Classification of anemia for gastroenterologists

Table 1 Etiopathogenic classification of anemia

Regenerative anemia

Acute or chronic bleeding

Hemolytic anemia

Hereditary (hemoglobinopathy, enzymopathy, membrane-cytoskeletal defects)

Acquired (autoimmune, mechanical destruction, toxic-metabolic, drugs, infectious, PNH, hypersplenism)

Hypo-regenerative anemia

Bone marrow failure caused by stem cell pathology

Quantitative disorder

Selective: erythroblastopenia (pure red cell aplasia)

Global: aplastic anemia

Qualitative disorder (dysmyelopoiesis)

Inherited: hereditary dyserythropoiesis

Acquired: myelodysplasia

Bone marrow infiltration

Leukemia, lymphoma, multiple myeloma

Solid tumors

Myelofibrosis

Thesaurismosis (Gaucher disease)

Inflammatory chronic diseases, microorganisms (Histoplasma, HIV)

Drugs, hypothyroidism, uremia

Erythropoietic factors deficiency

Iron

IDA

ACD

Cobalamin and folate

Megaloblastic anemia

Hormones: erythropoietin, thyroid hormones, androgens, steroids

PNH: Paroxysmal nocturnal hemoglobinuria; IDA: Iron-deficiency anemia; ACD: Anemia chronic disease.

Table 2 Morphological classification

Microcytic anemia (MCV < 82 fL)

IDA

Thalassemia

Non thalassemic conditions associated with microcytosis

ACD (e.g. rheumatoid arthritis, Hodgkin’s lymphoma, chronic infection, neoplasia)

Sideroblastic anemia (e.g. hereditary, lead poisoning)

Normocytic anemia (MCV = 82-98 fL)

Nutritional anemia (iron deficiency, cobalamin y/o folate)

Anemia of renal insufficiency

Hemolytic anemia

Red cell intrinsic causes: membranopathy, enzymopathy, hemoglobinopathy

Red cell extrinsic causes: immune-mediated, microangiopathic, associated with infection, chemical agent (spider venoms), metabolic

ACD

Primary bone marrow disorder

Causes that are intrinsic to hematopoietic stem cells: bone marrow aplasia (idiopathic, PNH, Fanconi syndrome), pure red cell aplasia (acquired, congenital, Diamond-Blackfan syndrome), myelodysplastic syndrome

Extrinsic causes: drugs, toxins, radiation, viruses, immune-mediated, bone marrow infiltration (metastatic and lymphoma)

Macrocytic anemia (MCV > 98 fL)

Drugs (hydroxyurea, zidovudine, methotrexate)

Nutritional (vitamin B12 and folate deficiency)

Drug-induced hemolytic anemia

Dyserythropoiesis, myelodysplastic syndrome, clonal hematologic disorder

Hereditary hematologic disorders

Mild macrocytosis (MCV = 100-110 fL)

Reticulocytes

Excess alcohol intake, liver disease, smoking

Hypothyroidism, Waldenström’s macroglobulinemia

Copper deficiency, bone marrow aplasia, erythroblastopenic anemia

Down syndrome

Chronic obstructive pulmonary disease

MCV: Mean corpuscular volume.

Table 3 Classification of anemia as RDW and MCV

	↓MCV	Normal MCV	↑MCV
Normal RDW	β-thalassemia	Normocytic	Bone marrow aplasia
	α-thalassemia
Increased RDW	Iron deficiency	Inflammatory anemia Hypothyroidism	Megaloblastic anemia

RDW: Red blood cell distribution width.

Table 4 Serum levels that differentiate ACD, IDA and mixed anemia

	ACD	IDA	Mixed anemia
Iron	↓	↓	↓
Transferrin	↓ or N	↑	↓
Transferrin saturation	↓	↓	↓
Ferritin	N or ↑	↓	↓ or N
Serum transferrin receptor	N	↑	N or ↑
Ratio: soluble receptor of transferrin/log ferritin	< 1	> 2	> 2
Cytokine levels	↑	N	↑

N: Normal; ↑: Increase; ↓: Decrease.

