Back to base pairs: What is the genetic risk for red bloodcell alloimmunization?
Blood reviews. 2021;:100794
Red blood cell (RBC) alloimmunization is a serious complication of blood transfusions, challenging selection of compatible units for future transfusions. Genetic characteristics may be associated with the risk of RBC alloimmunization and may therefore serve to identify high-risk patients. The aim of this systematic review was to summarize the available evidence on genetic risk factors for RBC alloimmunization. Electronic databases were searched up to April 2020 for studies (Search terms included transfusion, alloimmunization and genetic). A total of 2581 alloimmunized cases and 26,558 controls were derived from 24 studies. The alleles that were most frequently studied and that demonstrated significant associations in a meta-analysis with alloimmunization to the Duffy(a) antigen were HLA-DRB1*04 (Odds Ratio 7.80 (95%CI 4.57-13.33)), HLA-DRB1*15 (OR 3.76 (95%CI 2.14-6.59)), and HLA-DRB1*03 (OR 0.12 (95%CI 0.05-0.29)). Furthermore, significant associations with anti-K formation was found for the alleles HLA-DRB1*10 (OR 2.64 (95%CI 1.41-4.95)), HLA*DRB1*11 (OR 2.11, (95%CI 1.34-3.32)), and HLA-DRB1*13 (OR 1.71 (95%CI 1.26-2.33)). Overall, the available evidence was of moderate to low quality, hampering interpretation of reported results. There is an urgent need for high quality evidence on genetic risk factors for RBC alloimmunization.
Blood transfusions may adversely affect survival outcomes of patients with lung cancer: a systematic review and meta-analysis
Translational lung cancer research. 2021;10(4):1700-1710
BACKGROUND Despite common use in clinical practice, the impact of blood transfusions on prognosis among patients with lung cancer remains unclear. The purpose of the current study is to perform an updated systematic review and meta-analysis to evaluate the influence of blood transfusions on survival outcomes of lung cancer patients. METHODS We searched PubMed, Embase, Cochrane Library, and Ovid MEDLINE for publications illustrating the association between blood transfusions and prognosis among people with lung cancer from inception to November 2019. Overall survival (OS) and disease-free survival (DFS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the random-effects model. Study heterogeneity was evaluated with the I(2) test. Publication bias was explored via funnel plot and trim-and-fill analyses. RESULTS We included 23 cohort studies with 12,175 patients (3,027 cases and 9,148 controls) for meta-analysis. Among these records, 22 studies investigated the effect of perioperative transfusions, while one examined that of transfusions during chemotherapy. Two studies suggested the possible dose-dependent effect in accordance with the number of transfused units. In pooled analyses, blood transfusions deleteriously influenced both OS (HR=1.35, 95% CI: 1.14-1.61, P<0.001, I(2)=0%) and DFS (HR=1.46, 95% CI: 1.15-1.86, P=0.001, I(2)=0%) of people with lung cancer. No evidence of significant publication bias was detected in funnel plot and trim-and-fill analyses (OS: HR=1.26, 95% CI: 1.07-1.49, P=0.006; DFS: HR=1.35, 95% CI: 1.08-1.69, P=0.008). CONCLUSIONS Blood transfusions were associated with decreased survival of patients with lung cancer.
Effects of stored autotransfusion on electrolytes and postoperative complications in patients undergoing elective orthopedic surgery
American journal of translational research. 2021;13(6):7200-7206
OBJECTIVE To ivestigate the effect of stored autotransfusion on the electrolytes and postoperative complications in patients undergoing elective orthopedic surgery. METHODS A total of 76 cases of patients undergoing elective orthopedic surgery were randomly divided into an observation group (38 cases, taking stored autotransfusion) and a control group (38 cases, taking allogeneic blood transfusion) according to a random number table method. The intraoperative-related indexes (intraoperative blood loss, autologous or allogeneic blood transfusion volume, urine volume, and length of hospital stay), electrolyte levels before and 48 hours after the operation, routine blood and coagulation function were compared between the two groups, and the postoperative complications related to blood transfusion were recorded. RESULTS The length of hospital stay of the observation group was significantly lower than that of the control group (P<0.05). The concentrations of K(+) and Na(+) in the control group 48 h after the operation were higher than those before the operation and than those in the observation group, while the concentration of Ca(2+) was lower than that before the operation and that in the observation group (all P<0.05). The levels of Hb, RBC, and HCT in the control group 48 h after the operation were lower than those before the operation and those in the observation group (all P<0.05). The levels of WBC in the two groups 48 h after the operation were significantly higher, but those in the observation group were lower than those in the control group (all P<0.05). There were no significant changes in Pt, APTT, D-D, and FIB levels between the two groups. There were no significant changes in Pt, APTT, D-D, and FIB levels 48 hours after the operation compared with those before the operation (P>0.05). The incidence of postoperative complications caused by blood transfusion in the observation group was lower than that in the control group (P<0.05). CONCLUSION Storage autotransfusion can effectively balance the electrolyte level and reduce the incidence of complications in patients undergoing elective orthopedic surgery. This is worthy of clinical application.
