Complete Blood Count (CBC) Dx

Last updated: November 3, 2014

Synonyms: CBC, Hemogram, blood count, hematology profile.

CPT Code:  85025

Description: CBC is a profile of tests providing quantitative measures of RBC, white blood cell, and platelet indices. The CBC is useful for the diagnosis of anemia, bleeding disorders, infection, connective tissue disorders, and neoplasia and to monitor clinical status or response to medication.

Method: Most clinical laboratories use an automated electronic multichannel analyzer with aperture impedance or laser beam to estimate cell counts, size, and complexity. Venous blood should be collected in a lavender-top tube (containing the anticoagulant EDTA) and gently inverted several times to prevent coagulation. A peripheral smear of anticoagulated blood may be examined with Wright stain to evaluate RBC, white blood cell, and platelet morphology and relative cell number.

Normal Values: Consult local reference laboratory values.

RBC Abnormalities: RBC indices and abnormalities (see Table) are defined as follows:
—Mean corpuscular volume (MCV): Useful in the diagnosis of microcytic or macrocytic anemias, drug effects (i.e., methotrexate, sulfasalazine, and dapsone will increase the mean corpuscular volume), or occult alcohol abuse (higher MCV from folate deficiency).
—RBC distribution width (RDW): Measures anisocytosis (variation in RBC size); increased in iron deficiency and macrocytic anemias.
—Heinz bodies (owing to precipitated hemoglobin): Seen in thalassemia, glucose-6- phosphate or pyruvate kinase deficiency, postsplenectomy, and drug-induced RBC injury (e.g., antimalarials, sulfonamides).
—Schistocytes (fragmented RBCs): Caused by microangiopathic hemolytic anemia, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, prosthetic heart valves, hemolysis, severe burn, and snake bite.
—Acanthocytes (spiculated RBCs from abnormal membrane lipids): Seen with hyposplenism, abetalipoproteinemia, severe liver or renal disease, and hereditary acanthocytosis.
—Target cells (increase in cell membrane in relation to cell volume): May be artifactual or caused by hemoglobin C and S, thalassemia minor, iron deficiency, or liver disease or post-splenectomy.
—Howell-Jolly bodies (precipitated DNA in mature RBC): Seen post-splenectomy and in hyposplenism, megaloblastic anemia (pernicious anemia), sickle cell, hemolytic anemia, and hereditary spherocytosis.
—Burr cells (regularly scalloped, crenated RBCs): May be artifactual or owing to uremia, gastrointestinal bleeding, or gastric carcinoma.
—Elliptocytes (ovalocytes, oval-shaped RBCs): May be hereditary or seen with iron deficiency anemia.
—Sickle cells (caused by polymerization of hemoglobin S): Seen in sickle cell syndromes (not in S trait)
—Teardrop RBCs: Consider polycythemia, myelofibrosis, thalassemia.
—Basophilic stippling: May be seen in heavy metal poisoning (e.g., lead), severe hemorrhage, or hemolysis.

Anemia: Anemia in patients with rheumatic disease may arise from rheumatic disorder,  a comorbid condition, or from the adverse effects of medication.
—Anemia of chronic disease (ACD): With ACD, the hematocrit seldom drops below 27%. RBC morphology is normal or hypochromic. ACD results from ineffective erythropoiesis and an inability to mobilize iron or use bone marrow iron stores. Bone marrow iron content and serum transferrin levels are normal. Serum ferritin may be normal or high, especially with inflammatory states.  ACD often results from inflammation and interleukin-6 (not IL-1 or TNF) driven production of hepcidin.   Hepcidin lowers serum iron levels, intestinal iron absorption and iron release from macrophages and hepatocytes.   ACD is commonly seen in patients with chronic infection, neoplasia, or active chronic inflammatory disorders such as RA or SLE. ACD does not accompany noninflammatory disorders such as osteoarthritis or fibromyalgia. Therapy should be primarily directed at the underlying disorder. Supplemental iron is of little value.
—Iron deficiency anemia (IDA): Commonly caused by gastrointestinal (especially with NSAID use) or menstrual blood loss. Morphology reveals hypochromic and microcytic RBCs and low serum ferritin levels. However, normal ferritin levels are seen with inflammatory states because ferritin behaves as an acute-phase reactant. There is usually an elevated total iron-binding capacity.
—Hemolytic anemia: May be seen with the hemoglobinopathies (i.e., sickle cell, thalassemia, hemoglobin C), hereditary spherocytosis or elliptocytosis, paroxysmal nocturnal hemoglobinuria, transfusion reaction, autoimmune hemolytic anemia (i.e., Coombs positive, SLE, viral infection, lymphoma, drugs, idiopathic), prosthetic heart valves, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, scleroderma renal crisis, hemolyticuremic syndrome, malaria, snakebite, or glucose-6-phosphate or pyruvate kinase deficiency.
—Aplastic anemia: May be seen with NSAIDs (e.g., phenylbutazone, diclofenac), gold, penicillamine, azathioprine, cyclophosphamide, chlorambucil, methotrexate, viral infections, and hepatitis.


