Impact of restrictive red blood cell transfusion strategy on thrombosis-related events: A meta-analysis and systematic review
Vox sanguinis. 2022
BACKGROUND AND OBJECTIVES There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta-analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis-related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated. MATERIALS AND METHODS We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random-effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data. RESULTS Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44-0.94; p = 0.020; I(2) = 0.0%, very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR = 0.83; 95% CI 0.64-1.09; p = 0.180; I(2) = 0.0%, very low-quality evidence) or myocardial infarction (RR = 1.05; 95% CI 0.87-1.26; p = 0.620; I(2) = 0.0%, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups). CONCLUSIONS A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.
Adult patients in any clinical setting (30 studies, n= 17,334).
Restrictive red blood cell transfusion.
Liberal red blood cell transfusion.
The pooled risk ratio (RR) for thromboembolic events was 0.65 (very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR= 0.83, very low-quality evidence) or myocardial infarction (RR= 1.05, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced thromboembolic events in trials conducted in North America, and myocardial infarctions in the subgroup of trials where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups).
Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis
Clinical reviews in allergy & immunology. 2022;:1-33
Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4(+) T/CD8(+) T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3(+) T,CD4(+)T and CD8(+)T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4(+) and CD8(+) T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.
Artificial Dermis and Autologous Platelet-Rich Plasma for Treatment of Refractory Wounds: A Clinical Study
The international journal of lower extremity wounds. 2021;:15347346211050710
Refractory wounds present a complex and serious clinical dilemma in plastic and reconstructive surgery. However, there are currently no standard guidelines for the treatment of refractory wounds. Artificial dermis (AD) has achieved some satisfactory results, but also has some limitations. Autologous platelet-rich plasma (PRP), as a cell-therapy material, was a valuable and safe treatment dressing for chronic non-healing wounds. This study aimed to evaluate the efficacies of artificial dermis (AD) with and without autologous platelet-rich plasma (PRP) in patients with refractory wounds. Sixteen patients with refractory wounds were randomly allocated to autologous PRP therapy combined with artificial dermis (PRP + AD [N = 8]) or an artificial dermis program only (AD [N = 8]). We compared the efficacies of the two methods in terms of times to wound healing, infection control, and AD vascularization, as well as hospitalization days and eventual clinical outcomes.13 patients achieved complete healing, including seven (87.5%) in the PRP + AD group and six (75.0%) in the AD group (P > .05). The times to wound healing, infection control, and AD vascularization, and hospitalization time after transfer were significantly shorter in the PRP + AD group compared with the AD group (P < .05). In conclusion, the combination of AD and PRP promoted refractory wound healing and shortened waiting times compared with simple dermal grafts.
Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study
BMC musculoskeletal disorders. 2021;22(1):425
BACKGROUND We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P < 0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).
Synergistic Effect of a Prolonged Combination Course of Tranexamic Acid and Dexamethasone Involving High Initial Doses in Total Knee Arthroplasty: A Randomized Controlled Trial
The journal of knee surgery. 2021
The optimal regimes of tranexamic acid (TXA) and dexamethasone (DXM) in total knee arthroplasty (TKA) are still uncertain. The aim of this study was to assess the efficacy and safety of a prolonged course of intravenous TXA and DXM involving a high initial dose in TKA. Patients who underwent primary TKA at our center were randomized to receive one of four regimes: control (group A), prolonged course of TXA (B), prolonged course of DXM (C), or the combination of a prolonged course of TXA and DXM (D). The four groups were compared in primary outcomes (fibrinolytic and inflammatory markers, knee function, postoperative pain levels, and consumption of opioids) and secondary outcomes (blood loss, maximal drop in hemoglobin, coagulation, fasting blood glucose, and complications). A total of 162 patients were enrolled. On postoperative days 2 and 3, fibrinolytic markers were lower in groups B and D than in groups A and C; inflammatory markers were lower in groups C and D than in groups A and B. Inflammatory markers were lower in group B than in group A on postoperative day 3. Postoperative pain levels and oxycodone consumption were lower, and knee function was better in groups C and D. The four groups did not differ in any of the secondary outcomes. A prolonged course of intravenous TXA and DXM involving high initial doses can effectively inhibit postoperative fibrinolytic and inflammatory responses, reduce pain, and improve knee function after TKA.