Liberal blood transfusion strategies and associated infection in orthopedic patients: A meta-analysis
OBJECTIVE It remains unclear whether transfusion strategies during orthopedic surgery and infection are related. The purpose of this study is to evaluate whether liberal blood transfusion strategies contribute to infection risk in orthopedic patients by analyzing randomized controlled trials (RCTs). METHODS RCTs with liberal versus restrictive red blood cell (RBC) transfusion strategies were identified by searching PubMed, Embase, the Cochrane Central Register of Controlled Trials from their inception to July 2019. Ten studies with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. RESULTS Ten trials involving 3938 participants were included in this study. The pooled risk ratio (RR) for the association between liberal transfusion strategy and infection was 1.34 (95% confidence intervals [CI], 0.94-1.90; P = .106). The sensitivity analysis indicated unstable results, and no significant publication bias was observed. CONCLUSION This pooled analysis of RCTs demonstrates that liberal transfusion strategies in orthopedic patients result in a nonsignificant increase in infections compared with more restrictive strategies. The conclusions are mainly based on retrospective studies and should not be considered as recommendation before they are supported by larger scale and well-designed RCTs.
Prognostic impact of perioperative blood transfusions on oncological outcomes of patients with bladder cancer undergoing radical cystectomy: A systematic review
Arab journal of urology. 2020;19(1):24-30
Objective: To conduct a systematic review of whether blood transfusions may be associated with worse outcomes for patients with bladder cancer treated with radical cystectomy (RC), as there has been a recent increase in studies addressing this clinically relevant topic. Methods: PubMed, Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), Google Scholar, and the ClinicalTrials.gov databases were searched with pre-specified search terms for studies published between January 2010 and May 2020. The systemic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 17 studies with 19 627 patients were included after 183 records were screened for eligibility. In all, 10 studies proposed perioperative blood transfusion to be associated with impaired prognosis regarding overall survival, nine studies regarding cancer-specific and four studies regarding recurrence-free survival. The timing of blood transfusion might affect patient outcomes. Notably, several studies did not find a significant correlation between blood transfusions and prognosis. As all studies to date are of retrospective design, the grade of evidence is still limited. Conclusions: Despite the lack of prospective trials, perioperative blood transfusion may lead to worse oncological outcomes. These results, as well as known non-oncological side-effects and associated costs, are important arguments to carefully consider the indication for blood transfusion. Abbreviations BCa: bladder cancer; CSS: cancer-specific survival; HR: hazard ratio; (N)MIBC: (non-) muscle-invasive BCa; OS: overall survival; PBT, perioperative blood transfusion; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RC: radical cystectomy; RFS: recurrence-free survival.
Randomized controlled trial of effect of N-acetylcysteine as an antioxidant on iron overload in children with thalassemia major
Clinical and experimental pediatrics. 2020
BACKGROUND β-Thalassemias are characterized by the presence of mutations in the globin gene that result in the absence or reduced synthesis of β-globin chains of the hemoglobin tetramer. Several studies have reported increased oxidative stress in β-thalassemia major (β-TM) patients. N-acetylcysteine (NAC), a derivative of L-cysteine amino acid, is commonly used as a mucolytic drug. Numerous studies have reported efficient antioxidant activity of NAC. PURPOSE To evaluate the effects of NAC on oxidative stress status and hemoglobin levels in children with β-TM. METHODS This study was conducted between June and December 2019. One hundred β-TM patients were divided into two groups: 50 received NAC 10 mg/kg orally for 3 months (treatment group), while the other 50 received no treatment (non-treatment group). Total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and hemoglobin (Hb) and ferritin levels were measured and compared between groups. RESULTS At the end of the study period, Hb and TAC levels were significantly higher in the treatment group than in the non-treatment group (P < .001 and .01, respectively). On the other hand, serum ferritin levels, TOS, and OSI were significantly lower (P = .004, .01, and .001, respectively) in the treatment group. CONCLUSION NAC can effectively reduce the oxidative status and increase the pre-transfusion Hb levels in children with β-TM. Furthermore, NAC could reduce iron overload in these patients.
