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Diagnostic Algorithm for Anemia
These three flowcharts facilitate interpretation of the complete blood count for the diagnosis of the most common forms of anemia.
A table summarizing the main laboratory abnormalities for each type of anemia is also provided at the end of the page.
First parameter to assess
Hb below the reference limit for age, sex, and physiologic status
General diagnosis of anemia
Second parameter
MCV
Classification of anemia
MCV < 80 fLMicrocytic AnemiaImpaired hemoglobin synthesis
MCV 80-100 fLNormocytic AnemiaReduced production, blood loss, or hemolysis
MCV > 100 fLMacrocytic AnemiaMegaloblastic or nonmegaloblastic forms
< 80 fL
80-100 fL
> 100 fL
MCV < 80 fLMicrocytic AnemiaImpaired hemoglobin synthesis
First parameter to assessFerritin and transferrin saturation
Iron deficiencyAnemia Anemia of
Chronic Inflammation
Next evaluationHPLC or hemoglobin electrophoresis and peripheral blood smear
HereditaryThalassemias Structural
Hemoglobinopathy Alpha thalassemia Sideroblastic anemia
or lead toxicity
Low ferritin or, in the presence of inflammation, an overall iron profile consistent with absolute iron deficiency
Normal or high ferritin, reduced transferrin saturation, and inflammation: anemia of inflammation ± associated iron deficiency
Iron profile does not explain the anemia
Thalassemic profile
Structural variant
Nondiagnostic HPLC/electrophoresis with suspected alpha thalassemia
Suspected sideroblastic anemia or lead exposure
MCV 80-100 fLNormocytic AnemiaReduced production, blood loss, or hemolysis
MCV > 100 fLMacrocytic AnemiaMegaloblastic or nonmegaloblastic forms
First parameter to assessAbsolute or corrected reticulocyte count
Compensatory hyperproduction due toRed Blood Cell Loss or Destruction
Insufficient erythropoietic responseDeficiencies, kidney or inflammatory disease, endocrinopathies, or bone marrow disease
HemolyticAnemias Acute Hemorrhagic
Anemias
Etiologic assessment of reduced production
IneffectiveErythropoiesis Multilineage bone marrow
failure or aplasia Reduced erythroid
production
Liver disease, alcohol, medications,
other nonmegaloblastic causes
other nonmegaloblastic causes
increased
decreased or inappropriately normal
Hemolysis markers
Acute Setting
Assess MCV, B12, folate, kidney function, thyroid function, and inflammation
Deficiency or ineffective maturation
Associated cytopenias or suspected bone marrow failure
Isolated reticulocytopenia with preserved white blood cell and platelet counts
Nonmegaloblastic macrocytosis
Diagnostic Table
Below is a summary table that brings together all investigations and the main laboratory values useful for diagnosing the various forms of anemia described in this chapter.
On some devices, the table may be displayed only after clicking the “show table” button.
| Anemia | MCV | MCH and MCHC | Reticulocytes and RDW | Peripheral blood smear | Key complementary test | Advanced investigation |
|---|---|---|---|---|---|---|
| Reduced erythroid production: erythroblastopenias | Normal or increased | Normal or decreased | Low reticulocytes, normal or increased RDW | Nonspecific peripheral blood morphology | Low reticulocytes | Marked erythroid hypoplasia or aplasia with preservation of the other bone marrow lineages |
| Aplastic anemia | Normal or increased | Normal or decreased | Low reticulocytes, normal or increased RDW | Peripheral blood morphology generally nonspecific; immature cells are rare | Pancytopenia with reticulocytopenia | Hypocellular bone marrow replaced by adipose tissue |
| Pure red cell aplasia | Normal | Normal | Low reticulocytes, normal RDW | Peripheral blood morphology generally nonspecific | Low reticulocytes | Absent erythroblasts in bone marrow, with preserved granulopoiesis and megakaryopoiesis |
| Diamond-Blackfan anemia | Increased | Normal or increased MCH, generally normal MCHC | Low reticulocytes, normal or increased RDW | Macrocytosis; erythroid precursors are evaluated in the bone marrow | Low reticulocytes | Reduced erythroid precursors; a pathogenic variant in one of the DBA genes is present in a proportion of cases |
| Transient erythroblastopenia of childhood | Normal | Normal | Low reticulocytes, normal RDW | No specific abnormality | Low reticulocytes | Spontaneous recovery during follow-up, after exclusion of other causes |
