Activate Windows

Go to Settings to activate Windows.

H-l Hematology Toronto Notes 2023

Table 2. Common Erythrocyte Shapes

Shape Definition Associated Conditions

Discocyte Biconcave disc Normal RBC

Spheroidal RBC (due to membrane defect or loss Hereditary spherocytosis,immune hemolytic anemia

of membrane)

Sphcrocytc

Oval-shaped,elongated RBCs

• Elliptocytes:the RBC long axis is >2x the length

of theshort axis

•Ovalxytes:the RBC long axis is <2xthe length

of the short axis

Schistocyte (helmet cell,fragment) Fragmented cells (due to traumatic disruption of

membrane)

Elliptocyte/Ovalocyte Hereditary elliplocytosis.megaloblastic anemia.ME.

Iron-deficiency anemia (pencil forms),and MDS Q

MAKJUMA (HUS.aHUS.TIP.DIC.preeclampsia.HELLP.

malignant HTN),vasculibs.glomerulonephritis,bums,

P

and prosthetic heart valves

Sickle Cell Sickle-shaped RBC (due to potyrreriration of HbS) Sickle cell disorders:HbSC.HbSS

y

Codocyte (target cell) “Bull's eye"(due to a surface tiiat is

disproportionately large compared to their volume) anemia,and asplenia

Liver disease,HbSC.thalassemia,iron deficiency

o

Single pointed end.looks like a teardrop ME.MDS.3-thalassemia,megaloblastic anemia,and

BM infiltration

Dacrocyte (teardrop cell)

6

Distorted RBC with irregularly distributed thornlike projections|due toabnormal membrane lipid

or proteincomposition)

Severe liver disease (spur cell anemia),starvation/

anoreiia.and post

-splenectomy

Acanthocyte (spurcell)

&

Echinocyte (burr cell) RBC with numerous regularlyspaced,small,spiny

projections

Uremia.HUS,burns,cardiopulmonary bypass,posttiansfusion.and storage artifact o

Aggregates of RBCs resembling stacks of coins

(due to increased plasma concentration of high

molecular weight proteins)

Rouleaux Formation Pregnancy is most common cause (due to

physiological increase m fibrinogen),inflammatory

conditions (due lo polyclonal immunoglobulins),

plasma cell dyscrasias (due to monoclonal

paraproteinemia,e.g.MM.macroglobulinemia),and

storage artifact

Illustrations: Ayarah Hutchinsand Merry Shryu Wang 2012

Table 3. RBC Inclusions

Inclusions Definition Associated Conditions

Hudeus Present in erythroblasts (immature RBCs) Hyperplastic erythropoiesis (seen in hypoxia,

hemolytic anemia).BM infiltrationdisorders,and

HPNs IMF)

Heinz Bodies E6PD deficiency (post-exposure to oxidant),

tha'assemia,and unstab'

e Hb

Denatured and precipitated Hb

0

Small spherical nuclear remnant,typically in

periphery and ordinarily removed by the spleen

Post-spieredomy.hyposplemsm (SCO),neonates,

and megaloblastic anemia

Howell-Jolly Bodies

Basophilic Stippling Deep blue granulations Indicating ribosome

aggregation

Thalassemia,heavy metal(Pb.In.Ag.Hg)

poisoning,megaloblastic anemia. MDS.and

hereditary (pyrimidine 5'

-nudeotidase deficiency)

Sideroblasts late erythrocytes in BM with Fe-containing granules Hereditary,idiopathic,drugs,ethanol.

hypothyroidism (see SideroblasticAnemia.//17).

MDS.and toxins (Pb)

in thecytoplasm

*

r1

L J

Illustrations:Ayalah Hutchinsand Merry Sh.,u Wang 2012

+

Activate Windows

Go to Settings to activate Windows.

H5 Hematology Toronto Notes 2023

WHITE BLOOD CELLS

lymphocytes

comprise 30-40% of WBCs;great variation in “normal" lymphocyte morphology

the major classes oflymphocytes include:Tcells, B cells, and natural killer (NK) cells

nucleus occupies -90% of cytoplasm

• neutrophils

normally,only mature neutrophils (with 3-4 lobed nuclei) and band neutrophils(immediate

precursor with horseshoe-shaped nuclei) are found in circulation

hypersegmented neutrophil: >5 lobes suggests megaloblastic process (B12 or folate deficiency)

left shift (increased granulocyte precursors)

seen in leukemoid reactions: acute infections, pregnancy, neonates, hypoxia,shock, MPNs

