RESUMO
We aimed to identify any detrimental effects on platelet quality and clinical effectiveness, of irradiated platelets compared to non-irradiated platelets for transfusion. The review was conducted in accordance with PRISMA guidelines. The protocol was prospectively registered on PROSPERO [CRD42023441930]. Our search identified 3002 references, of which we included 44 studies. Forty-one were in vitro only studies, two studies were in healthy volunteers, and one study reported clinical outcomes in thrombocytopenic patients. X-ray was used exclusively in three studies, and alongside gamma irradiation in one study. Two studies did not report the source of irradiation. The remaining 38 studies used gamma irradiation only. We assessed risk of bias (ROB) for studies reporting clinical and in vivo outcomes using ROB 2.0 (3 studies). We adapted a ROB tool designed for animal studies to assess ROB for the studies reporting in vitro outcomes (43 studies). We assessed the certainty of the evidence for the eight outcomes deemed most important to assess platelet quality and clinical effectiveness (where day 0 is the day of the blood draw). Overall, gamma irradiation has little to no effect on most markers of platelet quality and effectiveness. Where there is evidence of detriment from irradiation, differences are small in vitro, and are unlikely to affect clinical outcomes following transfusion. However, the evidence base is limited. Only half the studies could be included in any analysis. There is very limited evidence for x-ray as a source of irradiation and, given the potential benefits of using x-ray over gamma irradiation (ease of use and safety requirements), we would welcome further research comparing x-ray to gamma, and x-ray to a non-irradiated control.
RESUMO
There is wide interindividual variation in the efficacy of CD34+ cell mobilization and collection in healthy allogenic hematopoietic stem cell donors. Donor characteristics, blood cell counts, and various factors related to mobilization and collection have been associated with blood CD34+ cell count and CD34+ cell yield after granulocyte colony-stimulating factor (G-CSF) mobilization and collection. Given the heterogenous nature of the literature reporting these associations, in this scoping review we clarify the determinants of CD34+ count and yield. Studies published between 2000 and 2023 reporting allogeneic donors undergoing G-CSF mobilization and peripheral blood stem cell (PBSC) collection were evaluated. Eligible studies were those that assessed blood CD34+ cell count or CD34+ cell yield in the first PBSC collection after mobilization with 4 or 5 days of G-CSF treatment. Associations were recorded between these outcomes and donor factors (age, sex, weight, ethnicity), mobilization factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume [PBV]) or laboratory factors (blood cell counts at baseline or after mobilization). The 52 studies evaluated between 15 and 20,884 donors. Forty-three studies were retrospective, 33 assessed blood CD34+ cell counts, and 39 assessed CD34+ cell yield from PBSCs. Blood CD34+ cell counts consistently predicted CD34+ cell yield. Younger donors usually had higher blood CD34+ cell counts and CD34+ cell yield. Most studies that investigated the effect of donor ancestry found that donors of non-European ancestry had higher blood CD34+ cell counts after mobilization and higher CD34+ cell yields from collection. The poor consensus about the best predictors of blood CD34+ cell count and yield necessitates further prospective studies, particularly of the role of donor ancestry. The current focus on donor sex as a major predictor requires re-evaluation.
Assuntos
Fator Estimulador de Colônias de Granulócitos , Mobilização de Células-Tronco Hematopoéticas , Doadores de Tecidos , Humanos , Doadores de Tecidos/estatística & dados numéricos , Antígenos CD34 , Células-Tronco de Sangue Periférico/metabolismo , Transplante Homólogo/métodos , Células-Tronco Hematopoéticas/citologia , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , FemininoRESUMO
BACKGROUND: An estimated one-quarter to one-half of people diagnosed with haematological malignancies experience anaemia. There are different strategies for red blood cell (RBC) transfusions to treat anaemia. A restrictive transfusion strategy permits a lower haemoglobin (Hb) level whereas a liberal transfusion strategy aims to maintain a higher Hb. The most effective and safest strategy is unknown. OBJECTIVES: To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). SEARCH METHODS: We searched for randomised controlled trials (RCTs) and non-randomised studies (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2023, Issue 2), and eight other databases (including three trial registries) to 21 March 2023. We also searched grey literature and contacted experts in transfusion for additional trials. There were no language, date or publication status restrictions. SELECTION CRITERIA: We included RCTs and prospective NRS that evaluated restrictive versus liberal RBC transfusion strategies in children or adults with malignant haematological disorders receiving intensive chemotherapy or radiotherapy, or both, with or without HSCT. DATA COLLECTION AND ANALYSIS: Two authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed the risk of bias. Any disagreement was discussed and resolved with a third review author. Dichotomous outcomes were presented as a risk ratio (RR) with a 95% confidence interval (CI). Narrative syntheses were used for heterogeneous outcome measures. Review Manager Web was used to meta-analyse the data. Main outcomes of interest included: all-cause mortality at 31 to 100 days, quality of life, number of participants with any bleeding, number of participants with clinically significant bleeding, serious infections, length of hospital admission (days) and hospital readmission at 0 to 3 months. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: Nine studies met eligibility; eight RCTs and one NRS. Six hundred and forty-four participants were included from six completed RCTs (n = 560) and one completed NRS (n = 84), with two ongoing RCTs consisting of 294 participants (260 adult and 34 paediatric) pending inclusion. Only one completed RCT included children receiving HSCT (n = 6); the other five RCTs only included adults: 239 with acute leukaemia receiving chemotherapy and 315 receiving HSCT (166 allogeneic and 149 autologous). The transfusion threshold ranged from 70 g/L to 80 g/L for restrictive and from 80 g/L to 120 g/L for liberal strategies. Effects were reported in the summary of findings tables only for the trials that included adults to reduce indirectness due to the limited evidence contributed by the prematurely terminated paediatric trial. Evidence from RCTs Overall, there may be little to no difference in the number of participants who die within 31 to 100 days using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 451 participants; RR 1.00, 95% CI 0.27 to 3.70, P=0.99; very low-certainty evidence). There may be little to no difference in quality of life at 0 to 3 months using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 431 participants; analysis unable to be completed due to heterogeneity; very low-certainty evidence). There may be little to no difference in the number of participants who suffer from any bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies; 448 participants; RR 0.91, 95% CI 0.78 to 1.06, P = 0.22; low-certainty evidence). There may be little to no difference in the number of participants who suffer from clinically significant bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (four studies; 511 participants; RR: 0.94, 95% CI 0.74 to 1.19, P = 0.60; low-certainty evidence). There may be little to no difference in the number of participants who experience serious infections at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies, 451 participants; RR: 1.20, 95% CI 0.93 to 1.55, P = 0.17; low-certainty evidence). A restrictive transfusion strategy likely results in little to no difference in the length of hospital admission at 0 to 3 months compared to a liberal strategy (two studies; 388 participants; analysis unable to be completed due to heterogeneity in reporting; moderate-certainty evidence). There may be little to no difference between hospital readmission using a restrictive transfusion strategy compared to a liberal transfusion strategy (one study, 299 participants; RR: 0.89, 95% CI 0.52 to 1.50; P = 0.65; low-certainty evidence). Evidence from NRS The evidence is very uncertain whether a restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-certainty evidence); or decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-certainty evidence). No NRS reported on the other eligible outcomes. AUTHORS' CONCLUSIONS: Findings from this review were based on seven studies and 644 participants. Definite conclusions are challenging given the relatively few included studies, low number of included participants, heterogeneity of intervention and outcome reporting, and overall certainty of evidence. To increase the certainty of the true effect of a restrictive RBC transfusion strategy on clinical outcomes, there is a need for rigorously designed and executed studies. The evidence is largely based on two populations: adults with acute leukaemia receiving intensive chemotherapy and adults with haematologic malignancy requiring HSCT. Despite the addition of 405 participants from three RCTs to the previous review's results, there is still insufficient evidence to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days, we would need a total of 1492 participants to have an 80% chance of detecting, at a 5% level of significance, an increase in all-cause mortality from 3% to 6%. Further RCTs are needed overall, particularly in children.
Assuntos
Anemia , Transfusão de Eritrócitos , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Transfusão de Eritrócitos/estatística & dados numéricos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Anemia/terapia , Adulto , Criança , Viés , Qualidade de Vida , Hemoglobina A/análise , Ensaios Clínicos Controlados não Aleatórios como Assunto , Hemoglobinas/análiseRESUMO
BACKGROUND: Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care. OBJECTIVES: To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology. SEARCH METHODS: We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants. DATA COLLECTION AND ANALYSIS: We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received. MAIN RESULTS: We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials). AUTHORS' CONCLUSIONS: We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.
Assuntos
Procedimentos Ortopédicos , Acidente Vascular Cerebral , Ácido Tranexâmico , Masculino , Feminino , Adulto , Humanos , Ácido Tranexâmico/uso terapêutico , Aprotinina/uso terapêutico , Desamino Arginina Vasopressina , Metanálise em Rede , Hemorragia/etiologia , Ácido Aminocaproico/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Procedimentos Ortopédicos/efeitos adversos , FibrinaRESUMO
BACKGROUND: Concerns regarding the safety and availability of transfused donor blood have prompted research into a range of techniques to minimise allogeneic transfusion requirements. Cell salvage (CS) describes the recovery of blood from the surgical field, either during or after surgery, for reinfusion back to the patient. OBJECTIVES: To examine the effectiveness of CS in minimising perioperative allogeneic red blood cell transfusion and on other clinical outcomes in adults undergoing elective or non-urgent surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases and two clinical trials registers for randomised controlled trials (RCTs) and systematic reviews from 2009 (date of previous search) to 19 January 2023, without restrictions on language or publication status. SELECTION CRITERIA: We included RCTs assessing the use of CS compared to no CS in adults (participants aged 18 or over, or using the study's definition of adult) undergoing elective (non-urgent) surgery only. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 106 RCTs, incorporating data from 14,528 participants, reported in studies conducted in 24 countries. Results were published between 1978 and 2021. We analysed all data according to a single comparison: CS versus no CS. We separated analyses by type of surgery. The certainty of the evidence varied from very low certainty to high certainty. Reasons for downgrading the certainty included imprecision (small sample sizes below the optimal information size required to detect a difference, and wide confidence intervals), inconsistency (high statistical heterogeneity), and risk of bias (high risk from domains including sequence generation, blinding, and baseline imbalances). Aggregate analysis (all surgeries combined: primary outcome only) Very low-certainty evidence means we are uncertain if there is a reduction in the risk of allogeneic transfusion with CS (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.59 to 0.72; 82 RCTs, 12,520 participants). Cancer: 2 RCTs (79 participants) Very low-certainty evidence means we are uncertain whether there is a difference for mortality, blood loss, infection, or deep vein thrombosis (DVT). There were no analysable data reported for the remaining outcomes. Cardiovascular (vascular): 6 RCTs (384 participants) Very low- to low-certainty evidence means we are uncertain whether there is a difference for most outcomes. No data were reported for major adverse cardiovascular events (MACE). Cardiovascular (no bypass): 6 RCTs (372 participants) Moderate-certainty evidence suggests there is probably a reduction in risk of allogeneic transfusion with CS (RR 0.82, 95% CI 0.69 to 0.97; 3 RCTs, 169 participants). Very low- to low-certainty evidence means we are uncertain whether there is a difference for volume transfused, blood loss, mortality, re-operation for bleeding, infection, wound complication, myocardial infarction (MI), stroke, and hospital length of stay (LOS). There were no analysable data reported for thrombosis, DVT, pulmonary embolism (PE), and MACE. Cardiovascular (with bypass): 29 RCTs (2936 participants) Low-certainty evidence suggests there may be a reduction in the risk of allogeneic transfusion with CS, and suggests there may be no difference in risk of infection and hospital LOS. Very low- to moderate-certainty evidence means we are uncertain whether there is a reduction in volume transfused because of CS, or if there is any difference for mortality, blood loss, re-operation for bleeding, wound complication, thrombosis, DVT, PE, MACE, and MI, and probably no difference in risk of stroke. Obstetrics: 1 RCT (1356 participants) High-certainty evidence shows there is no difference between groups for mean volume of allogeneic blood transfused (mean difference (MD) -0.02 units, 95% CI -0.08 to 0.04; 1 RCT, 1349 participants). Low-certainty evidence suggests there may be no difference for risk of allogeneic transfusion. There were no analysable data reported for the remaining outcomes. Orthopaedic (hip only): 17 RCTs (2055 participants) Very low-certainty evidence means we are uncertain if CS reduces the risk of allogeneic transfusion, and the volume transfused, or if there is any difference between groups for mortality, blood loss, re-operation for bleeding, infection, wound complication, prosthetic joint infection (PJI), thrombosis, DVT, PE, stroke, and hospital LOS. There were no analysable data reported for MACE and MI. Orthopaedic (knee only): 26 RCTs (2568 participants) Very low- to low-certainty evidence means we are uncertain if CS reduces the risk of allogeneic transfusion, and the volume transfused, and whether there is a difference for blood loss, re-operation for bleeding, infection, wound complication, PJI, DVT, PE, MI, MACE, stroke, and hospital LOS. There were no analysable data reported for mortality and thrombosis. Orthopaedic (spine only): 6 RCTs (404 participants) Moderate-certainty evidence suggests there is probably a reduction in the need for allogeneic transfusion with CS (RR 0.44, 95% CI 0.31 to 0.63; 3 RCTs, 194 participants). Very low- to moderate-certainty evidence suggests there may be no difference for volume transfused, blood loss, infection, wound complication, and PE. There were no analysable data reported for mortality, re-operation for bleeding, PJI, thrombosis, DVT, MACE, MI, stroke, and hospital LOS. Orthopaedic (mixed): 14 RCTs (4374 participants) Very low- to low-certainty evidence means we are uncertain if there is a reduction in the need for allogeneic transfusion with CS, or if there is any difference between groups for volume transfused, mortality, blood loss, infection, wound complication, PJI, thrombosis, DVT, MI, and hospital LOS. There were no analysable data reported for re-operation for bleeding, MACE, and stroke. AUTHORS' CONCLUSIONS: In some types of elective surgery, cell salvage may reduce the need for and volume of allogeneic transfusion, alongside evidence of no difference in adverse events, when compared to no cell salvage. Further research is required to establish why other surgeries show no benefit from CS, through further analysis of the current evidence. More large RCTs in under-reported specialities are needed to expand the evidence base for exploring the impact of CS.
Assuntos
Artrite Infecciosa , Transplante de Células-Tronco Hematopoéticas , Infarto do Miocárdio , Embolia Pulmonar , Acidente Vascular Cerebral , Infecção dos Ferimentos , Feminino , Gravidez , Adulto , Humanos , Procedimentos Cirúrgicos Eletivos , Transfusão de SangueRESUMO
BACKGROUND: Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017. OBJECTIVES: To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination. SEARCH METHODS: We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE). MAIN RESULTS: We included three RCTs with 385 participants. We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision. Hydroxyurea versus placebo One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m2, 95% confidence interval (CI) -14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD-related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty). No deaths occurred in either trial arm and the RCT did not report quality of life. Angiotensin-converting enzyme inhibitors versus placebo One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD -49.00 mg/day, 95% CI -124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty). The RCT did not report serious adverse events, all-cause mortality, or quality of life. Angiotensin-converting enzyme inhibitors versus vitamin C One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect. The RCT did not report serious adverse events, all-cause mortality, or quality of life. AUTHORS' CONCLUSIONS: We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.