| Postinfectious aplasia due to parvovirus B19 | Normal | Normal | Low reticulocytes, normal RDW | Nonspecific peripheral blood morphology | Low reticulocytes; serology and PCR according to immune status and clinical phase | Positive viral DNA, giant erythroblasts in bone marrow |
| Anemias due to ineffective erythropoiesis | Variable: increased in megaloblastic forms, normal or decreased in other forms | Variable according to the cause | Low or inappropriately normal reticulocytes, variable RDW | Morphology varies according to the cause; macro-ovalocytes in megaloblastic forms | Variable MCV, low or inappropriately normal reticulocytes | Cause-specific bone marrow findings; megaloblasts only in megaloblastic forms |
| Vitamin B12 deficiency anemia | Increased | Increased MCH, normal MCHC | Low reticulocytes, increased RDW | Macro-ovalocytes and hypersegmented neutrophils | Low serum B12 | Increased homocysteine and methylmalonic acid |
| Pernicious anemia | Increased | Increased MCH, normal MCHC | Low reticulocytes, increased RDW | Macro-ovalocytes and hypersegmented neutrophils | Positive intrinsic factor antibodies; parietal cell antibodies are less specific and supportive | Intrinsic factor antibodies and evaluation for autoimmune gastritis; Schilling test is obsolete |
| Folate deficiency anemia | Increased | Increased MCH, normal MCHC | Low reticulocytes, increased RDW | Macro-ovalocytes and hypersegmented neutrophils | Low serum folate | Increased homocysteine |
| Sideroblastic anemia | Frequently decreased in congenital forms, but sometimes normal; frequently normal or increased in acquired forms | Decreased MCH in microcytic/hypochromic forms; normal or decreased MCHC, with variable values in other forms | Low or normal reticulocytes, increased RDW | Poikilocytosis and variable findings; ring sideroblasts are identified in the bone marrow | Elevated ferritin | Ring sideroblasts in bone marrow |
| Anemia in myelodysplastic syndrome | Normal, increased, or decreased | Normal or increased MCH; generally normal MCHC | Low or normal reticulocytes, increased RDW | Dysplasia of one or more lineages; blasts may be normal or increased depending on the subtype | Bone marrow morphology, cytogenetics, and molecular analysis; blasts are not necessarily increased | Cytogenetics or specific mutations |
| Hemoglobin disorders | Variable; often decreased in thalassemias | Variable according to the defect | Variable reticulocytes and RDW | Variable morphology; microcytosis especially in thalassemias | Iron studies to exclude associated deficiency | HPLC or hemoglobin electrophoresis and targeted molecular analysis |
| Thalassemias | Often decreased; may be normal in silent forms | Both decreased or normal MCHC | Normal or increased reticulocytes, normal or increased RDW | Microcytosis, erythroblasts, target cells | Ferritin and serum iron generally normal in the absence of deficiency or iron overload | Hemoglobin fraction profile depends on the type of thalassemia; molecular diagnosis in indicated cases |
| β Thalassemia | Generally decreased; may be normal in silent β+ variants | MCH generally decreased in typical forms, MCHC normal or decreased; normal values are possible in silent variants | Normal or increased reticulocytes, normal or increased RDW | Microcytosis, erythroblasts, target cells | Ferritin and serum iron are variable; elevated in the presence of iron overload | Hemoglobin fraction profile depends on genotype: HbA2 is often increased in β-thalassemia trait, HbF is variable; HBB analysis in indicated cases |
| α Thalassemia | Decreased in trait and HbH disease; normal or nearly normal in silent carriers | MCH is decreased in trait and HbH disease, with generally normal MCHC; normal values are possible in silent carriers | Increased or normal reticulocytes, normal or increased RDW | Microcytosis and target cells in overt forms; Heinz bodies (HbH) with supravital staining | Ferritin and serum iron are generally normal in the absence of deficiency or overload; elevated values are possible in iron overload | HbH present in HbH disease; α-globin genotype analysis |
