Analysis of the efficacy of prophylactic tranexamic acid in preventing postpartum bleeding: systematic review with meta-analysis of randomized clinical trials
Brazilian journal of anesthesiology (Elsevier). 2022
BACKGROUND Postpartum Hemorrhage (PPH) is one of the main causes of maternal mortality, mainly in the poorest regions of the world, drawing attention to the need for strategies for preventing it. This study aims to evaluate the efficacy of prophylactic administration of Tranexamic Acid (TXA) in decreasing blood loss in pregnant women in delivery, preventing PPH. METHODS Systematic review of randomized clinical trials. We searched for publications in PubMed, EMBASE and Cochrane Library databases, with the uniterms "postpartum, puerperal hemorrhage" and "tranexamic acid", published between January of 2004 and January of 2020. The eligibility criteria were trials published in English with pregnant women assessed during and after vaginal or cesarean delivery about the effect of prophylactic use of TXA on bleeding volume. The random-effects model was applied with the DerSimonian-Laird test and the Mean Difference (MD) was calculated for continuous variables together with each 95% CI. This systematic review was previously registered in the PROSPERO platform under the registration n° CRD42020187393. RESULTS Of the 630 results, 16 trials were selected, including one with two different doses, performing a total of 6731 patients. The intervention group received a TXA dose that varied between 10 mg.kg(-1) and 1g (no weight calculation). The TXA use was considered a protective factor for bleeding (MD: -131.07; 95% CI: -170.00 to -92.78; p = 0.000) and hemoglobin variation (MD: -0.417; 95% CI: -0.633 to -0.202; p = 0.000). In the subgroup analysis related to the cesarean pathway, the effect of TXA was even greater. CONCLUSION The prophylactic use of tranexamic acid is effective in reducing the post-partum bleeding volume. PROSPERO REGISTRATION ID CRD42020187393.
The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
Open medicine (Warsaw, Poland). 2022;17(1):857-862
The aim of this study is to determine whether the use of tranexamic acid (TXA) in patients with hip fracture reduces intraoperative and postoperative blood loss, and on the other hand, whether it increases thromboembolic risk. The study was performed on patients with hip fracture for a period of one year. Patients were divided into two groups (1:1): the first group receiving TXA and the second group receiving placebo. The amount of blood aspiration during the surgery was measured as well as drainage in the postoperative period of 24 h. The occurrence of deep vein thrombosis (DVT) was monitored before and after the surgery by ultrasound of the lower extremities. The amount of total blood loss was two times lower in patients who received TXA (291.8 ± 65.5 mL of blood vs 634.7 ± 150.5 mL of blood). Among the patients who developed DVT, one patient was from the group that did not receive TXA, and two patients were from the group that received TXA. The use of TXA in patients with hip fracture significantly reduces intraoperative and postoperative blood loss, without a significant thromboembolic risk.
Comparison of early mortality between leukapheresis and non-leukapheresis in adult acute myeloid leukemia patients with hyperleukocytosis: a systematic review and meta-analysis
Hematology (Amsterdam, Netherlands). 2022;27(1):141-149
OBJECTIVES One of the treatment modalities that can be used for hyperleukocytosis is leukapheresis. However, the result of studies showing the benefit of early mortality through the use of leukapheresis versus no leukapheresis is still inconclusive. Hence, we aimed to conduct a systematic review with meta-analysis to determine the effect of leukapheresis on early mortality in AML patients with hyperleukocytosis. METHODS We conducted a literature search on five databases (PubMed, EBSCOhost, Scopus, Clinicalkey, and JSTOR) up to October 2021 for studies comparing early mortality outcomes between hyperleukocytosis AML patients treated with leukapheresis versus no leukapheresis. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity tests were presented in I(2) value and publication bias was analyzed using a funnel plot. RESULTS Eleven retrospective cohort studies were eligible based on the inclusion and exclusion criteria. Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm(3) or 100,000/mm(3) (OR: 1.17; 95% CI: 0.74-1.86; p: 0.50; I(2): 0%). Similarly, studies using hyperleukocytosis cutoff of 50,000/mm(3) also showed no benefits of early mortality (OR: 0.67; 95% CI: 0.43-1.05; p: 0.08; I(2): 0%). Most of the studies used had a moderate risk of bias due to being observational studies. Funnel plot showed an indication of publication bias on studies using hyperleukocytosis cutoff of ≥50,000/mm(3). CONCLUSION The use of leukapheresis does not provide early mortality benefit in adult AML patients with hyperleukocytosis.
