Age/sex Normal Hemoglobin, g/dL Normal Hematocrit, %
Adolescents 13.0 40
Adult men 16.0 (±2.0) 47 (±6)
Adult women 13.0 (±2.0) 42 (±5)
Adult women 14.0 (±2.0) 42 (±6)
(postmenopausal)
Pregnant women 12.0 (±2.0) 37 (±6)
(third trimester)
Normal Values for Red Blood Cell Indices
Mean cell volume (MCV) 80-95 fL
Mean cell hemoglobin (MCH) 32 ± 2 pg
Mean cell hemoglobin concentration (MCHC) 33 ± 3%
RDW-CV 13 ± 1%
RDW-SD 42 ± 5 fL
RDW, red-cell distribution width (a numerical index of the distribution of red blood cell volumes); RDW-CD, ratio
of the width of the histogram of the distribution of red blood cell volumes at one standard deviation divided by
the MCV; RDW-SD, width of the histogram of the distribution of red blood cell volumes at 20% frequency level
Classification of Anemia by Mean Corpuscular Volume
Microcytic Macrocytic Normocytic
Iron deficiency Megaloblastic: Many causes, including early
Thalassemia Vitamin B12 deficiency stages of all anemias
Sideroblastic anemia Folate deficiency Early stages of iron
Anemia of chronic disease Myelodysplasia, anemias deficiency
caused by chemotherapy
Nonmegaloblastic:
Liver disease
Increased reticulocytes
Myxedema/hypothyroidism
Cold agglutinin
Classification of Anemias by Pathophysiology
Decreased RBC production Increased destruction of RBC
Hemoglobin synthesis: Iron deficiency, Blood loss from hemolysis (inherited):
thalassemia, anemia of chronic Membrane: Hereditary spherocytosis,
disease, sideroblastic anemia elliptocytosis
DNA synthesis: Megaloblastic anemia Hemoglobin: Sickle cell (SC) disease,
Stem cell: Aplastic anemia unstable hemoglobin
Bone-marrow infiltration: Carcinoma, RBC enzyme abnormalities: Pyruvate kinase,
lymphoma glucose-6-phosphate dehydrogenase
Pure red-cell aplasia (G6PD) deficiency
Blood loss from hemolysis (acquired):
Immune: warm antibody, cold antibody
Traumatic hemolysis: thrombotic
thrombocytopenic purpura, hemolytic-
uremic syndrome, mechanical cardiac
valve
Infection: clostridial, malarial
Copper toxicity in Wilson's disease
Hypersplenism
Causes of Iron Deficiency
Deficient diet (rare)
Decreased absorption (rare)
Increased iron requirements:
Pregnancy
Lactation
Blood loss:
Gastrointestinal
Menstrual
Blood donation
Hemoglobinuria
Iron sequestration:
Pulmonary hemosiderosis (rare)
Key Findings from Patient History for Anemia Diagnosis
Finding Condition(s) to consider Comments
Change in bowel habits or Carcinoma of the colon Chronic blood loss leading to iron-deficiency
dark stools, or both anemia
Menorrhagias or Iron deficiency Anatomic or functional lesions of the uterus
metrorrhagia causing excessive bleeding
Dark urine Hemolytic anemia Hemoglobinuria
Poor diet and high alcohol Megaloblastic Reduced intake and diminished absorption of
intake anemia dietary folate
Alteration in mental Pernicious Vitamin B12 deficiency
status,paresthesias, and anemia
numbness of the feet
Recent infections Primary bone-marrow disorder Bone-marrow aplasia
causing pancytopenia (aplastic
anemia)
Bleeding into skin or mucus Primary bone marrow disorder Bone-marrow aplasia or replacement by leukemic
membranes causing pancytopenia (aplastic tissue
anemia or acute leukemia)
Leg ulcers Hereditary spherocytosis, sickle Hemolytic anemia
cell disease
Unexplained deep vein Paroxysmal nocturnal Hypercoagulable state
thrombosis hemoglobinuria, occult
malignancy
Drug use Drug-induced immune hemolysis Immunologic destruction caused by binding of
antigen or antigen-antibody complexes to the
RBCs
Oxidant hemolysis Oxidant injury to hemoglobin and RBC membrane
in susceptible patients (G6PD deficiency and
related conditions)
Blood loss Gastric irritation or bleeding (nonsteroidal anti-
inflammatory drugs)
Drug-induced cytopenia Bone-marrow suppression or aplasia
Family history of anemia, inherited hemolytic anemia Membrane protein mutations and deficiencies, RBC
splenomegaly, or enzyme deficiencies
gallstones
Occupational history Lead poisoning, aplastic anemia Toxic effect on the bone marrow
Back pain Multiple myeloma Bone-marrow plasmacytosis and osteolytic bone
lesions