(CML, Ml-

'

),and G-CSF (growth factor that stimulates neutrophil production) use

Left

m

Shift

• Refersto an increase in granulocyte

precursorsin the peripheral Wood

film (myelocytes,metamyelocytes,

promyelocytes, blasts).If present

implies increased marrow production

of granulocytes(e.g.inflammation,

infection.G-CSF administration.CML)

• The presence of predominantly blasts

in the peripheralsmear without

further differentiated precursor cells

or mature neutrophils,suggests

clonal cell disorder (MDS, acute

leukemias)

. If >20% of the total WBC differential

consists of blasts,this is acute

leukemia and is a medical emergency

• blasts

immature, undifferentiated precursors; associated with acute leukemia, MDS, and G-CSF use

Table 4. Abnormal WBC on Film

Appearance Definition Associated Conditions

SmudgeCell Lymphocytes damaged during blood film

preparation indicating cell fragility

CLL and other lymphoproliferative disorders

Or

Cytoplasmic inclusions lhal form long needles in Pathognomonic for AML

the cytoplasm of myeloblasts

Auer Rod

Atypical Lymphocyte Pale blue cytoplasm withpink granules.

Cytoplasm is indented by RBC edges

Viruses [particularly EBV) and T-LGL leukemia

Illustrations:Ayalah Hutchins and Merry Shiyu Wang 2012 and Danielle Sayeau 2017

PLATELETS

• small, purple, anuclear cell fragments

Bone Marrow Aspiration and Biopsy

•sites: posterior iliac crest/spine, sternum (aspiration only)

•analyses: most often done together

• aspiration: takes a fluid marrow sample for cellular morphology (includes iron stain), flow

cytometry, cytogenetics, molecular studies, and microbiology (C&S, acid-fast bacilli smear and

culture, and PCR)

note: differential diagnosis for a

“

dry tap”: MF, hairy cell leukemia, BM infiltration

biopsy: takes a sample ofintact BM to assess histology (architecture) and immunohistochemistry

only aspirates, not biopsies, can be obtained from the sternal site

Indications

•unexplained CBC abnormalities

•diagnosis and evaluation of infiltrating cancers: plasma cell disorders, leukemias, and solid tumours

•diagnosis and staging oflymphoma or solid tumours

•evaluate iron metabolism and stores (gold standard, but rarely done)

•evaluate suspected deposition and storage disease (e.g. amyloidosis, Gaucher’

s disease)

•evaluate fever of unknown origin,suspected mycobacterial, fungal, and parasitic infections, or

granulomatous disease

•evaluate unexplained splenomegaly

•confirm normal BM in potential allogeneic hematopoietic cell donor

Important Considerations

•do not perform a BM biopsy ifthere is evidence of infection over the targeted skin site

•risk of procedure: 1 /100 chance ofbleeding, very rare infection risk

r -i

L J 1

+

Activate Windows

Go to Settings to activate Windows.

H6 Hematology Toronto Xotes 2023

Common Presenting Problems

Anemia

Definition

• a decrease in RBC mass that can be detected by Hb concentration, Hct, and RBC count

adult males:Hb <130 g/L or Hct <38%

adult females:Hb <120 g/L or Hct <37% (changes with pregnancy and trimester)

[ Low Hemoglobin j

1 1

[Normal MCV (80-100) Low MCV (<80)

J

•Thalassemia

• Anemia of chronic disease

•Iron deficiency

•Lead poisoning

•Sideroblastic anemia

High MCV (>100)

Megaloblastic

• B

^

deficiency

• Folate deficiency

• Drugs that impair DNA

synthesis (methotrexate,

sulfa, chemotherapy)

• Orotic aciduria

Non-megaloblastic

• Liver disease

• Alcoholism

• Reticulocytosis (see

high reticulocyte,on left)

• Hypothyroidism

• MDS

1 I

High reticulocyte

Increased destruction (reties >2-3%)

Low reticulocyte

Decreased production (reties<2%)

I I

Non-pancytopenia

• Anemia of chronic disease

• Renal/liver disease

• Red cell aplasia

Hemolysis

Inherited

• Hemoglobinopathy (sickle cell disease,

thalassemia,unstable Hb)

• Membrane (spherocytic)

• Metabolic (HMP shunt,glycolytic pathway)

Acquired

•Immune (Coombs positive,drug-related,

cold agglutinin)

• Infection (malaria)

• MAHA/TMAIDIC,TTP,HUS, HELLP)