Table: Diagnostic Clues from Hemogram Components
Test Increased in Decreased in Comment
Hgb/Hct Polycythemia, hemoconcentration Iron deficiency anemia, anemia of chronic disease, hemolysis Hgb may be falsely elevated with lipemic plasma or with WBC > 50K
MCV Drugs (MTX, SSZ, dapsone, phenytoin, estrogen), megaloblastic anemia, liver disease, alcoholism, myxedema, cold agglutinin disease Microcytic anemia, iron deficiency, thalassemia, sideroblastic anemia, lead poisoning May be increased (with marked leukocytosis, reticulocytosis, or hyperglycemia) or decreased (with hemolysis or fragmented RBCs)
RDW IDA, sideroblastic, B12/folate deficiency, alcoholism, liver disease Thalassemia or ACD (normal or low RDW) Usually normal or low in ACD; more sensitive in microcytic anemias
Reticulocyte count Acute blood loss, hemolysis, sickle cell, RBC sequestration; Rx of IDA SLE, BM aplasia, pancytopenia, megaloblastic anemia, alcoholism, liver disease, chronic renal failure, myxedema Reticulocytes indicate effective
erythropoiesis; useful in gauging
response to iron, B12, folate therapy or bloodloss
WBC neutrophils Corticosteroids, epinephrine, lithium, acute infection, seizures, stress, myeloproliferative disorders, leukemia, vasculitis (PAN), Reiter’s syndrome, acute gout, septic arthritis, rheumatic fever, adult Still disease, Sweet’s syndrome, Kawasaki disease, familial Mediterranean fever MTX, azathioprine, chlorambucil,
cyclophosphamide, gold salts, NSAIDs (rare), SLE, drug-induced lupus, MCTD, overlap syndrome, RA, Sjögren syndrome, Felty’s syndrome, cyclic neutropenia, bacterial sepsis, viral infection, hypersplenism, aplastic anemia, radiation, CLL, hemodialysis, nutritional deficiency (folate, copper, etc.)
Falsely elevated WBC may be due to clumping associated with
monoclonal gammopathy,
cryoglobulins, cold agglutinins, or nucleated RBCs; African Americans may manifest lower WBC counts
than whites
Lymphocytes Mononucleosis, viral (EBV, CMV, mumps), pertussis, Crohn disease, ulcerative colitis, hypersensitivity drug reactions, serum sickness vasculitis Chemotherapy (azathioprine,
cyclophosphamide, chlorambucil),
corticosteroids, radiation, SLE,
MCTD, renal failure, myasthenia
Absolute lymphocyte counts may be helpful in diagnosing certain
disorders (e.g., SLE) or gauging
response to chemotherapy
Monocytes RA, SLE, sarcoidosis, inflammatory bowel disease, myeloproliferative disorders, postsplenectomy, SBE, Rocky Mountain spotted fever, tuberculosis, brucellosis Corticosteroids, acute stress, acute
infection, aplastic anemia, myelotoxic therapies
Eosinophils SLE, polyarteritis nodosa, Churg-Strauss angiitis, RA, Sjögren syndrome, eosinophilic fasciitis, Wegener’s granulomatosis, eosinophil myalgia syndrome, pemphigus, allergic disorders, asthma, Hodgkin disease, polycythemia vera, hypereosinophilic syndrome, parasitic infection, inflammatory bowel disease Corticosteroids, acute stress, bacterial infection
Basophils CML, polycythemia, myelodysplasia, Hodgkin’s disease Hyperthyroidism, pregnancy, acute
infection, chemotherapy, radiation
Platelets Inflammation (i.e., RA), infection, malignancy, sarcoidosis, essential thrombocytosis, polycythemia vera, CML, postsplenectomy, iron deficiency anemia, oral contraceptives Drugs (gold salts, penicillamine,
chloroquine, sulfasalazine,
penicillin, heparin, quinidine,
estrogen, cyclophosphamide,
chlorambucil), infection (EBV,
herpes), SLE, hypersplenism,
aplastic anemia, ITP, TTP, DIC, radiation, toxemia of pregnancy
May be falsely elevated with
cryoglobulins, malaria, or
fragmented RBCs; platelet
clumping may decrease counts and be caused by EDTA collection
tubes, cold agglutinins
MPV ITP, recovery from thrombo-cytopenia, myeloproliferative disorders, hyperthyroidism, massive hemorrhage, splenectomy, preeclampsia, smokers, vasculitis Wiskott-Aldrich syndrome, autoimmune thrombocytopenia, leukemia, hypersplenism Increased with effective thrombopoiesis.
Hgb, hemoglobin; Hct, hematocrit; WBC, white blood cell; MCV, mean corpuscular volume; MTX, methotrexate; SSZ, sulfasalazine; RBC, red blood cell; RDW, red cell distribution width; IDA, iron deficiency anemia; ACD, anemia chronic disease; SLE, systemic lupus erythematosus; BM, bone marrow; PAN, polyarteritis nodosa; NSAID, nonsteroidal antiinflammatory drug; MCTD, mixed connective tissue disease; RA, rheumatoid arthritis; CLL, chronic leukocytic leukemia; EBV, Epstein-Barr virus; CMV, cytomegalovirus; TTP, thrombotic thrombocytopenic purpura; DIC, disseminated intravascular coagulation; MPV, mean platelet volume; ITP, idiopathic thrombocytopenic purpura

