Dissecting the complexity of pediatric blood transfusions and risk of adverse reactions in Aotearoa New Zealand.

BACKGROUND: Children have different clinical and physiological drivers for transfusion from adult recipients. However, adverse transfusion reactions (ATRs) in pediatric patients are usually reported using the same criteria as for adults. Broad assessments of pediatric ATRs neglect substantial variation in different developmental stages. MATERIALS AND METHODS: This retrospective study included 342,950 patients, ~2.43 million transfusions, and 5,540 ATR reports collated from New Zealand hospitals between 2005 and 2021. Using 16 years as the upper age limit, 138,856 pediatric transfusions and 402 pediatric ATR reports were identified and dissected at three levels: pediatric as a whole, pediatric developmental stage (i.e., neonate, infant, preschool, and school), and chronological age to identify patients at high risk of ATRs. Multivariate logistic regression analysis was followed to quantify risk factors. RESULTS: Pediatric recipients had a higher ATR risk than adults (p=6.9-07) but the high risk was associated mainly with children older than 2 years. Neonates and infants accounted for 75.0% of pediatric recipients but had much lower ATR rates than adults. Pediatric transfusion recipients showed a clear male bias prior to age 11 years and then a female bias. However, gender difference in experiencing ATRs was significant only after age 13 years (p=2.3-04). Analyses focusing on the high-risk group revealed allergic reactions being the cause of the elevated risk and identified the main risk factors of number of transfusions (p=4.5-10) and multiple types of components transfused (p=2.0-13). DISCUSSION: The identified ATR risk factors signal linkage with the biological drivers for transfusion. Low ATR rates in infancy could also be attributed to use of neonatal components, low transfusions per patient, and less developed immunity. The relative increase in female recipients from age 11 may be associated with increased red blood cell demand following puberty.

National comparative audit of blood transfusion: 2014 audit of transfusion services and practice in children and adults with sickle cell disease.

OBJECTIVES: To determine the organisational resources in place; what blood was being transfused, why, how, where, when and by whom; whether laboratory support and policies met standards for patients with sickle cell disease (SCD). BACKGROUND: SCD affects 14 000 people in the United Kingdom (UK). Standards and guidelines do not cover all aspects of transfusion in SCD and there are no data on their use; people may become very sick without warning presenting to non-specialist hospitals; blood services are increasingly supplying units for transfusion in SCD with little data on their use. METHODS: A retrospective audit of transfusion services/practice for people with SCD who had received a transfusion in January-July 2014 in participating hospitals in the UK and Republic of Ireland (ROI). RESULTS: Eighty-four hospitals submitted 1290 cases, 75% of cases came from 18 hospitals submitting 25 or more cases. Transfusions (91.2% [1164/1276]) were administered to patients with HbSS, 60% (732/1227) of patients needed Rh CE negative blood. Transfusion episodes (4528) were recorded, of which 84% were elective. Stroke prevention accounted for 42% of all transfusions; adults received 56% of transfusions of which 50% were automated red cell exchange (RCE), children received 44% of transfusions of which 87% were simple transfusions. CONCLUSIONS: There was a paucity of appropriate clinical management protocols, adequately trained staff and network arrangements. The high numbers of children being transfused, disparity in transfusion modality between children and adults and the high frequency of the CE negative Rh phenotype were noted.

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease.

BACKGROUND: Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality. This is an update of a Cochrane Review first published in 2011 and updated in 2014 and 2016. OBJECTIVES: We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. Date of the last search: 19 September 2019. We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 10, 14 November 2018), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 14 November 2018. SELECTION CRITERIA: We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sߺ, SC, or Sß+ that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: No studies matching the selection criteria were found. AUTHORS' CONCLUSIONS: There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention.

SWIM (sickle with ibuprofen and morphine) randomised controlled trial fails to recruit: lessons learnt.

OBJECTIVES: Sickle With Ibuprofen and Morphine (SWIM) trial was designed to assess whether co-administration of ibuprofen (a non-steroidal anti-inflammatory drug) resulted in a reduction of opioid consumption delivered by patient-controlled analgesia (PCA) for acute pain in sickle cell disease. DESIGN: A randomised, placebo-controlled, double-blind trial. SETTING: UK multicentre trial in acute hospital setting. PARTICIPANTS: Adults with sickle cell disease of any gender and phenotype aged 16 years and over. INTERVENTIONS: Oral ibuprofen at a dose of 800 mg three times daily or placebo in addition to opioids (morphine or diamorphine) administered via PCA pump for up to 4 days. MAIN OUTCOME MEASURES: The primary outcome measure was opioid consumption over 4 days following randomisation. RESULTS: The SWIM trial closed early because it failed to randomise to its target of 316 patients within a reasonable time. CONCLUSIONS: The key issues identified include the unanticipated length of time between informed consent and randomisation, difficulties in randomisation of patients in busy emergency departments, availability of trained staff at weekends and out of hours, fewer centres than expected using PCA routinely for sickle cell pain treatment, lack of research staff and support for participation, and the trial design. There are implications for future UK trials in sickle cell disease. TRIAL REGISTRATION NUMBER: ISRCTN97241637, NCT00880373; Pre-results.

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease.

BACKGROUND: Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality.This is an update of a Cochrane review first published in 2011 and updated in 2014. OBJECTIVES: We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. Date of the last search: 25 April 2016.We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 26 January 2016), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 26 January 2016. SELECTION CRITERIA: We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sß(0), SC, or Sß(+) that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: No studies matching the selection criteria were found. AUTHORS' CONCLUSIONS: There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention.

