NOVEMBER 2017 | 1

FAR EASTERN UNIVERSITY – NICANOR REYES MEDICAL

FOUNDATION

HEMATOLOGY LECTURE
(WBC Non – Neoplastic Disorders)

References:
Henry’s Clinical Diagnosis and Management by
Laboratory Methods (22nd edition) by: McPherson and
Pincus

Hematology: Principles and Procedures (6th edition)

by: Barbara Brown

Clinical Hematology: Principles, Procedures,

Correlations by: E.A. Stiene – Martin, Cheryl A. Lotspeich
– Steininger, John A. Koepke

Hematology: Clinical Principles and Application (5th

edition) by: Bernadette F. Rodak
HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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REACTIVE/STRESS-RELATED
WBC DISORDERS

(QUANTITATIVE)

RELATED TERMS:

 __________________ - Increase in the number of WBC count

 __________________ - Decrease in the number of WBC count
 Normal Value of WBC count - 4-11 x 𝟏𝟎𝟗 /L

LEUKOCYTE -PHILIA -PENIA

NEUTOPHILIA NEUTROPENIA

 Absolute count: ______________  Absolute count: _______________

 ___________________________  ____________________________
 Strenuous exercise : ELA2 (neutrophil elastase)
 Labor
 Tachycardia
 Epinephrine  ____________________________
 Cortisone  aplasia
 ____________________________  leukemia
 acute infection  ineffective production
 inflammation (megaloblastic anemia)
NEUTROPHILS  intoxication  physical/chemical agents
 hemorrhage (drugs)
 hemolysis  hemodialysis
 growingtumors  splenic sequestration
 myeloproliferative disorders  autoimmune disorders
 3 MECHANISM OF PATHOLOGIC  debilitated states
NEUTROPHILIA  overwhelming infection
1.  ____________________ - <0.5 x 𝟏𝟎𝟗 /L
 aka: EXTREME NEUTROPENIA
 Associated drugs:
2. 1.
2.
 ___________________________
3. -
- <0.5 x 𝟏𝟎𝟗 /L for 6 months

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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EOSINOPHILIA EOSINOPENIA

 Absolute count: ______________  Absolute count: ________________

 Parasite infestation  Infection or inflammation with
 allergic disorders neutrophilia
EOSINOPHILS  hypersensitivity reaction  Rare:
 tumors  autoimmune disorders with
 malignant myeloproliferative disorders antieosinophil Ab
 ________________________________  hypogammaglobulinemia with
thymoma
 Eosinophilia of ____________  drug allergies
 Rare condition  urticaria

BASOPHILIA BASOPENIA

 Absolute count: _______________________  Difficult to establish

BASOPHILS  Myeloproliferative disorder  Chronic urticaria
 Rare:
 hypothyroidism
 ulcerative colitis
 bee stings
 nephrosis

MONOCYTOSIS MONOCYTOPENIA

 Absolute count: _____________________  Absolute count: ________________

 Relative count is frequently the first sign of  Causes:
MONOCYTES recovery from acute overwhelming infection  Steroid therapy
 Causes:  Hemodialysis
  EBV
  Overwhelming infection in
 immunocompromised patients
  Steroids
 Carcinomas  glucocorticoids
 Granulomatous disease
 Collagen vascular disease
 Malignancies of monocyte cell line

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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LYMPHOCYTOSIS LYMPHOCYTOPENIA

1. Absolute Lymphocytosis  Absolute count:

 Young children ____________
 _____________ in adults  Adults ___________________
LYMPHOCYTES  _____________ in infants
 _____________ in older children  Causes:
 Without morphologic alteration  Steroid therapy
 Pertussis  morphine
 Acute infectious lymphocytosis  Strenuous exercise
 With morphologic alteration  HIV
 IM  Genetic abnormalities
 Infectious hepatitis
 CMV
 Viral influenza
 Lymphoid malignancies
 “Virocytes”
 Reactive lymphocytes
 Atypical lymphocytes
 Variants lymphocytes
 THREE TYPES:
A. TYPE 1



B. TYPE 2



C. TYPE 3


2. Relative lymphocytosis
 w/ variant forms
 Toxoplasmosis
 Thyrotoxicosis
 measles
 mumps
 chickenpox
 w/ normal forms
 neutropenia