WBC Abnormalities
—LE cells: Phagocytic cells that have ingested an opsonized nucleus. Although rarely done or available, they may be incidentally found in joint, pleural, or pericardial fluid. They are found in 75% of patients with SLE but are also seen in mixed connective tissue disease, RA, Sjögren’s syndrome, chronic active hepatitis, PBC, and drug-induced lupus or with ANA-inducing drugs.
—Hypersegmented neutrophils:  May be seen with macrocytic anemia.
—Toxic granulation: Seen with severe bacterial or viral infections and sepsis.
—Atypical lymphocytes: Seen in viral infections (e.g., mononucleosis, mumps, cytomegalovirus, hepatitis), drug reactions, serum sickness, pertussis, and brucellosis.

Platelet Abnormalities
—Platelet clumping: May falsely lower platelets but increase leukocyte counts; may be induced by EDTA and large platelets associated with thrombocytopenia.
—Giant/large platelets: Recovery of thrombocytopenic states, myeloproliferative syndromes, hyperthyroidism, Bernard-Soulier syndrome.
—Mean platelet volume (MPV): Mean platelet volume is increased with large (young/immature) platelets and with increased platelet turnover and is inversely proportional to platelet count.

Confounding Factors: CBC is rendered inaccurate by hemolysis, hemodilution with intravenous fluids, and hypercalcemia (causes coagulation). Accuracy is lowered when numbers approach critical values (i.e., platelets <10,000/mm3).

Indications: CBC is useful in the evaluation or diagnosis of anemia, infection, connective tissue disorders, or neoplasia and in monitoring the effects of medication.

Cost: $20–30.

Comment: A peripheral smear should be requested and examined when evaluating anemia, suspected hemolysis, leukemia, or thrombocytopenia.

ARA Glossary Committee. Miscellaneous tests in the rheumatic diseases: A. Blood studies. In: ARA Glossary Committee, JL Decker, chairman. Dictionary of the rheumatic diseases, vol II: diagnostic testing. American Rheumatism Association. Atlanta: Contact Associates International Ltd., 1985:2–6.
Wallach J. Interpretation of diagnostic tests, 6th ed. Boston: Little, Brown, 1996.
Masson C. Rheumatoid anemia. Joint Bone Spine. 2011;78:131-7. PMID: 20851655

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