Abstract

The relationship between blood transfusion following kidney transplantation (KT) and the development of de novo donor-specific antibodies (dnDSA) is controversial. This was investigated by conducting a meta-analysis of studies on patients who underwent KT with or without blood transfusion, and by evaluating the effect of post-KT blood transfusion on clinical outcomes of kidney transplant recipients. Relevant studies in the PubMed, EMBASE, and Cochrane Library databases were identified from inception to July 1, 2022. Two reviewers independently extracted data from the selected articles and estimated study quality. A fixed effects or random effects model was used to pool data according to the heterogeneity among studies. Data included in the meta-analysis were derived from 11 studies with a total of 19,543 patients including 6191 with and 13,352 without blood transfusion post-KT. We assessed the pooled associations between blood transfusion and occurrence of dnDSA and clinical outcomes of transplant recipients. Blood transfusion was strongly correlated with the development of dnDSA (relative risk [RR] = 1.40, 95% confidence interval [CI]: 1.17-1.67; P < 0.05). Patients with blood transfusion had a higher risk of developing anti-human leukocyte antigen (HLA) class I dnDSA than non-transfused patients (RR = 1.75, 95% CI: 1.14-2.69; P < 0.05) as well as significantly higher rates of antibody-mediated rejection (AMR) (RR = 1.41, 95% CI: 1.21-2.35; P < 0.05) and graft loss (RR = 1.75, 95% CI: 1.30-2.35; P < 0.05). There were no statistically significant differences between the two groups in the development of anti-HLA antibodies, anti-HLA class II dnDSA, and anti-HLA class I and II dnDSA; delayed graft function; T cell-mediated rejection; acute rejection; borderline rejection; or patient death. Our results suggest that blood transfusion was associated with dnDSA development in KT recipients. The findings of this systematic review also suggest that post-KT blood transfusion recipients have a higher risk of AMR, and graft loss compared with non-transfused patients. Evidence from this meta-analysis indicates that the use of blood transfusion post-KT is associated with a significantly higher risk of immunological sensitization. More and higher quality results from large randomized controlled trials are still needed to inform clinical practice.

Abstract

INTRODUCTION Current treatment of severe haemophilia A includes prophylaxis with factor VIII (FVIII) replacement. The supply of plasma-derived FVIII is short in China. PURPOSE To evaluate the efficacy and safety of a new B-domain deleted (BDD) recombinant FVIII (TQG202) produced by human-derived cells for prophylaxis in severe haemophilia A patients and compare the bioequivalence with Xyntha. METHODS This multicentre, clinical trial consisted of an open-label, randomized, two-period cross-over trial assessing single-dose pharmacokinetics (PK), and a single-arm clinical trial evaluating the efficacy and safety of 24 weeks of TQG202 prophylaxis, and repeated PK were assessed after prophylaxis phase. The single-dose was 50 IU/kg in PK assessment, and the initial dose was 30 ± 5 IU/kg for prophylaxis. The primary endpoints of prophylaxis were the annualized bleeding rate (ABR) and the incremental recovery rate of the first administration. Adverse events (AEs) were recorded. RESULTS Twenty-six participants were enrolled in the PK assessment and 81 participants in the prophylaxis phase. Mean age was 25.9 ± 10.8 years and all participants were male. The results of PK assessment showed TQG202 is bioequivalent to Xyntha. The total ABR was 2.0 (95% CI: 1.2-2.9) in prophylaxis phase. The mean incremental recovery rate of the first administration was .027 (95% CI: .026-.028) (IU/ml)/(IU/kg). AEs occurred in 42 participants, with an incidence of 51.9%. One severe AE not related to TQG202 occurred. No participants developed FVIII inhibitors. CONCLUSION TQG202 shows bioequivalence with Xyntha. The promising efficacy and tolerability in the severe haemophilia A prophylaxis support the use of TQG202in clinical practice.

Abstract

BACKGROUND Although tranexamic acid (TXA) has been shown to reduce bleeding in joint replacement procedures, its effectiveness for anterior cruciate ligament reconstruction (ACLR) has not been widely reported. PURPOSE To evaluate the effectiveness of TXA to reduce postoperative hemarthrosis and improve clinical outcomes after ACLR. STUDY DESIGN Systematic review; Level of evidence, 2. METHODS A systematic review of the literature following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was performed; literature retrieval was carried out using the MEDLINE, Embase, and Cochrane Library electronic databases. The inclusion criteria were comparative studies in English that reported the administration of intravenous or intra-articular TXA versus other modalities or placebo in patients undergoing ACLR. RESULTS Six studies comprising 418 patients who were treated with TXA were included. Heterogeneity among studies did not allow for the pooling of data. Five studies showed decreased drainage volume in the first 24 or 48 hours postoperatively as compared with control (ACLR with no TXA). Four studies showed lower hemarthrosis grades and visual analog scale scores in TXA versus control in the early postoperative period, although this difference was not evident at 4 weeks postoperatively. No studies showed differences in infection, deep venous thrombosis, or adverse events between the TXA and control groups. CONCLUSION The current best available evidence suggests that TXA administration at the time of ACLR results in decreased intra-articular bleeding (measured using a drainage system), hemarthrosis grade, and pain when compared with control.