| δβ Thalassemia | Decreased | Both decreased or normal MCHC | Normal or increased reticulocytes, normal or increased RDW | Microcytosis, target cells | Increased HbF | Genetic analysis, specific electrophoretic profile |
| γδβ Thalassemia | Decreased | Both decreased or normal MCHC | Normal or increased reticulocytes, normal or increased RDW | Microcytosis, target cells | Variable HbA, HbA2, and HbF; after the neonatal period, the profile may be nonspecific or close to usual values | Genetic analysis of the beta-globin cluster; electrophoresis/HPLC are not always diagnostic |
| εγδβ Thalassemia | Decreased | Both decreased or normal MCHC | Normal or increased reticulocytes, normal or increased RDW | Microcytosis, target cells | Hemoglobin fraction analysis, not always diagnostic | Targeted genetic analysis |
| Composite Thalassemias and Mixed Phenotypes | Decreased | Both decreased or normal MCHC | Variable reticulocytes, normal or increased RDW | Target cells, microcytosis | Elevated or normal ferritin | Complex electrophoretic profiles, extended genetic testing |
| Regulatory Thalassemias and Rare Forms | Decreased | Both decreased or normal MCHC | Normal or increased reticulocytes, normal or increased RDW | Target cells, microcytosis | Normal or elevated ferritin | Targeted sequencing, rare Hb variants |
| Sickle cell disease | Variable: may be decreased with iron deficiency or α-thalassemia, normal, or increased because of reticulocytosis and/or hydroxyurea therapy | Variable MCH and MCHC; MCH typically increases during hydroxyurea therapy | Increased reticulocytes, increased RDW | Sickle cells, target cells | Identification and quantification of HbS by HPLC or electrophoresis | HbS on electrophoresis, HBB genetic testing |
| Unstable hemoglobins | Variable; may increase because of reticulocytosis and may be decreased in some phenotypes | Variable according to the variant and degree of reticulocytosis | Increased reticulocytes, increased RDW | Heinz bodies on supravital staining, bite cells, and blister cells | Heinz bodies and stability tests may be positive, with variable sensitivity | Stability testing as a supportive test; confirmation by molecular analysis of globin genes |
| Iron deficiency anemia | Normal in the early stages, progressively decreased in established disease | They may be normal in the early stages; MCH and often MCHC decrease as the deficiency progresses | Low or inappropriately normal reticulocytes, RDW often increased | Normocytosis may occur in the early stages; microcytosis, hypochromia, and poikilocytosis in established disease | Low ferritin, low serum iron | Increased transferrin, evaluation for chronic blood loss |
| Anemia due to malnutrition | Variable according to the predominant deficiency | Variable according to the predominant deficiency | Low or inappropriately normal reticulocytes, variable RDW | Variable: microcytosis, macrocytosis, or a mixed pattern | Ferritin is decreased only in iron deficiency | Evaluation for multiple nutritional deficiencies and assessment of nutritional status |
| Anemia due to malabsorption | Variable according to the predominant deficiency | Variable according to the predominant deficiency | Low or inappropriately normal reticulocytes, variable RDW | Microcytosis with iron deficiency; macrocytosis with vitamin B12 or folate deficiency; mixed patterns are possible | Iron studies, vitamin B12, and folate according to the clinical suspicion | Evaluation for the cause of malabsorption and targeted gastroenterologic investigations |
| Acute posthemorrhagic anemia | Normal (initially) | Both normal | Increased reticulocytes after 3-5 days, increased RDW | Polychromatophilia, normocytosis | Delayed reticulocytosis | Identification of the bleeding site, signs of shock |
| Anemia of chronic disease | Normal or decreased | Both normal or decreased | Low or normal reticulocytes, normal or slightly increased RDW | Normocytosis or microcytosis, mild hypochromia | Normal or elevated ferritin, low serum iron | Elevated inflammatory markers; assess for possible associated iron deficiency |
| Anemia of chronic inflammation | Normal or decreased | Both normal or decreased | Low or normal reticulocytes, normal or increased RDW | Normocytosis, microcytosis | Normal or increased ferritin, low serum iron | Elevated CRP and ESR; iron studies consistent with inflammation and assessment for concomitant absolute iron deficiency |