Adult acute myeloid leukemia patients (11 studies, n= 1,407).
Leukapheresis intervention (n= 1,090).
Not receiving leukapheresis (n= 317).
Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm3 or 100,000/mm3. Studies using hyperleukocytosis cutoff of 50,000/mm3 showed no benefits of early mortality.
Efficacy and Safety of Pathogen-Reduced Platelets Compared with Standard Apheresis Platelets: A Systematic Review of RCTs
Pathogens (Basel, Switzerland). 2022;11(6)
In this systematic review, we evaluate the efficacy and safety of blood components treated with pathogen reduction technologies (PRTs). We searched the Medline, Embase, Scopus, Ovid, and Cochrane Library to identify RCTs evaluating PRTs. Risk of bias assessment and the Mantel-Haenszel method for data synthesis were used. We included in this review 19 RCTs evaluating 4332 patients (mostly oncohematological patients) receiving blood components treated with three different PRTs. Compared with standard platelets (St-PLTs), the treatment with pathogen-reduced platelets (PR-PLTs) does not increase the occurrence of bleeding events, although a slight increase in the occurrence of severe bleeding events was observed in the overall comparison. No between-groups difference in the occurrence of serious adverse events was observed. PR-PLT recipients had a lower 1 and 24 h CI and CCI. The number of patients with platelet refractoriness and alloimmunization was significantly higher in PR-PLT recipients compared with St-PLT recipients. PR-PLT recipients had a higher number of platelet and RBC transfusions compared with St-PLT recipients, with a shorter transfusion time interval. The quality of evidence for these outcomes was from moderate to high. Blood components treated with PRTs are not implicated in serious adverse events, and PR-PLTs do not have a major effect on the increase in bleeding events. However, treatment with PRTs may require a greater number of transfusions in shorter time intervals and may be implicated in an increase in platelet refractoriness and alloimmunization.
Efficacy of ablative fractional carbon dioxide laser combined with autologous platelet-rich plasma versus ablative fractional carbon dioxide laser and placebo in the treatment of striae gravidarum: A randomized clinical trial
Journal of cosmetic dermatology. 2022
BACKGROUND Striae gravidarum (SG) is a connective tissue disorder seen commonly in primigravidas. It is associated with impairment in the quality of life. OBJECTIVE To determine the efficacy of ablative fractional carbon dioxide (CO2) laser combined with autologous platelet-rich plasma (PRP) versus ablative fractional CO2 laser and placebo in the treatment of SG. STUDY DESIGN Randomized, double-blinded, placebo-controlled trial METHODOLOGY The study was conducted in 16 patients with SG. The assigned treatment area (abdomen) was divided into two sides and was randomly assigned to the PRP side and the control side. All patients received ablative fractional CO2 laser. Immediately after each laser procedure, the PRP side received autologous PRP, while the control side received plain normal saline solution (pNSS) as a placebo. The study was done for three sessions, at intervals of 4 weeks. An independent assessor used the photographs taken at weeks 6, 10, 14 and 16 to assess the clinical improvement. The patient satisfaction was reported at the same intervals. A quartile grading scale was used to measure both the clinical improvement and patient satisfaction. Data were analyzed using the Jonckheere-Terpstra test. Histopathology was done before treatment, and at the end of the study period. RESULTS The combination of ablative fractional CO2 laser and autologous PRP had better clinical improvement and patients' satisfaction compared to ablative fractional CO2 laser and placebo. However, both outcome measures were not statistically significant. CONCLUSION Ablative fractional CO2 laser combined with autologous PRP appears to be an effective treatment in SG.
Economic evaluation of Restrictive Vs. Liberal Transfusion Strategy Following Acute Myocardial Infarction (REALITY): trial-based cost effectiveness and cost utility analyses
European heart journal. Quality of care & clinical outcomes. 2022
AIM: To estimate the cost effectiveness and cost utility ratios of a restrictive vs liberal transfusion strategy in acute myocardial infarction (AMI) patients with anemia. METHODS AND RESULTS Patients (n = 666) with AMI and hemoglobin between 7-8 and 10 g/dL recruited in 35 hospitals in France and Spain were randomly assigned to a restrictive (n = 342) or a liberal (n = 324) transfusion strategy with 1-year prospective collection of resource utilization and quality of life using the EQ5D3L questionnaire. The economic evaluation was based upon 648 patients from the per-protocol population. The outcomes were 30-day and 1-year cost-effectiveness, with major adverse cardiovascular event averted (MACE) as the effectiveness outcome; and 1-year cost utility ratio.The 30-day incremental cost-effectiveness ratio was €33,065€ saved per additional MACE averted with the restrictive versus the liberal strategy, with an 84% probability for the restrictive strategy to be cost-saving and MACE reducing (i.e.dominant). At 1-year, the point estimate of the cost-utility ratio was 191,500 € saved per QALY gained; however cumulated MACE were outside the pre-specified non-inferiority margin, resulting in a decremental cost effectiveness ratio with a point estimate of €72,000 saved per additional MACE with the restrictive strategy. CONCLUSION In patients with acute myocardial infarction and anemia, the restrictive transfusion strategy was dominant (cost-saving and outcome-improving) at 30 days. At 1 year, the restrictive strategy remained cost-saving but clinical noninferiority on MACE was no longer maintained. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02648113.
