HEMATOLOGICAL

DISEASES
OF RELEVANCE TO
DENTISTRY
(RBCS AND WBCS DISORDERS)

Assoc. Pr. Shahinaz Elashiry

Spring 2021
 Chapter: Hematological disorders of relevance to Dentistry
Given by: Assoc. Pr. Shahinaz Elashiry
Lectures Subtitles of the topic
Online- • RBCs disorders (by A. Online lecture (80
Lecture (1) Prof. Shahinaz Elashiry) min)
Tuesday 4/5
Online- • Rest of RBCs disorders (Thalassemia) Online lecture (80
Lecture (2) min)
• WBCs disorders (by A. Tuesday 11/5
Prof. Shahinaz Elashiry)
On campus- • Case-based discussion On campus lectures
Lecture • Answers to Student’s questions sent on after midterm exams
(3) moodle (by A. (Saturday 29/5 –
Prof. Shahinaz Elashiry) Thursday 3/6)
Online + on • Bleeding and coagulation disorders (by Pr.
campus Hala Abouelela)
lecture
HEMATOPOIESIS (GENERAL
PHYSIOLOGY)
 ALL NORMAL VALUES OF LABORATORY
INVESTIGATIONS
STUDIED LAST YEAR IN ORAL DIAGNOSIS COURSE
(OMP301)
ARE NEEDED TO BE REVISED FOR
WRITTEN/PRACTICAL AND ORAL EXAMS OF ORAL
MEDICINE COURSE (OMP411)
References for this chapter include:
 Burket’s Oral Medicine (12th edition)
 Website shown below: Medscape
 Evidence-based
dentistry
depends on scientific
knowledge available
(book references,
scientific articles …
etc)
and
dentist expertise to
meet the patients
needs
ORAL MEDICINE COURSE IS MAINLY CONCERNED BY:

1) Case history of the disease:

 Oral manifestations (symptoms)
 Medical Hx (general manifestations; knowledge must be present from general
medicine)
 Other manifestations: skin, nails, etc …

2) Clinical examination: intraoral and extraoral signs (e.g. skin, nails …etc)

3) Laboratory investigations:
 List them according to each condition

Diagnosis and Dental management

Note that: Knowledge about etiology and pathophysiology of disease from
medical sciences is important as in Oral Medicine we just put an overview of
that as a reminder.
LECTURE
1
RBCs
DISORDE
RS
 RBCS DISORDERS

Anemia Polycythemia
• Iron Deficiency Anemia (Erythrocytosis)
• Pernicious Anemia study from 3rd
OMP301 year notes
• Aplastic anemia
• Hemoglobinopathies
 Sickle cell disease
 Thalassemia
 White Blood Cells
Disorders
Platelets Disorders
• Agranulocytosis • Thrombocytopenia
• Cyclic neutropenia • Thrombocytosis
• Leukemia Coagulation Disorders
• Multiple Myeloma • Hemophilia
• Infectious • Anticoagulants therapy
Mononucleosis
(Glandular Fever)
 RBCS DISORDERS

ANEMIA
 Definition:
Reduction in oxygen carrying capacity of the
blood.
It may be due to:
1. decrease in number of circulating red blood cells
AND/OR
2. decrease in quantity of hemoglobin.
 TYPES OF ANEMIA

microcytic
Classification according to

normocytic,
macrocytic

normochromic hypochromic

decreased RBCs
production
blood loss
increased RBCs
destruction.
IRON DEF. ANEMIA / VITAMIN B12 DEF. ANEMIA

https://youtu.be/WvD4p8FkQpY https://youtu.be/Z8WmHK_QDtw

• Definition
• Pathophysiology: watch the above videos given by
url
• Clinical manifestation: (general manifestations,
oral manifestations, other manifestations
• Laboratory investigations
• Medical magement - Dental managemet
IRON DEFICIENCY ANEMIA

 It is a type of microcytic hypochromic anemia.

 It is the most common type of anemia.

 RBCs count is less than 3-4 millions/ mm3 and

hemoglobin concentration is less than 11 g/dL.

