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The Haemoglobin Colour Scale, Sahli's meter and Haemocue®analyser for rapid assessment of haemoglobin status.
Source publication
Background: Severe anaemia in children requiring hospital admission is a major public health problem in malaria-endemic Africa. Affordable methods for the assessment of haemoglobin have not been validated against gold standard measures for identifying those with severe anaemia requiring a blood transfusion, despite this resource being in short supp...
Contexts in source publication
Context 1
... three different methods for haemoglobin assessment are shown in Figure 1. The HemoCue® Hb 301 system (Hemocue AB, Angelholm, Sweden) is a portable point of care Hb testing device that uses disposable microcuvettes and requires no calibration. ...
Context 2
... mean difference with limits of agreement between HemoCue® and the calorimetric method and between HemoCue® and Sahli's method were 0.5 (95% CI -−12.3, 3.3) g/dl There was no statistically significant difference between the mean of the Hb determination for the three methods 0.1 (95% CI-−2.3, 2.4) g/dl respectively (Figure 1), implying good agreement between these methods, particularly for Sahli's method. ...
Similar publications
Background: Severe anaemia in children requiring hospital admission is a major public health problem in malaria-endemic Africa. Affordable methods for the assessment of haemoglobin have not been validated against gold standard measures for identifying those with severe anaemia requiring a blood transfusion, despite this resource being in short supp...
Citations
... Haemoglobin was assessed using HemoCue Hb 301 system (HemoCue, Angelholm, Sweden) every 8 h in the first 24 h, then at 48 h, or if triggered by clinical deterioration. 13 Patients were actively monitored for serious adverse events, particularly suspected cardiac or pulmonary overload or transfusion-related events, following modified guidelines recom mended by the UK Serious Hazards of Transfusion initiative. 14 Post-discharge, children were clinically assessed and haemoglobin was measured at 28, 90, and 180 days. ...
Background
The TRACT trial established the timing of transfusion in children with uncomplicated anaemia (haemoglobin 4–6 g/dL) and the optimal volume (20 vs 30 mL/kg whole blood or 10 vs 15 mL/kg red cell concentrates) for transfusion in children admitted to hospital with severe anaemia (haemoglobin <6 g/dL) on day 28 mortality (primary endpoint). Because data on the safety of blood components are scarce, we conducted a secondary analysis to examine the safety and efficacy of different pack types (whole blood vs red cell concentrates) on clinical outcomes.
Methods
This study is a secondary analysis of the TRACT trial data restricted to those who received an immediate transfusion (using whole blood or red cell concentrates). TRACT was an open-label, multicentre, factorial, randomised trial conducted in three hospitals in Uganda (Soroti, Mbale, and Mulago) and one hospital in Malawi (Blantyre). The trial enrolled children aged between 2 months and 12 years admitted to hospital with severe anaemia (haemoglobin <6 g/dL). The pack type used (supplied by blood banks) was based only on availability at the time. The outcomes were haemoglobin recovery at 8 h and 180 days, requirement for retransfusion, length of hospital stay, changes in heart and respiratory rates until day 180, and the main clinical endpoints (mortality until day 28 and day 180, and readmission until day 180), measured using multivariate regression models.