Rigorous Assessment of Guidelines on COVID-19-Related Thrombotic or Thromboembolic Disease: Implications for Clinical Practice of Prevention, Diagnosis, and Treatment
Evidence-based complementary and alternative medicine : eCAM. 2021;2021:5513744
PURPOSE Severe COVID-19 patients were prone to develop venous thromboembolism. Unfortunately, to date, there is no evidence of any effective medications for thromboembolism in COVID-19. The management of the disease relies on symptomatic and supportive treatments, giving rise to a variety of guidelines. However, the quality of methodology and clinical recommendations remains unknown. MATERIALS AND METHODS We searched Medline, Cochrane Library, Web of Science, websites of international organizations and medical societies, and gray literature databases. Four well-trained appraisers independently evaluated the quality of eligible guidelines and extracted recommendations using well-recognized guideline appraisal tools. Furthermore, recommendations were extracted and reclassified according to a composite grading system. RESULTS The search identified 23 guidelines that offered 108 recommendations. Guidelines scored average on AGREE II criteria, with Scope and Purpose and Clarity of Presentation highest. Only five (22%) guidelines provided high-quality recommendations. The existed clinical recommendations were inconsistent in terms of prophylaxis, diagnosis, and treatment of thromboembolic disease to some extent. CONCLUSION Current guidelines for COVID-19 thromboembolism are generally of low quality, and clinical recommendations on thromboembolism are principally supported by insufficient evidence. There is still an urgent need for more well-designed clinical trials as evidence to prevent adverse events and improve prognosis during COVID-19 treatment.
Tranexamic acid attenuates inflammatory effect and modulates immune response in primary total knee arthroplasty: a randomized, placebo-controlled, pilot trial
AIMS: To explore the effect of intravenous tranexamic acid (IV-TXA) on inflammation and immune response following primary total knee arthroplasty (TKA). METHODS Primary TKA patients (n = 125) were randomized into the following four groups: group A to receive placebo; group B to receive a single dose of 20 mg kg(-1) IV-TXA and 20 mg of intravenous dexamethasone (IV-DXM); group C to receive six doses of IV-TXA (total dosage > 6 g); and group D to receive six doses of IV-TXA combined with three doses of IV-DXM (total dosage = 40 mg). The primary outcomes were C-reactive protein (CRP) and interleukin (IL)-6 levels and the secondary outcomes were complement C3 and C4 and T-cell subset levels, which were measured preoperatively and at 24 h, 48 h, 72 h, and 2 weeks postoperatively. RESULTS The postoperative peak CRP and IL-6 levels in group C (93.7 +/- 22.2 mg L(-1), 108.8 +/- 41.7 pg mL(-1)) were lower compared with those in group A (134.7 +/- 28.8 mg L(-1), P < 0.01; 161.6 +/- 64.4 pg mL(-1), P < 0.01). Groups B and D exhibited significantly lower CRP and IL-6 levels compared with groups A and C at 24 h, 48 h, and 72 h postoperatively (P < 0.05 for all). In group C, complement C3 and C4 levels were higher compared with those in group A at 48 h (0.967 +/- 0.127 g L(-1) vs. 0.792 +/- 0.100 g L(-1), P < 0.01; 0.221 +/- 0.046 g L(-1) vs. 0.167 +/- 0.028 g L(-1), P < 0.01) and 72 h (1.050 +/- 0.181 g L(-1) vs. 0.860 +/- 0.126 g L(-1), P = 0.01; 0.240 +/- 0.052 g L(-1) vs. 0.182 +/- 0.036 g L(-1), P < 0.01) postoperatively and CD3 and CD4 subset levels were higher compared with those in group B at 24 h postoperatively (66.78 +/- 9.29% vs. 56.10 +/- 12.47%, P < 0.05; 36.69 +/- 5.78% vs. 28.39 +/- 8.89%, P < 0.05). CONCLUSION Six doses of IV-TXA could attenuate the inflammatory effect, modulate the immune response, and reduce immunosuppression caused by DXM in patients after TKA.
Effect of Multiple Doses of Intravenous Tranexamic Acid on Perioperative Blood Loss in Total Knee Arthroplasty: A Randomized Controlled Study
Orthopaedic surgery. 2020
OBJECTIVE To identify the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) following primary total knee arthroplasty (TKA) with a tourniquet. METHODS This is a single-blind randomized controlled study that recruited osteoarthritis patients who had undergone primary unilateral TKA from May 2019 to May 2020 at our medical center. A total of 300 patients were randomly divided into three groups to receive: one dose (1 g) of IV-TXA before skin incision combined with one dose (1.5 g) of intra-articular tranexamic acid（IA-TXA) followed by a single dose of IV-TXA (1 g) for 3 h (group A); two doses of IV-TXA (1 g) for 3 and 6 h (group B); or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group C) postoperatively. TKA with a tourniquet was performed by the same surgical team. The primary outcomes were total blood cell loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were levels of C-reactive protein (CRP) and D-dimer, and the incidence of postoperative complications. One-way analysis of variance, subgroup analysis, and multivariate correlation analysis were used to calculate the differences among the three groups. RESULTS The study included 56 male and 244 female patients aged 60-80 years. The mean TBL, the mean HBL, and the maximum Hb drop in group C (471.2 ± 190.6 mL, 428.4 ± 190.3 mL, and 21.2 ± 3.8 g/L, respectively) were significantly lower than those in groups B (563.4 ± 224.6 mL, P = 0.030; 519.9 ± 226.4 mL, P = 0.033; and 23.2 ± 4.1 g/L, P = 0.001, respectively), and A (651.6 ± 254.1 mL, P < 0.001; 607.1 ± 254.3 mL, P < 0.001; and 25.1 ± 4.3 g/L, P < 0.001, respectively). No transfusions were required. The postoperative acute inflammatory reaction was less problematic for patients in Group C, and the incidence of thromboembolic events was similar among the groups (P > 0.05). In addition, there were positive correlations between the HBL and the tourniquet inflation time (r = 0.844, P < 0.001). Similarly, the level of CRP on POD1 (r = 0.393, P < 0.001) and POD3 (r = 0.149, P = 0.010), and the level of D-dimer on POD1 (r = 0.382, P < 0.001) were positively correlated with the HBL. CONCLUSION Three doses of postoperative IV-TXA decreased blood loss and diminished the postoperative inflammatory and fibrinolytic response more than a single dose or two doses in elderly patients following TKA without increasing the incidence of adverse events.