Assuntos
Síndrome Torácica Aguda , Anemia Falciforme , Falência Renal Crônica , Criança , Adulto , Humanos , Adolescente , Hidroxiureia/uso terapêutico , Antidrepanocíticos/uso terapêutico , Síndrome Torácica Aguda/induzido quimicamente , Síndrome Torácica Aguda/complicações , Síndrome Torácica Aguda/tratamento farmacológico , Captopril/uso terapêutico , Lisinopril/uso terapêutico , Creatinina , Anemia Falciforme/complicações , Proteinúria/etiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Ácido Ascórbico/uso terapêuticoRESUMO
Anemia is common in Myelodysplastic Syndromes (MDS). Different anemia treatments have been tested in clinical studies, but the full impact on patients' health-related quality of life (HRQoL) and physical function is unknown. The main aim of this review was to assess whether improvements in anemia are associated with changes in HRQoL/physical function. Twenty-six full-text publications were identified, enrolling 2211 patients: nine randomized trials (RCTs), fourteen non-randomized studies of interventions and three cross-sectional studies. Interventions included: growth factors/erythropoiesis-stimulating agents (n = 14), red cell transfusion (n = 9), erythroid maturation agents (n = 1), or a combination (n = 2). Five RCTs reported no changes in HRQoL despite erythroid response to the intervention, raising the question of whether anemia treatment alone can effectively improve HRQoL. Many studies were considered at high risk of bias for assessing HRQoL. There is a pressing need for future clinical trials to better define the nature of the relationship between anemia and HRQoL/functional outcomes.
Assuntos
Anemia , Hematínicos , Síndromes Mielodisplásicas , Humanos , Anemia/etiologia , Anemia/terapia , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Hematínicos/uso terapêutico , Transfusão de Eritrócitos , Qualidade de VidaRESUMO
BACKGROUND: Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT. METHODS: We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure. RESULTS: Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5). CONCLUSIONS: Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.
Assuntos
Hemorragia , Hemostáticos , Adulto , Humanos , Hemorragia/tratamento farmacológico , Hemostáticos/uso terapêutico , Transfusão de Sangue , Plaquetas , Transfusão de EritrócitosRESUMO
BACKGROUND: Pelvic, hip, and long bone fractures can result in significant bleeding at the time of injury, with further blood loss if they are treated with surgical fixation. People undergoing surgery are therefore at risk of requiring a blood transfusion and may be at risk of peri-operative anaemia. Pharmacological interventions for blood conservation may reduce the risk of requiring an allogeneic blood transfusion and associated complications. OBJECTIVES: To assess the effectiveness of different pharmacological interventions for reducing blood loss in definitive surgical fixation of the hip, pelvic, and long bones. SEARCH METHODS: We used a predefined search strategy to search CENTRAL, MEDLINE, PubMed, Embase, CINAHL, Transfusion Evidence Library, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) from inception to 7 April 2022, without restrictions on language, year, or publication status. We handsearched reference lists of included trials to identify further relevant trials. We contacted authors of ongoing trials to acquire any unpublished data. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people who underwent trauma (non-elective) surgery for definitive fixation of hip, pelvic, and long bone (pelvis, tibia, femur, humerus, radius, ulna and clavicle) fractures only. There were no restrictions on gender, ethnicity, or age. We excluded planned (elective) procedures (e.g. scheduled total hip arthroplasty), and studies published since 2010 that had not been prospectively registered. Eligible interventions included: antifibrinolytics (tranexamic acid, aprotinin, epsilon-aminocaproic acid), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants, and non-fibrin sealants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using GRADE. We did not perform a network meta-analysis due to lack of data. MAIN RESULTS: We included 13 RCTs (929 participants), published between 2005 and 2021. Three trials did not report any of our predefined outcomes and so were not included in quantitative analyses (all were tranexamic acid versus placebo). We identified three comparisons of interest: intravenous tranexamic acid versus placebo; topical tranexamic acid versus placebo; and recombinant factor VIIa versus placebo. We rated the certainty of evidence as very low to low across all outcomes. Comparison 1. Intravenous tranexamic acid versus placebo Intravenous tranexamic acid compared to placebo may reduce the risk of requiring an allogeneic blood transfusion up to 30 days (RR 0.48, 95% CI 0.34 to 0.69; 6 RCTs, 457 participants; low-certainty evidence) and may result in little to no difference in all-cause mortality (Peto odds ratio (Peto OR) 0.38, 95% CI 0.05 to 2.77; 2 RCTs, 147 participants; low-certainty evidence). It may result in little to no difference in risk of participants experiencing myocardial infarction (risk difference (RD) 0.00, 95% CI -0.03 to 0.03; 2 RCTs, 199 participants; low-certainty evidence), and cerebrovascular accident/stroke (RD 0.00, 95% CI -0.02 to 0.02; 3 RCTs, 324 participants; low-certainty evidence). We are uncertain if there is a difference between groups for risk of deep vein thrombosis (Peto OR 2.15, 95% CI 0.22 to 21.35; 4 RCTs, 329 participants, very low-certainty evidence), pulmonary embolism (Peto OR 1.08, 95% CI 0.07 to 17.66; 4 RCTs, 329 participants; very low-certainty evidence), and suspected serious drug reactions (RD 0.00, 95% CI -0.03 to 0.03; 2 RCTs, 185 participants; very low-certainty evidence). No data were available for number of red blood cell units transfused, reoperation, or acute transfusion reaction. We downgraded the certainty of the evidence for imprecision (wide confidence intervals around the estimate and small sample size, particularly for rare events), and risk of bias (unclear or high risk methods of blinding and allocation concealment in the assessment of subjective measures), and upgraded the evidence for transfusion requirement for a large effect. Comparison 2. Topical tranexamic acid versus placebo We are uncertain if there is a difference between topical tranexamic acid and placebo for risk of requiring an allogeneic blood transfusion (RR 0.31, 95% CI 0.08 to 1.22; 2 RCTs, 101 participants), all-cause mortality (RD 0.00, 95% CI -0.10 to 0.10; 1 RCT, 36 participants), risk of participants experiencing myocardial infarction (Peto OR 0.15, 95% CI 0.00 to 7.62; 1 RCT, 36 participants), cerebrovascular accident/stroke (RD 0.00, 95% CI -0.06 to 0.06; 1 RCT, 65 participants); and deep vein thrombosis (Peto OR 1.11, 95% CI 0.07 to 17.77; 2 RCTs, 101 participants). All outcomes reported were very low-certainty evidence. No data were available for number of red blood cell units transfused, reoperation, incidence of pulmonary embolism, acute transfusion reaction, or suspected serious drug reactions. We downgraded the certainty of the evidence for imprecision (wide confidence intervals around the estimate and small sample size, particularly for rare events), inconsistency (moderate heterogeneity), and risk of bias (unclear or high risk methods of blinding and allocation concealment in the assessment of subjective measures, and high risk of attrition and reporting biases in one trial). Comparison 3. Recombinant factor VIIa versus placebo Only one RCT of 48 participants reported data for recombinant factor VIIa versus placebo, so we have not presented the results here. AUTHORS' CONCLUSIONS: We cannot draw conclusions from the current evidence due to lack of data. Most published studies included in our analyses assessed the use of tranexamic acid (compared to placebo, or using different routes of administration). We identified 27 prospectively registered ongoing RCTs (total target recruitment of 4177 participants by end of 2023). The ongoing trials create six new comparisons: tranexamic acid (tablet + injection) versus placebo; intravenous tranexamic acid versus oral tranexamic acid; topical tranexamic acid versus oral tranexamic acid; different intravenous tranexamic acid dosing regimes; topical tranexamic acid versus topical fibrin glue; and fibrinogen (injection) versus placebo.
Assuntos
Artroplastia de Substituição , Fraturas Ósseas , Hemostáticos , Infarto do Miocárdio , Embolia Pulmonar , Acidente Vascular Cerebral , Ácido Tranexâmico , Reação Transfusional , Trombose Venosa , Humanos , Ácido Tranexâmico/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Hemostáticos/uso terapêutico , Fibrinogênio , Trombose Venosa/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Fraturas Ósseas/cirurgiaRESUMO
BACKGROUND: Blood transfusion can be a lifesaving intervention after perioperative blood loss. Many prediction models have been developed to identify patients most likely to require blood transfusion during elective surgery, but it is unclear whether any are suitable for clinical practice. STUDY DESIGN AND SETTING: We conducted a systematic review, searching MEDLINE, Embase, PubMed, The Cochrane Library, Transfusion Evidence Library, Scopus, and Web of Science databases for studies reporting the development or validation of a blood transfusion prediction model in elective surgery patients between January 1, 2000 and June 30, 2021. We extracted study characteristics, discrimination performance (c-statistics) of final models, and data, which we used to perform risk of bias assessment using the Prediction model risk of bias assessment tool (PROBAST). RESULTS: We reviewed 66 studies (72 developed and 48 externally validated models). Pooled c-statistics of externally validated models ranged from 0.67 to 0.78. Most developed and validated models were at high risk of bias due to handling of predictors, validation methods, and too small sample sizes. CONCLUSION: Most blood transfusion prediction models are at high risk of bias and suffer from poor reporting and methodological quality, which must be addressed before they can be safely used in clinical practice.
Assuntos
Transfusão de Sangue , Modelos Estatísticos , Humanos , Prognóstico , Transfusão de Sangue/métodos , HemorragiaRESUMO
BACKGROUND: Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands, which can be prevented and treated with iron-chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and wellbeing, which may affect adherence. OBJECTIVES: To identify and assess the effectiveness of different types of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) and interventions specific to different age groups, to improve adherence to iron chelation therapy compared to another listed intervention, or standard care in people with SCD or thalassaemia. SEARCH METHODS: We searched CENTRAL (Cochrane Library), MEDLINE, PubMed, Embase, CINAHL, PsycINFO, ProQuest Dissertations & Global Theses, Web of Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (13 December 2021). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (1 August 2022). SELECTION CRITERIA: For trials comparing medications or medication changes, only randomised controlled trials (RCTs) were eligible for inclusion. For studies including psychological and psychosocial interventions, educational interventions, or multi-component interventions, non-randomised studies of interventions (NRSIs), controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion. DATA COLLECTION AND ANALYSIS: For this update, two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 19 RCTs and one NRSI published between 1997 and 2021. One trial assessed medication management, one assessed an education intervention (NRSI) and 18 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral chelating agents, deferiprone and deferasirox. We rated the certainty of evidence as very low to low across all outcomes identified in this review. Four trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL. We identified nine comparisons of interest. 1. Deferiprone versus deferoxamine We are uncertain whether or not deferiprone affects adherence to iron chelation therapy (four RCTs, unpooled, very low-certainty evidence), all-cause mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.18 to 1.21; 3 RCTs, 376 participants; very low-certainty evidence), or serious adverse events (SAEs) (RR 1.43, 95% CI 0.83 to 2.46; 1 RCT, 228 participants; very low-certainty evidence). Adherence was reported as "good", "high" or "excellent" by all seven trials, though the data could not be analysed formally: adherence ranged from 69% to 95% (deferiprone, mean 86.6%), and 71% to 93% (deferoxamine, mean 78.8%), based on five trials (474 participants) only. 2. Deferasirox versus deferoxamine We are uncertain whether or not deferasirox affects adherence to iron chelation therapy (three RCTs, unpooled, very low-certainty evidence), although medication adherence was high in all trials. We are uncertain whether or not there is any difference between the drug therapies in serious adverse events (SAEs) (SCD or thalassaemia) or all-cause mortality (thalassaemia). 