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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REACTIVE/STRESS-RELATED
WBC DISORDERS

(QUALITATIVE)

CONDITION / INCLUSION MORPHOLOGIC / FUNCTIONAL DEFECT IMPORTANT REMARKS

LEFT SHIFT  Increase in the number of

_____________________________ 1. MILD
 2 types:  band
1. Degenerative left shift  occasional metamyelocyte
 Often accompanied by 2. MODERATE
_____________________  metamyelocytes
 ex: Tuberculosis  myelocyte
 occasional promyelocytes
2. Regenerative left shift 3. MARKED
 often accompanied by  myelocytes
__________________  promyelocytes
 Ex: Appendicitis  occasional blasts

NUCLEUS

1. Toxic Nuclear Changes

TOXIC  Chronic infection  Seen also in _______________

HYPERSEGMENTATION
 borderline folate deficiency

 Darkly stained nucleus

 condensed chromatin
PYKNOSIS  Imminent cell death

2. Hereditary
 Failure of normal segmentation of nuclei  Most common genetic WBC disorder
 Bilobed, rounded with characteristic  Heterozygous: Normal function
PELGER – HUET spectacle or pince-nez appearance
ANOMALY  DEFECT:

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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TRUE PELGER ACQUIRED PHA /

– HUET PSEUDO

PHA

>80% <50%

NO With
MALIGNANCY myeloproliferative

neoplasm

AML , CML, MDS

 Nucleus has 5 – 10 lobes

 TWO DISORDERS:
HEREDITARY
NEUTROPHIL a. Hereditary Megaloblastic
HYPERSEGMENTATION  Hypersegmented neutrophils
Neutrophil Anemia
 BM myeloid hyperplasia
 Neutropenia Hypersegmentation
 WHIM syndrome
Majority of <50% of
b.
neutrophils are
Must be differentiated with MEGALOBLASTIC neutrophils
ANEMIA hypersegmented

No macrocytic With macrocytic

anemia
anemia

CYTOPLASM

1. TOXIC CYTOPLASMIC CHANGES

 Round or oval blue – staining
DOHLE INCLUSION cytoplasmic inclusions found in DOHLE BODIES MAY – HEGGLIN
BODIES neutrophils ANOMALY
 arranged in parallel rows and consisting
of _____________ Smaller and Round Larger and Spindle
 Must be differentiated from
MAY – HEGGLIN ANOMALY PAS POSITIVE PAS NEGATIVE

rRNA mRNA

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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TOXIC GRANULATIONS  Altered ___________________  Peroxidase (+)

 Due to ____________________  Increase in mucosubstance within
 Dark-blue to purple cytoplasmic granules primary granules
 Seen in: Metamyelocyte, band,  Important marker of
neutrophil  inflammation
 correlates with CRP

TOXIC VACUOLATION  Phagocytosis

 Septic processes
 up to 6 um

 Autophagocytosis

2. HEREDITARY
ALDER-REILLY ANOMALY  Characterized by DENSE AZUROPHILIC  Found in
GRANULATION IN MUCOPOLYSACCHARIDOSES
________________________  Resembles toxic granules
 Normal function

 Granulation is due to ABNORMAL

DEPOSITION OF and STORAGE of
MUCOPOLYSACCHARIDES ( deficiency of
LYSOSOMAL ENZYMES for the
DEGRADATION OF
MUCOPOLYSACCHARIDE)

CHÉDIAK-HIGASHI  Characterized by the presence of  Patient also has immune

SYNDROME (CHS) deficiency, neurologic defects,
bleeding and frequent
 PARTIAL ALBINISM is observed due to bacterial/pyogenic infection
ABNORMAL PACKAGING OF (death)
MELANOSOMES

 Abnormality in granule maturation and

fusion of lysosomes (granules) and
phagosomes (vesicles)

MAY-HEGGLIN  Structural alterations  Pale-blue resembling Dohle

ANOMALY (MHA) bodies but larger and more

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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 Defect: prominent
 Blue staining is abolished with
ribonuclease
 Normal function  Neutrophils, eosinophils,
basophils and monocytes
 Also characterized by:
LEUKOPENIA,
THROMBOCYTOPENIA and
GIANT PLATELETS