Table 5 Causes of megaloblastic anemia

Cobalamin deficiency

Poor diet

Deficiency of intrinsic factor

Pernicious anemia

Total or partial Gastrectomy

Ingestion of caustic (lye)

Functional defect of intrinsic factor

Alteration of ileal (microenvironment)

Insufficient pancreatic protease activity

Inactivation enzyme (Sd. Zollinger-Ellison)

Competition for cobalamin

Alteration of ileal mucosa

Acquired

Surgical resection or by-pass

Regional enteritis (Crohn’s disease)

Tropical esprue

Celiac disease, Tuberculosis

Lymphomatous infiltration

Induced by drugs

Congenital

Sd Immerslund-Gräsbeck

Congenital transcobalamin II deficiency or abnormality

Congenital methylmalonic acidemia and aciduria

Hemodialysis

Urinary losses (congestive heart failure)

Folate deficiency

Dietary

Old age, infancy, poverty, alcoholism, chronic invalids, psychiatrically disturbed, scurvy and kwashiorkor

Excess utilization or loss

Physiologic: pregnancy and lactation, prematurity

Pathologic: Hematologic diseases

Malignant diseases

Inflammatory disease

Metabolic disease

Excess urinary loss, congestive heart failure, active liver disease

Hemodialysis, peritoneal dialysis

Malabsorption

Congenital

Anti-folate drugs

Alcoholism

Tropical sprue, gluten-induced enteropathy

Extensive jejune resection, Crohn’s disease, partial gastrectomy, systemic bacterial infection, Whipple’s disease

Congenital abnormalities of folate metabolism

Cyclohydrolase, methionine synthetase

Combined deficit of folate and cobalamin

Celiac disease

Regional enteritis (Crohn’s disease)

Congenital disorder of DNA synthesis

Disorders of DNA synthesis induced by drugs

Anti-folate

Purine antagonists

Pyrimidine antagonists

Alkylating

Eritroleucemia

Table 6 Differential diagnosis of anemia from a gastrointestinal point of view

Gastrointestinal causes of anemia

Microcytic anemia

Iron deficiency

Decreased iron absorption

Frequent: Celiac disease, gastrectomy, H pylori colonization

Infrequent: Bowel resection, bacterial overgrowth

Occult gastrointestinal blood loss

Frequent: aspirin and nonsteroidal anti-inflammatory drug use, colonic carcinoma, gastric ulceration, angiodysplasia, inflammatory bowel diseases

Infrequent: esophagitis, esophageal carcinoma, gastric antral vascular carcinoma, small bowel tumors, ampullary carcinoma, Ancylomasta duodenale

Non-gastrointestinal blood loss

Frequent: menstruation, blood donation, ACD

Infrequent: Hematuria, epistaxis

Sideroblastic anemia (alcohol, lead, drugs), vitamin B6

ACD

Normocytic anemia

Frequent: ACD (liver disease, renal insufficiency, malignancy, nutritional deficiency, drug effects, alcoholism, recent trauma or surgery, iron deficiency

Infrequent: primary bone marrow disorder

Macrocytic anemia

Non-megaloblastic

Systemic disease:

Frequent: liver disease, alcoholism

Infrequent: primary bone marrow disease (myelodysplastic syndrome, aplastic anemia), metastatic infiltration, hemolytic anemia, hypothyroidism

Megaloblastic anemia

Vitamin B12 deficiency: pernicious anemia, gastrectomy, hereditary deficiency of intrinsic factor, inflammatory bowel disease, primary intestinal malabsorptive disorders, parasitic colonization, nutritional deficiencies

Folate deficiency: diet poor in folates, regional enteritis, Whipple’s disease, scleroderma, amyloidosis, increase requirements (liver disease, hemolytic anemia)

Antifolate drugs: methotrexate