Key Physical Examination Findings in Patients with the Diagnosis of Anemia
Finding Important diagnostic considerations
Pallor without jaundice Iron deficiency, anemia of chronic disease, aplastic anemia
Pallor with jaundice Hemolytic anemias
Megaloblastic anemias or other conditions associated with ineffective
erythropoiesis (intramedullary hemolysis)
Anemia in liver disease
Petechiae, ecchymoses Primary bone-marrow disorder affecting production of both red blood cells
and platelets (aplastic anemia, acute leukemia, and related disorders)
Koilonychia (spoon nails) Longstanding iron deficiency
Spider hemangiomas Anemia of chronic liver disease
Telangiectasias Gastrointestinal blood loss
Adenopathy Lymphoproliferative disorders
Tuberculosis
Disseminated fungal infections
AIDS/advanced HIV infection
Splenomegaly Myeloproliferative or lymphoproliferative disorders
Hemolytic anemias
Liver disease
Dry skin Anemia of hypothyroidism
Palmar erythema, loss of body Anemia of chronic liver disease
hair, gynecomastia
Atrophy of tongue mucosa Vitamin B12 or iron deficiency
Diagnostic Criteria For Various Types of Anemia
Cause of anemia Essentials of diagnosis
Iron-deficiency anemia Absent bone-marrow iron stores or serum ferritin <12 mcg/L.
Nearly always caused by bleeding in adults. Responds to iron Rx.
Anemia of chronic Suspect in patients with chronic disease.
disease Low serum iron, low TIBC, and normal or increased serum ferritin (or normal or increased
bone-marrow stores).
Coexisting iron and folic acid deficiency possible in severe cases.
Elevated sedimentation rate.
Thalassemias: alpha- Microcytosis out of proportion to the degree of anemia.
thalassemia trait, Positive family history or life-long personal history of microcytic anemia. Abnormal
hemoglobin H morphology of RBC, microcytosis, and target cells. In beta-thalassemia, elevated levels of
disease, beta- A2or fetal Hgb.
thalassemia minor,
beta-thalassemia
major
Diagnosis made by bone-marrow exam, which shows marked erythroid hyperplasia.
Sideroblastic anemia Fe stain shows elevation in Fe stores and ringed sideroblasts.
High serum Fe and high transferrin saturation. (The anemia is usually moderate, with a
hematocrit of 20%-30%. MCV is usually normal or slightly increased; it also may be low,
erroneously suggesting iron deficiency)
Vitamin B12 deficiency Macrocytic anemia. Macro-ovalocytes and neutrophils with hypersegmentation. Serum
B12<100-150 pg/mL.
Folic acid deficiency Macrocytic anemia.Macro-ovalocytes and neutrophil hypersegmentation.Normal serum
B12.Reduced RBC folate.
Hemolytic anemias Reticulocytosis, unless a second disorder, such as folate deficiency or infection, is present.
Hereditary Positive family history; splenomegaly; spherocytes and increased reticulocytes on peripheral
spherocytosis blood smear; microcytic, hyperchromic indices
Paroxysmal nocturnal Classically, patients report episodic reddish-brown urine, often in the first morning
hemoglobinuria urine.Patients are prone to thrombosis, especially of the mesenteric and hepatic
vein.Urinary hemosiderin, LDH elevated.Iron deficiency common.
G6PD deficiency X-linked recessive disorder common in African-American men. Episodic hemolysis in response
to oxidant drugs or infection.
Minimally abnormal peripheral blood smear. Reduced levels of G6PD between hemolytic
episodes.
SC anemia and related Irreversibly sickled cells on peripheral blood smear; positive family history and lifelong
syndromes history of hemolytic anemia;
recurrent painful episodes. Hemoglobin S is the major hemoglobin seen on electrophoresis.
Autoimmune hemolytic Acquired anemia caused by IgG autoantibody;
anemia spherocytes and reticulocytosis on peripheral blood smear; positive Coombs test.
Traumatichemolysis Hallmark is fragmented RBC on the peripheral blood smear.
(including Hemoglobinemia, hemoglobinuria.
microangiopathic Methemalbuminemia in severe cases.
hemolytic anemias)
Aplastic anemia Pancytopenia.No abnormal cells.
Hypocellular bone marrow.(Pancytopenia is the hallmark of aplastic anemia, although early in
the evolution of the disorder only one or two cell lines may be reduced.)