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.
Effect of quercetin on oxidative stress and liver function in beta-thalassemia major patients receiving desferrioxamine: A double-blind randomized clinical trial
Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences. 2019;24:91
Background: Blood transfusion therapy is lifesaving for beta-thalassemia major patients, yet it indirectly causes complications such as oxidative stress and liver dysfunction. In the present study, we investigated the effect of quercetin supplementation on oxidative stress and liver function in beta-thalassemia major patients. Materials and Methods: In this double-blind clinical trial, 84 beta-thalassemia patients who received desferrioxamine (DFO) were randomly assigned to two groups; the treatment group received 500 mg quercetin tablet daily for 12 weeks, and the control group received placebo. In addition to demographic and anthropometric assessment, malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were biochemically assessed to detect the effect of quercetin on oxidative stress and liver function, respectively. The data were analyzed using SPSS 21. P < 0.05 was considered statistically significant. Results: Before adjusting for confounding variables, within-group comparison showed that quercetin supplementation reduced ALT (P < 0.001) and TAC (P < 0.001) significantly. Between-group comparison using analysis of covariance analysis though showed that quercetin could significantly reduce ALT (P = 0.002), but there was an insignificant increase in SOD and TAC, and insignificant decrease in GPx, MDA, AST, and ALP (P > 0.05). Conclusion: According to our results, consumption of 500 mg quercetin supplement daily for 3 months along with DFO treatment might be able to alter liver function, but not the oxidative stress in beta-thalassemia major patients.
Efficacy of Oral Acetaminophen and Intravenous Chlorpheniramine Maleate versus Placebo to Prevent Red Cell Transfusion Reactions in Children and Adolescent with Thalassemia: A Prospective, Randomized, Double-Blind Controlled Trial
Background: Thalassemia is a common congenital hemolytic disorder. In severe cases, regular blood transfusion is essentially required. The role of premedications to prevent transfusion reactions is varied among institutions with no standard guideline. Objective: To prospectively compare the risk of transfusion reactions in thalassemia patients premedicated with acetaminophen and chlorpheniramine maleate (CPM) versus placebo prior to blood transfusion. Material and Method: A randomized, double-blinded, placebo-controlled transfusion reaction study of 147 eligible patients was analyzed. All administered red blood cell (RBC) products were leukoreduced blood products. Patients were monitored and followed for the development of transfusion reactions for 24 hours after RBC transfusion. Results: A total of 73 patients randomized to receive active drugs consisting of acetaminophen and CPM were compared to 74 patients receiving placebo. The overall incidences of febrile reaction and urticarial rash were 6.9% and 22% in the patients randomized to receive active drugs comparing with 9.5% and 35.2% in the patients receiving placebo with no significant differences between two groups. However, delayed development of urticarial rash at 4-24 hours after RBC transfusion was significantly higher in female and patients receiving placebo. Conclusion: Administration of premedications in thalassemia patients receiving RBC transfusion without a history of transfusion reactions does not decrease the overall risk of transfusion reactions. However, the use of CPM might be beneficial to prevent delayed urticarial rash in those patients especially in females (Thai Clinical Trial Registry (TCTR) study ID: 20140526001).
Patient-reported outcomes from a randomized phase II study of the deferasirox film-coated tablet in patients with transfusion-dependent anemias
Health and Quality of Life Outcomes. 2018;16((1)):216.
BACKGROUND Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal. METHODS The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary. RESULTS One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations. CONCLUSIONS These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014.
New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, Phase II ECLIPSE study
American Journal of Hematology. 2017;92((5):):420-428
Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, Phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naive or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low- or intermediate-risk myelodysplastic syndromes. 173 patients were randomized 1:1 to DT (n=86) or FCT (n=87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine/protein creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications. This article is protected by copyright. All rights reserved.
Safety and efficacy of early start of iron chelation therapy with deferiprone in young children newly diagnosed with transfusion-dependent thalassemia: a randomized controlled trial
American Journal of Hematology. 2017;93((2):):262-268
Iron overload is inevitable in patients who are transfusion dependent. In young children with transfusion-dependent thalassemia (TDT), current practice is to delay the start of iron chelation therapy due to concerns over toxicities, which have been observed when deferoxamine was started too early. However, doing so may increase the risk of iron accumulation that will be manifested as toxicities later in life. This study investigated whether deferiprone, a chelator with a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. Recently diagnosed TDT infants (N=64 their age ranged from10-18 (median 12) months, 54.7% males; receiving < or = 6 transfusions; serum ferittin (SF) >400-< 1000 ng/ml were randomized to "early start deferiprone" (.ES-DFP) at a low dose (50 mg/kg/day) or to "delay chelation" (DC), and remained in the study until their serum ferritin (SF) level reached ≥1000 mug/L. 61 patients continued the study Levels of transferrin saturation (TSAT) and labile plasma iron (LPI) were measured as well. By approximately 6 months post-randomization, 100% of the subjects in DC group had achieved SF > 1000 microg/L and TSAT > 70% compared with none in the ES-DFP group. LPI level >0.6 microM was observed in 97% vs. 40% of the DS and ES groups, respectively, (p<0.001). The time to reach SF>1000 microg/L was delayed by 6 months in the ES-DFP group (P<0.001) without escalating DFP dose. No unexpected, serious, or severe adverse events were seen in the ES-DFP group. This article is protected by copyright. All rights reserved.