A survey on the implementation of Patient Blood Management programs in Italy.

BACKGROUND: Since 2012, in line with the World Health Organization (WHO) resolution WHA63.12 of 05/21/2010, the Italian National Blood Center has been promoting patient blood management (PBM). In order to verify the level of PBM implementation nationwide, we submitted a survey to all healthcare providers. MATERIAL AND METHODS: In line with what was proposed in the international scientific literature in the field, a series of indicators were used derived from the four main blocks related to PBM strategies: the management of patient anemia; the optimization of hemostasis; blood conservation strategies; patient-centred decision-making. We also added two blocks containing important information on general PBM management and other PBM-related aspects. RESULTS: The survey showed good implementation of anemia screening programs in accordance with the timelines established by national and international guidelines, and the single unit policy is used in line with national guideline recommendations. However, the survey also revealed limited auditing of PBM programs and reduced monitoring and reporting of clinical outcomes and indicators. DISCUSSION: The first national survey on the level of PBM implementation in Italy shows widespread adoption of diagnostic-therapeutic care pathways aimed at the diagnosis and treatment of anemia in the perioperative setting.

Ultrasound-guided injection of platelet-rich plasma for tendinopathies: a systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we evaluated ultrasound (US)-guided injections of platelet-rich plasma (PRP) as conservative treatment of tendinopathies. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, SCOPUS, OVID, and the Cochrane Library to identify randomized controlled trials (RCT) on the use of US-guided PRP for tendinopathies. RESULTS: We found 33 RCT (2,025 subjects) that met our inclusion criteria: 8 in lateral epicondylitis, 5 in plantar fasciitis, 5 in Achilles tendinopathy, 7 in rotator cuff tendinopathy, 3 in patellar tendinopathy and 5 in carpal tunnel syndrome. PRP, given as a single injection (20 trials) or multiple injections (13 trials), was compared to US-guided injection of steroids, saline, autologous whole blood, local anesthetic, dry needling, prolotherapy, bone marrow mesenchymal stem cells, or with non-injective interventions. The outcomes more commonly reported included pain and functional measures, subgrouped as in the short-term (<3 months from the intervention), medium-term (3 to 6 months) or long-term (≥12 months). No clear between-group differences in these outcomes were observed in patients with lateral epicondylitis, plantar fasciitis, or Achilles, rotator cuff or patellar tendinopathy. In patients with carpal tunnel syndrome, visual analog scale scores for pain at 3 and 6 months and Boston Carpal Tunnel Questionnaire severity scores at 1, 3 and 6 months were significantly lower in PRP recipients than in controls. The certainty of evidence of all these comparisons was graded as low or very low due to risk of bias, imprecision and/or inconsistency. Pain at the injection site was more common among PRP recipients than among controls receiving other US-guided injections. DISCUSSION: In patients with tendinopathies, a trend towards pain reduction and functional improvement from baseline was observed after US-guided PRP injection, but in the majority of the comparisons, the effect size was comparable to that observed in control groups.

Vasovagal reactions in whole blood and apheresis donors: a cross-sectional study on donor haemovigilance data from 2016 to 2019 in Italy.

BACKGROUND: Acute and delayed vasovagal reactions (VVR) are the most frequent adverse reactions (AR) associated with donations. The aim of this study was to provide the data of the Italian donor haemovigilance system and contextualise the VVR data within the international framework, as well as evaluating, among first-time donors, the association of gender and age and the prevalence of VVR compared to other AR. MATERIALS AND METHODS: The prevalence analysis was performed on VVR and other AR notified to the Italian haemovigilance system from 2016 to 2019. The analysis on the association of gender and age group and VVR prevalence was performed on first-time donations. The definitions and severity of AR were as set out in the 2014 ISBT/IHN international standards. RESULTS: From 2016 to 2019, 34,519 AR were notified, of which 87.1% were VVR. The overall VVR prevalence was 25.0/10,000 donations and the overall prevalence of other AR was 3.7/10,000 donations. All the estimated prevalences of AR were higher for first-time donations than for regular donations and lower for whole blood than for apheresis donations. No difference was noted between whole blood and apheresis donations for VVR with complications or injuries. The prevalence of AR among first-time donors was higher in females than in males. The prevalence of VVR decreased as donor age increased. DISCUSSION: The prevalence of VVR related to blood donation was very low and similar to those calculated by other haemovigilance systems. Among first-time donors, the prevalence of AR was higher in females than in males. The higher prevalence of VVR in young donors and a significant decreasing trend by age group confirmed the results reported in the literature. Finally, no trend by age group in first-time donors was observed for other AR to donations.

A forecasting model to estimate the drop in blood supplies during the SARS-CoV-2 pandemic in Italy.

