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White Blood Cells
(WBC)
Normal and Abnormal
Dr. Alia ALFARAEDI
Consultant Haematologist
This normal peripheral smear demonstrates a segmented
neutrophil and a band neutrophil.
This normal peripheral smear demonstrates a segmented
neutrophil and a lymphocyte.
This normal peripheral smear demonstrates a monocyte.
This normal peripheral smear demonstrates an eosinophil
and a lymphocyte.
Normal WBCs
Functions of White Blood Cells
Phagocytosis
The neutrophils and the monocytes engulf foreign particles and
bacteria through their phagocytic action, thereby destroying their
action.
Body defense
WBC manufactures anti-bodies and immune bodies to increase the
power of resistance against any infection.
Formation of fibroblast
Lymphocytes may be converted to fibroblasts in the area of
inflammation and help the process of tissue repair and regeneration.
Functions of White Blood Cells
Secretion of heparin
The basophile leucocytes are supposed to secrete heparin (a substance of
liver), which prevent, intravascular clotting.
Anti histamine functions
The eosinophils are believed to defend the body against allergic
conditions in which histamine like bodies are produced in excess.
Destroy Cancer Cells
In addition to recognizing and killing virally infected cells, T lymphocytes
can also target and kill tumor cells or abnormal cells that may represent the
early beginnings of a tumor.
Functions of White Blood Cells
Production of thromboplastic substances
Due to the production of such substances, the process of
coagulation and the deposit of clot are facilitated.
Manufacture of trephones:
Leucocytes manufacture certain substances called trephones from
plasma protein, which exert great influence on the nutrition, growth
and repair of tissues.
WBCs ABNORMALITIES
Benign
Quantitative
Leukocytosis
Leukopenia
Qualitative Abnormalities
Leukemia
Laboratory Evaluation
Morphology
Cytochemistry
Genetic analyses
chromosomal
molecular
Immunology
Acute
Myeloid Leukemia
Lymphoid Leukemia
Chronic
Myeloproliferative Disorders
Lymphoid Leukemia
Myelodysplastic Syndromes
Lymphoma
Immunosecretory Disorders
Myeloma
Other Plasma Cell Disorders
Neutrophilia
Causes
• Acute infections:
Bacterial, viral, fungal,
mycobacterial and rickettsial
•
Physical stimuli:
Trauma, electric shock,
anoxia, pregnancy
•
Drugs and chemicals:
Corticosteroids
adrenaline, lead,
mercury poisoning, lithium
•
Hematological causes:
Acute haemorrhage, acute haemolysis,
transfusion reactions, post-splenectomy,
leukaemia and myeloproliferative disorders.
•
Malignant disease:
Carcinoma, especially of gastro-intestinal tract, liver or bone marrow
•
Miscellaneous conditions:
Certain dermatoses, hepatic necrosis, chronic idiopathic leucocytosis
Lymphocytosis
Non-Malignant causes
• Virus infections:
Infectious mononucleosis
Infectious lymphocytosis
Cytomegalovirus infection
Occasionally mumps, varicella,
hepatitis, rubella, influenza
• Bacterial Infections:
Pertussis
Occasionally cat-scratch fever, tuberculosis, syphilis, brucellosis
• Protozoal infections:
Toxoplasmosis
Occasionally malaria
• Other rare causes:
Hyperthyroidism, congenital adrenal hyperplasia
Monocytosis
Causes
• Chronic bacterial infections:
Tuberculosis, subacute bacterial endocarditis, brucellosis
• Other Specific Infections:
Malaria, Kala-azar, trypanosomiasis,
typhus, Rocky Mountain spotted fever
• Malignant diseases:
Hodgkin’s disease, carcinoma
• Leukaemia:
Acute myeloid leukaemia
Chronic monocytic leukaemia
• Neutropenias:
Familial benign and severe neutropenia
Cyclical neutropenia
Drug-induced Agranulocytosis
• Miscellaneous:
Cirrhosis, systemic lupus erythematosus, rheumatoid arthritis
Eosinophilia
Causes
• Allergic reactions:
Asthma, hay fever, urticaria,
angioneurotic oedema
• Parasitic Infestation:
Tissue parasites – trichinosis, filariasis,
visceral larva migrans, etc..
Intestinal parasites – Ascaris, Taenia, etc. (less regularly)
• Skin disorders:
Pemphigus, pemphigoid, eczema, psoriasis, (dermatitis herpetiformis)
• Drug hypersensitivity reactions::
Especially iodides, penicillin, allopurinol, gold salts, tartrazine
Loffler’s pulmonary syndrome and Loffler’s endomyocarditis
Tropical eosinophilia (probably filarial)
Eosinophilia
Causes (Cont…)
• Malignant diseases:
Especially Hodgkin’s disease,
carcinoma of ovary, lung stomach,
angioimmunoblastic lymphadenopathy.
