Safety and Efficacy of Convalescent Plasma in COVID-19: An Overview of Systematic Reviews
Diagnostics (Basel, Switzerland). 2021;11(9)
Convalescent plasma (CP) from patients recovered from COVID-19 is one of the most studied anti-viral therapies against SARS-COV-2 infection. The aim of this study is to summarize the evidence from the available systematic reviews on the efficacy and safety of CP in COVID-19 through an overview of the published systematic reviews (SRs). A systematic literature search was conducted up to August 2021 in Embase, PubMed, Web of Science, Cochrane and Medrxiv databases to identify systematic reviews focusing on CP use in COVID-19. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. The following outcomes were analyzed: mortality, viral clearance, clinical improvement, length of hospital stay, adverse reactions. In addition, where possible, subgroup analyses were performed according to study design (e.g., RCTs vs. non-RCTs), CP neutralizing antibody titer and timing of administration, and disease severity. The methodological quality of included studies was assessed using the checklist for systematic reviews AMSTAR-2 and the GRADE assessment. Overall, 29 SRs met the inclusion criteria based on 53 unique primary studies (17 RCT and 36 non-RCT). Limitations to the methodological quality of reviews most commonly related to absence of a protocol (11/29) and funding sources of primary studies (27/29). Of the 89 analyses on which GRADE judgements were made, effect estimates were judged to be of high/moderate certainty in four analyses, moderate in 38, low in 38, very low in nine. Despite the variability in the certainty of the evidence, mostly related to the risk of bias and inconsistency, the results of this umbrella review highlight a mortality reduction in CP over standard therapy when administered early and at high titer, without increased adverse reactions.
Hemostatic therapy as a management strategy for acquired hemophilia: what does the future hold?
Expert review of hematology. 2021;:1-8
Introduction: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies that bind and inactivate factor VIII (FVIII), predisposing to a potentially life-threatening bleeding.Areas covered: The main epidemiological, clinical, laboratory and therapeutic features of AHA are critically discussed. In particular, we focus on the hemostatic management of AHA patients analyzing the currently available treatment options and showing the latest data on the innovative hemostatic agents still under investigation. Authors searched the Medline and PubMed electronic databases for publication on AHA in the last twenty years.Expert opinion: While a rapid recognition of suspected cases of AHA is essential to make a correct diagnosis and appropriately and timely treat the hemorrhagic manifestations, the multidisciplinary approach to this challenging, rare and life-threatening bleeding disorder is of equal importance to improve patients' outcome. Although promising, the safety and efficacy of the clinical use of emicizumab in AHA needs to be validated by trials including an adequate number of patients, before registering the drug also for this indication.
The use of whole blood in traumatic bleeding: a systematic review
Internal and emergency medicine. 2020
Hemostatic resuscitation is currently considered a standard of care for the management of life-threatening hemorrhage, but in some critical settings the access to high quantities of blood components is problematic. Whole blood (WB) transfusion has been proposed as an alternative modality for hemostatic resuscitation of traumatic major bleeding. To assess the efficacy and safety of WB in trauma-associated massive bleeding, we performed a systematic review of the literature. We selected studies comparing WB transfusions to transfusion of blood components (COMP) in massive trauma bleeding; both randomized clinical trial (RCT) and observational studies were considered. The outcomes were mortality (30-day/in-hospital and 24-h mortality) and adverse events/transfusion reactions. The effect sizes were crude odds ratio (OR), adjusted OR and hazard ratio (HR). The methodological quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs, and the ROBIN-1 tool for observational studies. The overall quality of the available evidence was assessed with the GRADE system. One RCT (2 reports) and 6 cohort studies were included (3642 adult patients; 675 receiving WB, 2967 receiving COMP). Three studies were conducted in military setting, and 4 in civilian setting. In the overall analysis, 30-day/in-hospital and 24-h mortality did not differ significantly between groups (very low quality of the evidence due to high risk of bias, imprecision and inconsistency). After adjustment for baseline covariates in three cohort studies, the OR for mortality was significantly lower in WB recipients compared to COMP (OR 0.22; 95% CIs 0.10/0.45) (moderate grade of evidence). Adverse events and transfusion reactions were overlooked and not consistently reported. The available evidence does not allow to draw definite conclusions on the short-term and long-term efficacy and safety of WB transfusion compared to COMP transfusion. Further well designed research is needed.