OBJECTIVES: To estimate the number of actually Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infected blood donors applying a statistical forecasting model. BACKGROUND: Following the outbreak of the SARS-CoV-2 epidemic, a drop in blood donation has been observed. It is crucial to determine the actual number of potential SARS-CoV-2-positive donors to define the measures and ensure adequate blood supply. METHODS: The cumulative incidence of SARS-CoV-2 positivity, calculated on the general population, was applied to the donor population by estimating the number of positive subjects. The calculation model was validated by the linear interpolation method. The number of blood units actually discarded based on post-donation information was also taken into account. RESULTS: Three months after the outbreak, 5322 donors were estimated to be positive for SARS-CoV-2 and were therefore potentially excluded from donation. A total of units of blood components were discarded following post donation information. The estimated number of donors deceased (180) and the number of clinically recovered individuals in the same period was also considered. CONCLUSION: This forecasting model can be used to obtain information on blood donors' involvement during future SARS-CoV-2 outbreaks, especially in case of changes concerning epidemiology, incidence by age bracket and geographical distribution and also for new outbreaks of emerging viruses.

The use of whole blood in traumatic bleeding: a systematic review.

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.

How donor selection criteria can be evaluated with limited scientific evidence: lessons learned from the TRANSPOSE project.

BACKGROUND AND OBJECTIVE: Donor selection criteria (DSC) are a vital link in the chain of supply of Substances of Human Origin (SoHO) but are also subject to controversy and differences of opinion. Traditionally, DSC have been based on application of the precautionary principle. MATERIALS AND METHODS: From 2017 to 2020, TRANSPOSE (TRANSfusion and transplantation PrOtection and SElection of donors), a European research project, aimed to identify discrepancies between current DSC by proposing a standardized risk assessment method for all SoHO (solid organs excluded) and all levels of evidence. RESULTS: The current DSC were assessed using a modified risk assessment method based on the Alliance of Blood Operators' Risk-based decision-making framework for blood safety. It was found that with limited or diverging scientific evidence, it was difficult to reach consensus and an international standardized method for decision-making was lacking. Furthermore, participants found it hard to disregard their local guidelines when providing expert opinion, which resulted in substantial influence on the consensus-based decision-making process. CONCLUSIONS: While the field of donation-safety research is expanding rapidly, there is an urgent need to formalize the decision-making process regarding DSC. This includes the need for standardized methods to increase transparency in the international decision-making process and to ensure that this is performed consistently. Our framework provides an easy-to-implement approach for standardizing risk assessments, especially in the context of limited scientific evidence.

Putting the spotlight on donation-related risks and donor safety - are we succeeding in protecting donors?

BACKGROUND AND OBJECTIVE: The European consortium project TRANSPOSE (TRANSfusion and transplantation: PrOtection and SElection of donors) aimed to assess and evaluate the risks to donors of Substances of Human Origin (SoHO), and to identify gaps between current donor vigilance systems and perceived risks. MATERIALS AND METHODS: National and local data from participating organizations on serious and non-serious adverse reactions in donors were collected from 2014 to 2017. Following this, a survey was performed among participants to identify risks not included in the data sets. Finally, participants rated the risks according to severity, level of evidence and prevalence. RESULTS: Significant discrepancies between anticipated donor risks and the collected data were found. Furthermore, many participants reported that national data on adverse reactions in donors of stem cells, gametes, embryos and tissues were not routinely collected and/or available. CONCLUSIONS: These findings indicate that there is a need to further develop and standardize donor vigilance in Europe and to include long-term risks to donors, which are currently underreported, ensuring donor health and securing the future supply of SoHO.

COVID-19-associated coagulopathy.

Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized as a systemic disorder inducing a prothrombotic state. The molecular mechanisms underlying the hypercoagulable state seen in patients with COVID-19 is still incompletely understood, although it presumably involves the close link between inflammatory and hemostatic systems. The laboratory coagulation monitoring of severely ill COVID-19 patients is mandatory to identify those patients at increased thrombotic risk and to modulate thromboprophylaxis accordingly. In this review, we summarize the current understanding on the pathogenesis, epidemiology, clinical and laboratory features and management of coagulopathy associated with COVID-19.

Advances in managing rare acquired bleeding disorders.