• Oxidative/drug-related

• Prosthetic heart valve

Bleeding Pancytopenia

• Aplastic anemia

• MDS

• MF

• Leukemia

• TB

• Amyloidosis, sarcoidosis

• Drugs (e.g. chemotherapy)

• BM infiltration

• PNH

• Gl

• GU

• Other

HMP - hexose monophosphate

Figure 2. Approach to anemia -classification by MCV

Clinical Features

•history

symptoms of anemia:fatigue, headache,light-headedness, malaise, weakness, decreased exercise

tolerance,dyspnea, palpitations, dizziness, tinnitus, and syncope

acute vs. chronic, bleeding,systemic illness,travel, medications, diet (l-

'

e, Bi > sources), alcohol,

and family history

menstrual history:menorrhagia, menometrorrhagia

rule out pancytopenia (recurrent infection, mucosal bleeding, easy bruising)

•physical signs

HEENT:pallor in mucous membranes and conjunctiva at Hb <90 g/L, ocular bruits at Hb <55

g/L, angular cheilitis, jaundice

cardiac:tachycardia, orthostatic hypotension,systolic flow murmur, wide pulse pressure, signs of

CHE

dermatologic: ecchymosis, petechiae, pallor in palmarskin creases at Hb <75 g/L, jaundice (if due

to hemolysis), nail changes (spooning), and glossitis

splenomegaly, lymphadenopathy

Investigations

•rule out dilutional anemia (low Hb due to increased effective circulating volume)

•CBC with differential, reticulocyte count, and blood film

•rule out nutritional deficit, gastrointestinal and genitourinary disease in iron deficiency anemia

•additional laboratory investigations as indicated (see Microcytic Anemia, HI4,Normocytic Anemia,

H17, Hemolytic Anemia, HIS, and Macrocytic Anemia, H25)

•N.B. may have a mixed picture with multiple concomitant nutritional deficiencies

Treatment

•treat underlying cause (see Microcytic Anemia, H14, Normocytic Anemia, H17, Hemolytic Anemia,

H18, and Macrocytic Anemia, H25)

Reticulocytes

• Reticulocytes are immature

erythrocytes and are markers of

erythrocyte production (t colour,

*

central pallor,» size)

• The reticulocyte count should always

be interpreted in the context of Hb

concentration

• The reticulocyte count should

normally increase in response to a

decrease in RBC

• With blood loss,reticulocytes should

increase 2-3x initially and then 5-7x

over the next week

• A normal reticulocyte count in

anemia should be interpreted as

a sign of decreased production,

and may result from BM infiltration,

nutritional deficiency,or other causes

• Anemia with reticulocytosis suggests

appropriate bone marrow response

rn

L J

+

Activate Windows

Go to Settings to activate Windows.

H7 Hematology Toronto Notes 2023

Erythrocytosis

Definition

• an increase in Hb and/or Hct: Hb >165 g/L or Hct >49% (males); Hb >160 g/L or Hct >48% (females)

Etiology

• relative/spurious erythrocytosis (decreased plasma volume); diuretics,severe dehydration, burns, and

“stress" (Gaisbdck'

ssyndrome)

• absolute erythrocytosis

Table 5. Etiology of Erythrocytosis

Primary Secondary Inappropriate Production of Erythropoietin

Physiologic (poor tissue oxygenation/hypoxla)

(see PolycythemiaVeto.H43) Carbon monondc poisoning

Heavy smoking

High altitude

Pulmonary Oiseaso

COPO

Sleep apnea

Pulmonary hypertension

Cardiovascular Disease

R tolshunt (Eisenmenger syndrome)

Hemoglobinopathy

High Ot affinity Hb

Methemoglobinemia

Tumours

Hepatocellular carcinoma

Renal cell carcinoma

Cerebellar hemangioblastoma

Phcochromocytoma

Uterine leiomyoma

Ovarian tumour

Other

Polycystic kidney disease

Renal artery stenosis

Post-kidney transplant

Hydronephrosis

Androgens

Exogenous EPO

PV

Clinical Features

• secondary to high red cell mass and hyperviscosity

headache, dyspnea, dizziness, tinnitus, visual disturbances, hypertensive symptoms, and paresthesia

symptoms of angina,CHE, and aquagenic pruritus(only in MPNs)

• thrombosis (venous or arterial) or bleeding (seen with acquired V WD or acquired platelet dysfunction

in MPNs)

• physical findings

splenomegaly ± hepatomegaly,facial plethora/ruddy complexion (70%) and/or palms,gout