Patients with massive trauma bleeding (7 studies, n= 3642).
Whole blood (WB) transfusion (n= 675).
Blood components (COMP), (n= 2967).
In the overall analysis, 30-day/in-hospital and 24-h mortality did not differ significantly between groups. After adjustment for baseline covariates in three cohort studies, the odds ratio for mortality was significantly lower in WB recipients compared to COMP. Adverse events and transfusion reactions were overlooked and not consistently reported.
The use of platelet-rich plasma in oral surgery: a systematic review and meta-analysis
Blood transfusion = Trasfusione del sangue. 2019;17(5):357-367
BACKGROUND The aim of this systematic review and meta-analysis was to evaluate the benefit of platelet rich plasma (PRP) in oral surgery. MATERIALS AND METHODS We performed a systematic search of the literature. The GRADE system was used to assess the certainty of the body of evidence. RESULTS We found 21 randomised controlled trials that met our inclusion criteria: 12 studies included patients with periodontal defects, five studies focused on healing of extraction sockets, three studies on sinus lift augmentation, and one study on periapical osseous defects. However, for the quantitative synthesis (meta-analysis), we evaluated "periodontal defects" studies only, since for other clinical contexts the number of studies were too low and the procedural heterogeneity was too high to allow pooling of data. PRP-containing regimens were compared to non-PRP-containing regimens. Primary outcomes for the evaluation of periodontal defects were probing depths, clinical attachment level, gingival recession, and radiographic bone defect. It is not usually clear whether or not the use of PRP compared to controls affects "probing depth" at long-term follow up; the between group differences were small and unlikely to be of clinical importance (i.e., very low quality of evidence). For the other outcomes analysed ("clinical attachment levels", "gingival recession", "bony defect"), we observed a very slight marginal clinical benefit of PRP compared to controls. The available evidence for these comparisons was rated as low quality as most of the studies selected showed inconsistency, imprecision, and risk of bias. DISCUSSION Evidence from a comparison between the use in oral surgery of PRP-containing regimens compared to other regimens not-containing PRP was of low quality. The results of the meta-analysis, limited to studies in patients with periodontal defects, document that PRP was slightly more effective compared to controls not-containing PRP.
Red blood cell alloimmunisation in transfusion-dependent thalassaemia: a systematic review
Blood transfusion = Trasfusione del sangue. 2019;17(1):4-15
BACKGROUND Chronic red blood cell transfusion is the first-line treatment for severe forms of thalassaemia. This therapy is, however, hampered by a number of adverse effects, including red blood cell alloimmunisation. The aim of this systematic review was to collect the current literature data on erythrocyte alloimmunisation. MATERIALS AND METHODS We performed a systematic search of the literature which identified 41 cohort studies involving 9,256 patients. RESULTS The prevalence of erythrocyte alloimmunisation was 11.4% (95% CI: 9.3-13.9%) with a higher rate of alloimmunisation against antigens of the Rh (52.4%) and Kell (25.6%) systems. Overall, alloantibodies against antigens belonging to the Rh and Kell systems accounted for 78% of the cases. A higher prevalence of red blood cell alloimmunisation was found in patients with thalassaemia intermedia compared to that among patients with thalassaemia major (15.5 vs 12.8%). DISCUSSION Matching transfusion-dependent thalassaemia patients and red blood cell units for Rh and Kell antigens should be able to reduce the risk of red blood cell alloimmunisation by about 80%.
Patients with transfusion-dependent thalassaemia (41 studies, n= 9,256).
Systematic review on the prevalence of red blood cell alloimmunisation.
The prevalence of erythrocyte alloimmunisation was 11.4% with a higher rate of alloimmunisation against antigens of the Rh (52.4%) and Kell (25.6%) systems. Overall, alloantibodies against antigens belonging to the Rh and Kell systems accounted for 78% of the cases. A higher prevalence of red blood cell alloimmunisation was found in patients with thalassaemia intermedia compared to that among patients with thalassaemia major (15.5 vs. 12.8%).
