vitro oxidative stress of five different tissues investigated, demonstrating the drug's ability to limit oxidative injury. This may have future application in limiting organ dysfunction after periods of tissue ischemia (which results in oxidative damage).     

回血方向对血液透析患者残血红细胞存数的影响

目的 比较单向回血法透析器不同方向回血对血液透析患者残血红细胞存数的影响.方法 选择血液透析患者35例,采用自身对照方法,每例患者分别实施动脉端向上回血法和静脉端向上回血法各5次.评估血液透析器凝血状况,测量透析器及管路中残血红细胞存数及回血时间等.结果 在回水量相同的情况下,动脉端向上回血法与静脉端向上回血法相比,透析器凝血状况回血时间以及透析器管路中残血红细胞存数差异均有统计学意义(P＜0.05).结论 动脉端向上回血法能最大限度降低透析器中残血红细胞存数,减少回血时间.     

High dose propofol enhances red cell antioxidant capacity during CPB in humans

PURPOSE: To compare low vs. high dose propofol and isoflurane on red cell RBC antioxidant capacity in patients during aortocoronary bypass surgery (ACBP). METHODS: Twenty-one patients, for ACBP, were anesthetized with sufentanil 0.5-10 microg x kg(-1) and isoflurane 0-2%; ISO = control; n = 7), or sufentanil 0.3 microg x kg(-1), propofol 1-2.5 mg x kg(-1) bolus then 100 microg x kg(-1) min(-1) before, and 50 microg x kg(-1) x min(-1) during CPB (LO; n = 7), or sufentanil 0.3 microg x kg(-1), propofol 2-2.5 mg x kg(-1) bolus then 200 microg x kg(-1) x min(-1) (HI; n = 7). Venous blood was drawn pre- and post-induction, after 30 min CPB, 5, 10, and 30 min of reperfusion, and 120 min post-CPB to measure red cell antioxidant capacity (malondialdehyde (MDA) production in response to oxidative challenge with t-butyl hydrogen peroxide) and plasma propofol concentration. Pre- induction blood samples were analyzed for antioxidant effects of nitrates on red cells. The tBHP concentration response curves for RBC MDA in ISO, LO and HI were determined. RESULTS: Preoperative nitrate therapy did not effect RBC MDA production. Perioperative RBC MDA production was similar in ISO and LO groups. Sustained intraoperative decrease in RBC MDA was seen with propofol 8.0+/-2.4 - 11.8+/-4.5 microg x ml(-1) in HI (P<0.05-0.0001). MDA production vs. log plasma propofol concentration was linear in HI dose. CONCLUSIONS: During CPB, RBC antioxidant capacity is enhanced and maintained with HI dose propofol. Propofol, at this dose, may prove useful in protecting against cardiopulmonary ischemia-reperfusion injury associated with ACBP.     

Oral supplementation with gamma-linolenic acid extracted from Mucor circinelloides improves the deformability of red blood cells in hemodialysis patients

BACKGROUND: The development of abnormalities in red blood cell (RBC) deformability in patients undergoing hemodialysis remains a major problem, because it is related to peripheral microcirculation, oxygen supply, and various complications in such patients. gamma-Linolenic acid (GLA; 18:3n-6), one of the polyunsaturated fatty acids and a precursor of prostaglandin E(1), is reported to have a favorable effect on the deformability of circulating blood cells in diabetic patients. METHODS: In order to clarify the efficacy of GLA on RBC deformability in 7 patients undergoing maintenance hemodialysis, we examined in a pilot study the changes in the deformability of RBC and the changes in the phospholipid fatty acid composition in both plasma and RBC membrane before and after high-dose oral supplementation with GLA derived from Mucor circinelloides for 12 weeks. RESULTS: Before supplementation, the micropore passage time of RBC suspension, which is an indicator of RBC deformability, in these patients was markedly longer than that in healthy control subjects. After administering GLA, the prolonged passage time of the patients both rapidly and steadily decreased and nearly reached control levels. Light microscopic observations of RBCs using Giemsa stain revealed a decreased number of poikilocytes after supplementation. An analysis of the fatty acid composition before treatment and 8 weeks after starting the treatment showed the dihomo-gamma-linolenic acid (DGLA; 20:3n-6) level in the plasma to have increased (p < 0.05), while the arachidonic acid (AA; 20:4n-6) concentration in the RBC membrane decreased (p < 0.05). The level of DGLA in the RBC membrane, the level of GLA, and the ratio of GLA + DGLA/AA in plasma and RBC membrane did not change significantly; however, these all tended to increase. CONCLUSION: The results of this pilot study indicate that the oral supplementation of GLA extracted from M. circinelloides improves the poor RBC deformability in hemodialysis patients, partly by inducing changes in the composition of fatty acids in plasma and RBC membrane.     