Investigations

• serum EPO:differentiates primary (low/normal) from other etiologies(elevated)

search for tumour assource of EPO asindicated (e.g. abdominal U/S,CT head)

JAK-2 mutation analysis:positive in >96% of cases of PV

only send if low/normal EPO level

• ferritin (iron deficiency can mask the diagnosis; if iron deficient with reticulocytosis,suggestive of PV)

Treatment

• if primary:see Polycythemia Vera, H43

• ifsecondary: treat underlying cause

02 for hypoxemia, CPAP forsleep apnea,surgery for EPO-secreting tumours, counselling

and education (e.g.smoking cessation,work environment), use the lowest dose possible if on

androgen therapy

often cardiologists will be hesitant to treat high Hct in cyanotic patients

&

Rule-of

-thumb:a deficit in all cell

(nessuggests decreased production,

sequestration, or hemodilution. A deficit

in platelets and RBCssuggests nonimmune destruction or Evan'

ssyndrome.

An isolated thrombocytopenia suggests

an immune-mediated process. In

hospitalized patients, drugs and

Infection account for the majority of

cases of thrombocytopenia

Thrombocytopenia

Definition

• platelet count <150 x 10 9/L

Clinical Features

• history: mucocutaneous bleeding (easy bruising, gingival bleeding), epistaxis, perioperative bleeding

(including dental procedures), heavy menstrual bleeding, peripartum bleeding, and G1 bleeding

• physical exam: bruising, pctcchiae, ccchymoses, non-palpable purpura, and wet purpura

• see Disorders of Primary Hemostasis, H28 for complications

Investigations

• CBC and differential

• blood film

• rule out pseudothrombocytopenia (platelet clumping or platelet satellitism)

decreased production: other cell line abnormalities, blasts (suggesting myeloid malignancy),

hypersegmented PM Ns (suggesting megaloblastic anemia), and leukoerythroblastic changes

(suggesting BM infiltration or fibrosis)

• increased destruction:large platelets (often seen in 1TP),schistocytes (seen in MAHA/TMA)

• workup for nutritional deficiencies: B i R B C, folate

• Pl/INR, aPTT, and fibrinogen if DIG suspected

• LPT'

sif findings of liver disease are present

• H. pylori,HIV, and HCV serology

• abdominal ultrasound to look for splenomegaly

§>

Must rule out

pseudothrombocytopenia: platelet

clumping secondary to EDTA Abs present

In serum. This can be seen on blood film

and confirmed by repeating in a citrated

sample (i.e. using a sodium citrate tube

tocollect blood, rather than EDTA)

ri

Wet vs.Dry Purpura

Wet purpura: hemorrhaging of mucous

membranes

Dry purpura:bruising or petechiae on

skin surface

+

Activate Windows

Go to Settings to activate Windows.

H8 Hematology Toronto Notes 2023

Treatments

• life-threatening bleeding: platelet transfusion (repeat CBC I h post-transfusion to confirm an

appropriate rise in counts)

• ifsecondary: treat underlying cause

• I

'

l

'

P:see Immune thrombocytopenia, H28

(§>

References

APS: see Hematology. H36

Aplastic Anemia:see Hematology. H17

Bi2/Folate Deficiency:see Hematology.

H2S.H26

DIC:seeHematology. H34

HIT:seeHematology.H30

HIV:seeInfectious Diseases.ID27

ITP:see Hematology. H28

Myelodysplasia: see Hematology. H41

Preeclampsia:see Obstetrics.OB26

SLE:see Rheumatology,RH11

( Thrombocytopenia J

$ t T

Decreased f Sequestration ]

Production

Increased

Destruction

Hemodilution

l

Splenomegaly

• Liver disease

• Malignancy

• MF

• Massive

transfusion

• Cardiopulmonary

bypass i I i

Nutritional

• B,deficiency

• Folate

deficiency

Congenital

• Alport

• Fanconi

syndrome

Marrow damage

Aplastic anemia

• Chemotherapy,

radiation

• Drug-induced*

• Malignancy

• MDS

Non - illumine

• DIC

•HP

• HUS

• Preeclampsia

• HELLP

• APS

Immune

•ITP

• Viral (HIV)*

• Systemic (SLE)

• Alloimmune

• HIT

• Drug-induced*

*ln hospitalizedpatientsmost commoncausesof thrombocytopenia are drugs and infection

Figure 3. Approach to thrombocytopenia

Adapted from:Cedi Essentials at Medicine

Thrombocytosis

Definition

• platelet count >450 x 10’/L

• primary thrombocytosis (uncommon): due to MPNs (e.g.CML, PV, primary MP, and ET;rarely

associated with MDS)