3. Deferiprone versus deferasirox We are uncertain if there is a difference between oral deferiprone and deferasirox based on a single trial in children (average age 9 to 10 years) with any hereditary haemoglobinopathy in adherence, SAEs and all-cause mortality. 4. Deferasirox film-coated tablet (FCT) versus deferasirox dispersible tablet (DT) One RCT compared deferasirox in different tablet forms. There may be a preference for FCTs, shown through a trend for greater adherence (RR 1.10, 95% CI 0.99 to 1.22; 1 RCT, 88 participants), although medication adherence was high in both groups (FCT 92.9%; DT 85.3%). We are uncertain if there is a benefit in chelation-related AEs with FCTs. We are uncertain if there is a difference in the incidence of SAEs, all-cause mortality or sustained adherence. 5. Deferiprone and deferoxamine combined versus deferiprone alone We are uncertain if there is a difference in adherence, though reporting was usually narrative as triallists report it was "excellent" in both groups (three RCTs, unpooled). We are uncertain if there is a difference in the incidence of SAEs and all-cause mortality. 6. Deferiprone and deferoxamine combined versus deferoxamine alone We are uncertain if there is a difference in adherence (four RCTs), SAEs (none reported in the trial period) and all-cause mortality (no deaths reported in the trial period). There was high adherence in all trials. 7. Deferiprone and deferoxamine combined versus deferiprone and deferasirox combined There may be a difference in favour of deferiprone and deferasirox (combined) in rates of adherence (RR 0.84, 95% CI 0.72 to 0.99) (one RCT), although it was high (> 80%) in both groups. We are uncertain if there is a difference in SAEs, and no deaths were reported in the trial, so we cannot draw conclusions based on these data (one RCT). 8. Medication management versus standard care We are uncertain if there is a difference in QoL (one RCT), and we could not assess adherence due to a lack of reporting in the control group. 9. Education versus standard care One quasi-experimental (NRSI) study could not be analysed due to the severe baseline confounding. AUTHORS' CONCLUSIONS: The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects, though often follow-up was not good (high dropout over longer trials), with adherence based on a per protocol analysis. Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation. Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy. Due to lack of evidence this review cannot comment on intervention strategies for different age groups.
Assuntos
Anemia Falciforme , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Talassemia , Criança , Humanos , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Quelantes , Terapia por Quelação , Desferroxamina/efeitos adversos , FerroRESUMO
BACKGROUND: Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion. OBJECTIVES: To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss. SEARCH METHODS: We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants). The five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies. None of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. The other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days. We identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes. AUTHORS' CONCLUSIONS: Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.
Assuntos
Ácido Tranexâmico , Adulto , Humanos , Aprotinina , Transfusão de Sangue , Desamino Arginina Vasopressina/uso terapêutico , Adesivo Tecidual de Fibrina , Hemorragia/etiologia , Hemorragia/prevenção & controle , Metanálise em Rede , Ácido Tranexâmico/uso terapêuticoRESUMO
Many medications have been reported to be associated with thrombotic thrombocytopenic purpura (TTP) through pharmacovigilance data and published case reports. Whilst there are existing data available regarding drug-induced thrombotic microangiopathy, there is no available synthesis of evidence to assess drug-induced TTP (DI-TTP). Despite this lack of evidence, patients with TTP are often advised against using many medications due to the theoretical risk of DI-TTP. This systematic review evaluated the evidence for an association of medications reported as potential triggers for TTP. Of 5098 records available 261 articles were assessed further for eligibility. Fifty-seven reports, totalling 90 patients, were included in the final analysis. There were no cases where the level of association was rated as definite or probable, demonstrating a lack of evidence of any drug causing DI-TTP. This paucity of evidence was also demonstrated in the pharmacovigilance data, where 613 drugs were reported as potential causes of TTP without assessment of the strength of association. This systematic review demonstrates the need for standardised reporting of potential drugs causing TTP. Many reports omit basic information and, therefore, hinder the chance of finding a causative link if one exists.
Assuntos
Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Humanos , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Farmacovigilância , América do NorteRESUMO
OBJECTIVE: Evaluate the safety and effectiveness of convalescent plasma (CP) or hyperimmune immunoglobulin (hIVIG) in severe respiratory disease caused by coronaviruses or influenza, in patients of all ages requiring hospital admission. METHODS: We searched multiple electronic databases for all publications to 12th October 2020, and RCTs only to 28th June 2021. Two reviewers screened, extracted, and analysed data. We used Cochrane ROB (Risk of Bias)1 for RCTs, ROBINS-I for non-RCTs, and GRADE to assess the certainty of the evidence. RESULTS: Data from 30 RCTs and 2 non-RCTs showed no overall difference between groups for all-cause mortality and adverse events in four comparisons. Certainty of the evidence was downgraded for high ROB and imprecision. (1) CP versus standard care (SoC) (20 RCTS, 2 non-RCTs, very-low to moderate-high certainty); (2) CP versus biologically active control (6 RCTs, very-low certainty); (3) hIVIG versus SoC (3 RCTs, very-low certainty); (4) early CP versus deferred CP (1 RCT, very-low certainty). Subgrouping by titre improved precision in one outcome (30-day mortality) for the 'COVID high-titre' category in Comparison 1 (no difference, high certainty) and Comparison 2 (favours CP, very-low certainty). Post hoc analysis suggests a possible benefit of CP in patients testing negative for antibodies at baseline, compared with those testing positive. CONCLUSION: A minimum titre should be established and ensured for a positive biological response to the therapy. Further research on the impact of CP/hIVIG in patients who have not yet produced antibodies to the virus would be useful to target therapies at groups who will potentially benefit the most.