Findings
Between Sept 17, 2014, and May 15, 2017, 3199 children with severe anaemia were enrolled into the TRACT trial. 3188 children were considered in our secondary analysis. The median age was 37 months (IQR 18–64). Whole blood was the first pack provided for 1632 (41%) of 3992 transfusions. Haemoglobin recovery at 8 h was significantly lower in those who received packed cells or settled cells than those who received whole blood, with a mean of 1·4 g/dL (95% CI –1·6 to –1·1) in children who received 30 mL/kg and –1·3 g/dL (–1·5 to –1·0) in those who received 20 mL/kg packed cells versus whole blood, and –1·5 g/dL (–1·7 to –1·3) in those who received 30 mL/kg and –1·0 g/dL (–1·2 to –0·9) in those who received 20 mL/kg settled cells versus whole blood (overall p<0·0001). Compared to whole blood, children who received blood as packed or settled cells in their first transfusion had higher odds of receiving a second transfusion (odds ratio 2·32 [95% CI 1·30 to 4·12] for packed cells and 2·97 [2·18 to 4·05] for settled cells; p<0·001) and longer hospital stays (hazard ratio 0·94 [95% CI 0·81 to 1·10] for packed cells and 0·86 [0·79 to 0·94] for settled cells; p=0·0024). There was no association between the type of blood supplied for the first transfusion and mortality at 28 days or 180 days, or readmission to hospital for any cause. 823 (26%) of 3188 children presented with severe tachycardia and 2077 (65%) with tachypnoea, but these complications resolved over time. No child developed features of confirmed cardiopulmonary overload.
Interpretation
Our study suggests that the use of packed or settled cells rather than whole blood leads to additional transfusions, increasing the use of a scarce resource in most of sub-Saharan Africa. These findings have substantial cost implications for blood transfusion and health services. Nevertheless, a clinical trial comparing whole blood transfusion with red cell concentrates might be needed to inform policy makers.
Funding
UK Medical Research Council (MRC) and the Department for International Development.
Translation
For the French translation of the abstract see Supplementary Materials section.
... 30 In Uganda, in children identified by health personnel (nurses and clinicians) as severely anaemic (based on assessment of pallor) for which they would empirically order a blood transfusion (if haemoglobin was unknown) the WHO Hemoglobin Colour Scale had a high specificity of 95Á6 (90Á7-98Á4) but lacked sensitivity [43Á1 (34Á2-52Á3)] for those with Hb < 50 g/l diagnosed using HemoCue. 14 Relevant to this question, a study conducted in Malawi evaluated the characteristics of various manual Hb methods for accuracy, including assessment of the WHO HCS. The performance was judged against a reference standard (haemiglobincyanide method). ...
... The Ugandan study, conducted a decade later, found the cost of the HemoCue test had increased (~4Á0 USD/test at 2019 prices, after an initial cost of between 250 and 350 USD for the HemoCue analyser). This was more costly than then next best test, Sahli's method (0Á25 USD/test, after an initial cost of 40-50 USD for the meter); however, Sahli's Hb estimation requires a functioning and accessible laboratory service 14 and it is less ...
Owing to the rapid turnaround time in the assessment of haemoglobin level by point‐of‐care tests (POC Hb), these have grown in popularity and scope in large parts of the world. However, whilst POC testing for malaria and HIV remains has been integrated into patient management in Africa, the use of POC haemoglobin testing remains neglected by health services. The main users of transfusions (paediatric, maternity and trauma services) present largely as emergencies. Ward‐based POC Hb could result in more rapid and accurate diagnosis of anaemia, contributing to saving of lives and at the same time reduce unnecessary transfusions which deplete the limited supplies of donated blood in Africa. Severe anaemia requiring transfusion is a major cause of paediatric admission in Africa. At a dissemination meeting to discuss the results of a large phase III paediatric transfusion trial and steps to implementation of the findings participants strongly recommended that one of the most pressing actions required was to prioritise the use of POC haemoglobin testing. This would facilitate implementation of the new transfusion algorithm, developed at the meeting, which refines patient management including blood transfusions. We present the rationale for the strongly recommended prioritisation of POC Hb, using paediatric transfusion as an exemplar.
... Children with suspected severe anaemia based on presenting symptoms and signs (eg, severe pallor 19 ) were screened using a rapid bedside test (HemoCue Hb301 system; HemoCue AB, Angelholm, Sweden 20 ) to determine haemoglobin concentration, and clinically assessed for severity, including history of passing dark or red urine (haemoglobinuria) 21 or known sickle cell disease. Randomisation was stratified by clinical centre and complicated versus uncomplicated severe anaemia. ...
Background:
Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes.
Methods:
Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally and were given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusion management. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population; follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN84086586, and follow-up is complete.