Platelet-rich plasma for sports-related muscle, tendon and ligament injuries: an umbrella review
Blood transfusion = Trasfusione del sangue. 2019;17(6):465-478
BACKGROUND Platelet-rich plasma (PRP) has been used in different non-transfusion indications due to its role in tissue regeneration and healing. The aim of this overview of systematic reviews (umbrella review) is to provide a summary of the existing research syntheses related to PRP use for sports-related muscle, tendon and ligament injuries. MATERIALS AND METHODS Literature searches were performed in MEDLINE, Embase, and Cochrane Library to identify systematic reviews focusing on PRP use for sports-related muscle, tendon and ligament injuries. The methodological quality of included studies was assessed using the checklist for systematic reviews and research syntheses developed by the Joanna Briggs Institute and the GRADE assessment. RESULTS Twenty-two studies met the inclusion criteria. Five studies evaluated PRP use for acute muscle injury, and 17 evaluated PRP use for tendon and ligament injury. Studies were heterogeneous in terms of the dose and number of PRP injections, and the control groups. Three of the 5 reviews evaluating acute muscle injury concluded that PRP had no effect on the outcomes considered. One review shows superior efficacy of rehabilitation exercise compared to PRP. One review shows that PRP may result in an earlier return to sport for acute grade I-II injury. Eight out of the 17 reviews evaluating PRP for tendon and ligament injuries show a statistically significant (p<0.05) difference in pain and/or function outcome measures favouring PRP compared to controls, although most of the observed differences were small. Adverse events data and quality of life outcomes were rarely analysed or reported in the included studies and were considered clinically insignificant. DISCUSSION In most of the included reviews, the available evidence was judged to be of low/very low quality due to risk of bias, inconsistency and imprecision, thus making the level of certainty of these findings low and not adequate to support the general use of PRP in this setting.
The use of viscoelastic haemostatic assays in non-cardiac surgical settings: a systematic review and meta-analysis
Blood Transfusion = Trasfusione Del Sangue. 2018;:1-9.
BACKGROUND Thrombelastography (TEG) and rotational thromboelastometry (ROTEM) are viscoelastic haemostatic assays (VHA) which exploit the elastic properties of clotting blood. The aim of this systematic review and meta-analysis was to evaluate the usefulness of these tests in bleeding patients outside the cardiac surgical setting. MATERIALS AND METHODS We searched the Cochrane Library, MEDLINE, EMBASE and SCOPUS. We also searched clinical trial registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. RESULTS We found 4 randomised controlled trials (RCTs) that met our inclusion criteria with a total of 229 participants. The sample size was small (from 28 to 111 patients) and the follow-up periods very heterogenous (from 4 weeks to 3 years). Pooled data from the 3 trials reporting on mortality (199 participants) do not show any effect of the use of TEG on mortality as compared to standard monitoring (based on the average treatment effect from a fixed-effects model): Risk Ratio (RR) 0.71; 95% Confidence Interval (CI): 0.43 to 1.16. Likewise, the use of VHA does not reduce the need for red blood cells (mean difference -0.64; 95% CI: -1.51 to 0.23), platelet concentrates (mean difference -1.12; 95% CI: -3.25 to 1.02), and fresh frozen plasma (mean difference -0.91; 95% CI: -2.02 to 0.19) transfusion. The evidence on mortality and other outcomes was uncertain (very low-certainty evidence, down-graded due to risk of biases, imprecision, and inconsistency). CONCLUSIONS Overall, the certainty of the evidence provided by the trials was too low for us to be certain of the benefits and harms of viscoelastic haemostatic assay in non-cardiac surgical settings. More, larger, and better-designed RCTs should be carried out in this area.
Safety of intravenous tranexamic acid in patients undergoing major orthopaedic surgery: a meta-analysis of randomised controlled trials
Blood Transfusion = Trasfusione Del Sangue. 2018;16((1)):36-43.
