Diseases of blood and

blood forming organs

• To understand the etiology, clinical
features, radiographic features(if
any), cytological features and
prognosis of BBC-related pathologies.
 Contents
Disorders involving RBC’s
Anemia
• Classification
• Nutritional deficiency anemia
– Iron deficiency
– Pernicious anemia
– Folate deficiency anemia
– Protein deficiency anemia
• Aplastic anemia
• Haemolytic anemia
– Thalassemia
– Sickle cell anemia
– Erythroblastosis fetalis

Polycythemia
• Disorders involving WBC’s
• Agranulocytosis
• Cyclic neutropenia
• Lazy leukocyte syndrome
• Chédiak-Higashi syndrome

• Infectious mononucleosis

• Leukemia
•Disorders involving platelets
–Purpura

•Diseases involving specific blood factors

–Hemophilia
–Von Willebrand’s disease
Diseases involving the red blood cells

1. Anemia:
Definition: An abnormal reduction in the
number of circulating red blood cells, the
quantity of hemoglobin and the volume of
packed red cells in a given unit of blood.
Structure of hemoglobin
‘Heme’ + ‘globin’
Classifications of anemia…
Classification based on:
– Etiology

– Morphology of RBC’s

– Factors responsible for impaired

production of RBC’s
 Classification based on etiology

A. Blood loss
– Acute
– Chronic

B. Increased destruction of RBC’s

– Extra corpuscular
– Intra corpuscular
• Hereditary
– Abnormalities in RBC membrane
– Abnormalities in globin protein
• Acquired
C. Inadequate proliferation and differentiation of stem cells
– Atrophy of bone marrow: Aplastic anemia

– Chronic renal disease

– Chronic inflammatory disease

D. Impaired proliferation and maturation

– Because of deficiencies

• Iron deficiency

• Folic acid deficiency

• Vitamin B12 deficiency

• Protein deficiency
 Based on the morphology
• Macrocytic anemia:
– (MCV - ↑, MCH - ↑, MCHC – N)

• Normocytic anemia – blood loss anemia

– (MCV – N, MCH- N, MCHC – N)

• Microcytic anemia – anemia due to infection

– (MCV - ↓ , MCH - ↓, MCHC- N)

• Microcytic hypochromic anemia –

Iron deficiency anemia, Thalassemia, Sickle cell anemia
– (MCV- ↓, MCH ↓, MCHC ↓)
Based on the factors responsible for
impaired production of RBC’s
Anemia due to bone marrow dysfunction
- Aplastic anemia

Anemia due to lack of hemopoietic nutrients

- Nutritional anemia

Anemia due to excessive breakdown of RBC’s

- Hemolytic anemia
 Common
Whatever clinical features
its cause???
• Patients appear pale.

• Weakness, malaise, and easy fatigability.

• The lowered oxygen content of the circulating blood leads to:

– dyspnea on mild exertion (lung hypoperfusion)

– angina pectoris (particularly when complicated by preexisting coronary

artery disease)

– headache, dimness of vision, and faintness (CNS)

– oliguria and anuria (renal especially with acute blood loss and shock)

• Koilonychia
Nutritional deficiency anemia…
• Nutritional anemia
– Nutrients required for haemopoiesis –

Iron, folic acid, vitamin B12,

cobalt, copper, ascorbic acid, pyridoxine

• Nutritional anemias are:

– Iron deficiency anemia
– Megaloblastic anemia due to Vit B12/folic acid
deficiency
– Protein deficiency anemia
– Dimorphic anemia
 Iron deficiency anemia
• Hypochromic microcytic anemia

• Most common type of anemia

• Seen more often in females

 Etiology

1. Inadequate dietary intake

2. Faulty iron absorption

3. Chronic blood loss

4. Increased requirement of iron (infancy,

childhood, during pregnancy)
Pathological effects of iron deficiency

– Decrease in haem

– Disturbed nuclei acid synthesis

– Decreased activity/ alterations of iron containing enzymes:

• epithelial atrophy of the tongue/ gastric mucosa

• koilonychia

• alopecia
 Oral manifestations

– Atrophy of the mucosa

– Lemon-tinted pallor of skin/ mucosa

(keratinization loss)