FUNCTION

 Neutrophils have  aka HYPERIMMUNOGLOBULINEMIA E

 Elevated IgE, skeletal abnormalities,
JOB SYNDROME recurrent severe bacterial infection
 Dysregulated T cell-cytokine production
aà poor directional motility of
neutrophils (IFNγ, TGFβvs IL4)

 Poor neutrophil response to chemotactic  Also characterized by NEUTROPENIA

LAZY LEUKOCYTE agents
SYNDROME  Abnormal

LEUKOCYTE ADHESION  LAD I

DISORDER  CD11/ CD18 or β2 Integrin
(ICAM) mutation leading to
absence of or abnormal Integrin;
Adhesion; Neutrophilia
 LAD II
 mutation affecting fucose
transport leading to impaired
CD15 or Sialyl Lewis X (Selectin);
Rolling; Neutrophilia
 LAD III
 mutation in G-protein coupled
receptors on leukocytes leading
to failure of integrinactivation

KILLING

CHRONIC  Inherited disorder characterized by  Neutrophils has NORMAL MORPHOLOGY

GRANULOMATOUS DSE.  Formation of GRANULOMA can
(CGD) OBSTRUCT Hollow organs

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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 Mutation in one 1 of the 4 genes for  Neutrophils, eosinophils, monocytes and

NADPH oxidase macrophages
 Cells are able to engulf but

 Test for CGD:

 Nitroblue Tetrazolium Test
 Normal neutrophil can reduce
the yellow nitroblue tetrazolium
to dark-blue formazan
 Flow cytometry
 Dihydrorhodamine-123
 measures intracellular
production of reactive oxygen
species

MPO DEFICIENCY  Low or Absent MPO enzyme  Most Common Neutrophil Abnormality
 Decreased microbial killing because of  Normal WBC morphology
defective MPO—H2O2 system  Commonly BENIGN
 Patients manifest with MILD SYMPTOMS

MACROPHAGE OVERLOAD

STORAGE DISEASES
 Deficiency of enzyme necessary for  Peripheral blood may be normal
degradation of  Reilly bodies in neutrophils,
 Hurlers (dermatan sulfate, heparan sulfate, keratan lymphocytes and monocytes
 Hunter sulfate and or chondroitin sulfate)  BM with macrophages has the presence
 Sanfalippo of metachromatic granules
 Morqui  Lysosomal GAG build-up  Diagnosis is based on assay of specific
 Morqui enzyme
 Ullrich

LIPID STORAGE DISEASE

GAUCHER DISEASE  defect in  Most common lysosomal storage disease

 Cytoplasm – appears as CRUMPLED (AR)
TISSUE PAPER  Macrophage, osteoclasts, microglial cells
  Patients manifest with: Anemia and
– Large macrophage with SMALL, thrombocytopenia
ECCENTRIC NUCLEUS and found in the
BONE MARROW

NIEMANN-PICK  Deficiency of  There is an accumulation of

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM
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 SPHINGOMYELIN in the
– aka PICK CELL – Abnormal cytoplasm of cells in the body.
macrophage whose cytoplasm is filled  More commonly seen in
with many small LIPID DROPLETS ASHKENAZI JEWS
 BM and other organs: foamy  Signs of diseases begins in
macrophages infancy with POOR PHYSICAL
DEVELOPMENT
 Spleen and Liver are greatly
enlarged

This handout is to be used only AS A GUIDE AND NOT AS A SOLE REFERENCE FOR YOUR LECTURE
ABOUT WBC DISORDERS (NON – NEOPLASTIC DISORDERS) IN HEMATOLOGY1. PLEASE READ YOUR
REFERENCE BOOKS FOR A MORE COMPLETE and DETAILED EXPLANATION OF YOUR TOPICS.

If you have any questions about this topic or any topic in other subjects, feel free to ask me  Thank
you! ♥

♥ This may be tough, but so are you! Whenever you find yourself doubting if you can go on, just
remember how far you’ve come. Remember everything you have faced, all the battles you have won and
all the fears you have overcome. Then raise your head high and forge on ahead! Knowing that YOU GOT
THIS and THAT GOD IS WITH YOU!!! ♥

HEMATOLOGY 1 WBC NON –NEOPLASTIC DISORDERS By: TJ Rivera Jaula, RMT, IMLS(ASCPi)CM