Total hip arthroplasty in sickle cell disease: a systematic review
EFORT Open Rev. 2020;5(3):180-188
Total hip arthroplasty (THA) in sickle cell disease (SCD) patients can be a challenging procedure.This systematic review evaluated the revision rate, functional outcomes and complications of THA in sicklers.A systematic search was conducted according to the PRISMA guidelines, using four search engines from inception to May 2019.Fifteen studies with 971 THAs were included. There were 437 cemented and 520 uncemented THAs.There were 164 revision THAs (16.8%); 52 uncemented and 105 cemented THAs.Forty-two infections were recorded; 16 infections for cemented and 23 for uncemented THAs.Fifty-seven cups, 26 stems, eight cup/stem with aseptic loosening that were more frequently cemented were reported. The 28 unspecified aseptic loosening cases were more frequently uncemented THAs.All studies demonstrated the functional improvement of patients.There were 109 medical complications (14.3%). Sickle cell crises (SCC) and transfusion reactions were most usually recorded.Forty-six intraoperative complications (4.7%) were reported; 18 femoral fractures, four acetabular and 18 femoral perforations. Seventeen femoral fractures occurred during uncemented THA.THA in SCD is still related to a high risk of complications. The outcomes in properly selected sicklers have been improved. Perioperative adequate hydration, warming, oxygen supply and transfusion protocols are mandated to prevent SCC and transfusion reactions. The surgeon must be prepared to deal with a high rate of intraoperative fractures and have different implant options readily available. No definite conclusion can be made regarding the best fixation mode. Cemented implants demonstrated a higher revision rate and uncemented implants a higher risk for intraoperative complications. Cite this article: EFORT Open Rev 2020;5:180-188. DOI: 10.1302/2058-5241.5.190038.
N-acetylcysteine Restored Heart Rate Variability and Prevented Serious Adverse Events in Transfusion-dependent Thalassemia Patients: a Double-blind Single Center Randomized Controlled Trial
Int J Med Sci. 2020;17(9):1147-1155
Regular blood transfusions in transfusion-dependent thalassemia (TDT) patients can lead to iron overload, causing oxidative stress and sympathovagal imbalance, resulting in increased cardiac complications. We hypothesized that administrating of N-acetylcysteine (NAC) prevents serious adverse events including cardiac complications in TDT patients by reducing systemic oxidative stress and balancing cardiac sympathovagal control. This study was double-blind, randomized control trial, investigating in 59 Thai TDT patients. After randomization, the participants were divided into two groups. The control group received standard care of TDT patient plus placebo, whereas the intervention group received 600 mg of NAC orally for six months. Serum 8-isoprostane, TNF-alpha, IL-10, 24-hour ECG monitoring, echocardiograms and the incidence of thalassemia-related complications were collected. At baseline, no significant difference in any parameters between the control and the intervention groups. At the end of intervention, the incidence of serious adverse events (i.e. infection, worsening thalassemia) was significantly higher in the control group when compared with the intervention group (24.1% vs. 3.3%, p=0.019) (Chi-square test; absolute risk reduction=20.8%, number needed to treat=4.8). The control group also had significantly lower time-dependent HRV parameters, compared with the intervention group (p=0.025 and 0.030, independent t-test). Treatment with NAC restored HRV and reduced serious adverse event in TDT patients, however, no difference in cardiac complications could be demonstrated. NAC could prevent serious adverse events in TDT patients. The proposed mechanism might be the balancing of sympathovagal control.
