practical utilization of the complete blood count joseph m. flynn, d.o.,mph, facp division...

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