INTRODUCTION: Rare acquired bleeding disorders include a wide spectrum of coagulopathies characterized by spontaneous or post-trauma and post-surgery hemorrhages in patients without a previous personal or family history of bleeding. AREAS COVERED: This review, based on a Medline/PubMed search during the last 20 years, will focus mainly on rare acquired bleeding disorders caused by autoantibodies against coagulation factors, including autoantibodies against factor VIII (acquired hemophilia A), von Willebrand factor (acquired von Willebrand syndrome) and other coagulation factors (factors V, X, XI, and XIII). The pathogenic, laboratory, and clinical features of these rare hemorrhagic conditions will be discussed, with particular attention to their management. EXPERT OPINION: The treatment of rare acquired bleeding disorders includes the control of bleeding and the elimination of the autoantibody and of the underlying disease, when present. As the bleeding clinical phenotype is often severe, the management of affected patients is particularly challenging. Thus, while an early diagnosis of the acquired coagulopathy is essential to start the most appropriate treatment and to improve patients' outcomes, the support of specialized centers is equally important to provide a correct management of such complicated cases.

Investigational drugs to treat hemophilia.

Introduction: Hemophilia A and B are congenital bleeding disorders. The current standard management of patients with severe hemophilia is prophylaxis which is given intravenously two or three times weekly; however, this is associated with a significant burden on the quality of life of the patient. The main attempts to improve the management of hemophilia is hence through the development of a new generation of products with properties facilitating prophylaxis and/or a better control of bleeding.Areas covered: This review describes the preclinical and phase 1/2 studies investigating the innovative products for the management of hemophilia patients with or without coagulation factor inhibitors.Expert opinion: Numerous innovative therapeutics, including factor concentrates and non-clotting factor-based therapies with extended half-life, are under clinical investigation. Among replacement therapies for hemophilia A, the results from phase 1/2 studies indicate that the most interesting products are those bioengineered using XTEN fusion technology. The anti-tissue factor pathway inhibitor antibody concizumab is the most innovative and interesting agent among non-clotting factor products. If the results of ongoing trials confirm the preliminary positive results, these promising agents will provide further improvements in the management and quality of life of patients with hemophilia.

Prevalence, incidence and residual risk of transfusion-transmitted hepatitis B virus infection in Italy from 2009 to 2018.

BACKGROUND: In Italy, the use of nucleic acid testing for hepatitis B virus (HBV) in donor screening has allowed the detection of infections in the window phase, as well as the presence of occult infections which could potentially be transmitted. The aim of this study was to analyse the trends of epidemiological data focused on HBV infection in blood donors and to estimate the residual risk of transmitting HBV from both the window phase and occult infection over a 10-year period in Italy. MATERIALS AND METHODS: Data were obtained from the Italian Haemovigilance System which includes the results of screening tests for transfusion transmissible infections. During the period of this survey (2009-2018), the molecular methods used for HBV screening were transcription-mediated amplification and polymerase chain reaction tests. Prevalence and incidence were calculated. The residual risk was estimated by applying the incidence-window period model for acute cases and a more recently reported model for estimating the risk due to occult infections. RESULTS: A total of 17,424,535 blood donors and 30,842,794 donations were tested for HBV. Altogether, 6,250 donors tested positive for HBV markers: 4,782 (175.6×105) were first time donors and 1,468 (10.0×105) were repeat donors. The prevalence of HBV markers in first time donors was 275.9×105 in 2009, declining to 143.6×105 in 2018. The incidence of new infections was 3.37×105 in 2009 and 2.17×105 in 2018. The overall residual risk for HBV amounted to 1 in 2,566,854 donations calculated as the sum of risks of both acute infections in the window period (1 in 5,835,306 donations) and occult infections (1 in 4,582,270 blood units). DISCUSSION: In Italy, the residual risk of transfusing a blood unit infected with HBV, both from window phase and occult infections, is currently very low, amounting to levels that can be considered tolerable.

Platelet-rich plasma for sports-related muscle, tendon and ligament injuries: an umbrella review.

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 platelet-rich plasma in oral surgery: a systematic review and meta-analysis.

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.

Patient Blood Management: a revolutionary approach to transfusion medicine.

Patient Blood Management (PBM) is a multimodal, multidisciplinary approach adopted to limit the use and the need for allogeneic blood transfusion in all at-risk patients with the aim of improving their clinical outcomes. Although PBM usually refers to surgical patients, its clinical use has gradually evolved over the last few years and it now also refers to medical conditions. This review will critically analyse the current knowledge on the use of PBM programmes in surgical and non-surgical patients.

Serum eye drops for the treatment of ocular surface diseases: a systematic review and meta-analysis.