Among the various pharmacological options to decrease peri-operative bleeding, tranexamic acid appears to be one of the most interesting. Several trials have consistently documented the efficacy of this synthetic drug in reducing the risk of blood loss and the need for allogeneic blood transfusion in patients undergoing total hip and knee arthroplasty. The safety of intravenous tranexamic acid in major orthopaedic surgery, particularly regarding the risk of venous thromboembolism, was systematically analysed in this review. A systematic search of the literature identified 73 randomised controlled trials involving 4,174 patients and 2,779 controls. The raw overall incidence of venous thromboembolism was 2.1% in patients who received intravenous tranexamic acid and 2.0% in controls. A meta-analytic pooling showed that the risk of venous thromboembolism in tranexamic acid-treated patients was not significantly different from that of controls (risk difference: 0.01%, 95% confidence interval [CI]: -0.05%, 0.07%; risk ratio: 1.067, 95% CI: 0.760-1.496). Other severe drug-related adverse events occurred very rarely (0.1%). In conclusion, the results of this systematic review and meta-analysis show that intravenous tranexamic acid is a safe pharmacological treatment to reduce blood loss and transfusion requirements in patients undergoing major orthopaedic surgery.
Safety and efficacy of tranexamic acid for prevention of obstetric haemorrhage: an updated systematic review and meta-analysis
Blood Transfusion = Trasfusione Del Sangue. 2018;:1-10.
BACKGROUND A number of clinical systematic review and meta-analysis have been published on the use of tranexamic in the obstetric setting. The aim of this meta-analysis was to evaluate the safety and effectiveness of tranexamic acid in reducing blood loss when given prior to caesarean delivery. MATERIALS AND METHODS We searched the Cochrane Wounds Specialized Register, Cochrane Central, MEDLINE (through PUBMED), Embase, and SCOPUS electronic databases. We also searched clinical trials registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. We used no restrictions with respect to language and date of publication. Two review authors independently performed study selection, "Risk of bias" assessment, and data extraction. Initial disagreements were resolved by discussion, or by including a third review author when necessary. RESULTS We found 18 randomised controlled trials (RCTs) that met our inclusion criteria. Overall, 1,764 women receiving intravenous tranexamic acid for prevention of bleeding following caesarean sections and 1,793 controls receiving placebo were enrolled in the 18 RCTs evaluated. The use of tranexamic acid compared to controls (placebo or no intervention) reduces post-partum haemorrhage >400 mL (risk ratio [RR] 0.40, 95% confidence interval [CI] 0.24-0.65; 5 trials with a total of 786 participants), severe post-partum haemorrhage >1,000 mL (RR 0.32, 95% CI: 0.12-0.84; 5 trials with a total of 1,850 participants), and need for red blood cell transfusion (RR 0.30, 95% CI: 0.18-0.49; 10 trials with a total of 1,873 participants). No particular safety concerns on the use of this antifibrinolytic agent emerged from the analysis of the 18 RCTs included. DISCUSSION Overall, the results of this meta-analysis support the evidence of a beneficial effect of tranexamic acid in reducing blood loss and need for blood transfusion in pregnant women undergoing caesarean section.
Efficacy of platelet-rich plasma as conservative treatment in orthopaedics: a systematic review and meta-analysis
Blood Transfusion = Trasfusione Del Sangue. 2018;:1-12.
BACKGROUND The aim of this systematic review and meta-analysis was to evaluate the benefit of platelet-rich plasma (PRP) in non-surgical orthopaedic procedures. MATERIAL AND METHODS We searched the Cochrane Wounds Specialized Register, CENTRAL, MEDLINE (through PUBMED), Embase, and SCOPUS. We also searched clinical trials registries for ongoing and unpublished studies and checked reference lists to identify additional studies. RESULTS We found 36 randomised controlled trials (2,073 patients) that met our inclusion criteria. The included studies mostly had small numbers of participants (from 20 to 225). Twenty-eight studies included patients with lateral epicondylitis or plantar fasciitis. PRP was compared to local steroids injection (19 studies), saline injection (6 studies), autologous whole blood (4 studies), local anaesthetic injection (3 studies), dry needling injection (3 studies), and to other comparators (4 studies). Primary outcomes were pain and function scores, and adverse events. On average, it is unclear whether or not use of PRP compared to controls reduces pain scores and functional score at short- (up to 3 months) and medium- (4-6 months) term follow-up. The available evidence for all the comparisons was rated as very low quality due to inconsistency, imprecision, and risk of bias in most of the selected studies. There were no serious adverse events related to PRP injection or control treatments. CONCLUSIONS The results of this meta-analysis, which documents the very marginal effectiveness of PRP compared to controls, does not support the use of PRP as conservative treatment in orthopaedics.