Hemoglobin measurement in venous blood compared with pooled and single-drop capillary blood: a method-comparison study in a controlled and survey setting in Uganda among children and women.

BACKGROUND: Standard practice for estimating anemia in population-based surveys is to use a point-of-care device to measure hemoglobin (Hb) in a single drop of capillary blood. Emerging evidence points to larger than expected differences in Hb concentration depending on the blood source. OBJECTIVE: We evaluated use of different blood sources to measure Hb with a HemoCue 201+ analyzer compared with the reference method of venous blood tested with a Sysmex XN-450 hematology analyzer. METHODS: Hb concentration in venous, pooled capillary, and single-drop capillary blood were collected in controlled (laboratory) and survey (Demographic Health Survey-8 pilot) settings in Uganda among children 6-59 mo and nonpregnant women 15-49 y. Venous and capillary blood collected from the same individual was tested using a HemoCue 201+ analyzer and the venous blood was also measured with a Sysmex XN-450 hematology analyzer. Agreement between measures was estimated using Lin's concordance correlation coefficient, Bland-Altman plots, and Deming regression. Means and prevalences were compared using paired t-tests and McNemar's tests, respectively. RESULTS: The limits of agreement between Hb measured using a HemoCue 201+ analyzer and the reference method were lowest for venous (1.1-1.96 g/dL), followed by pooled capillary (1.45-2.27 g/dL), and single-drop capillary blood (2.23-3.41 g/dL). Mean differences were <0.5 g/dL across comparators. There were statistically significant differences in Hb concentration from both types of capillary blood. Anemia prevalence was lower in pooled capillary blood compared with the reference method. CONCLUSIONS: The variability of Hb measured by capillary blood using the HemoCue 201+ analyzer is higher than venous blood but the extent to which this impacts the validity of Hb and anemia estimates requires further exploration. Future research is also needed to evaluate the implications of using venous compared with capillary blood in population-based surveys. This trial was registered at clinicaltrials.gov (NCT05059457).

Perspective: Emerging evidence and critical issues with the use of single-drop capillary blood for the measurement of hemoglobin concentration in population-level anemia surveys.

Accurate and precise measurement of hemoglobin concentration is critical for reliable estimations of anemia prevalence at the population-level. When systematic and/or random error are introduced in hemoglobin measurement, estimates of anemia prevalence might be significantly erroneous and, hence, limit their usefulness. For decades, single-drop capillary blood has been the most common blood source used for the measurement of hemoglobin concentration in surveys, especially in low- and middle-income countries. Here, we highlight historical and emerging evidence that single-drop capillary blood introduces a high degree of random error (variability) to hemoglobin estimates, leading to less reliable estimates of anemia prevalence at the population-level. At present, the best practice is to collect and use venous blood for measurement of hemoglobin with an automated hematology analyzer, following standard operating procedures and quality assurance measures. Where use of an automated analyzer is not possible, the analysis of venous blood in a point-of-care hemoglobinometer by trained phlebotomists or specimen collectors should be considered. A forthcoming systematic review will provide additional evidence on the accuracy and precision of single-drop capillary blood for hemoglobin assessment. In the meantime, we raise caution when using single-drop capillary blood for hemoglobin measurement as it can result in inaccurate hemoglobin estimates and less reliable anemia prevalence estimates.