BACKGROUND: The use of blood-derived eye drops for topical treatment of ocular surface diseases has progressively increased in recent years. MATERIALS AND METHODS: To evaluate the use of serum eye drops in ocular surface disorders, we performed a systematic search of the literature. RESULTS: In this systematic review, we included 19 randomised controlled trials (RCTs) investigating the use of serum eye drops in 729 patients compared to controls. For the quantitative synthesis, we included only 10 RCTs conducted in patients with dry eye syndrome comparing autologous serum to artificial tears. At 2-6 weeks, no clear between-group differences in Schirmer test (MD 1.05; 95% CI: -0.17-2.26) and in fluorescein staining (MD -0.61; 95% CI: -1.50-0.28) were found (very low-quality evidence, down-graded for inconsistency, serious risk of biases, and serious imprecision). Slightly higher increase in tear film break-up time (TBUT) scores in autologous serum compared to control (MD 2.68; 95% CI: 1.33-4.03), and greater decrease in ocular surface disease index (OSDI) in autologous serum compared to control (MD -11.17; 95% CI: -16.58 - -5.77) were found (low quality evidence, down-graded for serious risk of bias, and for inconsistency). For the Schirmer test, fluorescein staining and TBUT, data were also available at additional follow-up timing (2-12 months): no clear between-group differences were found, and the quality of the evidence was graded as low/very-low. CONCLUSIONS: In patients with dry eye syndrome, it is unclear whether or not the use of autologous serum compared to artificial tears increases Schirmer test and fluorescein staining scores at short-term and medium-/long-term follow up. Some benefit at short-term follow up for the outcome of TBUT and OSDI was observed, but the quality of the evidence was low.

Emicizumab for the treatment of haemophilia A: a narrative review.

One of the most serious complications of the treatment of severe haemophilia A is the development of alloantibodies against exogenous factor VIII (FVIII). Inhibitors render factor replacement therapy ineffective, exposing patients to a remarkably high risk of morbidity and mortality. Besides the well-known bypassing agents (i.e. activated prothrombin complex concentrate and recombinant activated factor VII) used to treat or prevent bleeding in haemophilia patients with inhibitors, there is growing interest in newer haemostatic therapies that are not based on the replacement of the deficient FVIII. This review will focus on the most interesting among these innovative therapies, emicizumab, and will provide an update on its current stage of clinical development.

Red blood cell alloimmunisation in transfusion-dependent thalassaemia: a systematic review.

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%.

Rare congenital bleeding disorders.

The rare congenital bleeding disorders are a heterogeneous group of diseases which include deficiencies of fibrinogen, prothrombin and factors V, V + VIII, VII, X, XI and XIII. They are usually transmitted as autosomal recessive disorders, and the prevalence of the severe forms ranges from one case in 500,000 for factor VII up to one in 2,000,000 for factor XIII in the general population. Patients with rare congenital bleeding disorders may have a broad spectrum of clinical symptoms, ranging from mucocutaneous bleeding to life-threatening haemorrhages, such as those occurring in the central nervous system. The treatment of these disorders is based principally on the replacement of the deficient factor using, when available, specific plasma-derived or recombinant products. The aim of this narrative review is to summarise current knowledge about these rare bleeding conditions.

Budget impact of implementing platelet pathogen reduction into the Italian blood transfusion system.

BACKGROUND: Despite improvements in blood donor selection and screening procedures, transfusion recipients can still develop complications related to infections by known and emerging pathogens. Pathogen reduction technologies (PRT) have been developed to reduce such risks. The present study, developed whithin a wider health technology assessment (HTA) process, was undertaken to estimate the costs of the continuing increase in the use of platelet PRT in Italy. MATERIALS AND METHODS: A multidisciplinary team was established to perform the HTA and conduct a budget impact analysis. Quantitative data on platelet use were derived from the 2015 national blood transfusion report and from the Italian Platelets Transfusion Assessment Study (IPTAS). The current national fee of 60 Euro per platelet PRT procedure was used to quantify the costs to the Italian National Health Service (INHS). The analysis adopts a 3-year time-frame. In order to identify the impact on budget we compared a scenario representing an increased use of PRT platelets over time with a control scenario in which standard platelets are used. RESULTS: Progressive implementation of PRT for 20%, 40% and 66% of annual adult platelet doses could generate an increase in annual costs for the INHS amounting to approximately 7, 14 and 23 million Euros, respectively. Use of kits and devices suitable for the treatment of multiple adult platelet doses in one PRT procedure could lower costs. DISCUSSION: In order to fully evaluate the societal perspective of implementing platelet PRT, the increase in costs must be balanced against the expected benefits (prevention of transfusion-transmissible infections, white cell inactivation, extension of platelet storage, discontinuation of pathogen detection testing). Further studies based on actual numbers of platelet transfusion complications and their societal cost at a local level are needed to see the full cost to benefit ratio of platelet PRT implementation in Italy, and to promote equal treatment for all citizens.

Efficacy of platelet-rich plasma as conservative treatment in orthopaedics: a systematic review and meta-analysis.

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.