| Anemia of kidney disease | Generally normal; may decrease with concomitant iron deficiency or increase because of other associated causes | Normal or decreased | Low or inappropriately normal reticulocytes; normal or increased RDW | Normocytosis, mild hypochromia | Creatinine, eGFR, complete blood count, and iron status | Assessment according to the stage of kidney disease, iron status, and indications for erythropoiesis-stimulating agents |
| Anemia due to endocrinopathies | Variable according to the endocrinopathy: decreased, normal, or increased | Variable according to the endocrinopathy and associated deficiencies | Reticulocytes are generally low or normal; RDW varies according to the cause | Normocytosis, microcytosis, or macrocytosis according to the cause | Endocrine tests targeted to the clinical suspicion; abnormalities depend on the specific endocrinopathy | Treatment of the endocrinopathy may improve the anemia; the response depends on etiology and comorbidities |
| Anemia associated with malignancy | Normal, decreased, or increased | Normal or decreased | Low or normal reticulocytes, normal or increased RDW | Normocytosis or macrocytosis, with malignant cells sometimes present | Clinical assessment and investigations targeted to the suspected malignancy; tumor markers are not a general screening test for anemia | If there are associated cytopenias, a leukoerythroblastic picture, or suspected infiltration: bone marrow evaluation |
| Hemolytic anemias | Normal or increased because of reticulocytosis; may be decreased depending on the cause or associated conditions | Variable according to the cause | Increased reticulocytes, increased RDW | Morphology depends on the etiology: polychromatophilia, spherocytes, schistocytes in microangiopathic forms, or other specific abnormalities | Increased indirect bilirubin and LDH, low haptoglobin | Coombs testing, enzyme assays, genetic testing |
| Autoimmune hemolytic anemia | Normal or increased | Variable MCH; MCHC normal or increased in the presence of spherocytosis | Increased reticulocytes, increased RDW | Spherocytes and polychromasia; schistocytes are not typical of AIHA | Direct antiglobulin test generally positive; a small proportion of AIHA may be DAT negative | Increased indirect bilirubin and LDH, low haptoglobin |
| Paroxysmal nocturnal hemoglobinuria | Variable: normal or increased; may be decreased with concomitant iron deficiency caused by chronic urinary iron loss | Generally normal; may decrease with concomitant iron deficiency | Increased reticulocytes in hemolytic forms; normal, decreased, or inappropriately normal if bone marrow failure coexists; variable RDW | Peripheral blood findings are often nonspecific; polychromasia varies according to hemolysis and bone marrow function | Reduced/absent FLAER and GPI-anchored markers on granulocytes and monocytes; complementary red blood cell analysis | Flow cytometry with FLAER and CD55/CD59; PIGA analysis only in selected cases |
| Microangiopathic hemolytic anemia | Normal or increased because of reticulocytosis; may be decreased because of red blood cell fragmentation or associated conditions | Normal or decreased | Increased reticulocytes, increased RDW | Schistocytes, polychromatophilia | Platelets often decreased, LDH increased | ADAMTS13 activity <10% in TTP; evaluation of other underlying causes according to the clinical picture |
| Hereditary spherocytosis | Normal or decreased | Increased MCHC | Increased reticulocytes, increased RDW | Spherocytes, polychromatophilia | Reduced EMA binding test; ektacytometry or osmotic fragility as supportive tests depending on availability | Genetic testing in selected or complex cases |
| Hereditary elliptocytosis | Normal or decreased | Normal or decreased | Normal reticulocytes in nonhemolytic forms, increased in the presence of hemolysis; variable RDW | Elliptocytes, polychromatophilia | Increased elliptocytes on peripheral smear; reticulocytosis if hemolysis is present | Mutations in SPTA1, SPTB, EPB41, or GYPC |
| Pyruvate kinase deficiency | Normal or increased | Normal or decreased | Increased reticulocytes, increased RDW | Polychromasia and possible echinocytes; Howell-Jolly bodies especially after splenectomy | Reduced pyruvate kinase activity | PKLR genetic testing |
