practical utilization of the complete blood count joseph m. flynn, d.o.,mph, facp division...
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Practical Utilization of the Complete Blood Count
Practical Utilization of the Complete Blood Count
Joseph M. Flynn, D.O.,MPH, FACP Division Hematology-Oncology
THE Ohio State UniversityColumbus, OHApril 18, 2008
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Introduction
Overview of Components of CBCOverview of Components of CBCWhite Blood CellsWhite Blood CellsHemoglobin / HematocritHemoglobin / HematocritPlateletsPlateletsCell MorphologyCell MorphologySecondary TestingSecondary Testing
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Complete Blood Count - CBCComplete Blood Count - CBC
WBCWBC Hemoglobin / HematocritHemoglobin / Hematocrit MCVMCV RDWRDW MCHC / MCHMCHC / MCH PlateletsPlatelets Differential CountDifferential Count
Manual Manual MachineMachine
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When Assessing CytopeniasAlways Think Three ThingsWhen Assessing CytopeniasAlways Think Three Things
Not making enoughNot making enoughLosing cellsLosing cellsCell destructionCell destruction
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WHITE BLOOD CELLSWHITE BLOOD CELLS
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Blood Cell FormationBlood Cell Formation
ProerythoblastStem Cell
Myeloblast
Promyelocyte
Eosinophil Neutrophil Basophil Monocyte
Erythrocyte
Lymph
PlasmaCells
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White Blood CellsWhite Blood Cells
NeutrophilsAbsolute Neutrophil Count
WBC x Neu% (segmented neutrophils and bands)
LymphocytesMonocytesEosinophilsBasophils
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What to Do if WBC AbnormalWhat to Do if WBC Abnormal
Take a Good HistoryPhysical Examination
Look at Old CBC’s!!!!Look at Old CBC’s!!!!
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NeutrophilsNeutrophils
60 - 70 % of Circulating LeukocytesHalf Life
Six to Seven Hours in bloodOne to Two Days in Connective Tissue
Primary Defense against Bacteria
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NeutrophilsNeutrophils
NeutropeniaAbsolute Neutrophil Count < 1500
(Often < 1000 in African Americans)
NeutrophiliaAbsolute Neutrophil Count > 8000
Leukemoid ReactionElevation in WBC
Typically < 50,000
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NeutropeniaNeutropenia Decreased Production
Infections Severe Bacterial Viral Rickettsial
Drugs Antibiotics NSAIDS Others
Hematological DiseaseDietaryShockSevere Renal Disease
Decreased Survival InfectionsDrugs Immune mediatedSLECyclic
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Evaluation of NeutropeniaEvaluation of Neutropenia
Adapted from Goldman: Cecil Medicine, 23rd ed.
Consider Heme ConsultConsider Heme Consult
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Benign (Ethnic) NeutropeniaBenign (Ethnic) Neutropenia
Characterized by neutrophil counts 800 to 1400/mm3
Generally a benign courseSometimes associated with periodontal disease No increase in infections
Bone marrow is typically normocellular Seen in African American, some Jewish
populations
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NeutrophiliaNeutrophilia Acute Infections
Leukocyte: 15-25 X 109/L. Inflammation
Postoperatively, neutrophilia occurs for 12-36 hours as a result of tissue injury
Metabolic Uremia, DKA Eclampsia
Chemicals Steroids Epinephrine
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NeutrophiliaNeutrophilia
Acute Hemorrhage Related to the release of adrenal corticosteroids and/or
epinephrine Acute Hemolysis Myeloproliferative disorders Tissue Injury Tobacco Use Physiological Stress
Exercise Emotional Stress Menstruation
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Steroid EffectSteroid Effect
Increases total and relative PMN’sPeak is 4-6 hoursNormalizes in 24 hours after steroids
stoppedUsually see a concurrent decrease in
Lymphocytes and Monocytes
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LymphocytosisLymphocytosis
InfectionsViral
Hepatitis CMV
Tuberculosis Addisons Disease Leukemia Ulcerative Colitis / Crohn’s Disease Vasculitis Drug Hypersensitivity
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LymphopeniaLymphopenia
Increased DestructionCorticosteroids
Congestive Heart FailureLoss through GI tract
Decreased ProductionMalignancies Immunoglobulin DisordersHIV InfectionLupus
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EosinophiliaEosinophilia
> 250/ CU MM Highest Levels in am Allergic Diseases Parasitic Infections: Trichinosis, Schistosomiasis Leukemias Familial Addison’s Disease, Hypopituitarism Drugs: Aspirin Collagen Vascular Diseases: Churg-Strauss,
Scleroderma/dermatomyositis, RA, SLE, Periarteritis Nodosa
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MonocytosisMonocytosis
> 10% of differential Elevated in:
LeukemiaHodgkins / Non Hodgkins lymphomaPost SplenectomyProtozoan InfectionsRickettsial Infections: Rocky Mountain Fever, TyphusSarcoidosisCollagen Vascular DiseasesEnteritis
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HemoglobinHemoglobin
Boys and girls are same until @ age 11Boys values slowly become higherAdult levels reached
Age 15 Women Age 18 Men
African Americans 0.5 - 1.0gm (5-10 g/dL) lower than northern Europeans
Positional differences Upright vs post bedtime
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Changes in HgbNot Due to Blood Loss or Abherrent Condition
Changes in HgbNot Due to Blood Loss or Abherrent Condition
Increased:Increased WBC
WBC >50,000
SmokingDehydrationTriglycerides
>2000
DecreasedPositionPregnancyDiurnalRaceFemalesIV fluids
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MCVFalsely Abnormal
MCVFalsely Abnormal
Cold AgglutininsHyperglycemiaReticulocytosisLeukocytosisAcute Hemolysis
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RDW vs MCVRDW vs MCV
Normal RDW ; Low MCVThalassemiaChronic Disease
Normal RDW ; High MCVAplastic AnemiaMyelodysplasiaAlcohol
Normal RDW ; Normal MCVChronic disease
(90%)Hereditary
SpherocytosisAcute BleedCirrhosisUremia
Adapted: Ravel; 1995; 14
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RDW vs MCVRDW vs MCV
HIGH RDW ; Low MCV Iron DeficiencyS-ThalassemiaRBC fragmentation
HIGH RDW ; HIGH MCVB12/FolateAutoimmune hemolysisCold Agglutinins
HIGH RDW ; Normal MCVEarly Factor
DeficiencySS diseaseSC dzSideroblastic anemiaMyelofibrosis
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Pathophysiologic ClassificationAnemia
Due to Decreased RBC ProductionDue to RBC Destruction
0.8 % rbc’s destroyed dailyBest suited for relating disease processes
to their mechanismsLimited in the complexity of mechanisms
and lack of solidly established mechanisms
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MicrocytosisDifferential Diagnosis
Iron DeficiencyIron DeficiencyThalassemiaThalassemia
Beta-Thalassemia: Elevated Hgb A2 or Falpha Thalassemia diagnosis of exclusion
Anemia of Chronic DiseaseAnemia of Chronic DiseaseThough 75% patients are normocytic
Sideroblastic anemia - rareSideroblastic anemia - rareLead poisoning - rareLead poisoning - rare
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Iron Deficiency
Most common cause of microcytosisMost common cause of microcytosisClinical CluesClinical Clues Iron StudiesIron Studies
IronTotal Iron Binding CapacityFerritin
Iron Saturation (Serum Iron / TIBC ) < 10 % saturation
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Iron
Serum IronSerum Iron TIBC TIBC Ferritin Ferritin
Iron DeficiencyIron Deficiency
SideroblasticSideroblastic
ThalassemiaThalassemia
Anemia of ChronicAnemia of ChronicDiseaseDisease
LowLow
ElevatedElevated
ElevatedElevated
LowLow
ElevatedElevated
NmlNml
NmlNml
LowLow
LowLow
ElevatedElevated
ElevatedElevated
ElevatedElevated
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When Do I Get a Hemoglobin Electropheresis
Iron studies not indicative of another Iron studies not indicative of another processprocess
Family history of hemoglobinopathyFamily history of hemoglobinopathyAfrican AmericanAsian decentMediterranean decentMicrocytosis in face of mild-No Microcytosis in face of mild-No
anemiaanemia
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Macrocytosis MCV > 100MCV > 100
Macrocytosis MCV > 100MCV > 100
Folate/B12 20 - 30% Chronic Liver dx 15 - 20% ** Alcoholism 10 - 12% - Chemotherapy 10 - 15% Reticulocytosis 7% Myelodysplastic Common Unknown 25% Distance runners Hypothyroidism ** Hyperlipidemia **
**Lipid membrane defects
Can occur with 1bottleof wine per day
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Evaluation of Macrocytosis
HistoryHistoryPhysicalPhysicalFalse MacrocytosisFalse Macrocytosis
Cold agglutinins: RBC clumpingHyperglycemia: HyperosmolarityLeukocytosis: WBC counted as RBC
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Evaluation of Macrocytosis
B12 / FolateB12 / FolateLook for hypersegmented neutrophils
Thyroid StudiesThyroid StudiesIf clinically indicated
Liver Associated EnzymesLiver Associated EnzymesReticulocyte CountReticulocyte Count
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Megaloblastic AnemiaMegaloblastic Anemia