• Following irradiation or splenectomy:
Hypereosinophilic syndromes
Eosinophilic leukaemia
• Miscellaneous Conditions:
Polyarteritis nodosa, ulcerative colitis, sardoidosis, scarlet fever,
pernicious anaemia, chronic active hepatitis, eosinophilic granuloma,
familial eosinophilia
Leukaemoid Reaction or Leucoerythroblastic
Anaemia
Causes
• Severe infections, especially in children:
a. Pneumonia, septicaemia, meningococcal meningitis
b. Infectious mononucleosis, pertussis
• Intoxications:
Eclampsia, severe burns, mercury poisoning
• Neoplasia:
Especially with bone-marrow infiltration
• Severe haemorrhage or haemolysis
Neutropenia
Causes
• Drugs:
Selective neutropenia
Agranulocytosis (Aplastic anaemia)
• Infections:
Viral – including hepatitis, influenza, rubella
Bacterial – typhoid fever, brucellosis, miliary tuberculosis
Rickettsial and protozoal infections (Sometimes)
• Megaloblastic anaemia:
Vitamin B12 or folate deficiency
• Chronic neutropenia:
Chronic idiopathic neutropenia
Immune neutropenia
Congenital neutropenias
Cyclical neutropenia
Neutropenia
Causes (cont…)
• Hypersplenism:
Primary
In association with cirrhosis, Felty’s syndrome, etc…
• Ionizing radiation and cytotoxic drugs:
Radiotherapy
Alkylating agents, antimetabolites, others
• Malignant disease:
Acute leukaemia
Leuco-erythroblastic anaemia due to metastatic carcinoma,
multiple myeloma or lymphoma
• Micscellaneous conditions:
Systemic lupus erythematosus, myxoedema, hypopituitrism,
iron deficiency, anaphylactic shock
Lymphopenia
Causes
• Loss:
Mostly from gut as in intestinal lymphangiectasia,
Whipple’s disease and rarely Crohn’s disease
Thoracic-duct fistula
• Maturation:
Primary, or secondary to gut disease
Vit B12 or folate deficiency
Zinc deficiency
• Pharmacological agents:
Antilymphocyte globulin
Corticosteroids
Cytotoxic drugs
Lymphopenia
Causes (Cont…)
• Infections:
Severe septicaemias
Influenza, occasionally other virus infections
Colorado tick fever
Miliary tuberculosis
• Other miscellaneous conditions:
Collagen vascular diseases, especially SLE
Malignant disease
Other conditions with lymhocytotoxins
Radiotherapy
Graft-versus-host disease
Leukocyte
Morphological Abnormalities
Congenital and Aquired
Leucocytes Congenital Abnormalities
Alder Reily Anomaly
May-Hegglin Anomaly
Alder Reily Anomaly
Pelger Huet Anomaly
Chediac Higashi Anomaly
Leucocytes Congenital Abnormalities
Pelger Huet Anomaly
(MPO)
(MPO)
(MPO)
Myeloperoxidase (MPO) Deficeincy
Leukocyte Abnormalities
Dohle Body
Cytoplasmic Vaculation
Toxic Granulation
Hypersegmented Neut.
Case Studies
CASE 1
• History:
This 20 year old male came to the emergency
room with severe abdominal pain in the right
lower quadrant. He had a fever of 39 0C. On
examination, he had a rigid abdomen & rebound
tenderness in the right lower quadrant. There
were no other abnormalities.
CASE 1
CASE 1
Urinalysis was within normal limits. A CBC
showed Hgb 140 g/l, WBC 25 X 109/L, and
platelet count 350 X 109/L.
CASE 1
What are the WBCs predominantly seen?
Mainly neutrophils
Notice that the WBC count is higher than in a normal
smear.
In addition a small but increased number of band forms
are seen.
The platelets are moderately increased in number.
CASE 1
What is the name for this type of leukocyte reaction?
This reaction is known as neutrophilia.
CASE 1
What do you think the diagnosis is?
The diagnosis is acute appendicitis
(most, but not all, cases of acute appendicitis are
associated with neutrophilia).
CASE 2
• History:
This 17 year old female was sent home from
summer camp because of weakness,
lassitude, and sore throat. On examination
she was found to have an inflamed pharynx,
enlarged tonsils, several enlarged and slightly
tender lymph nodes in the neck, a palpable
spleen, and a tender palpable liver edge.
CASE 2
CASE 2
CBC showed Hgb 149 g/l, WBC 12.5 X 109/L,
and platelet count 282 X 109/L
CASE 2
What are the WBCs predominantly seen?
