By Prof Ahmed Abdelwarith

What you need to know about CBC and coagulation profile

Slide credits to many contributors

Including PPT & Text Books

Introduction

HematologyStudy of normal and pathologic aspects of different blood components

1-complete blood count (CBC) reports

2- Bone Marrow 3- coagulation and hemeostasis

Blood &Plasma

Suspension of cells in a solute of water, proteins, and electrolytes

Average volume is 5 liters70mL per kg body weight

Blood &PlasmaPlasma

Blood from which the cellular components (RBCs, WBCs, platelets) have been removed by centrifugeColor is yellowContains coagulation

proteins (clotting factors)

HematopoiesisDevelopment of blood cells and other formed elements

Sites vary throughout developmentFetal: yolk sac, liver, spleenPediatric: axial and appendicular skeleton

Adult: axial skeleton (sternum and pelvis)

HematopoiesisStem cells

Primitive; self-replicate and differentiate to become increasingly specialized progenitor cells which form mature cellsProcess regulated by growth factors

(interleukins, erythropoietin, thrombopoietin, G-CSF)

Early lineage division between progenitors for lymphoid and myeloid cells

B lymphocyte development markers

CELL ARREST

X

CLONAL EXPANSION

Complete Blood CountWhite blood cells (WBC)

DifferentialNeutrophils, lymphocytes, monocytes, eosinophils,

basophils, bandsMust specify whether to include with CBC order

Red blood cells (RBC, HGB, HCT)PlateletsMean corpuscular volume (MCV)Red cell distribution width (RDW)

Fish bone diagram

Hematocrit : (packed cell volume)It is ratio of the volume of red cell to the volume of whole blood.

M: 40.7 to 50.3 % F: 36.1 to 44.3 %

Red Blood Cells

Transport oxygen via hemoglobin from lungs to peripheral tissues and organs

Normal lifespan = 120 days

Red Blood CellsPeripheral blood smear

Normal

AnemiaCondition resulting from decrease in total body erythrocyte mass

Defined by measurement of hemoglobin concentrationNormal range

Males 14-16 g/dLFemales 12-14 g/dL

Almost 1/3 of the world population is anemic!

AnemiaManifestations related to duration and severity of anemiaBody has physiologic responses to chronic anemia such that many patients are asymptomatic until hgb < 8 g/dL

AnemiaSymptoms

Easy fatigueHeadacheDyspnea on exertion

SignsPallorTachycardiaSystolic ejection murmurOrthostatic hypotension

Anemia

Decrease production-No raw material-Malfunction of the factoryIncrease destruction- Hemolysis-SequestrationBlood lossAcute , chronicExternal , internal

Determining reticulocyte count and MCV are first steps in determining etiology

1- Reticulocyte Count

ReticulocytesImmature red blood cells

Measurement assists in determining cause of anemiaNormal = 1-2%

oMust correct for degree of anemiaoObserved retic count (Actual

HCT/Normal HCT) = Corrected retic count

Reticulocyte CountLow suggests decreased production (i.e. nutritional or bone marrow problem)

High suggests bleeding or premature destruction of red blood cells (i.e. hemolysis)

2- Check the MCV

– MCV = mean corpuscular volume HCT/RBC count= 80-100fL

• small = microcytic• normal = normocytic• large = macrocytic

– MCHC= mean corpuscular hemoglobin concentration HB/RBC count= 26-34%

• decreased = hypochromic• normal = normochromic

Microcytic AnemiaMicrocytosis – small cells (MCV <80) Most common type of anemia encountered in

primary careDifferential diagnosis

Hemoglobinopathy (inherited)Iron deficiencyChronic disease (may also be normocytic)InflammationLead poisoning

Check iron studies for clarificationBe familiar with interpretation (see next slide)

Microcytic AnemiaMicrocytosis – small cells (MCV <80) Most common type of anemia encountered

in primary careDifferential diagnosis

Hemoglobinopathy (inherited)Iron deficiencyChronic disease (may also be normocytic)InflammationLead poisoning

Check iron studies for clarification

Microcytic AnemiaPeripheral blood smear

Microcytosis, Hypochromic

RDW ( RBCs distribution width)= 6–8 um

Dx RDW MCV

Iron deficiency

FOLATE &VIT B12

RECENT Hge

NORMAL

. High RDW

-Iron Deficiency Anemia: usually presents with high RDW with low MCV-Folate and vitamin B12 deficiency anemia: usually presents with high RDW and high MCV-Recent Hemorrhage: typical presentation is high RDW with normal MCV

Macrocytic AnemiaMacrocytosis – large cells (MCV >100)Differential diagnosis

B12 deficiencyPernicious anemiaFolate deficiencyMyelodysplasia (pre-leukemia)Medication effect

Check vitamin B12, RBC folate, Fasting homocysteine, and

methylmalonic acid (MMA)are elevated in subclinical B12 and folate deficiency

Hemolytic AnemiaHistory and physical findings

Review PMH, FH, and medicationsJaundiceAbdominal discomfort

Lab findingsElevated reticulocyte count

Reflects bone marrow compensating for peripheral RBC destruction

Elevated LDH Elevated total bilirubin (indirect/unconjugated)Decreased haptoglobinAbnormal cells on peripheral blood smear

examination

Hemolytic AnemiaCongenital

Membrane defects Hereditary spherocytosis

Splenectomy is curative Hereditary elliptocytosis

Enzyme defectsG6PD deficiency

Affects 10% of world population Common in patients of African descent Precipitated by stress, infection, drugs, and fava beans Hemolysis mostly extravascular but may be intravascular if

severe case

Hemolytic AnemiaAcquired

Classified according to site of RBC destruction and whether mediated by immune systemIntravascularExtravascularAutoimmuneNon-immune

