*1.1. Background*

Anemia is a blood disorder in which the number of red blood cells is inadequate to carry oxygen to human tissues and organs. It affects about a third of the global population, being the most common blood disorder according to the epidemiological results [1–3]. Each different form of this condition has its specific underlying causes. The process of erythrocyte production in the blood involves bone marrow and erythropoietin, a hormone produced by the kidneys, which regulates the process of erythropoiesis, favoring a constant rate of change in the number of erythrocytes in the blood [4]. Adequate production of red blood cells prevents conditions such as anemia and tissue hypoxia. To promote normal erythropoiesis, correct hemoglobin synthesis is required. Hemoglobin, the iron-containing protein, represents the predominant protein found in erythrocytes, responsible for transporting oxygen from the lungs to the other tissues. Anemia caused by deficiencies of the aforementioned factors results in production patterns of abnormal and different erythrocytes [5]. Diagnosing anemia requires in most cases a complete blood count (CBC) to check different properties, including hemoglobin and hematocrit levels. Each physiological need depends on several factors, such as gender, age, different stages of pregnancy and altitude. The thresholds presented in Table 1 are used to diagnose anemia in individuals in a screening or clinical setting according to World Health Organization diagnostic guidelines [6].

**Table 1.** Hemoglobin (Hb) thresholds used to define anemia living at sea level according to the World Health Organization guidelines [6].


There has always been a worldwide interest in providing simple, cheap and robust procedures to measure hemoglobin without requiring specialized primary health-care workers or medical laboratories [7]. In response to this need, WHO developed the hemoglobin color scale (HCS) in 2001. It consists of a small card of six shades of red from lighter to darker representing a hemoglobin g/dL concentration from 4 to 14 with a step size of 2 g/dL. The specificity of this method has been disputed in literature; for instance, in 2005 14 studies mostly reported a high sensitivity for detecting anemia (75–97%) [8]. Nevertheless, what is crucial about HCS is its potential for opening the way to different approaches requiring a mixture of expertise from different disciplines, such as computer science, in the future. Like other diagnostic-clinical and analytical-laboratory medical disciplines that are beginning to make extensive use of image, sound or signal analysis; and machine and deep learning techniques [9–18], it is worthwhile to invest in research and development of technologies such as those we deal with in this paper, with the dual purpose of significantly reducing the costs borne by the national health systems and powering the healthcare and medical services that would be exempted from a considerable amount of practically useless activities. Since the importance of the objective evaluation of the pallor of the conjunctiva has been understood, a lot has been done. Numerous researchers have worked to develop methods, techniques and devices to make the estimate of the level of hemoglobin or the determination of the condition of severe anemia, in a non-invasive way, as reliable as possible. We will report a summary of this path in the section "Related Works."