Acute myocardial infarction patients with anaemia, enrolled in the REALITY trial in 35 hospitals in France and Spain (n= 666).
Restrictive transfusion strategy (n= 342).
Liberal transfusion strategy (n= 324).
The 30-day incremental cost-effectiveness ratio was €33,065 saved per additional major adverse cardiovascular event (MACE) averted with the restrictive versus the liberal strategy, with an 84% probability for the restrictive strategy to be cost-saving and MACE reducing. At 1-year, the point estimate of the cost-utility ratio was €191,500 saved per quality-adjusted life year gained; however cumulated MACE were outside the pre-specified non-inferiority margin, resulting in a decremental cost effectiveness ratio with a point estimate of €72,000 saved per additional MACE with the restrictive strategy.
The Effect of Topical Tranexamic Acid in Endoscopic Sinus Surgery: A Triple Blind Randomized Clinical Trial
The Annals of otology, rhinology, and laryngology. 2022;:34894221086086
OBJECTIVE Our aim is to evaluate the effect of topical tranexamic acid (TA) on bleeding and surgical quality field in the functional endoscopic sinus surgery (FESS). METHODS A total of 74 patients who underwent FESS due to chronic rhinosinusitis were included. The patients were randomized into 2 groups. TA group (n = 37) received a topical cotton pledget soaked with TA and placebo (PL) group (n = 37) received a pledget soaked with saline solution. RESULTS A significant effect was noted for the TA group versus the PL group in the grade 1 of the Boezaart scale at 35 minutes (4 for TA group and no case for PL group). This effect was absent for higher grades. We did not notice a significant effect between the 2 groups at 5 minutes. Blood loss was 359 ml in the TA group versus 441 ml in the PL group. No significant change was observed between the 2 groups concerning the blood parameters. No side effects were reported. CONCLUSION Despite its safety when administrated locally and its low cost, TA provides limited effect on quality of surgical field after 35 minutes of the start of FESS in the patients with chronic rhinosinusitis. This effect was absent at the start of the intervention and when analyzing the blood loss and hematologic parameters.
The Statistical Fragility of Platelet-Rich Plasma as Treatment for Chronic Noninsertional Achilles Tendinopathy: A Systematic Review and Meta-analysis
Foot & ankle orthopaedics. 2022;7(3):24730114221119758
BACKGROUND Randomized controlled trial (RCT) outcomes reaching statistical significance, frequently determined by P <.05, are often used to guide decision making. Noted lack of reproducibility of some RCTs has brought special attention to the limitations of this approach. In this meta-analysis, we assessed the robustness of RCTs evaluating platelet-rich plasma (PRP) for the treatment of chronic noninsertional Achilles tendinopathy (AT) by using fragility indices. METHODS The present study was a systematic review and meta-analysis of RCTs comparing outcomes after PRP injection vs alternative treatment in patients with AT. Representative data sets were generated for each reported continuous outcome event using summary statistics. Fragility indices refer to the minimal number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result into a nonsignificant result, or vice versa. The fragility index (FI) and continuous FI (CFI) were determined for dichotomous and continuous outcomes, respectively, by manipulating each data set until reversal of significance (a=0.05) was achieved. The corresponding fragility quotient (FQ) and continuous FQ (CFQ) were calculated by dividing FI/CFI by sample size. RESULTS Of 432 studies screened, 8 studies (52 outcome events) were included in this analysis. The 12 dichotomous outcomes had a median FI of 4.5 (FQ: 0.111), and the 40 continuous outcomes had a median CFI of 5 (CFQ: 0.154). All 52 outcome events included lost-to-follow-up data, and 12 (23.1%) indicated a greater number of patients lost to follow-up than the FI or CFI. CONCLUSION Our findings suggest that RCTs evaluating PRP for AT therapy lack statistical robustness, because changing only a small number of events may alter outcome significance. LEVEL OF EVIDENCE Level II, therapeutic study.