Many causes… be aware of these – Transfusion of incompatible blood (details later) Autoimmune

Warm (IgG-mediated) ; most common Cold (IgM-mediated)

Prosthetic valves TTP/HUS DIC Cancer Drugs

Hemolytic Anemia

Coomb’s Test (DAT)Used to screen for autoimmune hemolytic anemia

Polycythemia / ErythrocytosisAbnormal elevation of hemoglobinRule out “relative” polcythemia caused by contraction of plasma volume, e.g. dehydration

PrimaryPolycythemia Vera

SecondaryRBC production in response to increased EPO productionEPO level is usually high

White Blood CellsDifferential

Neutrophils 45-65%“Segs” / “Polys”

Lymphocytes 15-40%Monocytes 2-8%Eosinophils 0-5%Basophils 0-3%

Do you remember the physiologic role of each type of WBC?

LeukopeniaNeutropenia is most common cause

Absolute neutrophil count (ANC) < 1.5 x 109

cells/LMany causes

Viral infectionsEpstein-Barr, Hepatitis B, HIV

Drugs *Careful review of medications ;

SplenomegalyAutoimmune disorders = SLE (lupus),

RheumatoidBone marrow disorders

NeutropeniaCommon Medicinal Causes of Neutropenia

Cytotoxic agents

Antibiotics (Penicillins, Cephalosporins, Sulfonamides)

Anticonvulsants

NSAIDs

Antithyroid agents (Methimazole, PTU)

Phenothiazines

Allopurinol

Cimetidine

Diuretics (HCTZ, Spironolactone)

LeukocytosisWBC count > 11,000Determine which type of WBC is

leading to the leukocytosisNeutrophilia = most common

InfectionConnective tissue disordersMedications (especially steroids, growth

factors)Cancer (CML and solid tumors)Myeloproliferative disordersCigarette smokingStress (physiologic)

Pain, seizure, traumaIdiopathic

LeukocytosisPatients with acute bacterial infection

often present with neutrophilia and band formation ; i.e. “left shift”Bands = young neutrophils

Viral infections are usually associated with low WBCs ; leukocytosis may suggest complicationsEx: bacterial pneumonia with underlying influenza infection

Chronic LeukemiaChronic myelogenous leukemia (CML)

Translocation between long arms of chromosomes 9 and 22 ; “Philadelphia Chromosome” ; bcr/abl protein

Patients usually middle-age at diagnosis, average age 55 years

Fatigue, fever, night sweats, abdominal fullness (splenomegaly)

Symptoms of leukostasis may be present if WBC > 500,000Blurred vision, respiratory distress, priapism

Three phases of diseaseEarly / Chronic phaseAcceleratedBlast crisis

Chronic LeukemiaCML, Vs leukomoid reaction

Can you recognize early CML from infection?WBC usually < 50,000 with infectionWBC average 150,000 at time of

diagnosis with CMLLAP score is decreased with CMLSplenomegaly NOT present with

infectionChromosomal abnormality and

detection of bcr/abl protein by peripheral blood PCR is diagnostic of CML

Acute LeukemiaMyeloblast

Bleeding DisordersCoagulation cascade

Bleeding DisordersReview coagulation cascade ; general

understanding is essential for clinical practice

Prothrombin time (PT) evaluates extrinsic systemFactors I, II, V, X, VII

Activated partial thromboplastin time (PTT) evaluates intrinsic systemFactors I, II, V, X, VIII, IX, XI, XII

Bleeding time reflects platelet number and function

Bleeding Disorders

Bleeding DisordersApproach to patient

History of trauma? Time between injury and bleeding?

Ask about bleeding at times of life eventsCircumcisionTooth eruptionDental extractionEar piercingChildbirthMenstrual cycles

Family historyDid you know 30% of patients with hemophilia have

unremarkable family history? Spontaneous mutation of X chromosome

Bleeding Disorders

Patterns of bleedingPrimary hemostasis – platelet and vascular function

Secondary hemostasis – clotting factors

Characteristic Primary hemostasis

Secondary hemostasis

Onset Spontaneous and immediate

Delayed after trauma

Usual site Skin, mucous membranes

Deep tissues / hemarthrosis

Other sites Rare Retroperitoneum, CNS

Examples Thrombocytopenia, platelet defects (vWD)

Factor deficiency or inhibitor

Bleeding Disorders

Bleeding Disorders

Acute hemarthrosis

Bleeding DisordersPetechiae in patient with acute ITP ;

platelet count = 10,000

Heparin-Induced Thrombocytopenia (HIT)Occurs in 3% of patients exposed to UFH ;

0.6% with LMWHDrop in platelet count ≥ 50% within 5-10

days of heparin exposureMay occur within 48 hours of exposure in those

previously exposed to drugsThrombosis (NOT bleeding) is of great

clinical concernThrombotic events detected in about half of HIT

patientsMust STOP heparin and consult hematologyDirect thrombin inhibitor (alternative anticoagulant)

may be startedArgatroban®Refludan®