• reactive/secondary thrombocytosis (common):acute phase reactant (e.g.surgery, inflammation,

infection, trauma, bleeding,iron deficiency, neoplasm,ischemic injury, and hyposplenia/asplenia)

Clinical Features

• history:trauma,surgery,splenectomy, infection, inflammation, bleeding, iron deficiency, prior

diagnosis of chronic hematologic disorder,and constitutional symptoms (malignancy)

• vasomotor symptoms:headache, visual disturbances,lightheadedness, atypical chest pain, acral

dysesthesia, crythromelalgia, livedo reticularis, and aquagenic pruritus

• clotting risk, bleeding risk (rare)

• physical exam:splenomegaly is a common finding among patients with MPNs

Investigations

• CBC and differential, peripheral blood film,serum ferritin

• non-specific markers of infection or inflammation (e.g. CRP, HSR, ferritin)

• if reactive process has been ruled out, BM biopsy may be required to rule out MPN/MDS

Treatment

• primary:ASA ± cytoreductive agents (e.g. hydroxyurea, anagrelide, interferon-a)

• secondary:treat underlying cause

Pancytopenia

Definition

• a decrease in all hematopoietic cell lines below normal reference ranges

Clinical Features

• anemia:fatigue (see Anemia, H6 )

• leukopenia:recurrent infections (see Neutropenia, H 9)

• thrombocytopenia:mucocutaneous bleeding (see thrombocytopenia, H7)

Investigations

• CBC and differential, peripheral blood film,serum ferritin,reticulocyte count, PT, PTT,blood type

and screen, complete metabolic panel,B12,folate

• non-specific markers of infection or inflammation (e.g.CRP,HSR, ferritin)

• workup as per Figure 4, H 9 and presenting symptoms/physical exam

• if reactive process has been ruled out, BM biopsy may be required

j

+

Activate Windows

Go to Settingsto activat ndows,

H9 Hematology Toronto Notes 2023

( Pancytopenia )

T i

[HypocellularBM ) ( Cellular BM )

I

1" BM disease

• MDS

•Lymphoma

•Leukemia

• Myeloma

2°to systemic disease

• SLE

• Hypersplenism

• Vitamin B»

•Folate deficiency

• Alcoholism

• TB

• Sarcoidosis

• Acquired aplastic anemia

• Inherited aplastic anemia

• SomeMOSs

• MF

• Overwhelming infections

•Toxic depression ol BM

• Anorexia nervosa

• PNH

•HIV

• MF

Figure 4. Approach to pancytopenia

Neutrophilia

Definition

• variable definition, but generally an ANC >7.7 x lO’/L (WHO definition)

Etiology

• primary neutrophilia

CML,chronic neutrophilic leukemia

- other MPNsPV.ET.MF

hereditary neutrophilia (autosomal dominant)

chronic idiopathic neutrophilia in otherwise healthy patients

leukocyte adhesion deficiency

• secondary neutrophilia

stress/exercise/epinephrine:movement of neutrophils from marginated pool into circulating pool

obesity

• infection

inflammation:e.g.rheumatoid arthritis(RA), 1BD,chronic hepatitis, Ml, PE, and burns

• malignancy: hematologic (i.e. marrow invasion by tumour) and non-hematologic (especially large

cell lung cancer)

• medications:glucocorticoids, (3-agonists,lithium, G-CSF

Clinical Features

• signs and symptoms of fever, inflammation, malignancy to determine appropriate further

investigations

• including LAD and organomegaly

• examine oral cavity, teeth, peri-rectal area, genitals, and skin for signs of infection

Investigations

• CBC and differential: mature neutrophils or bands >20% of total WBC suggests infection/

inflammation

• blood film: left shifted WBt.

'

s, Dohle bodies (intracytoplasmic structures composed of agglutinated

ribosomes), toxic granulation, and cytoplasmic vacuoles in infection

• may require BM biopsy if MPN suspected

Treatment

• directed at underlying cause

Neutropenia

Definition

• mild:ANC 1.0-1.5 X lO’/L

• moderate:ANC 0.5-1.0 x lO’/L (risk of infection startsto increase)

• severe:ANC <0.5 x 109/L

• profound:ANC <0.1 x 109/L for >7 d

ANC'WBC count x f%PMNs+ %bands)

Beware of fever + ANC<0.5 x 10’/L -

FEBRILE NEUTROFtNIA

n

L J

+

Activate Windows

^

erto Settingrto^

ctivate Windowsr

H10 Hematology Toronto Notes 2023

Etiology

Table 6. Etiology of Neutropenia

Peripheral Destruction/Sequestration Excessive Margination (Transient

Neutropenia)

Decreased Production

Infection

Viral hepatitis.EBV.HIV.TB.typhoid,malana

HematologicalDiseases

Idiopathic,aplastic anemia.MF.