Clinical Usefulness of Furosemide to Prevent Volume Overload Among Children and Young Adults with Transfusion-Dependent Thalassemia: A Randomized, Open-Label, Crossover Study
Journal of blood medicine. 2020;11:503-513
PURPOSE Red blood cell transfusion is a key element of treatment among patients with transfusion-dependent thalassemia (TDT). Volume overload and HCC syndrome (hypertension, convulsion, and intracranial hemorrhage) are fatal complications related to transfusion. Furosemide has been widely used to prevent hypertension secondary to volume overload with unclear supportive evidence. This study aimed to evaluate the efficacy of furosemide to prevent volume overload among children and young adults diagnosed with TDT. METHODS Patients diagnosed with TDT were enrolled and randomized to receive either furosemide pretransfusion or no furosemide pretransfusion. After 3 weeks to 4 months of wash-out periods, those patients underwent the alternate regimens as per crossover design of the study. Clinical and laboratory parameters including blood pressure and NT-proBNP levels were measured before and after each transfusion. The difference of those parameters between two randomized groups and their potential associated factors were analyzed. RESULTS In all, 30 patients undergoing 60 red blood cell transfusions were enrolled in the study. All were randomized and crossover was designed as receiving and not receiving furosemide pretransfusion. No transfusion reactions, symptoms of volume overload and HCC syndrome were observed. No statistically significant correlation was found between pretransfusion furosemide and the difference between pre- and posttransfusion systolic blood pressure (2 mmHg systolic blood pressure difference in pretransfusion furosemide and 1.5 mmHg in no pretransfusion furosemide; p-value = 0.721), as well as between pretransfusion furosemide and the difference between pre- and posttransfusion NT-proBNP levels (-3.8 pg/mL NT-proBNP level difference in pretransfusion furosemide and -2.4 pg/mL in no pretransfusion furosemide; p-value = 0.490). No significant correlation was also observed even in selected patients with high NT-proBNP levels (p-value = 0.262). Associated factors affecting the difference between pre- and posttransfusion NT-proBNP levels were analyzed, and none of those were affected concerning the difference in the levels. CONCLUSION Furosemide has been included in standard transfusion guidelines in many institutions. Our study provided important evidence of the unnecessary use of the drug in preventing volume overload particularly in pediatric and young adult patients with TDT. THAI CLINICAL TRIALS REGISTRY TCTR NUMBER TCTR20180209001. Registered 6 February 2018, https://www.clinicaltrials.in.th/.
Cost-utility of new film-coated tablet formulation of deferasirox vs deferoxamine among major beta-thalassemia patients in Iran
Medicine (Baltimore). 2020;99(28):e20949
OBJECTIVES Thalassemia is a hereditary disease, which caused economic burden in developing countries. This study evaluated the cost utility of new formulation of deferasirox (Jadenu) vs deferoxamine (Desferal) among B-Thalassemia-major patients from payer perspective in Iran. METHODS An economic-evaluation through Markov model was performed. A systematic review was conducted in order to evaluate the clinical effectiveness of comparators. Because of chelating therapy is weight-dependent, patients were assumed to be 2 years-old at initiation in first and 18 years-old in second scenario, and model was estimated lifetime costs and utilities. Costs were calculated to the Iran healthcare system through payer perspective and measured effectiveness using quality-adjusted life years (QALYs). One-way sensitivity analysis and budget impact analysis was also employed. RESULTS The 381 studies were retrieved from systematic searching through databases. After eliminating duplicate and irrelevant studies, 2 studies selected for evaluating the effectiveness. Jadenu was associated with an incremental cost-effectiveness ratio (ICER) of 1470.6 and 2544.7 US$ vs Desferal in first and second scenario respectively. The estimated ICER for Jadenu compared to generic deferoxamine was 2837.0 and 6924.1 US$ for first and second scenario respectively. For all scenarios Jadenu is presumed as cost-effective option based on calculated ICER which was lower than 1 gross domestic product per capita in Iran. Sensitivity analysis showed that different parameters except discount rate and indirect cost did not have impact on results. Based on budget impact analysis the estimated cost for patients using Desferal (based on the market share of brand) was 44,021,478 US$ in 3 years vs 42,452,606 US$ in replacing 33% of brand market share with Jadenu. This replacement corresponded to the cost saving of almost 1,568,872 US$ for the payers in 3 years. The calculated cost of using generic deferoxamine in all patients was 68,948,392 US$. The increase in the cost of using Jadenu for 10% of all patients in this scenario would be 934,427 US$ (1.36%) US$ at the first year. CONCLUSIONS Based on this analysis, film-coated deferasirox appeared to be cost-effective treatment in comparison with Desferal for managing child and adult chronic iron overload in B-thalassemia major patients of Iran.