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Background Severe anemia is common and frequently fatal for hospitalized patients in limited-resource settings. Lack of access to low-cost, accurate, and rapid diagnosis of anemia impedes the delivery of life-saving care and appropriate use of the limited blood supply. The WHO Haemoglobin Colour Scale (HCS) is a simple low-cost test but frequently inaccurate. AnemoCheck-LRS (limited-resource settings) is a rapid, inexpensive, color-based point-of-care (POC) test optimized to diagnose severe anemia. Methods Deidentified whole blood samples were diluted with plasma to create variable hemoglobin (Hb) concentrations, with most in the severe (≤ 7 g/dL) or profound (≤ 5 g/dL) anemia range. Each sample was tested with AnemoCheck-LRS and WHO HCS independently by three readers and compared to Hb measured by an electronic POC test (HemoCue 201+) and commercial hematology analyzer. Results For 570 evaluations within the limits of detection of AnemoCheck-LRS (Hb ≤ 8 g/dL), the average difference between AnemoCheck-LRS and measured Hb was 0.5 ± 0.4 g/dL. In contrast, the WHO HCS overestimated Hb with an absolute difference of 4.9 ± 1.3 g/dL for samples within its detection range (Hb 4–14 g/dL, n = 405). AnemoCheck-LRS was much more sensitive (92%) for the diagnosis of profound anemia than WHO HCS (22%). Conclusions AnemoCheck-LRS is a rapid, inexpensive, and accurate POC test for anemia. AnemoCheck-LRS is more accurate than WHO HCS for detection of low Hb levels, severe anemia that may require blood transfusion. AnemoCheck-LRS should be tested prospectively in limited-resource settings where severe anemia is common, to determine its utility as a screening tool to identify patients who may require transfusion.

Severe anemia is common in limited-resource settings (LRS) of sub-Saharan Africa, affecting up to 30% of hospitalized patients and associated with high mortality rates. The World Health Organization (WHO) recommends blood transfusion for patients with hemoglobin (Hb) concentration Lack of timely transfusions for children with severe anemia has been associated with significant increase in mortality in several studies within Africa. However, accurate diagnosis of anemia is often difficult or impossible in LRS due to lack of equipment, inadequate replenishment of reagents, poor maintenance or calibration of existing equipment, inadequately trained laboratory personnel, or unreliable and inconsistent access to electricity. A recent publication (Opoka RO et al. BMC Health Serv Res2018) examining transfusion practices in Uganda demonstrated that over half of blood transfusions were administered inappropriately, either without a Hb measurement or with Hb values for which transfusion would not be recommended. The WHO Haemoglobin Colour Scale (HCS), a simple, rapid, point-of-care (POC) test requiring a single drop of blood on filter paper, was developed in an effort to improve the accurate diagnosis of anemia in settings where more definitive laboratory testing is not available. There have been many published reports of the HCS with heterogeneous results, including a recent meta-analysis demonstrating significant variation in sensitivity for the detection of anemia and severe anemia, defined as Hb ≤11 g/dL and Hb ≤7 g/dL respectively (36-76%, Marn H. Lancet Glob Health 2016). The lower limit of the HCS is 4 g/dL, and there is very limited data on its accuracy to diagnose severe anemia requiring transfusion (Hb ≤5 g/dL). The AnemoCheckTMis a rapid, inexpensive, color-based POC test initially designed to diagnose anemia in higher-resource settings, and subsequently modified for use in limited-resource settings (Tyburski et al. J Clin Invest 2014). Based on mixed results both in controlled settings within the US and in the field in Tanzania, AnemoCheck was adapted to focus on its ability to detect severe anemia warranting transfusion. The newly modified AnemoCheck-LRS test allows identification of Hb ranging from 2-8 g/dL, with sharp color changes especially differentiable at the clinically relevant 5 g/dL threshold (Figure 1) to allow accurate diagnosis of clinically meaningful severe anemia in settings where this is common. We prepared and tested 200 samples of varying Hb concentration, each of which was evaluated independently by three separate readers, for a total of 1200 evaluations. By standard CBC measurement, the 200 samples had a mean (±SD) Hbof 5.2±1.9 g/dL (range 1.7 to 10.1 g/dL). Of the 570 samples with Hb ≤8 g/dL (upper limit of AnemoCheck), the absolute difference between AnemoCheck and the gold standard CBC Hb was 0.5±0.4 g/dL (actual difference 0.2±0.7 g/dL). The WHO HCS was inaccurate, with Hb readings consistently higher than the CBC Hb, and an absolute and actual difference of 4.9±1.3 g/dL for samples within the detection range of the HCS (4-14 g/dL, n=405). Table 1 summarizes the ability of both tests to diagnose severe anemia (Hb ≤5 g/dL), demonstrating the accuracy of AnemoCheck-LRS. Furthermore, given that most readings that missed the diagnosis of anemia were within 1 g/dL of actual Hb, if 6 g/dL was used as the screening threshold to identify patients who need a more definitive diagnosis, the sensitivity of AnemoCheck increased to 99%. This study demonstrates that the new AnemoCheck-LRS assay is an accurate POC test to diagnosis very severe anemia in a controlled laboratory setting. The widely cited WHO HCS performed poorly, with a stark inability to diagnose very severe anemia in most cases. This study provides important preliminary data to support follow-up field studies that will use AnemoCheck-LRS to diagnose severe anemia, with the goal of the assay serving as a primary screening test for rapid and accurate diagnosis in settings where laboratory capacity and resources are limited. Disclosures Tyburski: Sanguina, LLC: Employment, Equity Ownership. Ware:Bristol Myers Squibb: Research Funding; Nova Laboratories: Consultancy; Biomedomics: Research Funding; Global Blood Therapeutics: Other: advisory board; Addmedica: Research Funding; Agios: Other: advisory board; Novartis: Membership on an entity's Board of Directors or advisory committees.