CLASSIFICATION OF ANEMIA

I.

ABSOLUTE ANEMIA (DECREASED RED CELL VOLUME)

A. Decreased red cell production
1. Acquired
a. Pluripotential stem cell failure
1) Aplastic anemia (see Chap. 34)
a)
Radiation induced
b) Drugs and chemicals (chloramphenicol, benzene, etc.)
c) Viruses (hepatitis, Epstein-Barr virus, etc.)
d) Idiopathic
2) Anemia of leukemia and of myelodysplastic syndromes (see Chaps.
88, 89, and 93)
3) Anemia associated with marrow infiltration (see Chap. 44)
4) Postchemotherapy (see Chap. 20)
b. Erythroid progenitor cell failure
1) Pure red cell aplasia (parvovirus B19 infection, drugs, associated with
thymoma, autoantibodies, etc. [see Chap. 35])
2) Endocrine disorders (see Chap. 38)
3) Acquired sideroblastic anemia (drugs, copper deficiency, etc. [see
Chaps. 58 and 88])
c. Functional impairment of erythroid and other progenitors due to nutritional
and other causes
1) Megaloblastic anemias (see Chap. 41)
a) B12 deficiency
b) Folate deficiency
c) Acute megaloblastic anemia because of nitrous oxide (N2O)
d) Drug-induced megaloblastic anemia (pemetrexed,
methotrexate, phenytoin toxicity, etc.)
2) Iron-deficiency anemia (see Chap. 42)
3) Anemia resulting from other nutritional deficiencies (see Chap. 43)
4) Anemia of chronic disease and inflammation (see Chap. 37)
5) Anemia of renal failure (see Chap. 36)
6) Anemia caused by chemical agents (lead toxicity [see Chap. 51])
7) Acquired thalassemias (seen in some clonal hematopoietic disorders
[see Chaps. 47 and 88])
8) Erythropoietin antibodies (see Chap. 35)
2.Hereditary
a. Pluripotential stem-cell failure (see Chap. 34)
1) Fanconi anemia
2) Shwachman syndrome
3) Dyskeratosis congenital
b. Erythroid progenitor cell failure
1) Diamond-Blackfan syndrome (see Chap. 34)
2) Congenital dyserythropoietic syndromes (see Chap. 39)
c. Functional impairment of erythroid and other progenitors from nutritional
and other causes
1) Megaloblastic anemias (see Chap. 41)
a) Selective malabsorption of vitamin B12 (Imerslund-Grsbeck
disease)
b) Congenital intrinsic factor deficiency
c) Transcobalamin II deficiency
d) Inborn errors of cobalamin metabolism (methylmalonic
aciduria, homocystinuria, etc.)

e) Inborn errors of folate metabolism (congenital folate

malabsorption, dihydrofolate deficiency, methyltransferase
deficiency, etc.)
2) Inborn purine and pyrimidine metabolism defects (Lesch-Nyhan
syndrome, hereditary orotic aciduria, etc.)
3) Disorders of iron metabolism (see Chap. 42)
a) Hereditary atransferrinemia
b) Hypochromic anemia caused by divalent metal transporter
(DMT)-1 mutation
4) Hereditary sideroblastic anemia (see Chap. 58)
5) Thalassemias (see Chap. 47)
B. Increased red cell destruction
1.Acquired
a. Mechanical
1) Macroangiopathic (march hemoglobinuria, artificial heart valves [see
Chap. 50])
2) Microangiopathic (disseminated intravascular coagulation [DIC];
thrombotic thrombocytopenic purpura [TTP]; vasculitis [see Chaps.
50, 123, and 130])
3) Parasites and microorganisms (malaria, bartonellosis, babesiosis,
Clostridium perfringens, etc. [see Chap. 52])
b. Antibody mediated
1) Warm-type autoimmune hemolytic anemia (see Chap. 53)
2) Cryopathic syndromes (cold agglutinin disease, paroxysmal cold
hemoglobinuria, cryoglobulinemia [see Chaps. 53 and 137])
3) Transfusion reactions (immediate and delayed [see Chaps. 53 and
137])
c. Hypersplenism (see Chap. 55)
d. Red cell membrane disorders (see Chap. 45)
1) Spur cell hemolysis
2) Acquired acanthocytosis and acquired stomatocytosis, etc.
e. Chemical injury and complex chemicals (arsenic, copper, chlorate, spider,
scorpion, and snake venoms, etc. [see Chap. 51])
f. Physical injury (heat, oxygen, radiation [see Chap. 51])
2.Hereditary
a. Hemoglobinopathies (see Chap. 48)
1) Sickle cell disease
2) Unstable hemoglobins
b. Red cell membrane disorders (see Chap. 45)
1) Cytoskeletal membrane disorders (hereditary spherocytosis,
elliptocytosis, pyropoikilocytosis)
2) Lipid membrane disorders (hereditary abetalipoproteinemia,
hereditary stomatocytosis, etc.)
3) Membrane disorders associated with abnormalities of erythrocyte
antigens (McLeod syndrome, Rh deficiency syndromes, etc.)
4) Membrane disorders associated with abnormal transport (hereditary
xerocytosis)
c. Red cell enzyme defects (pyruvate kinase, 5' nucleotidase, glucose-6phosphate dehydrogenase deficiencies, other red cell enzyme disorders [see
Chap. 46])
d. Porphyrias (congenital erythropoietic and hepatoerythropoietic porphyrias,
rarely congenital erythropoietic protoporphyria [see Chap. 57])
1. Acute blood loss
2. Splenic sequestration crisis (see Chap. 55)