– Glossitis

– Angular cheilitis

– Associated candidiasis
 Atrophic tongue

Angular cheilitis
 Plummer Vinson syndrome
( Paterson-Kelly syndrome or sideropenic
dysphagia )
• Age: 4th-5th decade

• Sex : Females

• Clinical features: Dysphagia due to

esophageal stricture or web
• Significance : Potentially malignant condition
• Complication: Carcinoma of hypo pharynx, upper part of
esophagus, oral cavity
 Laboratory findings
– Decrease in Serum iron

– Hemoglobin level:↓

– RBC count: ↓ (3-4 million/cc)

– Hypochromic microcytic anemia

– Exfoliated squamous epithelial cells show abnormal

maturation (reduced keratinization and cytoplasmic
diameter, enlarged nucleus, increased/double
nucleoli)
 Blood picture

Microcytic
hypochromic Normal blood
anemia
Blood picture
Megaloblastic anemias
Pernicious anemia (Addison’s anemia):

“Pernicious anemia is a specific form of

megaloblastic anemia caused by atrophic gastritis
and an attendant failure of intrinsic factor
production that leads to vitamin B12 deficiency”

– Antibodies against gastric parietal cells;

autoimmune
Other causes of vitamin
B12 deficiency
– inadequate dietary intake

– intestinal diseases interfering

with absorption

– intestinal infestations
 Clinical features:

Triad
– weakness

– sore, painful tongue

– numbness, tingling of extremities

 Other features:
• Smooth and dry skin

• 75% cases: CNS involvement

– Sensory disturbances
– Stiffness/ general irritability/ depression/drowsiness
– In coordination and loss of vibratory sensations
 Oral manifestations:
Hunters glossitis or
Moeller’s glossitis
Glossitis
• Atrophy of the
papillae
• Smooth ‘bald’
tongue Glossodynia Glossopyrosis

• Fiery red/beefy
red
Recurrent attacks
 Laboratory findings:

– RBC count : ↓ (1 million / cc)

– Macrocytosis

– Poikilocytosis [variation in shape (tear – drop, pear)]

– Polychromatophilic cells

– Nucleated cells

– Stippled cells

– Howell-Jolly bodies, Cabot’s rings

Howell-Jolly bodies Cabot’s ring

Tear-drop shaped RBC

• Bone marrow studies
– Immature cells, megaloblast, few normoblast

• Gastric alterations:
– Gastric atrophy
– Altered epithelial cells
– Destruction of parietal cells
– Lack of HCl secretion/Achlorhydria
– Increased risk of carcinoma development
Foliate deficiency anemia

• Similar to pernicious anemia

• No neurological symptoms
• Schilling test:
– To differentiate pernicious anemia from folic acid
deficiency anemia

“It is very important to rule out pernicious anemia

before starting the folic acid therapy because
neurological symptoms are present in pernicious
anemia and thus, folic acid therapy can be a waste”
• Protein deficiency anemia

• Dimorphic anemia
– Concomitant occurrence of iron deficiency and folic
acid deficiency.
Impaired production..
 Aplastic anemia
• Etiology
– lack of bone marrow activity

• Primary:
– unknown etiology.
– E.g. Fanconi’s syndromes

• Secondary:
– known etiology such as drugs, x- ray irradiation
 Clinical features:
– weakness
– dyspnea
– pallor
– numbness
– tingling sensation of the extremities
– petechiae
– gingival haemorrhage
 Laboratory findings
– RBC’s : < 1million/cc

– Reduced leukocyte – granular series

– Thrombocytopenia – prolonged bleeding time only

– Bone marrow

• Anemia – erythropoietic depression

• Pancytopenia – hypoplasia of all marrow element

Haemolytic anemias
 Haemolytic anemias

• Haemolytic anemias result from excessive

destruction of erythrocytes that may be caused

by

– Intra-corpuscular defects in the RBC’s

– Extra-corpuscular defects
 Extra corpuscular factors:

– Infections and toxins

– Hypersplenism/ Chronic liver disease

– Rh factor incompatibility (Erythroblastosis

fetalis)

– Autoimmune hemolytic disease e.g. SLE

– Transfusion reactions
 Intra corpuscular defects:
– Abnormal shape of the erythrocytes
• E.g., Spherocytosis

