How to Interpret and Pursue an Abnormal Complete Blood Cell Count in Adults
AYALEW TEFFERI, MD; CURTIS A. HANSON, MD; AND DAVID J. INWARDS, MD Mayo Clin Proc. 2005;80(7):923-936
Introduction
Complete blood cell count (CBC) is one of the most common laboratory test in medicine
In Mayo Clinics: 1800 CBCs per day; 10-20% abnormal finding
Circulation blood cells including:
Red blood cells (RBCs)
White blood cells (WBCs)
Platelets (PLTs) White counts
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils Hgb: genral indicator of anemia or polycythemia
MCV: key parameter for classification of anemia
RDW: useful parameter in differential diagnosis of anemia
RBC count: increased RBC count associated with anemia: in thalassemia trait
Platelet
Thrombocytopenia
Thrombocythemia WBC with differential
Up to 5% of general population without disease may display laboratory values outside the statistically assigned normal reference range
Reference Range of Complete Blood Cell Count in Adult White Persons and Persons of African Ancestry
White African
Variable Male Female Male Female
Hemoglobin9 (g/dL) 12.7-17.0/(13.5-17.5) 11.6-15.6/(12.0-15.5) 11.3-16.4 10.5-14.7 RBCs9 (× 1012/L) 4.0-5.6/(4.3-5.7) 3.8-5.2/(3.9-5.0) 3.8-5.7 3.6-5.2 Mean corpuscular
volume9 (fL) 81.2-101.4/(81.2-95.1)
81.1-99.8/
(81.6-98.3) 77.4-103.7 74.2-100.9 RBC distribution width (%) (11.8-15.6) (11.9-15.5)
Platelets8 (× 109/L) 143-332/(150-450) 169-358/(150-450) 115-290 125-342 WBCs8 (× 109/L) 3.6-9.2/(3.5-10.5) 3.5-10.8/(3.5-10.5) 2.8-7.2 3.2-7.8 Neutrophils8 (× 109/L) 1.7-6.1/(1.7-7.0) 1.7-7.5/(1.7-7.0) 0.9-4.2 1.3-4.2 Lymphocytes8 (× 109/L) 1.0-2.9/(0.9-2.9) 0.95-3.3/(0.9-2.9) 1.0-3.2 1.1-3.6 Monocytes8 (× 109/L) 0.18-0.62/(0.3-0.9) 0.14-0.61/(0.3-0.9) 0.15-0.58 0.15-0.39 Eosinophils8 (× 109/L) 0.03-0.48/(0.05-0.50) 0.04-0.44/(0.05-0.50) 0.02-0.79 0.02-0.41
Basophils (× 109/L) (0-0.3) (0-0.3)
*Abstracted from population-based studies from Bain8 and NHANES-II.9 Mayo Clinic
normal values, based primarily on white subjects, are in parentheses for comparison. RBC = red blood cell; WBC = white blood cell.
Anemia
Microcytic: MCV < 80fl
Normocytic: MCV 80-100fl
Macrocytic: MCV > 100fl
Strongly recommend obtaining a PBS during the initial evaluation of anemia, regardless of subtype
Microcytic Anemia
3 major diagnostic possibilities
Iron deficiency anemia (IDA)
Thalassemia
Anemia of chronic disease (ACD)
Sideroblastic anemia: not prevalent enough for routine consideration
Serum ferritin: initial step for all patient with microcytic anemia
Not recommend other serum iron studies
(serum iron, total iron-binding capacity, transfering saturation or bone
marrow biopsy)
Normal ferritin
Chronic microcytosis Ö thalassemia Ö Hb electrophoresis
Thalassemia concomitant IDA may mask typical abnormality seen in β-thalassemia trait (increase Hb A2(α2δ2) level from the normal value of 2% to a value 3-6%)
Newly onset of microcytosis Ö systemic disease Ö further investigationClues From CBC and PBS in the Differential Diagnosis of Anemias
Category of anemia Differential diagnosis CBC clues PBS clues
Iron deficiency anemia Increased RDW Thrombocytosis
Anisocytosis Poikilocytosis Elliptocytosis
Thalassemia Normal or elevated RBC count Normal or elevated RDW
Polychromasia Target cells Basophilic stippling Microcytic
Anemia of chronic disease Normal RDW
Unremarkable (typically) Rouleaux formation (CD) Myelophthisis (MMM)
Diagnostic algorithm for microcytic anemia
Normocytic Anemia
Potential treatable disease
Bleeding
Nutritional anemia
Anemia of renal insufficiency
Hemolysis
Normocytic ACD
Primary bone marrow disorder History taking
Lab: serum iron, vit.B12, folic acid, creatitine
Additional laboratory test
Coombs test, if negative, osmotic fragility test for spherocytosis
Coagulation, haptoglobin, LDH for patient with schistocytosis
Urinary hemosiderin for intravascular hemolysis Drug-induced hemolysis
Clues From CBC and PBS in the Differential Diagnosis of Anemias
Category of anemia Differential diagnosis CBC clues PBS clues
Bleeding Usually unremarkable Polychromasia
Nutritional anemia Increased RDW Anisocytosis Dimorphic RBCs Anemia of renal insufficiency Normal RDW Usually unremarkable Hemolysis Normal or elevated RDW