Platelet-Rich Plasma Versus Microfragmented Adipose Tissue for Knee Osteoarthritis: A Randomized Controlled Trial
Orthopaedic journal of sports medicine. 2022;10(9):23259671221120678
BACKGROUND Platelet-rich plasma (PRP) has been established as safe and effective for knee osteoarthritis (OA). Another orthobiologic therapy, microfragmented adipose tissue (MFAT), has gained attention because of its heterogeneous cell population (including mesenchymal stem cells). However, prospective comparative data on MFAT are lacking. Because of the safety, efficacy, and simplicity of PRP, new therapeutics such as MFAT should be compared directly with PRP. PURPOSE To compare patient-reported outcomes of a single injection of PRP versus MFAT for knee OA. STUDY DESIGN Randomized controlled trial; Level of evidence, 2. METHODS A total of 58 patients with symptomatic knee OA (Kellgren-Lawrence grades 1-4) were randomized to receive a single injection of either leukocyte-rich PRP or MFAT under ultrasound guidance. PRP was created by processing 156 mL of whole blood. MFAT was created by harvesting 30 mL of adipose tissue via standard lipoaspiration. Scores for the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales and visual analog scale for pain with Activities of Daily Living (VAS-ADL) were recorded at baseline and at 1, 3, and 6 months after the injection. The primary outcome was the KOOS-Pain subscore at 6 months after the injection. RESULTS The PRP group (n = 30) had a mean volume of 5.12 ± 1.12 mL injected. This consisted of a mean platelet count of 2673.72 ± 1139.04 × 10(3)/µL and mean leukocyte count of 25.36 ± 13.27 × 10(3)/µL (67.81% lymphocytes, 18.66% monocytes, and 12.33% neutrophils). The MFAT group (n = 28) had a mean volume of 7.92 ± 3.87 mL injected. The mean total nucleated cell count was 3.56 ± 4.62 million/mL. In both groups, KOOS subscale and VAS-ADL scores improved from baseline, and there was no significant difference between the PRP and MFAT groups in the final KOOS-Pain subscore (80.38 ± 16.07 vs 81.61 ± 16.37, respectively; P = .67) or any other outcome score. CONCLUSION A single injection of either PRP or MFAT resulted in a clinically meaningful improvement for patients with knee OA at 6 months, with no difference between treatment groups. REGISTRATION NCT04351087 (ClinicalTrials.gov identifier).
Assessing quality of blood components derived from whole blood treated with riboflavin and ultraviolet light and separated with a fully automated device
Blood transfusion = Trasfusione del sangue. 2022
BACKGROUND Combining pathogen reduction and automated separation of whole blood (WB), together with the use of improved additive solutions, may increase reproducibility and extend shelf-life of blood components. MATERIALS AND METHODS Forty WB units were collected from volunteer donors and randomised 1:1 into two groups: 1) pathogen reduction with riboflavin and ultraviolet light (PRT); or 2) no treatment (Control). After two hours (h) at room temperature, all units underwent fully automated separation into red blood cell concentrate (RBCC), plasma and leukopack components. RBCCs were leukoreduced and stored in phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) solution while plasma units were shock frozen within 8 h of collection and stored at ≤ -25°C. RBCCs were sampled on day 1 and weekly thereafter until day 42, while plasma was sampled on days 1 and 30. The main study objective was to assess the in vitro quality of separated RBCCs using biochemical and haematological parameters. Plasma protein content after one cycle of freeze-thaw was also analysed. RESULTS The quality of RBCCs was largely comparable between the PRT and Control groups, except for a significantly higher degree of haemolysis and extracellular potassium levels in the PRT group after 35 days of storage. While potassium concentration was significantly higher in the PRT group at all timepoints, the degree of haemolysis exceeded the accepted European threshold (i.e., <0.8% of red cell mass in ≥90.0% of tested units) after day 35. Most plasma protein levels were significantly lower in the PRT than the Control group at both day 1 and day 30. DISCUSSION Pathogen reduction with riboflavin and ultraviolet light treatment of WB can be combined with fully automated separation to obtain RBCCs that may be stored for up to 35 days in PAGGSM solution with acceptable quality, comparable to that of RBCCs from untreated blood. The relative differences between factor concentrations in plasma from the PRT and the Control groups were similar during the 30-day storage.