Findings:
From Sept 17, 2014, to May 15, 2017, 3983 eligible children were randomly assigned to treatment, and followed up for 180 days. 164 (4%) were lost to follow-up. 1901 (95%) of 1997 assigned multivitamin multimineral supplement, 1911 (96%) of 1986 assigned iron and folate, and 1922 (96%) of 1994 assigned co-trimoxazole started treatment. By day 180, 166 (8%) children in the multivitamin multimineral supplement group versus 169 (9%) children in the iron and folate group had died (hazard ratio [HR] 0·97, 95% CI 0·79-1·21; p=0·81) and 172 (9%) who received co-trimoxazole versus 163 (8%) who did not receive co-trimoxazole had died (HR 1·07, 95% CI 0·86-1·32; p=0·56). We found no evidence of interactions between these randomisations or with transfusion randomisations (p>0·2). By day 180, 489 (24%) children in the multivitamin multimineral supplement group versus 509 (26%) children in the iron and folate group (HR 0·95, 95% CI 0·84-1·07; p=0·40), and 500 (25%) children in the co-trimoxazole group versus 498 (25%) children in the no co-trimoxazole group (1·01, 0·89-1·15; p=0·85) had had one or more serious adverse events. Most serious adverse events were re-admissions, occurring in 692 (17%) children (175 [4%] with at least two re-admissions).
Interpretation:
Neither enhanced supplementation with multivitamin multimineral supplement versus iron and folate treatment or co-trimoxazole prophylaxis improved 6-month survival. High rates of hospital re-admission suggest that novel interventions are urgently required for severe anaemia, given the burden it places on overstretched health services in Africa.
Funding:
Medical Research Council and Department for International Development.
... At screening, the hemoglobin level was measured in children with signs or symptoms of severe anemia (e.g., severe pallor 14 ) with the use of the ...
Background:
The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes.
Methods:
In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole.
Results:
A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group.
Conclusions:
There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).
... In the first stratum, children with complicated severe anemia (a hemoglobin level <4 g per deciliter, reduced consciousness, respiratory distress, acute hemoglobinuria, 16 disclosed sickle cell disease, or a combination of these severity features) were randomly assigned in a 1:1 ratio to receive 30 ml of whole blood per kilogram (15 ml of packed or settled cells per kilogram) or 20 ml of whole blood per kilogram (10 ml of packed or settled cells per kilogram). In the second stratum, children with uncomplicated severe anemia (4 to 6 g per deciliter without signs of severity) were randomly assigned in a 1:1 ratio to immediate transfusion of whole-blood equivalent or no immediate transfusion (until or unless severity criteria were met). ...
Background:
Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level.
Methods:
In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. The primary outcome was 28-day mortality.
Results:
A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P = 0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days.
Conclusions:
Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.).
... This may have been due to the availability of repeated measures of Hb post admission to monitor children. This finding contrasts for other reports where adherence to transfusion guidelines were not followed 9,10 , since many transfusions initiated solely for severe pallor, a sign with poor specificity 13 . ...
Background : Provision of adequate supplies of donor blood for paediatric transfusion remains a challenge. Guidelines recommend restrictive transfusion practices, based on expert opinion. We examined whether survival among children admitted to hospital varied by admission haemoglobin status and whether this was influenced by malaria infection and/or transfusion.
Methods : A retrospective analysis in an unselected population of children admitted to a rural district hospital in Kenya over an 8-year period. We describe baseline parameters with respect to categories of anaemia and outcome (in-hospital death) with respect to haemoglobin, malaria and transfusion status.