Assuntos
COVID-19 , Influenza Humana , Humanos , Soroterapia para COVID-19 , ImunoglobulinasRESUMO
Background The limited supply of universal plasma has resulted in transfusion of ABO incompatible plasma to patients. As the need to implement whole blood transfusion in pre-hospitals setting rises, the lowest cut-off for anti-A/anti-B that does not cause haemolysis remains unknown. In this first scoping review, we aimed to determine the lowest ABO titre and volume reported in the literature to cause haemolysis from ABO incompatible plasma transfusions (plasma, platelets, cryoprecipitate, and whole blood). Methods We searched several databases from inception to April 2022, including all study types. Three independent reviewers extracted and reviewed the data. Primary outcome was the anti-A and anti-B titre (measured by IgM or IgG) that resulted in measurable haemolysis following ABO incompatible plasma transfusion. Results We identified 5681 citations, of which 49 studies were eligible, reporting a total of 62 cases (34 adults, 14 children and 14 did not specify age). The methods for antibody measurement and antibody type (IgG or IgM) varied significantly between studies. Component volumes were poorly reported. The most common component responsible for the haemolysis was apheresis platelets followed by pooled platelets and whole blood. Most haemolytic cases reported were due to anti-A. The lowest anti-A titre reported to cause haemolysis (children and adults) was 32 (IgG), while for anti-B it was 512 (IgG and IgM) for adults, 16,384 for paediatrics (IgG and IgM) and 128 (IgM) in cases where the age was not specified. The lowest reported volume associated with haemolysis were 100 ml (adults) and 15 ml (children). Of the 62 15 (24%) died. Conclusion The lowest titre reported to cause haemolysis was an anti-A of 32. ABO mismatch plasma transfusion may be associated with significant mortality. There is a need to agree/standardise methods for ABO titration measurement internationally for plasma components and agree the lowest anti-A/anti-B titre for transfusing ABO mismatched plasma.
Assuntos
Anemia Hemolítica Autoimune , Reação Transfusional , Adulto , Humanos , Criança , Incompatibilidade de Grupos Sanguíneos/etiologia , Hemólise , Sistema ABO de Grupos Sanguíneos , Transfusão de Componentes Sanguíneos , Plasma , Reação Transfusional/etiologia , Transfusão de Sangue , Imunoglobulina G , Imunoglobulina MRESUMO
OBJECTIVE: The aim of this systematic scoping review is to identify and categorize the outcome measures that have been reported in clinical studies, where therapeutic plasma exchange (TPE) has been used as an intervention in any clinical settings, excluding thrombotic thrombocytopenic purpura (TTP). METHODS: We searched electronic databases using a predefined search strategy from inception to October 9, 2020. Two reviewers independently screened and extracted data. RESULTS: We included 42 studies (37 RCTs and 5 prospective cohort studies) grouped into six main categories (neurology, immunology, renal, rheumatology, hematology, and dermatology). Primary outcomes were defined in eight studies (19%, 8/42) and were categorized as efficacy (five studies) or patient reported outcomes (three studies). A power calculation was reported in six studies (75%, 6/8): five neurology studies (mainly patient reported outcomes) and a single immunological study (efficacy outcome). Disease-specific efficacy outcomes were dependent on the clinical setting of the population receiving TPE. Most of the trials (43%, 18/42) were undertaken in patients with neurology conditions where clear, disease-specific, clinical outcome measures were used, including neurological disability scales (11/18, 61%), change in neurological examination (9/18, 50%), and functional improvement scores (7/18, 39%). For other conditions, the reporting of disease-specific outcomes was poorly reported. Safety outcomes were mainly related to replacement fluid type rather than being disease-specific. The most common outcome reported was hypotension (19%, 8/42), and this was primarily in patients exchanged with albumin. CONCLUSION: Future clinical studies to determine which fluid replacement option is most efficacious and safe should use disease-specific outcomes, as a trial in one therapeutic area may not necessarily translate to another therapeutic area. Patient reported outcomes are not universally reported for all disease areas. Safety measures focused primarily on fluid safety.