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease.

BACKGROUND: Sickle cell disease can cause severe vaso-occlusive crises and dysfunction of most organ systems. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality. OBJECTIVES: The aim of this review is to find out whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with an alternative treatment or no treatment show differences in the following:1. the incidence of chronic chest complications (chronic sickle lung disease or pulmonary hypertension);2. the 'severity' or progression of established chronic chest complications;3. the mortality associated with chronic chest complications; and4. unacceptable adverse events. SEARCH METHODS: We searched the Group's Haemoglobinopathies Trials Register. Specific websites were also searched for information of ongoing or newly completed trials. The search included the reference lists of any randomised controlled trials identified using the above methods.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 22 July 2013. SELECTION CRITERIA: We included randomized controlled trials. Trials that used quasi-randomized methods were to be included if sufficient evidence existed that the treatment and control groups were similar at baseline. Trials were eligible for inclusion if they investigated regular red blood cell transfusion regimens (either simple top-up or exchange transfusions) aimed at reducing the incidence, mortality, or objective measures of severity or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension) among men or women of any age and with one of four common sickle cell disease genotypes, ie Hb SS, Sß(0), SC, or Sß(+). These interventions would be compared to an alternative treatment with the same aim or to no treatment. DATA COLLECTION AND ANALYSIS: No studies matching the selection criteria were found. MAIN RESULTS: No studies matching the selection criteria were found. AUTHORS' CONCLUSIONS: There is a need for randomized controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants during an extended 'steady state' baseline, and after the intervention.

The association between tricuspid regurgitation velocity and 5-year survival in a North West London population of patients with sickle cell disease in the United Kingdom.

Raised tricuspid regurgitant velocity (TRV) occurs in approximately 30% of adults with sickle cell disease (SCD), and has been shown to be an independent risk factor for death. TRV was assessed in 164 SCD patients who were subsequently followed up for survival. Raised pulmonary pressures were defined as a TRV jet ≥2.5 m/s on echocardiography. Elevated TRV was present in 29.1% of patients and it was associated with increased age and left atrial diameter. There were 15 deaths (9.1%) over a median of 68.1 months follow up; seven patients had increased TRV, and eight patients had a TRV<2.5 m/s. Higher TRV values were associated with a greater than 4-fold increased risk of death (Hazard Ratio: 4.48, 99% confidence interval 1.01-19.8), although we found a lower overall mortality rate than has been reported in previous studies. TRV was not an independent risk factor for death. We have confirmed the association between raised TRV and mortality in a UK SCD population whose disease severity appears to be less than that reported in previous studies. Further prospective studies are needed to more clearly characterize which patient factors modify survival in SCD patients with raised TRV.

Patient self-assessment of hospital pain, mood and health-related quality of life in adults with sickle cell disease.

INTRODUCTION: Acute pain is a hallmark of sickle cell disease (SCD) for which frequent hospital admissions may be required, affecting the quality of life of patients. OBJECTIVES: To characterise the relationship between adult patient self-reported sickle cell pain, mood and quality of life during and after hospital admissions. DESIGN: Longitudinal study across three time-points. SETTING: Secondary care, single specialist sickle cell centre. PARTICIPANTS: 510 adult patients with SCD admitted to hospital daycare or inpatient units. OUTCOME MEASURES: Self-assessments of pain, mood and health-related quality of life with health utility (measured on the EQ-5D) on admission, before discharge and at 1-week postdischarge. RESULTS: Mood, general health and quality of life showed significant steady improvements with reduction of pain in patients with SCD on admission to hospital, before discharge and at 1-week follow-up (p<0.01). Health utility scores derived from the EQ-5D showed a negative association with pain in regression analysis over the three time-points. CONCLUSION: Examining health-related quality of life and health utility in relation to pain during hospital admissions is valuable in terms of targeting appropriate psychological interventions within the context of a multidisciplinary approach to managing sickle cell pain. This has implications for healthcare costs.

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease.

BACKGROUND: Sickle cell disease can cause severe vaso-occlusive crises and dysfunction of most organ systems. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality. OBJECTIVES: The aim of this review is to find out whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with an alternative treatment or no treatment show differences in the following:1. the incidence of chronic chest complications (chronic sickle lung disease or pulmonary hypertension); 2. the 'severity' or progression of established chronic chest complications; 3. the mortality associated with chronic chest complications; and 4. unacceptable adverse events. SEARCH STRATEGY: We searched the Group's Haemoglobinopathies Trials Register. Specific websites were also searched for information of ongoing or newly completed trials. The search included the reference lists of any randomised controlled trials identified using the above methods.Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 18 April 2011. SELECTION CRITERIA: We included randomized controlled trials. Trials that used quasi-randomized methods were to be included if sufficient evidence existed that the treatment and control groups were similar at baseline. Trials were eligible for inclusion if they investigated regular red blood cell transfusion regimens (either simple top-up or exchange transfusions) aimed at reducing the incidence, mortality, or objective measures of severity or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension) among men or women of any age and with one of four common sickle cell disease genotypes, ie Hb SS, Sß(0), SC, or Sß(+). These interventions would be compared to an alternative treatment with the same aim or to no treatment. DATA COLLECTION AND ANALYSIS: No studies matching the selection criteria were found. MAIN RESULTS: No studies matching the selection criteria were found. AUTHORS' CONCLUSIONS: There is a need for randomized controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants during an extended 'steady state' baseline, and after the intervention.