II.

RELATIVE (INCREASED PLASMA VOLUME)

A. Macroglobulinemia (see Chap. 111)
B. Pregnancy (see Chap. 7)
C. Athletes (see Chap. 32)
D. Postflight astronauts (see Chap. 32)

CLASSIFICATION OF POLYCYTHEMIA
I.

ABSOLUTE (TRUE) POLYCYTHEMIA (INCREASED RED CELL VOLUME) (SEE CHAP. 56)
A. Primary polycythemia
1.Acquired
a. Polycythemia vera (see Chap. 86)
2.Hereditary (see Chap. 56)
a. Primary familial and congenital polycythemia
1) Erythropoietin receptor mutations
2) Unknown gene mutations
B. Secondary polycythemia
1.Acquired (see Chap. 56)
a. Hypoxemia
1) Chronic lung disease
2) Sleep apnea
3) Right-to-left cardiac shunts
4) High altitude
5) Smoking
b. Carboxyhemoglobinemia (see Chap. 49)
1) Smoking
2) Carbon monoxide poisoning
c. Autonomous erythropoietin production (see Chap. 56)
1) Hepatocellular carcinoma
2) Renal cell carcinoma
3) Cerebellar hemangioblastoma
4) Pheochromocytoma
5) Parathyroid carcinoma
6) Meningioma
7) Uterine leiomyoma
8) Polycystic kidney disease
d. Exogenous erythropoietin administration ("EPO doping") (see Chap. 56)
e. Complex or uncertain etiology
1) Postrenal transplant (probable abnormal angiotensin II signaling) (see
Chap. 56)
2) Androgen/anabolic steroids (see Chaps. 28 and 56)
2.Hereditary
a. High-oxygen affinity hemoglobins (see Chap. 48)
b. 2,3-Bisphosphoglycerate deficiency (see Chap. 46)
c. Congenital methemoglobinemias (recessive, i.e., cytochrome b5 reductase
deficiency, dominant globin mutations [see Chap. 49])
d. Recessive high erythropoietin polycythemias not due to von Hippel-Lindau
gene mutations (see Chap. 56)
e. Autosomal dominant high erythropoietin polycythemias not due to von
Hippel-Lindau gene mutations (see Chap. 56)
C. Mixed primary and secondary polycythemia (see Chap. 56)
1.Proven or suspected congenital disorders of hypoxia sensing
a. Chuvash polycythemia
b. High erythropoietin polycythemias due to mutations of von Hippel-Lindau
gene other than Chuvash mutation

II.

RELATIVE (SPURIOUS) POLYCYTHEMIA (NORMAL RED CELL VOLUME) (SEE CHAP.

56)
A. Dehydration
B. Diuretics
C. Smoking
D. Gaisbck syndrome