Thrombocytosis
Polychromasia Spherocytes Schistocytes Bite cells Anemia of chronic disease Normal RDW Unremarkable Normocytic
Primary bone marrow disorder
Increased RDW Other cytopenias Monocytosis Leukocytosis Thrombocytosis Abnormal differential
Dimorphic RBCs (MDS) Pseudo Pelger-Huët anomaly (MDS)
Oval macrocytes (MDS) Myelophthisis (MMM)†
Rouleaux (myeloma) Blasts (acute leukemia) Presence of abnormal cells
Diagnostic algorithm for normocytic anemia
Macrocytic Anemia
Drugs: Hydroxyurea, zidovudine, MTX, 5-FU
Alcohol consumption
Nutritional cause: Vit.B12 or folic acid
Primary bone marrow disease
Marked MCV > 110 fl
Mild MCV 100-110 fl
Clues From CBC and PBS in the Differential Diagnosis of Anemias
Category of anemia Differential diagnosis CBC clues PBS clues Drug-induced Increased RDW
Marked or mild macrocytosis Oval macrocytes
Nutritional Increased RDW
Marked or mild macrocytosis
Oval macrocytes
Hypersegmented neutrophils MDS or other bone marrow
disorder
Increased RDW Dimorphic RBCs
Pseudo Pelger-Huët anomaly cells Oval macrocytes
Liver disease, alcohol use Normal RDW Thrombocytopenia
Round macrocytes Target cells Macrocytic
Hypothyroidism Normal RDW Round macrocytes
Hemolysis Normal or elevated RDW Polychromasia
Diagnostic algorithm for macrocytic anemia
Polycythemia
Primary
Secondary
Diagnostic algorithm for Polycythemia
Thrombocytopenia
First step
Exclude spurious thrombocytopenia caused by EDTA-induced platelet clumping
PBS or using sodium citrate
Healthy pregnancy: 75-150×103/μl
Second step
Consider TTP/HUS
Third step
Drug-related: antibiotics, cardiac medications, thiazide diuretics, anti-rheumatics and heparin
Hypersplenism
Idiopathic thrombocytopenia purpura
Diagnosis of exclusion
Neither platelet antibody test nor bone marrow biopsy
Hereditary thrombocytopenia
May-Hegglin anomaly
Gray platelet syndrome
Bernard-Soulier syndrome
X-linked Wiskott-Aldrich syndrome
MDS, a megakaryocytic thrombocytopenia, posttrasnsfusion purpura
Diagnostic algorithm for thrombocytopenia
Thrombocytosis
Primary (Myeloid malignancy)
ET, MDS, MMM, CML, PV, CMPD Secondary
Possible greater than 1000000/μl
IDA, Surgical asplenia, Infection, Chronic inflammation, Hemolysis,Tissue demage, Non-myeloid malignancy Initial lab
Serum ferritin: R/O IDA
C-reactive protein: R/O inflammation
PBS Rule-out reactive thrombocytosis
Bone marrow study with FISH for bcr/abl
JAK2 (JAK2V617F)Diagnostic algorithm for thrombocytosis
Neutropenia
Congenital
Kostmann syndrome(congenital agranulocytosis)
Cyclic neutropenia Secondary
Medication
Infection
Autoimmune disease
Hematology malignancyLymphopenia
Congenital
Bruton X-lined agammablobulinemia (B-cell deficiency), DiGeorge syndrome (T-cell deficiency)
Acquired
Immunosuppressive drugs
Steroids, antilymphocyte monoclonal antibody
Infection
Virus(HIV), Sepsis, TB
Autoimmune
Chronic renal failure
Excess alcohol use
Old age
Thymoma
Leukocytosis
First step: WBC differential to determine which WBC type is increasing Neutrophilia
Leukemoid reaction
Infection, inflammation, malignancy, drugs Myeloid malignancy
Acute leukemia, CML, chronic neutrophilic leukemia Eosinophilia First step
exclude secondary eosinophilia by parasite infection, drugs, asthma, allergy, vasculitis, lymphoma, metastatic cancer
History taking
Stool test for ova and parasite Primary eosinophilia
Bone marrow study to distinguish clonal eosinophilia and hypereosinophilic syndrome
Suspected HES
FISH for FIP1L1-PDGFRA mutation
Immunohistochemical stain for tryptase and mast cell
Serum tryptase, T-cell immunophenotyping, serum IL-5 level, serum IgE level
Survey eosinophilic-mediated tissue damage
Basophilia
Rare condition, suggests basophilic leukemia
Need bone marrow study Monocytosis
Persistent monocytosis should be considered a marker of a myeloproliferative disorder (eg, CMMoL)
Relative monocytosis
Recovery from chemotherapy or drugs induced neutropenia
Chronic infections, Inflammation, Granulomatous process, metastatic cancer, lymphoma, radiation therapy, depression and follow AMILymphocytosis
PBS to review the morphology of excess lymphocytes
Reactive lymphocytosis: LGL morphology
Distinguish from LGL leukemia
Small-lymphocyte: CLL Flow cytometry