Preanalytic and analytic factors affecting the measurement of haemoglobin concentration: impact on global estimates of anaemia prevalence

Abstract

The accuracy of haemoglobin concentration measurements is crucial for deriving global anaemia prevalence estimates and monitoring anaemia reduction strategies. In this analysis, we examined and quantified the factors affecting preanalytic and analytic variation in haemoglobin concentrations. Using cross-sectional data from three field studies (in children, pregnant and nonpregnant women), we examined the difference in haemoglobin concentration between venous-drawn and capillary-drawn blood measured by HemoCue (ie, preanalytic) and modelled how the bias observed may affect anaemia prevalence estimates in population surveys and anaemia public health severity classification across countries. Using data from an international quality assurance programme, we examined differences due to instrumentation from 16 different haematology analyzers (ie, analytic). Results indicated that capillary and venous haemoglobin concentrations are not in agreement (bias +5.7 g/L (limits of agreement (LoA) −11.2, 22.6) in preschool age children; range from −28 g/L to +20 g/L in pregnant women; bias +8.8 g/L (LoA −5.2, 22.9) in non-pregnant women). The bias observed could introduce changes in population survey estimates of anaemia of up to −20.7 percentage points in children and −28.2 percentage points in non-pregnant women after venous adjustment. Analytic variation was minimal and unlikely to influence the diagnosis of anaemia. These findings suggest that global estimates of anaemia prevalence derived from capillary haemoglobin, as they often are, may be inaccurate and lead to erroneous public health severity classification, but that point-of-care, or other, instruments should not introduce variation if properly used.

Blood Draw Site and Analytic Device Influence Hemoglobin Measurements

“…Similar results of elevated capillary Hb were seen using HemoCue 201+ or HemoCue 301, so that capillary Hb levels were 2-4% higher than venous samples regardless of measurement device. Several previous studies have compared Hb levels from capillary and venous blood, and our findings are consistent with the majority of these showing elevated Hb levels in capillary samples [Chen 1992; Neufeld 2002; Cable 2012; Patel 2013; Chaudhary 2017; Neufeld 2019; Whitehead 2019; Larson 2021]. The reasons for the elevated capillary Hb values are not understood, but may include different flow characteristics of a colloidal suspension (blood) through vessels of disparate diameters, impact of interstitial fluid dynamics on capillary beds, and changes in vascular physiology due to sex or age [Neufeld 2019].…”

“…So regardless of blood draw location, the Hb values were 1-4% higher when measured by HemoCue 301 compared to the ADVIA-2120. Several previous studies have compared Hb measurements using automatic hematology analyzers to POC devices, and our findings are consistent with many showing elevated Hb levels in some HemoCue models under specific conditions [Paiva 2004; Karakochuk 2015; Chaudhary 2017; Boghani 2017; Hinnouho 2017; Whitehead 2017; Karakochuk 2019; Whitehead 2019], while other studies did not note significant differences [Larson 2021]. The reasons for the elevated Hb values in blood measured in specific POC devices are not clear, but may include performance differences between the Hb measurement instruments, inherent variability in capillary blood samples, and differences in technique with distinct operators and protocols [Karakochuk 2019].…”

“…Yet the current Hb thresholds for anemia are still based on venous blood read on automatic hematology analyzers, so it is important to quantify any bias inherent in capillary blood readings by POCs. A number of excellent studies have looked at this question, and the majority have noted small but significant differences in Hb values from these methods [Sari 2001; Cable 2012; Karakochuk 2015; Karakochuk 2019; Neufeld 2019; Whitehead 2019; Larson 2021]. However, those reports evaluated Hb data from large populations and/or field research with multiple complex analytical variables that are difficult to minimize, making it challenging to assign specific bias on any one parameter.…”

“…Larson and colleagues even concluded that “capillary and venous samples cannot be used interchangeably for the measurement of haemoglobin concentration and estimation of anaemia prevalence given the bias and imprecision when comparing the two. These findings call the global estimates of anaemia prevalence, which have been predominantly generated using capillary measurements, into doubt” [Larson 2021].…”

“…Given the importance placed on Hb measurement, it is perhaps surprising that the collection and processing of blood for Hb measurement is not a standardized procedure, varying in a number of analytical variables that include how blood samples are drawn and processed, and what method is used for Hb measurement. This has led to concerns about the comparison of Hb values between different studies and best practices for future studies [Sari 2001; Cable 2012; Karakochuk 2015; Karakochuk 2019; Neufeld 2019; Whitehead 2019; Larson 2021].…”