 Etiology

1- Chronic
blood loss
e.g. during
menstruation, 3- Increased iron
2- Inadequate
bleeding requirement e.g.
hemorrhoids or iron intake. pregnancy.
bleeding from
gastrointestinal
tract.
CLINICAL FEATURES:
GENERAL MANIFESTATIONS- ORAL
MANIFESTATION- OTHER MANIFESTATIONS (SKIN,
HAIR, NERVOUS SYSTEM…)

General manifestations:
1- Fatigue and diminished capability to perform hard
work.
2- Leg cramps on climbing the stairs.
3- Increase heart rate, pulse rate and palpitation.
3- Dyspnea on exertion.
4- Headache and vertigo.
5- Cold intolerance
Oral manifestations:
 Pallor + burning sensation of the oral mucosa.
 Atrophy (partial-complete)+ burning sensation of
the tongue coating + disturbed taste sensation.
 Aphthous-like ulcers.
 Delayed wound healing.
 Angular cheilitis.
Other manifestations:
Iron is essential for integrity of epithelium and ectoderms
(hair and nails).
So in severe cases of iron deficiency anemia

• hair is sparse and

• nails are (brittle) + (koilonychia= spoon
shaped nails).
CBC results in iron deficiency anemia include the
following:
• Microcytic and hypochromic (esp. in chronic cases)
• Decrease RBCs count and Hb level
• Low mean corpuscular volume (MCV)
• Low mean corpuscular hemoglobin concentration (MCHC)
• Elevated platelet count (>450,000/µL) in many cases
• Normal or elevated white blood cell count

Results of iron studies (iron profile) are as follows:

• Low serum iron and ferritin levels with an elevated total
iron binding capacity (TIBC) are diagnostic of iron
deficiency
TREATMENT OF MEDICAL CONDITION:

1-Patient education: to eat food rich in iron

2-Removal of the cause if present.

3- Drugs:
 Ferrous sulfate oral preparations is the drug of choice. To promote
absorption, patients should avoid tea and coffee and may take
vitamin C (500 units) with the iron pill once daily.

4- Follow-up: complications (e.g. dysphagia)

DENTAL MANAGEMENT: (EXAMPLE OF A SHORT ESSAY
QUESTION)
 Problems encountered:
 Delayed wound healing after any oral surgery.
 Oral lesions previously mentioned: pallor of oral mucosa, …
 Dental management:
1-Patient education: avoid spicy food, vinegar, excessive salty food. Inform the patient that
the oral condition will be improved once the anemia is being treated.
2- Removal of the cause: done by referral to the physician to treat of underlying systemic
condition
2- Drugs/procedures:
 Oral surgery not performed unless level of Hb reaches 7 gm/dl
 Symptomatic treatment of intraoral manifestation “burning sensation” (Tantum Verde
q.d.s. 10 min. before eating and at bedtime)
 For angular cheilitis: combined antifungal/antibiotic treatment is preferable such as
Quadriderm cream.
4- Follow-up
PLUMMER – VINSON
SYNDROME (PATTERSON –
KELLEY SYNDROME)
Characterized by a triad:
 Severe iron deficiency anemia.
 Smooth, red, painful tongue with atrophy of tongue
coating.
 Atrophy of the oral, pharyngeal and esophageal mucosa
+ formation of Webs causing Dysphagia or feeling “of
food sticking in throat”.
VITAMIN B12 DEFICIENCY ANEMIA
It is macrocytic normochromic anemia due to deficiency of
vitamin B12 (=cobalamin).
Vitamin B12 deficiency might be due to:
- dietary deficiency of vitamin B12
- Autoantibodies against parietal cells of the stomach (Pernicious
anemia)

maturation of RBCs in
Vit B12

bone marrow

myelination of nerves
 PATHOMECHANISM OF PERNICIOUS ANEMIA
“IT IS AN AUTOIMMUNE DISEASE”

Auto
Antibodies parietal
cells of Failure of
the production of
gastric intrinsic factor
mucosa

Failure of
absorption of Vit
B12 which takes
place in the ileum
Clinical features
Lack of Vit B12 results in defective DNA synthesis and
maturation of RBCs. This will lead to megaloblastic anemia &
depressed production of RBCs resulting in:

1. General manifestations: as iron def. anemia.

2. Oral manifestations: as iron def. anemia

3. Lemon yellow color of the skin due to: pallor and

Jaundice (increase serum bilirubin due to breakdown of
newly formed RBCs in the bone marrow).
3- Other manifestations:
Neurological manifestations
 Causes diseases of brain, spinal cord and
peripheral nerves.
 Neuromuscular incoordination.
 Ataxia.
 Muscular weakness.
 Tingling and numbness of the extremities.