Results : Among 29,226 admitted children, 1,143 (3.9%) had profound anaemia (Hb <4g/dl) and 3,469 (11.9%) had severe anaemia (Hb 4-6g/d). In-hospital mortality was; 97/1,143 (8.5%) in those with Hb<4g/dl and 164/2,326 (7.1%) in those with severe anaemia (Hb ≥4.0-<6g/dl). Admission Hb <3g/dl was associated with higher risk of death versus those with higher Hbs (OR=2.41 (95%CI: 1.8 - 3.24; P<0.001), increasing to OR=6.36, (95%CI: 4.21–9.62; P<0.001) in malaria positive children. Conversely, mortality in non-malaria admissions was unrelated to Hb level. Transfusion was associated with a non-significant improvement in outcome if Hb<3g/dl (malaria-only) OR 0.72 (95%CI 0.29 - 1.78), albeit the number of cases were too few to show a statistical difference. For those with Hb levels above 4g/dl, mortality was significantly higher in those receiving a transfusion compared to the non-transfused group. For non-malarial cases, transfusion did not affect survival-status, irrespective of baseline Hb level compared to children who were not transfused at higher Hb levels.
Conclusion : Although severe and complicated anaemia is common among children admitted to hospital in sSA (~16%), our data do not indicate that outcome is improved by transfusion irrespective of malaria status. Given the limitations of observational studies, clinical trials investigating the role of transfusion in outcomes in children with severe anaemia are warranted.
Objectives
Anaemia is a major cause of mortality and transfusion in children in low‐ and middle‐income countries (LMICs); however, current diagnostics are slow, costly and frequently unavailable. Point‐of‐care haemoglobin tests (POC(Hb)Ts) could improve patient outcomes and use of resources by providing rapid and affordable results. We systematically reviewed the literature to investigate what, where and how POC(Hb)Ts are being used by health facilities in LMICs to diagnose childhood anaemia, and to explore challenges to their use.
Methods
We searched a total of nine databases and trial registries up to 10 June 2022 using the concepts: anaemia, POC(Hb)T, LMIC and clinical setting. Adults ≥21 years and literature published >15 years ago were excluded. A single reviewer conducted screening, data extraction and quality assessment (of diagnostic studies) using QUADAS‐2. Outcomes including POC(Hb)T used, location, setting, challenges and diagnostic accuracy were synthesised.
Results
Of 626 records screened, 41 studies were included. Evidence is available on the use of 15 POC(Hb)Ts in hospitals (n = 28, 68%), health centres (n = 9, 22%) and clinics/units (n = 10, 24%) across 16 LMICs. HemoCue (HemoCue AB, Ängelholm, Sweden) was the most used test (n = 31, 76%). Key challenges reported were overestimation of haemoglobin concentration, clinically unacceptable limits of agreement, errors/difficulty in sampling, environmental factors, cost, inter‐observer variability and supply of consumables. Five POC(Hb)Ts (33%) could not detect haemoglobin levels below 4.5 g/dL. Diagnostic accuracy varied, with sensitivity and specificity to detect anaemia ranging from 24.2% to 92.2% and 70% to 96.7%, respectively.
Conclusions
POC(Hb)Ts have been successfully utilised in health facilities in LMICs to diagnose childhood anaemia. However, limited evidence is available, and challenges exist that must be addressed before wider implementation. Further research is required to confirm accuracy, clinical benefits and cost‐effectiveness.
Background
Acute kidney injury (AKI) has in the past been considered a rare complication of malaria in children living in high-transmission settings. More recently, however, a growing number of paediatric case series of AKI in severe malaria studies in African children have been published (Artesunate vs Quinine in the Treatment of Severe P. falciparum Malaria in African children and Fluids Expansion as Supportive Therapy trials). The Paracetamol for Acute Renal Injury in Severe Malaria Trial (PARIST) therefore, aims to assess feasibility, safety and determine the effective dose of paracetamol, which attenuates nephrotoxicity of haemoproteins, red-cell free haemoglobin and myoglobin in children with haemoglobinuric severe malaria.