The predominant cells are lymphocytes with
many atypical lymphocytes.
CASE 2
What is your diagnosis in this case?
infectious mononucleosis.
CASE 2
What is the differential diagnosis?
-
Other viral infections including hepatitis and
cytomegalovirus.
-
It should not be confused with leukemia.
CASE 2
What other laboratory test that may be helpful in arriving
at a specific diagnosis?
serologic test for infectious mononucleosis like
Paul-Bunnell test would confirm the diagnosis in most
cases.
CASE 3
• History:
This 40 year old male complains of
progressive weakness for a month. On
examination, few small lymph nodes were
palpable in both axillae with tip spleen and
sternal tenderness detected.
CASE 3
CASE 3
• CBC showed Hgb 102 g/l, WBC 67 X 109/L, and
platelet count 36 X 109/L
CASE 3
What are the WBCs predominantly seen?
The WBC's in this smear are myeloblasts. Platelets are
reduced in number with some large forms are seen.
CASE 3
What do you think the name of the intracytoplasmic
marker which is seen and diagnostic in this case?
The diagnostic marker
is
Auer rod
CASE 3
What is your diagnosis?
Acute myeloblastic leukemia (AML).
Most patients with acute leukemia have a markedly
decreased platelet count.
Myeloblasts will be positive for peroxidase or Sudan
black stain which is characteristic of granulocytic series.
M0
M1
M2
M3
M4
M5a
M5b
M6
Acute Myelogenous Leukemia
M7
CASE 4
• History:
This 70 year old male was in good health
except for mild hypertension., A CBC showed
at his last check-up a very high WBC count
and his examination revealed several slightly
enlarged lymph nodes in the neck and the
axillae with a palpable spleen.
CASE 4
CASE 4
CBC showed Hgb 128 g/dl, WBC 130 X 109/L,
and platelet count 330 X 109/L
CASE 4
1. What are the WBCs predominantly seen?
Those are small to medium-sized lymphocytes with
smudged lymphocytes. In addition, fewer number of
prolymphocytes is seen.
2. What is the differential diagnosis?
The only real diagnostic consideration in this case is
chronic lymphocytic leukemia (CLL).
CASE 5
• History:
This 46 year old male presented with
increasing fatigue and discomfort in the left
upper quadrant. His examination revealed a
moderately enlarged spleen, liver edge and
few slightly enlarged cervical lymph nodes.
CASE 5
CASE 5
CASE 5
CBC shows Hgb 132 g/l, WBC 56 X 109/L,
and platelet count 754X 109/L
CASE 5
What are the types of white blood cells seen?
The WBCs show a wide range of granulocytes at various
stages of maturation (rare blasts and promyelocytes,
myelocytes, metamyelocytes, bands and neutrophils).
There is an increase in eosinophils and basophils.
Platelets are moderately increased in number with some
large forms seen.
CASE 5
What is the differential diagnosis and how could it be resolved?
- The differential diagnosis is leukaemoid reaction versus chronic
granulocytic leukemia.
- The increase in eosinophils and basophils suggests leukemia.
- A neutrophil alkaline phosphatase (NAP) score would also be of help
(high with leukaemoid reaction, low with chronic myelogenous
leukaemia).
- A positive Philadelphia chromosome and BCR-ABLE gene mutaton
would confirm the diagnosis of CML.
CASE 5
What is your diagnosis in this case?
The diagnosis is chronic granulocytic (myelogenous) leukaemia (CML).
CASE 6
• History:
A 5 year old boy presented with high fever for
the last few days and easy fatigability for four
weeks. His mother complained that he gets
big bruises after any minor hits.
.
CASE 6
• CBC shows Hgb 98 g/l, Hct 28.2, MCV 95, platelet count
64x109/l and WBC count 2.1x109/l.
• Differential WBC count: 25% segs, 13% bands, 11%
monos, 46% lymphs, 4% eos, and 1% baso.
• Bone marrow examination showed replacement by blast
cells which have high nuclear / cytoplasmic ratio with fine
chromatin and indistinct nucleoli.
• Those blasts showed no Auer rods and were positive for
CD10 (CALLA) antigen.
CASE 6
Acute Lymphocytic Leukemia
1. What are the WBCs predominantly seen?
They are predominantly lymphoblasts.
2. What is the most likely diagnosis?
The most likely diagnosis is acute lymphocytic
leukemia (ALL).
M0
M1
M2
M3
M4
M5a
M5b
M6
Acute Myelogenous Leukemia
M7
Acute Lymphoblastic Leukaemia
Laboratory Diagnosis - FAB Classification
ALL (L1)
ALL (L2)
ALL (L3)
MULTIPLE MYELOMA
Mott Cell