– Abnormal hemoglobin's (haemoglobinopathies)

• E.g., Sickle cell anemia, Thalassemia

– Erythrocytic enzyme deficiencies

• E.g., Glucose 6 phosphate deficiency, pyruvate kinase
deficiency

– Erythrocyte defects associated with other disease

• E.g., Chronic granulocytic leukemia
Thalassemia :
(Cooley’s anemia, mediterranean anemia)

“The thalassemia syndromes are a heterogeneous group of

inherited disorders caused by genetic lesions leading to
decreased synthesis of either the α - or β -globin chain of HhA”
 Thalassemia

Alpha thalassemia Beta thalassemia

(↓ α chain) (↓β chain)

Heterozygous minor β - major

(α or β)

Haemoglobin Haemoglobin Bart’s disease

–H
 Clinical features:
– Age: early childhood
(first 2 year of life)

– Pallor, fever, malaise, weakness

– Mongoloid features, prominent premaxilla

(chipmunk facies) Malocclusion

– Splenomegaly, heptomegaly
 Laboratory investigation:

– hypochromic, microcytic anemia

– poikilocytosis, anisocytosis, target cells, safety

pin cells

– ↑ W B C count

– ↑ serum bilirubin
Hemolytic cells, hypochromic cells
Target eye cells Poikilocytosis
Radiograph of skull:
• Thinning of cortical plates
• inner and outer plates poorly
defined; ‘crew cut’ or ‘hair on
end’ appearance

IOPA:
• Coarsening of some trabeculae
and blurring and ‘Hair on end’ appearance
disappearance of others giving
the ‘salt and pepper’ effect
Sickle cell anemia…
Pathogenesis:

Hb A

Substitution of valine for glutamine

in the 6th position of β-globin chain

Hb S

HbS develops a tendency to

crystallize (gelation) within the RBC

Attains the shape of a sickle

Sickle cell anemia is a genetic disorder
(Autosomal dominant)

Father Mother
AS AS

Children

AA AS AS SS
Normal Sickle cell trait Sickle cell anemia
Sickle cell anaemia doesn’t manifest itself

until the third or fourth month of life

because fetal haemoglobin (HbF) protects

the child against the effects of the

‘sickling’ phenomenon.
Pathophysiology:
 Clinical features:

– More common in females

– weakness/fatigue

– chronic hemolysis; increased formation of bilirubin

– small vessel stasis and thrombosis to infarction

– pain in the joints, abdomen

Radiographic features
Similar to Thalassemia
‘Hair on end’ appearance and Bone marrow
expansion: Cheek bone prominent
 Laboratory findings:

– RBC count : < 1million/cc

– presence of sickle cells in the peripheral blood
smear
– Other abnormal cells may be present
Sickle cells
Sickle cells
 Erythroblastosis fetalis
Pathogenesis
– Rh factor incompatibility
• Clinical features:
– Anemia, jaundice, compensatory erythropoiesis

• Oral manifestations
– Green, blue or brown pigmentation of enamel, enamel
hypoplasia, ‘Rh hump’ on anteriors and molars

• Laboratory investigations
– anemia
– icterus (very high)
 Polycythemia

An abnormal increase in the number of red blood cells

in the peripheral blood, usually with an increased
hemoglobin level
 Forms of polycythemia:

– Relative Polycythemia

– Primary Polycythemia (Polycythemia rubra vera)

– Secondary Polycythemia (erythrocytosis).

 Polycythemia rubra vera

• Etiology : unknown

• Clinical features: headache, visual disturbances,

flushed, diffusely reddened skin, splenomegaly, deep
red mucosa, gingival bleeding.
 Laboratory investigations

– elevated RBC count –exceed 10 million/

– Increase in Hb – 20gm/dl

– leukocytosis
Commonly Asked Questions
• Classification of RBC disorders
• Anemias
• Polycythemias

71
References
Shafer, Hine,Levi. Textbook of Oral
Pathology; 5th Edition; Saunders
Publications.
Neville BW, Damm DD, Allen CM,
Bouquot JE. Oral & Maxillofacial
pathology. Second ed, W.B Sounders
Company, 2002