Assuntos
Troca Plasmática , Púrpura Trombocitopênica Trombótica , Albuminas , Humanos , Avaliação de Resultados em Cuidados de Saúde , Troca Plasmática/efeitos adversos , Estudos Prospectivos , Púrpura Trombocitopênica Trombótica/terapiaRESUMO
Hyperkalaemia following transfusion is widely reported in the literature. Our objective was to critically review recent evidence on hyperkalaemia in association with transfusion and to assess whether specific aspects of transfusion practice can affect the likelihood of developing hyperkalaemia. We searched 9 electronic databases (including MEDLINE, Embase, and Transfusion Evidence Library) using a predefined search strategy, from 2010 to April 8, 2021. Three reviewers performed dual screening, extraction, and risk of bias assessment. We used Cochrane risk of bias (ROB) 2 for assessment of RCTs, ROBINS-I for non-RCTs, and GRADE to assess the certainty of the evidence. We report 7 comparisons of interest in n = 3729 patients from 28 studies (11 RCTs, 4 prospective cohort studies, and 13 retrospective cohort studies): (1) age of blood, (2) washing, (3) filtration, (4) irradiation, (5) fluid type, (6) transfusion vs no transfusion, (7) blood volume/rate. Of the 28 studies included, 25 reported outcomes of potassium (K+) concentration, 17 the number developing hyperkalaemia, 13 mortality, 10 cardiac arrest, and 10 cardiac arrhythmia. Only 16 studies provided analysable data suitable for quantitative analysis. Evidence addressing our outcomes was of very low certainty (downgraded for incomplete outcome data, baseline imbalance, imprecision around the estimate, and small sample size). While 5 studies showed a difference in K+ concentration up to 6 hours posttransfusion for 3 comparisons (age of blood, washing, and transfusion volume/rate), and 3 studies showed a difference in the diagnosis of hyperkalaemia for 2 comparisons (age of blood, and transfusion volume/rate), the evidence was inconsistent across all included studies. There was no difference in any reported outcomes for 4 comparisons (filtration, irradiation, fluid type, or transfusion vs no transfusion). Overall, the reported evidence was too weak to support identification of groups most at risk of hyperkalaemia or to support recommendations on use of short-storage RBC. For other commonly used risk mitigations for hyperkalaemia in transfusion medicine, the (low certainty) evidence was either conflicting or not supportive.
Assuntos
Hiperpotassemia , Transfusão de Sangue , Humanos , Hiperpotassemia/epidemiologia , Hiperpotassemia/etiologia , Hiperpotassemia/terapia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Anaemia is a common sequela of advanced disease and is associated with significant symptom burden. No specific guidance exists for the investigation and management of anaemia in palliative care patients. AIM: We aim to offer a pragmatic overview of the approaches to investigate and manage anaemia in advanced disease, based on guidelines and evidence in disease specific patient groups, including cancer, heart failure and chronic kidney disease. DESIGN: Scoping review methodology was used to determine the strength of evidence supporting the investigation and management of anaemia in patients with advanced disease. DATA SOURCES: A search for guidelines was performed in 2020. National or international guidelines were examined if they described the investigation or management of anaemia in adult patients with health conditions seen by palliative care services written within the last 5 years in the English language. Searches of MEDLINE, the Cochrane library and WHO guidance were made in 2019 to identify key publications that provided additional primary data. RESULTS: Evidence supports patient-centred investigation of anaemia, results of which should guide targeted intervention. Blanket use of blood transfusion should be avoided, with evidence supporting a more restrictive approach to transfusion. Routine use of oral iron and erythropoetin stimulating agents (ESAs) are not recommended. Insufficient evidence exists to determine the effectiveness of IV iron in this patient group. CONCLUSION: We advocate early consideration and investigation of anaemia, guided by symptom burden and patient preferences. Correction of reversible causes should be the mainstay of treatment, with a restrictive approach to blood transfusion. Research is required to evaluate the efficacy of IV iron in these patients.
Assuntos
Anemia , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Adulto , Anemia/terapia , Humanos , Ferro , Cuidados PaliativosRESUMO
Our objective was to systematically evaluate the efficacy and safety of intravenous (IV) iron therapy for treating anaemia in critically ill adults (>16 years) admitted to intensive care or high dependency units. We excluded quasi-RCTs and other not truly randomised trials. We searched 7 electronic databases (including CENTRAL, MEDLINE, and Embase) using a pre-defined search strategy from inception to June 14, 2021. One reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane risk of bias (ROB) 1 and GRADE to assess the certainty of the evidence. We reported 3 comparisons across 1198 patients, in 8 RCTs: (1) IV iron vs control (7 RCTs, 748 participants); our primary outcome (hemoglobin (Hb) concentration at 10 to 30 days) was reported in 7 of the 8 included trials. There was evidence of an effect (very-low certainty) in favour of IV iron over control in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL [95%CI 0.23, 0.81], P = .0005). For the remaining outcomes there was no evidence of an effect in either direction (low certainty of evidence for Hb concentration at <10 days; very-low certainty of evidence for hospital duration, ICU duration, hospital readmission, infection, mortality; HRQoL outcomes were not GRADED). (2) IV iron + subcutaneous erythropoietin (EPO) vs control (2 RCTs, 104 participants); reported outcomes showed no evidence of effect in either direction, based on very-low certainty evidence (Hb concentration at 10-30 days, and <10 days, infection, mortality). (3) Hepcidin-guided treatment with IV iron or iron+ EPO vs standard care (1 RCT, 399 participants) reported evidence of an effect in favour of the intervention for 90-day mortality (low certainty of evidence), but no other group differences for the reported outcomes (low certainty evidence for Hb concentration at 10-30 days, hospital duration; HRQoL was not GRADED). The evidence across all comparisons was downgraded for high and unclear ROB for lack of blinding, incomplete outcome data, baseline imbalance, and imprecision around the estimate (wide CIs and small sample size). In conclusion, the current evidence continues to support further investigation into the role for iron therapy in increasing Hb in critically ill patients. Recent, small, trials have begun to focus on patient-centred outcomes but a large, well conducted, and adequately powered trial is needed to inform clinical practice.