Methods
PARIST is a phase I/II unblinded randomised controlled trial of 40 children aged >6 months and <12 years admitted with confirmed haemoglobinuric severe malaria (blackwater fever), a positive blood smear for P. falciparum malaria and either serum creatinine (Cr) increase by ≥0.3 mg/dL within 48 hours or to ≥1.5 times baseline and elevated blood urea nitrogen (BUN) >20 mg/dL. Children will be randomly allocated on a 1:1 basis to paracetamol intervention dose arm (20 mg/kg orally 6-hourly for 48 hours) or to a control arm to receive standard of care for temperature control (ie, tepid sponging for 30 min if fever persists give rescue treatment). Primary outcome is renal recovery at 48 hours as indicated by stoppage of progression and decrease of Cr level below baseline, BUN (<20 mg/dL). Data analysis will be on the intention-to-treat principle and a per-protocol basis.
Results from this phase I/II clinical trial will provide preliminary effectiveness data of this highly potential treatment for AKI in paediatric malaria (in particular for haemoglobinuric severe malaria) for a larger phase III trial.
Ethics and dissemination
Ethical and regulatory approvals have been granted by the Mbale Hospital Institutional Ethics Review Committee (MRRH-REC OUT 002/2019), Uganda National Council of Science and Technology (UNCST-HS965ES) and the National drug Authority (NDA-CTC 0166/2021). We will be disseminating results through journals, conferences and policy briefs to policy makers and primary care providers.
Trial registration number
ISRCTN84974248 .
Our study aimed at determining clinical factors associated with prolonged hospitalisation and death among children admitted with blackwater fever (BWF). We analysed 920 eligible records for the period January – December 2018 from Mbale and Soroti Regional Referral Hospitals in Eastern Uganda. The median hospitalisation was 3 (IQR: 2–5 days) days. Prolonged hospitalisation was in 251/920 (27.3%). Clinical features independently associated with prolonged hospitalisation included abdominal tenderness, body pain and mild fever. 29/920 (3.2%) died, of these 20 (69.0%) within 48 h of admission. Features of severity associated with mortality were noisy or interrupted breathing, tachypnoea, chest pain, convulsions, delayed capillary refill time (≥3 s), severe pallor, high fever (>38.5°C), altered level of consciousness, prostration and acidotic breathing.
Background : Owing to inadequate supplies of donor blood for transfusion in sub-Saharan Africa (sSA) World Health Organization paediatric guidelines recommend restrictive transfusion practices, based on expert opinion. We examined whether survival amongst hospitalised children by admission haemoglobin and whether this was influenced by malaria infection and/or transfusion.
Methods : A retrospective analysis of standardised clinical digital records in an unselected population of children admitted to a rural hospital in Kenya over an 8-year period. We describe baseline parameters with respect to categories of anaemia and outcome (in-hospital death) by haemoglobin (Hb), malaria and transfusion status.
Results : Among 29,226 children, 1,143 (3.9%) had profound anaemia (Hb <4g/dl) and 3,469 (11.9%) had severe anaemia (Hb 4-6g/d). In-hospital mortality rate was 97/1,143 (8.5%) if Hb<4g/dl or 164/2,326 (7.1%) in those with severe anaemia (Hb ≥4.0-<6g/dl). Admission Hb <3g/dl was associated with higher risk of death versus those with higher Hbs (OR=2.41 (95%CI: 1.8 - 3.24; P<0.001), increasing to OR=6.36, (95%CI: 4.21–9.62; P<0.001) in malaria positive children. Conversely, mortality in non-malaria admissions was unrelated to Hb level. Transfusion was associated with a non-significant improvement in outcome if Hb<3g/dl (malaria-only) OR 0.72 (95%CI 0.29 - 1.78), albeit the number of cases were too few to show a statistical difference. For those with Hb levels above 4g/dl, mortality was significantly higher in those receiving a transfusion compared to the non-transfused group. For non-malarial cases, transfusion did not affect survival-status, irrespective of baseline Hb level compared to children who were not transfused at higher Hb levels.
Conclusion : Although severe anaemia is common among children admitted to hospital in sSA (~16%), our data do not indicate that outcome is improved by transfusion irrespective of malaria status. Given the limitations of observational studies, clinical trials investigating the role of transfusion in outcomes in children with severe anaemia are warranted.