The plasma and red cell vitamin B levels of chronic hemodialysis patients: a longitudinal study

Plasma B12, folate, B6 and thiamine, and red blood cell folate, thiamine and niacin levels were monitored for a period of 6 months in 15 clinically stable, chronic hemodialysis patients who were not supplemented with the water-soluble vitamins. Microbiological assays were used to determine the blood levels of the water-soluble vitamins. Over the period of 6 months, none of the patients had plasma or red cell vitamin levels below the normal range. No appreciable changes were observed in the plasma and red blood cell vitamin levels before and after dialysis in 5 patients. This study showed that chronic hemodialysis patients are able to maintain normal plasma and red cell levels of some water-soluble vitamins without daily supplementation.     

Home blood pressure monitoring improves the diagnosis of hypertension in hemodialysis patients

Using interdialytic ambulatory blood pressure (BP) recordings as the reference standard, we compared the performance of routine, standardized and home BP monitoring in 104 predominantly black patients on chronic hemodialysis for at least 3 months. Dialysis unit BP recordings were averaged over 2 weeks and home BP over 1 week. Awake ambulatory BP of > or =135 mmHg systolic or > or =85 mmHg diastolic was taken as evidence of hypertension. Average awake ambulatory BP was 128.1+/-21.6/73.5+/-13.5 mmHg, home BP 141.3+/-21.9/78.7+/-11.9 mmHg, standardized pre-dialysis BP 141.7+/-22.6/74.2+/-13.5 mmHg and post-dialysis 119.9+/-20.5/69.1+/-13.1 mmHg, routine pre-dialysis 145.4+/-21.8/79.0+/-13.1 mmHg and post-dialysis 131.5+/-19.2/72.5+/-11.4 mmHg. Sixty-three percent of the patients had well-controlled BP by ambulatory BP monitoring and isolated diastolic hypertension was rare (3%). The standard deviation of the differences between ambulatory and routine pre-dialysis BP was 17.6 mmHg, routine post-dialysis was 16.1 mmHg, standardized pre-dialysis was 16.4 mmHg, standardized post-dialysis was 14.1 mmHg, and home BP was 14.2 mmHg. The area under receiver operating characteristic curves was similar for home and standardized BP but lower for routine BP. Home systolic BP of > or =150 mmHg averaged over 1 week had the best combination of sensitivity (80%) and specificity (84.1%) in diagnosing systolic hypertension--present in 94% of the hypertensive dialysis patients. Home BP monitoring is similar to standardized recording of BP in hemodialysis patients. A systolic BP threshold of 150 mmHg at home averaged over 1 week serves as a useful predictor of hypertension diagnosed by ambulatory BP monitoring.     

不同病种外科病人术前血浆量、红细胞量和血容量的测定

目的 研究不同外科疾病病人术前血浆量、红细胞量和血容量变化情况。方法 ５１例外科住院病人参加了本研究,术前分别测定其血浆量和红细胞量,二者相加得病人血容量值,与百科全书及生理教科书介绍的正常人资料对比。结果 （１）胆道疾病病人及胃、结肠癌病人每千克体重血浆量、红细胞量和血容量的测定值较正常人资料显著增高。结论 门静脉高压症病人的血浆量、红细胞量和血容量均较正常人资料显著增高,其它疾病病人则和正常人资料相近。     

Uremia impairs blood dendritic cell function in hemodialysis patients

Patients on hemodialysis have a general immunodeficiency involving both innate and adaptive responses. As the mechanisms contributing to this defect are uncertain, we sought to study the effects of uremia on circulating dendritic cells (DC) in hemodialysis patients. Immunomagnetic beads were used to isolate myeloid and plasmacytoid DCs from healthy donors. Immune-related functions were determined in these cells cultured in either a complete media containing ABO-compatible serum or media containing sera from uremic patients. The myeloid cells were analyzed for costimulatory molecule expression and allo-stimulatory capability following lipopolysaccharide stimulation. The production of interferon-alpha following herpes-simplex virus stimulation by the plasmacytoid cells was also measured. Myeloid DCs incubated with uremic sera demonstrated impaired maturation and decreased allo-stimulatory capacity. Similarly, herpes virus-stimulated plasmacytoid DCs incubated with uremic sera produced significantly less interferon-alpha compared with cells incubated in the complete media. Both small and large molecule uremic toxins inhibited DC functions in vitro. Use of more efficient dialysis to improve small molecule clearance reversed the inhibition of uremic sera on myeloid but not plasmacytoid DC function. We have shown that the immunodeficiency of hemodialysis patients is due to dialyzable uremic toxins.     

