Effect of blood transfusions on cognitive development in very low birth weight infants
Journal of perinatology : official journal of the California Perinatal Association. 2021
OBJECTIVE Preterm infants frequently receive red cell transfusions; however, the effect of transfusions on cognition is unclear. We evaluated the relationship between transfusions and cognitive outcomes in preterm infants enrolled in a randomized trial of erythropoiesis stimulating agents (ESAs). STUDY DESIGN Preterm infants were randomized to ESAs or placebo during initial hospitalization, and transfusions recorded. Children were evaluated using standard developmental tests of cognition at 18-22 months (56 ESA, 24 placebo) and 3.5-4 years (39 ESA, 14 placebo). RESULTS Cognitive scores at 18-22 months were inversely correlated with transfusion volume (p = 0.02). Among those receiving ≥1 transfusion, cognitive scores were significantly higher in the ESA-treated group (p = 0.003). At 3.5-4 years, transfusions were not correlated with cognitive scores. CONCLUSIONS In the placebo group, transfused children had lower cognitive scores than did non-transfused children at 18-22 months. In the ESA group, cognitive scores did not differ by transfusion status, suggesting ESAs might provide neuroprotection.
Psychological intervention in children with transfusion-dependent β-thalassaemia
Vox sanguinis. 2021
BACKGROUND AND OBJECTIVES Transfusion-dependent β-thalassaemia can lead to severe psychological issues in paediatric and adolescent patients. However, the psychological interventions for these patients are limited in clinical practice. We aimed to investigate the impact of a 3-month psychological intervention on the quality of life (QOL) of children with β-thalassaemia (12-18 years old) who relied on blood transfusion in this study. MATERIALS AND METHODS In the current randomized controlled trial, a total of 143 paediatric or adolescent patients (12-18 years old) with transfusion-dependent β-thalassaemia were recruited. They were randomized into the control group (n = 71) who received standard physiological treatment and the intervention group (n = 72) who received a 3-month intervention in addition to standard physiological treatment. The effects of the interventions on the QOL and psychological outcomes of these participants were analysed. RESULTS The 3-month intervention significantly improved the scores of PedsQoL 4.0 Generic Core Scales of paediatric patients with transfusion-dependent β-thalassaemia. It also significantly improved the psychological status and alleviated the depression among children and adolescent patients by alleviating anhedonia, negative mood and negative self-esteem among them. CONCLUSION Psychological intervention has positive effects on the treatment for children with transfusion-dependent β-thalassaemia.
A double-blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent β-thalassemia patients
International journal of clinical practice. 2021;75(8):e14337
BACKGROUND AND AIM This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent β-thalassemia (TDT), through a placebo-controlled, crossover study. METHODS Amlodipine (5 mg, daily) or placebo were prescribed to all patients (n = 19) for 6 months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL). RESULTS Seventeen patients completed the study. The mean ± standard deviation [SD] of myocardial MRI T2* at baseline was 9.83 ± 2.67 ms Myocardial MRI T2* value rose to 11.44 ± 4.14 ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29 ± 4.01 ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and -1.80 (95% CI -2.58 to -0.10), respectively. CONCLUSION Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results.
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.
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/.
Green tea influence on iron overload in thalassemia intermedia patients: a randomized controlled trial
Background: Although iron chelation therapies have been available for many years for thalassemia intermedia patients, iron accumulation remains the major cause of death. Therefore, the need for additional chelation options is in demand. This randomized controlled study aimed to understand the effects of green tea on iron balance in thalassemia intermedia patients. Methods: Using a random selection method, 141 thalassemia intermedia patients were initially screened for inclusion in this trial; only 68 patients included after applying exclusion criteria. Two equal groups were generated (n=34/group): green tea (three cups/day after meals) + usual treatment (deferasirox iron chelator and on demand blood transfusion); and control (only usual treatment). The study lasted for a period of 12 months. Patients failing to comply to the trial methodology were excluded, leaving a final total of 29 patients in the green tea group and 28 patients in the control group. Liver iron concentration, and serum ferritin were assessed at baseline and 12 months, while hemoglobin levels were assessed monthly. Results: At baseline, both groups were matched regarding general demographics. At 12 months, the net drop of liver iron concentration in the green tea group (7.3 mg Fe/g dry weight) was significantly higher than the control group (4.6 mg Fe/g dry weight) (p<0.05). This was also seen with serum ferritin; net reduction in green tea and control groups were 1289 ng/ml and 871 ng/ml, respectively (p<0.05). Hemoglobin levels were slightly higher in the green tea group compared with the control group, but this was not significant. Conclusions: Regular green tea consumption had a significant capability to improve iron deposition in thalassemia intermedia patients who already undergo deferesirox iron chelation therapy. Trial registration: UMIN-CTR Clinical Trials Registry, UMIN000040841 (retrospectively registered June 21, 2020).
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.
Recent insight on improving the iron chelation efficacy of deferasirox by adjuvant therapy in transfusion dependent beta thalassemia children with sluggish response
Expert opinion on drug metabolism & toxicology. 2020
Background: Deferasirox is the first line of treatment in iron overload. In spite of the many studies concerning the efficacy of deferasirox, some patients remain unresponsive to deferasirox.Methods: One hundred and sixty patients were enrolled in stratified randomized controlled study. Patients were randomly divided into four regimens, group I (n=40) received 30 mg/kg deferasirox, group II (n=40) received 20 mg omeprazole and 30 mg/kg deferasirox, group III (n=40) received 400 mg vitamin E and 30 mg/kg deferasirox and group IV (n=40) received 420 mg silymarin and 30 mg/kg deferasirox. Blood specimens were collected from each patient for up to 24 h, and then plasma deferasirox concentrations were inspected.Results: Silymarin, Vitamin E and omeprazole significantly increased the peak plasma concentration of deferasirox (P<0.001) by 27.9, 14.9 and 2.4 fold respectively as compared to deferasirox alone. The bioavailability of deferasirox was improved up to 3.03, 3.57 and 4.98-fold, respectively, following administration of omeprazole, vitamin E and silymarin compared to deferasirox alone.Conclusion: Silymarin, vitamin E and omeprazole represent promising adjuvant therapy to improve the chelation efficacy of deferasirox that might also be further applied to enhance the pharmacokinetics of deferasirox to overcome the lack of response.
Transfusion dependent beta thalassemia children with sluggish response (n=160).
Group I 30 mg/kg deferasirox. (n=40).
Group II 20 mg omeprazole and 30 mg/kg deferasirox (n=40); group III 400 mg vitamin E and 30 mg/kg deferasirox (n=40); group IV 420 mg silymarin and 30 mg/kg deferasirox (n=40).
Silymarin, Vitamin E and omeprazole significantly increased the peak plasma concentration of deferasirox by 27.9, 14.9 and 2.4 fold respectively as compared to deferasirox alone. The bioavailability of deferasirox was improved up to 3.03, 3.57 and 4.98-fold, respectively, following administration of omeprazole, vitamin E and silymarin compared to deferasirox alone.
Blood transfusion and ischaemic outcomes according to anemia and bleeding in patients with non-ST-segment elevation acute coronary syndromes: Insights from the TAO randomized clinical trial
Int J Cardiol. 2020
BACKGROUND The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI). METHODS The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status. RESULTS 12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001). CONCLUSION In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.