BM infiltration,cyclic.PNH.MBS.large

granular lymphocyte leukemia,hairy cell

leukemia,immune-mediated

Drug-Induced

Alkylating agents,antimetabotites.

anticonvulsants,antipsychotics.antiinflammatory agents,antithyroid drugs

Toxins/Chemicals

High dose radiation,benzene,dichloto

diphenyl trichloroethane (DDT)

Nutritional Deficiency

Bit.folate

Idiopathic

Constitutional neutropenia,benign cyclic

neutropenia

Idiopathic (most common)

Overwhelming bacterial infection

Hemodialysis

Cardiopulmonary bypass

Racial variation (e.g.African or Ashkenazi

Jewish descent)

Anti-neutrophil Abs

Spleen or lung trapping

Autoimmune disorders:RA (Felty syndrome). Prophylactic Hematopoietic Colony-Stimulating

Factors onMortality andInfection

Aon InternMed 20073(J:«IMT1

Purpose'

treienrerfecsofc:onysfimjlabng

factor (CSF)on mortaltj."Actions,aod fedrile

nentopenia z patects ccdergoagcseaotherapy

orSO.

Study Selection "A!80scnoparcgthe effects

of CSFs to etkeplacebo or so the^

py nere indaded.

Prophylacbc CSFs nere gnen coocrrendy nith or

after mtiaioe of chemotherapy

Results THEREKK no dderecces a a1 cause

modesty or nfectoc -rtlaaddeath between CSF and

placebo groups.Coopered to placebo or no therapy.

CSFs reducedofecioo rate (redar

-ate 38.9%n.

43.1%:raterateOiS).etroboiog-caiy docuoented

mfectnns |M8 23.5%n.28.6%:rate rate 0.88).

a;

dfeb-ienentrppeta (Ml25.3% ts.442%;rate

rebo071

Conclusions Avop-y lactc CSFs decrease infection

ratesaa1epsodesof iebrie oentroaeae npatents

nndergorgcheeotberepy or SCI.but hare toeffect

eneortahty.

Sti

Granulomatosis with polyangiitis (formerly

Wegener's)

Drugs:haptens(e.g.n-melhyldopa)

Clinical Features

• fever, chills (only if infection present)

• infection by endogenous bacteria ( e.g. S. aureus.Gram negatives from Cil and GU tract)

• painful ulceration on skin, anus, mouth, and throat following colonization by opportunistic

organisms

• avoid digital rectal exam

Investigations

• dependent on degree of neutropenia,history, and symptoms

• rangesfrom observation with frequent CBCs and differential with peripheral smears to BM aspiration

and biopsy

Treatment

• manage specific underlying causes and medicationsthat contribute to neutropenia

• regular dental care:chronic gingivitis and recurrent stomatitis are major sources of morbidity

• treatment of febrile neutropenia

• in severe immune-mediated neutropenia, G-CST may increase neutrophil counts

if no response to G-CST, consider immunosuppression (e.g.steroids, cyclosporine, and

methotrexate)

G-CSF-Neupogen: -

filgrastim

Lymphocytosis

Definition

• absolute lymphocyte count >4.0 x 10*/L

Etiology

• infection (reactive lymphocytosis)

• viral infections (majority); particularly mononucleosis

• TB, pertussis, brucellosis, toxoplasmosis

• smoking

• physiologic response to stress(e.g. trauma,status epilepticus)

• hypersensitivity (e.g. drugs,serum sickness)

• autoimmune (e.g.RA)

• neoplasm (e.g.CLL, thymoma, B-cell lymphocytosis of undetermined significance)

• asplenia (e.g. post-splenectomy)

Investigations

• CBC and differential,peripheral smear assessing lymphocyte morphology, and in select cases,flow

cytometry for assessing lineage and clonality

Treatment

• treat underlying cause

Presence of atypical lymphocytes

suggests viral infection

Presence of smudge cels suggests

a tymphoproliferatrve disorder if

persistently elevated above 5.0 x lOM.

for >3 mo:consider flow cytometry of

peripheralblood

r1

L J

+