TABLE 4.

Some of the basic indicators to be considered for the differential diagnosis of anemia

Etiology of anemia	Indicators to address iron metabolism	Determinants	Other indicators to identify cause
Iron and other nutritional deficiencies	Hemoglobin concentration + Ferritin Serum iron TIBC sTfR sTfR:SF Tf saturation Hepcidin RBC ZPP CHr CBC CRP/AGP Blood smear Bone marrow aspiration (rarely)	Iron, copper, zinc, vitamins A, B2, B6, B9, B12, C, D, and E deficiencies Dietary habits Increased loss of blood Increased requirements	Serum/plasma/urine/hair concentrations of the suspected micronutrient/vitamin deficiency 24-h food consumption recall questionnaire Menstrual losses Anthropometric status/nutritional status Cooking practices that might influence micronutrient absorption Comprehensive questionnaire on dietary habits, contraception, blood losses (menstrual, gastrointestinal), birth spacing, education/social level, genetic background
Infection and inflammation	Hemoglobin concentration + Ferritin Serum iron TIBC sTfR sTfR:SF Tf saturation Hepcidin RBC ZPP CHr CBC CRP/AGP Blood smear Bone marrow aspiration	Malaria, tuberculosis, soil-transmitted helminth infections, schistosomiasis, HIV, Helicobacter pylori infection, cancer, low-grade inflammation	Serum cytokines and inflammation markers (CRP/AGP) Microbiological detection of infection (bacteria/virus/parasite, chronic conditions) Malaria microscopic examination of stained thin or thick blood smears or rapid diagnostic tests, or molecular diagnostic methods (PCR) Stool parasitic count for soil-transmitted helminth infections Schistosoma eggs in feces and urine Blood test also possible Liver function, coagulation profile, hemolysis profile, serum creatinine Comprehensive questionnaire and clinical examination
Genetic red cell disorders	Hemoglobin concentration + Ferritin Serum iron TIBC sTfR sTfR:SF Tf saturation Hepcidin RBC ZPP CHr CRP/AGP Blood smear	Sickle cell anemia Thalassemia Glucose-6-phosphate dehydrogenase deficiency	Complete blood count (CBC) Genotyping for alpha thalassemia, and hemoglobin electrophoresis for beta thalassemia Electrophoresis of hemoglobin for HbS G6PD enzyme activity Clinical history and examination
Social, behavioral, and environmental determinants	Hemoglobin concentration + Ferritin Serum iron TIBC sTfR sTfR:SF Tf saturation Hepcidin RBC ZPP CHr CBC CRP/AGP Blood smear Bone marrow aspiration	Water hygiene and sanitation Economic, political, institutional capacity/resources Climatic/environmental conditions Multiple pregnancies Educational level Religion/cultural beliefs Access to care/services	Access to safe drinking water Data on social, economic, and health statistics Community/women empowerment assessment Access to health facilities Availability of antenatal care Deworming, WASH, family planning, and/ormalaria prevention campaigns Ongoing food fortification, micronutrients supplementation programs Food security Comprehensive questionnaire

Abbreviations: CBC, complete blood count; CHr, reticulocyte hemoglobin content; CRP/AGP, C-reactive protein, alpha-1-acid glycoprotein; RBC ZPP, red blood cells protoporphyrin; sTfR, soluble transferrin receptor; sTfR:SF, soluble transferrin receptor to ferritin ratio; TIBC, total iron binding capacity; WASH, water access, sanitation, and hygiene.