Abstract

BACKGROUND Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia. METHODS Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group (n = 56) and a twice or three times per week intravenous epoetin alfa group (n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis. CONCLUSION Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Abstract

BACKGROUND Albumin therapy in patients with decompensated liver cirrhosis has always been a controversial issue. This study aimed to investigate the efficacy and safety of albumin in reducing mortality and controlling complications in patients with liver cirrhosis and provide a reference for relevant decision-making. METHODS Databases such as PubMed, EMBASE, and Web of Science were searched to collect eligible articles published before January 2022, which were analyzed by Revman 5.3. RESULTS A total of 10 randomized controlled trials (2040 patients) were included. Based on the meta-analysis results, no significant difference in mortality was shown between the albumin administration group and the control group (HR = 1.01; 95% CI, 0.97-1.05; P = 0.62). Subgroup analysis showed that albumin administration had no significant short-term or long-term survival benefits in patients with decompensated liver cirrhosis and increased the risk of pulmonary edema adverse reactions (RR = 3.14; 95% CI, 1.48-6.65; P = 0.003). Subgroup analysis based on albumin administration time showed that short-term (HR = 0.93; 95% CI, 0.76-1.13; P = 0.47) or long-term (HR = 0.97; 95% CI: 0.87-1.08; P = 0.58) administration of albumin could not significantly reduce the mortality of patients with decompensated liver cirrhosis. In contrast, albumin administration could significantly reduce the recurrence rate of ascites (RR = 0.56; 95% CI, 0.46-0.68; P = 0.000). CONCLUSION Short-term(<1 month) or long-term (>1 month) administration of albumin can not significantly reduce the mortality of patients with decompensated liver cirrhosis, and a large amount of albumin infusion will increase the risk of pulmonary edema.

Abstract

This study aimed to evaluate the efficiency and safety of tranexamic acid for blood management during high tibial osteotomy (HTO). A systematic search was conducted in Medline, Embase, and the Cochrane library database. Six studies and 208 patients were included in this meta-analysis using Review Manager V.5.3 and Stata 15.1 software. For primary outcomes, tranexamic acid lowered the total blood loss (WMD = -219.47, 95% CI [-355.61, -83.33], P = 0.002). For secondary outcomes, a significant reduction was found for decreased hemoglobin (POD1: WMD = -9.86, 95% CI [-13.45, -6.28], P < 0.05; POD2: WMD = -8.41, 95% CI [-11.50, -5.32], P < 0.05; POD5: WMD = -11.48, 95% CI [-14.56, -8.39], P < 0.05) and drainage (total: WMD = -105.93, 95% CI [-187.08, -24.78], P < 0.05; POD1: WMD = -122.195, 95% CI [-168.902, -75.488], P < 0.05). The sex difference (male/female ratio) was determined (total blood loss: P = 0.025; total drainage amount: p = 0.018) using meta-regression analysis. Females benefited more from tranexamic acid in terms of total blood loss (M/F > 40%: WMD = -53.11, 95% CI [-100.16, -6.05], P = 0.03; 40% ≥ M/F ≥ 20%: WMD = -362.20, 95% CI [-423.96, -300.45], P < 0.05; M/F < 20%: WMD = -263.00, 95% CI [-277.17, -248.83], P < 0.05) and total drainage (M/F > 40%: WMD = -7.11, 95% CI [-10.75, -3.47], P < 0.05; 40% ≥ M/F ≥ 20%: WMD = -104.72, 95% CI [-155.36, -54.08], P < 0.05; M/F < 20%: WMD = -222.00, 95% CI [-297.42, -146.58], P < 0.05). No significant differences were found for drainage on POD2 and POD3, wound complications, orthromboembolic events. In conclusion, tranexamic acid is effective and safe for blood management during HTO. Females appeared to benefit more from it, and an additional postoperative dose is suggested fora better effect.

Abstract

BACKGROUND This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis. METHOD This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis. CONCLUSION The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Abstract