Prognostic value of red cell distribution width in maintenance hemodialysis patients

Objective To investigate the relationship of red cell distribution width (RDW) with all-cause mortality and cardiovascular disease (CVD) mortality in patients undergoing maintenance hemodialysis (MHD). Methods A retrospective analysis was performed in patients who initiated MHD from January 2008 to September 2017 in the hemodialysis center of the Second Affiliated Hospital of Soochow University. Basic data on demographic, dialysis and laboratory were collected, and echocardiography indicators and clinical outcomes were recorded. Patients were divided into four groups according to the quartile of RDW level. Kaplan-Meier survival analysis was used to compare the difference of survival rate among the groups. Cox regression analysis was used to analyze the risk factors of all-cause and CVD-related mortality, and predictive value of RDW for all-cause and CVD-related death in hemodialysis patients. Results A total of 268 MHD patients were enrolled in this study with age of (60.9±15.8) years and dialysis duration of (58.1±9.1) months, including 159 males(59.3%). Kaplan-Meier survival analysis showed that the 1-year overall survival rates of Q1 group (RDW≤13.8%, n=61), Q2 group (RDW 13.9%-14.6%, n=66), Q3 group (RDW 14.7%-15.6%, n=73) and Q4 group (RDW≥15.7%, n=68) were 96.8%, 95.1%, 93.1% and 85.7% respectively; 3-year overall survival rates were 88.5%, 87.5%, 59.2% and 51.8% respectively; 5-year overall survival rates were 71.5%, 65.4%, 33.6% and 17.7% respectively; The difference between the groups was statistically significant (all P＜0.01). The 1-year CVD survival rates were 98.4%, 96.6%, 95.8% and 92.4% respectively; 3-year CVD survival rates were 94.8%, 92.5%, 84.4% and 70.4% respectively; 5-year CVD survival rates were 86.9%, 81.3%, 65.6% and 51.3% respectively; The difference between the groups was statistically significant (all P＜0.01). Multivariate Cox regression analysis showed that RDW≥15.7% was an independent risk factor for all-cause and CVD-related mortality in MHD patients. The risk of all-cause mortality in Q4 group was 3.098 times higher than that in Q1 group (95%CI 1.072-8.950, P=0.037) and the risk of CVD-related mortality was 2.661 times (95%CI 1.111-8.342, P=0.048). Receiver operating characteristic curve (ROC) showed that RDW=14.85% was the best cut-off point for predicting the all-cause mortality in HD patients (P＜0.01), RDW=15.45% was the best cut-off point for predicting the cardiovascular disease mortality (P＜0.01), and RDW=14.45% had a higher 5-year survival rate (P＜0.01). Conclusion RDW can independently predict all-cause and CVD-related mortality risk in hemodialysis patients, and it has important value for prognosis.     

Effect of L-carnitine supplementation on red blood cells deformability in hemodialysis patients

Anemia is a serious problem in hemodialysis patients, the main cause of which is erythropoietin deficiency. After the discovery of recombinant human erythropoietin (rHuEpo) at the end of the last decade, the hematological profile of hemodialysis patients improved significantly but at considerable expense. The deformability of red blood cells (RBC) influences their microcirculation and tissue oxygen delivery along with their life span. We investigated the deformabilty of RBCs in 15 hemodialysis patients before and after three months on L-carnitine supplementation (30 mg/Kg body wt/dialysis session). We excluded from the study all patients who received blood transfusions three months before or during the study, patients who had hemorrhagic episodes, those with hyperparathyroidism or infections, and any who required surgical intervention during the study. The serum iron, folic acid and vitamin B-12 levels were kept normal during the duration of the study. The erythropoietin dose taken before the beginning of L-cartnitine supplementation was not changed. The deformability of RBCs before and after dialysis, prior to and following three months on L-carnitine was determined and compared to the deformability of RBCs from a control group. Hematocrit levels were measured before entry into the study and every month for three months. We found that the deformability of RBCs before the dialysis session was significantly greater than that found in the control group (t-test, p < 0.00001), and that there was a further increase after the end of the dialysis session. Three months following L-carnitine supplementation, we found a significant reduction of RBCs deformability (paired t-test, p < 0.004), and a significant increase in the hematocrit (ANOVA, p < 0.0001). We concluded that abnormalities in the deformability of RBCs improved after L-carnitine and that this was responsible for the increase in the hematocrit. This may allow a substantial reduction in rHuEpo dose.     

The survival impact of plasma to red blood cell ratio in massively transfused non-trauma patients

Purpose

High ratios of Plasma to Packed Red Blood Cells (FFP:PRBC) improve survival in massively transfused trauma patients. We hypothesized that non-trauma patients also benefit from this transfusion strategy.

Methods

Non-trauma patients requiring massive transfusion from November 2003 to September 2011 were reviewed. Logistic regression was performed to identify independent predictors of mortality. The population was stratified using two FFP:PRBC ratio cut-offs (1:2 and 1:3) and adjusted mortality derived.

Results

Over 8 years, 29 % (260/908) of massively transfused surgical patients were non-trauma patients. Mortality decreased with increasing FFP:PRBC ratios (45 % for ratio ≤1:8, 33 % for ratio >1:8 and ≤1:3, 27 % for ratio >1:3 and ≤1:2 and 25 % for ratio >1:2). Increasing FFP:PRBC ratio independently predicted survival (AOR [95 % CI]: 1.91 [1.35–2.71]; p < 0.001). Patients achieving a ratio >1:3 had improved survival (AOR [95 % CI]: 3.24 [1.24–8.47]; p = 0.016).

Conclusion

In non-trauma patients undergoing massive transfusion, increasing FFP:PRBC ratio was associated with improved survival. A ratio >1:3 significantly improved survival probability.