Hypersegmented NeutrophilsAny neutrophil with > six segments orMore than five percent with five segments
orMajority of cells with four segments
Presence of MacroovalocytesEgg - shaped cells
The combination is a result of absence of terminal divisionsof marrow precursors
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Megaloblastic AnemiaDiagnosis
Megaloblastic AnemiaDiagnosis
Serum folate levels may be misleadingAlcohol lowers the folate levelsCorrecting serum folate can be seen after a meal
Determine the cause of the deficiency Ie. Pernicious anemia, Malabsorption, Diet
Red cell changes are not seen in all vitamin deficient patientsMCV usually > 110 though > 130 more specificLook at RDWCell Morphology
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Diagnosing Vitamin DeficienciesDiagnosing Vitamin Deficiencies
Serum cobalamin < 200 pg/ml: consistent with Cobalamin
deficiency>300 pg/ml: Normal
Serum folate concentrations If Folate is >4ng/ml then not folate deficientIf Folate is < 2ng/ml then folate deficientIf Borderline, Check Red blood cell levels
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Diagnosing Vitamin DeficienciesDiagnosing Vitamin Deficiencies
Methylmalonic acid and Homocysteine Good if Cobalamin and Folate are equivocalBoth elevated = Cobalamin Deficiency
95% Sensitivity 99% Specificity
If Homocysteine only elevated = Folate Deficiency 85% Sensitivity
Anti-Intrinsic factor Antibodies Confirms Pernicious Anemia
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MCV >100MCV >100
Rule out DrugsRule out Drugs
Retic ctRetic ctHighHigh
Eval forEval forHemolysisHemolysis
Consider LabConsider Lab ErrorError
LFT’sLFT’sThyroidThyroid
B12 &B12 &FolateFolate LOWLOW
NormalNormal
Consider BmbxConsider BmbxMost commonlyMost commonlyMyelodysplasiaMyelodysplasia
Adapted from Colon-Otero, Med Clin of NA. 76(3)581-596. 1992Adapted from Colon-Otero, Med Clin of NA. 76(3)581-596. 1992
LDHLDHBilirubinBilirubinHaptoglobinHaptoglobin
Blood Loss
MMA & HC
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Normocytic AnemiaDifferential Diagnosis
Acute HemorrhageAcute Hemorrhage HemolysisHemolysis Aplastic AnemiaAplastic Anemia Renal FailureRenal Failure MyelophthisisMyelophthisis Sickle cell anemiaSickle cell anemia Chronic DiseaseChronic Disease Combined Microcytosis / MacrocytosisCombined Microcytosis / Macrocytosis
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Normocytic AnemiaEvaluation
Clinical HistoryClinical HistoryReview CBC for multiple Cell line Review CBC for multiple Cell line
deficienciesdeficienciesRDW / SmearRDW / Smear
MalnutritionDirect Antibody TestDirect Antibody TestChemistriesChemistriesConsider Bone Marrow BiopsyConsider Bone Marrow Biopsy
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Red Blood CellsRed Blood Cells
SpherocytesSickle CellsSchistocytesTear Drop CellsBasophilic StipplingHowell-Jolly Bodies
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SchistocytesDifferential Diagnosis
SchistocytesDifferential Diagnosis
Mechanical ValvesStenotic ValvesMalignant HypertensionDisseminated Intravascular Coagulation
DICHemolytic Uremic Syndrome – HUS Thrombotic Thrombocytopenic Purpura
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PlateletsPlatelets
Size should be <1/3 that of RBCThrombocytopenia: < 150,000
< 100,000 is important numberShould be suspected when platelets are
found in <1 in 10 fields on high powerThrombocytosis: >450,000/cu mmPseudothrombocytopenia
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ThrombocytopeniaThrombocytopenia
Decreased ProductionAcute Infection Increased DestructionConsumptionPrimary or Hereditary
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ThrombocytopeniaThrombocytopenia
> 50,000: Typically no bleeding20 – 50,000: Post operative bleeding
and minor mucosal bleeding5 – 20,000: Can have significant
bleeding<5,000: Severe bleeding possible
Unless ITP
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PseudothrombocytopeniaPseudothrombocytopenia
EDTA related platelet clumpingClinically insignificant
Cold AgglutininsGiant PlateletsErythrocytosis
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Idiopathic Thrombocytopenic Purpura
Idiopathic Thrombocytopenic Purpura
IDIOPATHICBleeding unlikely unless < 10,000Diagnosis of exclusionBone marrow biopsy necessary only in
those > 60 years old
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ThrombocytosisThrombocytosis
InfectionAcute Phase Reactant1/3 of patients
Inflammatory State Malignancy Recent Surgery Iron Deficiency Anemia Trauma Myeloproliferative Disorder
>600,000 on two occasions