| G6PD deficiency | Normal or increased | Normal or decreased | Increased reticulocytes, increased RDW | Bite cells, blister cells, and Heinz bodies on supravital staining | Reduced G6PD activity | Quantitative G6PD assay, repeated outside the acute episode if necessary; genetic testing in selected cases |
| Other red blood cell membrane disorders | Variable; may be increased in stomatocytosis and decreased in other membrane disorders | Variable; MCHC may increase in dehydrated forms and decrease in overhydrated forms | Increased reticulocytes, increased RDW | Anisocytosis, polychromatophilia, poikilocytosis | Specific red blood cell membrane tests | Specific genetic testing (band 3, spectrin, etc.) |
| Iatrogenic anemia | Variable | Variable | Variable reticulocytes and RDW | Abnormalities depend on the cause | History of exposure to medications/procedures | Exclusion of other causes, resolution after discontinuation |
| Drug-induced anemia | Variable | Variable | Variable reticulocytes and RDW | Pattern of hemolysis/hypoproliferation or morphologic abnormalities | Temporal association with the medication | Recovery after discontinuation; in indicated cases, specialized immunohematologic testing for drug-dependent antibodies |
| Anemia in pregnancy | Variable according to the cause: decreased, normal, or increased | Variable according to the cause | Reticulocytes and RDW vary according to the cause | Variable morphology; iron deficiency must be demonstrated and cannot be assumed from pregnancy alone | Variable ferritin and serum iron; ferritin is decreased in iron deficiency, whereas serum iron may also decrease in other settings, particularly in the presence of inflammation | Treatment directed at the cause; iron therapy if deficiency is documented; preventive supplementation according to obstetric recommendations |
| Anemia in children | Normal, decreased, or increased | Normal, decreased, or increased | Variable reticulocytes and RDW | Variable depending on the etiology | Complete blood count with age-appropriate reference values and reticulocyte count; further tests according to the pattern | Targeted diagnosis based on the clinical picture and specific tests |
| Anemia in older adults | Normal, decreased, or increased | Normal, decreased, or increased | Variable reticulocytes and RDW | Normocytosis is common, with variable RDW | Iron studies, kidney function, inflammatory markers, vitamin B12, and folate according to the clinical picture | Systematic evaluation for multiple causes; oncologic assessment guided by history, alarm features, and age-appropriate screening |
| Post-transfusion anemia | Variable according to the etiology | Variable according to the etiology | Variable reticulocytes and RDW | Variable peripheral blood morphology; delayed hemolytic reactions may show findings consistent with hemolysis, depending on the mechanism | Red blood cell antibodies may be present | Direct antiglobulin test (DAT), alloantibody screening, and eluate when indicated |
- Hoffbrand AV, Higgs DR, Keeling DM, Mehta AB, eds. Postgraduate Haematology. 7th ed. Wiley-Blackwell; 2016.
- McKenzie SB, Landis-Piwowar KR, Williams JL. Clinical Laboratory Hematology. 4th ed. Pearson; 2020.
- World Health Organization. Guideline on haemoglobin cutoffs to define anaemia in individuals and populations. Geneva: WHO; 2024.
- Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C. Laboratory diagnosis of iron-deficiency anemia: an overview. J Gen Intern Med. 1992;7(2):145-153.
- Bessman JD, Gilmer PR Jr, Gardner FH. Improved classification of anemias by MCV and RDW. Am J Clin Pathol. 1983;80(3):322-326.
- Van Vranken M. Evaluation of Microcytosis. Am Fam Physician. 2010;82(9):1117-1122.
- Bain BJ, Bates I, Laffan MA, eds. Dacie and Lewis Practical Haematology. 12th ed. Elsevier; 2016.
- Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832-1843.
- Diagnostic approach to anemia in adults. UpToDate. Accessed July 30, 2026.
- Cascio MJ, DeLoughery TG. Anemia: Evaluation and Diagnostic Tests. Med Clin North Am. 2017;101(2):263-284. doi:10.1016/j.mcna.2016.09.003.
References
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