INTRODUCTION This meta-analysis aimed to systematically review and evaluate randomized controlled trials (RCTs) and cohort studies examining the efficacy and safety of blood purification in the treatment of patients with deep burns. METHODS The PubMed, Cochrane Library, and Embase databases and relevant references were systematically searched for RCTs and cohort studies published until the end of September 2020 to investigate the potential of blood purification in improving the prognosis of severely burned patients. The primary outcome of this systematic review was overall patient mortality; secondary outcomes included the incidence of sepsis and infection prevention (vital signs and routine blood tests). RESULTS A total of 6 RCTs and 1 cohort study were included, with a total of 538 burn patients (274 patients who received blood purification and 264 control patients). Compared with patients who received conventional treatment, those treated with blood purification displayed significant 2-day reduction in mortality and sepsis with relative risks of 0.62 and 0.41, respectively (95% confidence intervals [CIs], 0.74-0.82 and 0.25-0.67, respectively; P < .05). In terms of vital signs and blood biochemistry, the respiratory rates and blood urea nitrogen levels of patients in the blood purification group 3 days post-treatment were significantly higher than those in the control group (randomized standard deviations (SMDs), 0.78 and 0.77, respectively; 95% CIs, 0.33-1.23 and 1.22-0.31, respectively; P < .05). However, there were no significant differences between groups on day 3 with regard to temperature (P = .32), heart rate (P = .26), white blood cell count (P = .54), or neutrophil count (P = .74), potentially owing to the small sample size or the relatively short intervention time. Heterogeneous differences existed between the groups with respect to blood urea nitrogen (SMD = -1.22; 95% CI, -2.16 to -0.40; P < .00001) and Cr (SMD = -3.13; 95% CI, -4.92 to -1.33; P < .00001) on day 7. No systematic adverse events occurred. CONCLUSIONS Blood purification treatment for deep burn patients can significantly reduce the mortality rate and the incidence of complications.

Abstract

BACKGROUND To explore the effects of isovolumic hemodilution and platelet-rich plasma separation on platelet activation state and function, complications, and inflammation in patients undergoing cardiac surgery. METHODS A total of 80 patients who needed cardiac surgery under extracorporeal circulation from February 2018 to December 2019 in our hospital were selected as research subjects and divided into observation group (n = 40) and control group (n = 40) according to the random number table method. The patients in the observation group underwent platelet-rich plasma separation, while those in control group received acute isovolumic hemodilution. Then the platelet activation state and functional indexes, hemorheological indexes, and the coagulation functional indexes were compared between the two groups of patients before operation. Next, the changes in the levels of hemoglobin and high-sensitivity C-reactive protein (hs-CRP), an inflammatory factor, during blood protection (before and at 6 hours and 12 hours after intervention) were analyzed. Moreover, the dosage of blood products during operation was compared between the two groups, and postoperative complications and recovery in the two groups were statistically assessed. RESULTS Before operation, the platelet adherence rate and aggregation rate in the observation group were significantly higher than those in control group (p < 0.05), while R and K values in thromboelastograms in the former were notably smaller than those in the latter (p < 0.05). Meanwhile, the whole blood low-shear viscosity, whole blood high-shear viscosity, and plasma viscosity in observation group were remarkably lower than those in control group (p < 0.05). In addition, the observation group exhibited shorter prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT) (p < 0.05) and a higher fibrinogen (Fib) level (p < 0.05) than the control group. At 6 hours and 12 hours after intervention and before operation, the hemoglobin level in observation group was markedly higher than that in control group (p < 0.05). In addition, the dosages of red blood cells, fresh frozen plasma, and platelets among blood products during operation in the observation group were evidently lower than those in the control group (p < 0.05), and the number of cases of hemorrhage, pulmonary infection, coagulation dysfunction, and paraplegia after operation in the former was distinctly smaller than that in the latter (p < 0.05). Furthermore, the observation group had an obviously smaller postoperative 24 hours drainage volume (p < 0.05) as well as shorter postoperative mechanical ventilation time and ICU treatment time than control group (p < 0.05). CONCLUSIONS For patients undergoing cardiac surgery under extracorporeal circulation, platelet-rich plasma separation and reinfusion technology can effectively ensure platelet activation state and function, reduce blood viscosity, ensure stable coagulation function, elevate hemoglobin level and decrease inflammatory reaction, and perioperative allogeneic blood infusion, with fewer adverse reactions in treatment, thus efficaciously facilitating the post-operative recovery of patients.

Abstract

INTRODUCTION The use of tranexamic acid (TXA) in hip fracture surgery remains inconclusive. The aim of the present meta-analysis was to assess the role of TXA use in hip fracture surgery, and attempt to disclose possible factors which might influence TXA efficacy and safety. MATERIALS AND METHODS A systematic computerized literature search was conducted to retrieve all randomized controlled trials (RCTs) and cohort studies regarding TXA use in hip fracture surgery. Overall efficacy and safety were evaluated. Then, subgroup and meta-regression analyses were conducted to disclose the influence of geographic area, fracture type, administration route, frequency and dosage of TXA, blood transfusion threshold, and follow-up duration on the overall effect. RESULTS Thirty-four RCTs and 11 cohort studies were included. Patients receiving TXA had a significant decrease in the need for blood transfusion, reduced total, intra-operative and post-operative blood loss, a decrease in pre- and postoperative hemoglobin difference, without increasing thromboembolic events risk. Subgroup analysis showed that topical TXA had a lower transfusion rate compared with controls, yet the result did not reach statistical significance. Also, TXA had similar efficacy and safety profiles in patients with different frequency and dosage of TXA. CONCLUSION Current evidence indicated that intravenous administration of TXA could significantly reduce blood transfusion and blood loss without increasing risk of thromboembolic events. The frequency and dosage of TXA might not alter the beneficial effect. The application of topical TXA should be cautious.