Additional benefits of multiple-dose tranexamic acid to anti-fibrinolysis and anti-inflammation in total knee arthroplasty: a randomized controlled trial
Arch Orthop Trauma Surg. 2020
BACKGROUND Consensus is lacking regarding the dose and timing of tranexamic acid (TXA). The aim of this study was to determine whether multiple-dose intravenous TXA further reduced blood loss and attenuated inflammation after total knee arthroplasty (TKA). MATERIALS AND METHODS We prospectively studied four regimens on TXA: no TXA (A), before incision, 3, 6, and 12 h later (B), before incision, 3, 6, 12, and 18 h later (C) and before incision, 3, 6, 12, 18, and 24 h later (D). The primary outcome was hidden blood loss (HBL). Other outcome measurements such as total blood loss (TBL), intraoperative blood loss (IBL), fibrinolysis parameters [fibrin(-ogen) degradation products, D-dimer], inflammatory factors (C-reactive protein, interleukin-6), visual analog scale (VAS) score, transfusion rate, length of stay (LOS) and complications were also compared. RESULTS The mean HBL and TBL were significantly lower in Group D than in Groups C, B and A. The level of inflammatory factors and fibrinolysis parameters were significantly lower in Group D than in Groups C, B and A at 24 and 72 h postoperatively. The VAS score on postoperative days 1 and 3 (POD1 and POD3) was significantly lower in Group D than in Groups C, B and A. There was no significant difference in LOS among groups. No patient underwent blood transfusion. No episodes of deep venous thrombosis or pulmonary embolism occurred in all the groups. CONCLUSION The repeated doses of TXA up to 24 h can further diminish HBL, provide additional fibrinolysis and inflammation control and ameliorate postoperative pain following TKA. LEVEL OF EVIDENCE I.
Histamine2-Receptor Antagonists, Proton Pump Inhibitors, or Potassium-Competitive Acid Blockers Preventing Delayed Bleeding After Endoscopic Submucosal Dissection: A Meta-Analysis
Frontiers in pharmacology. 2019;10:1055
Background: Endoscopic submucosal dissection (ESD) was commonly used for en bloc resection in gastric cancer and adenoma with the risk of delayed bleeding after ESD. We conducted a direct and indirect comparison meta-analysis to evaluate the best choice in preventing post-ESD bleeding among proton pump inhibitors (PPIs), histamine2-receptor antagonists (H2RAs), and the most widely used potassium-competitive acid blocker, vonoprazan. Methods: The Pubmed, Cochrane Library, and Embase were searched for randomized trials. We pooled odds ratios (OR) for preventing post-ESD bleeding using meta-analysis. Results: Sixteen randomized trials met the inclusion criteria including 2,062 patients. Direct comparisons showed slightly significant efficacy in PPIs rather than H2RAs in preventing post-ESD bleeding [OR: 1.83; 95% confidence interval (CI): 1.10 to 3.05] and vonoprazan was better than PPIs (OR: 0.46; 95% CI: 0.25 to 0.86). The adjusted indirect comparison indicated vonoprazan was superior to H2RAs (OR: 0.30, 95% CI: 0.12 to 0.74). In subgroup analysis, PPIs had similar efficacy as H2RAs in 4 weeks, while PPIs were better than H2RAs in 8 weeks' treatment (OR: 1.91; 95% CI: 1.08 to 3.40). The superiority of vonoprazan than PPIs was more significant in combination therapy (OR: 0.18; 95% CI: 0.04 to 0.69). There was a significant difference in vonoprazan for 8 weeks of medication (OR: 0.44; 95% CI: 0.21 to 0.92). Conclusions: The effects of vonoprazan is better than PPIs than H2RAs in preventing bleeding after ESD. When vonoprazan combined with mucosal protective antiulcer drug in treatment or used in 8 weeks of medication, the efficacy may be even better.