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
Introduction
Overview of Components of CBCOverview of Components of CBCWhite Blood CellsWhite Blood CellsHemoglobin / HematocritHemoglobin / HematocritPlateletsPlateletsCell MorphologyCell MorphologySecondary TestingSecondary Testing
Complete Blood Count - CBCComplete Blood Count - CBC
WBCWBC Hemoglobin / HematocritHemoglobin / Hematocrit MCVMCV RDWRDW MCHC / MCHMCHC / MCH PlateletsPlatelets Differential CountDifferential Count
Manual Manual MachineMachine
When Assessing CytopeniasAlways Think Three ThingsWhen Assessing CytopeniasAlways Think Three Things
Not making enoughNot making enoughLosing cellsLosing cellsCell destructionCell destruction
WHITE BLOOD CELLSWHITE BLOOD CELLS
Blood Cell FormationBlood Cell Formation
ProerythoblastStem Cell
Myeloblast
Promyelocyte
Eosinophil Neutrophil Basophil Monocyte
Erythrocyte
Lymph
PlasmaCells
White Blood CellsWhite Blood Cells
NeutrophilsAbsolute Neutrophil Count
WBC x Neu% (segmented neutrophils and bands)
LymphocytesMonocytesEosinophilsBasophils
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!!!!
NeutrophilsNeutrophils
60 - 70 % of Circulating LeukocytesHalf Life
Six to Seven Hours in bloodOne to Two Days in Connective Tissue
Primary Defense against Bacteria
NeutrophilsNeutrophils
NeutropeniaAbsolute Neutrophil Count < 1500
(Often < 1000 in African Americans)
NeutrophiliaAbsolute Neutrophil Count > 8000
Leukemoid ReactionElevation in WBC
Typically < 50,000
NeutropeniaNeutropenia Decreased Production
Infections Severe Bacterial Viral Rickettsial
Drugs Antibiotics NSAIDS Others
Hematological DiseaseDietaryShockSevere Renal Disease
Decreased Survival InfectionsDrugs Immune mediatedSLECyclic
Evaluation of NeutropeniaEvaluation of Neutropenia
Adapted from Goldman: Cecil Medicine, 23rd ed.
Consider Heme ConsultConsider Heme Consult
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
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
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
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
LymphocytosisLymphocytosis
InfectionsViral
Hepatitis CMV
Tuberculosis Addisons Disease Leukemia Ulcerative Colitis / Crohn’s Disease Vasculitis Drug Hypersensitivity
LymphopeniaLymphopenia
Increased DestructionCorticosteroids
Congestive Heart FailureLoss through GI tract
Decreased ProductionMalignancies Immunoglobulin DisordersHIV InfectionLupus
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
MonocytosisMonocytosis
> 10% of differential Elevated in:
LeukemiaHodgkins / Non Hodgkins lymphomaPost SplenectomyProtozoan InfectionsRickettsial Infections: Rocky Mountain Fever, TyphusSarcoidosisCollagen Vascular DiseasesEnteritis
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
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
MCVFalsely Abnormal
MCVFalsely Abnormal
Cold AgglutininsHyperglycemiaReticulocytosisLeukocytosisAcute Hemolysis
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
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
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
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
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
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
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
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
Evaluation of Macrocytosis
HistoryHistoryPhysicalPhysicalFalse MacrocytosisFalse Macrocytosis
Cold agglutinins: RBC clumpingHyperglycemia: HyperosmolarityLeukocytosis: WBC counted as RBC
Evaluation of Macrocytosis
B12 / FolateB12 / FolateLook for hypersegmented neutrophils
Thyroid StudiesThyroid StudiesIf clinically indicated
Liver Associated EnzymesLiver Associated EnzymesReticulocyte CountReticulocyte Count
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
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
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
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
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
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
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
Red Blood CellsRed Blood Cells
SpherocytesSickle CellsSchistocytesTear Drop CellsBasophilic StipplingHowell-Jolly Bodies
SchistocytesDifferential Diagnosis
SchistocytesDifferential Diagnosis
Mechanical ValvesStenotic ValvesMalignant HypertensionDisseminated Intravascular Coagulation
DICHemolytic Uremic Syndrome – HUS Thrombotic Thrombocytopenic Purpura
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
ThrombocytopeniaThrombocytopenia
Decreased ProductionAcute Infection Increased DestructionConsumptionPrimary or Hereditary
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
PseudothrombocytopeniaPseudothrombocytopenia
EDTA related platelet clumpingClinically insignificant
Cold AgglutininsGiant PlateletsErythrocytosis
Idiopathic Thrombocytopenic Purpura
Idiopathic Thrombocytopenic Purpura
IDIOPATHICBleeding unlikely unless < 10,000Diagnosis of exclusionBone marrow biopsy necessary only in
those > 60 years old
ThrombocytosisThrombocytosis
InfectionAcute Phase Reactant1/3 of patients
Inflammatory State Malignancy Recent Surgery Iron Deficiency Anemia Trauma Myeloproliferative Disorder
>600,000 on two occasions