Gastrointestinal manifestations: Constipation and/or

diarrhea. G.I.T manifestations are due to absence of gastric
acid (Hcl) (Achlorohydria).
Oral manifestations
 Pallor of the oral mucosa + burning sensation
 Atrophyof tongue coating (partial-complete) causing
burning sensation of the tongue
 Aphthous-like ulcers
 Delayed wound healing.
 Angular cheilitis.

 Disturbance in taste sensation (due to atrophy of tongue

coating and improper nerve metabolism. The latter
might lead to total loss of taste sensation)
 Xerostomia
DIAGNOSIS (SHORT ESSAY QUESTION)
A) CASE HX: patient complains can be characteristically described as a triad
of symptoms:
1-painful atrophic tongue
2-generalized weakness
3-tingling or numbness of the extremities
B) Clinical Examination
C) Laboratory Findings
1) macrocytic normochromic anemia (Increased MCV and MCH, Normal
MCHC).
2) decrease RBCs less than 1 million/mm3 and Hb level.
3) decreased leukocyte number.
4) decreased platelets number. Schilling test is diagnostic for pernicious
5) poikilocytosis and anisocytosis. anemia. Serum antibodies against parietal
6) low serum vit B12 level. cells of the stomach are found in 90% of the
7) increased serum bilirubin. patients.
Definitive diagnosis can be reached by Schilling test.
Read only:

 This is done by direct measurement of gastric intrinsic factor performed by radio- immune technique,

 patients reveal no detectable gastric intrinsic factor.

 A normal result shows at least 10% of the radiolabeled vitamin B12 in the urine over the first 24 hours.

 In patients with pernicious anemia or with deficiency due to impaired absorption, less than 10% of the
radiolabeled vitamin B12 is detected.
Medical management:
Patients are treated ( for life) with I.M. injection
of hydroxycobalamine

Dental management:
as iron def. anemia
STUDENTS’ QUESTIONS   
 Folate Deficiency Amemia
Def: macrocytic normochromic anemia due to
deficiency of folic acid

Etiology
1. Poor intake.
2. Malabsorption.
3. Increased demand
4. Drugs: alcohol, barbiturates , phenytion,
methotrexate and oral contraceptive.
Clinical picture
Folate & Vit.B12 deficiency may be clinically
indistinguishable except that folate deficiency
does not lead to degeneration of the nervous
system i.e. no nervous manifestations
Diagnosis
1. Serum folate level & serum vit.B12 is
normal.
2. Schilling test is normal.
Treatment of medical condition:
Folic acid 5 mg/daily orally.
 (listen to the voice over for aplastic
APLASTIC ANEMIA anemia and be ready with your
questions next lecture)

Normocytic, normochromic anemia due to bone

marrow depression.

It is characterized by laboratory findings called

pancytopenia.

Pancytopenia:   RBCs,
WBCs count
platelets
 Etiology

Secondary to:
Primary (idiopathic):
1. Drugs e.g. cytotoxic drugs and
chloramphenicol (the most common 1- Congenital (since birth)
cause in children & adults).
2- Acquired
2. Ionizing radiation
due to immune suppression
3. Chemicals e.g. insecticides,
of the bone marrow stem
benzene.
cells by T suppressor cells.
4. Viral infection e.g. Hepatitis and
measles.
 CLINICAL MANIFESTATIONS

1- Anemia ( RBCs) : as general + oral manifestations of

iron def. anemia
2- Thrombocytopenia (Platelets) ..see later
 Increased Bleeding tendency
 Persistent gingival bleeding.
 Petechia & ecchymosis with minimal trauma.
3- Agranulocytosis (leukocytic count) .. see later
- Increased susceptibility to infection.
- Oral ulcers are deep and not surrounded with red halo
(due to absence of PMNL).
 LABORATORY FINDINGS

1-Pancytopenia
a- Decrease number of RBCs and total Hb content
(normocytic, normochromic anemia)…(Normal MCV,
MCH, MCHC)
b- Decrease leukocytic count.
c- Decrease platelets count (thrombocytopenia), prolonged
bleeding time.
2- Absence of reticulocytes (RBCs precursors)
3- Bone marrow biopsy: Hypocellular with increased fat
spaces.
Treatment of Medical condition:
1. Patient education

2. Elimination of the cause

3. Drugs/therapy:
 Blood transfusion/Bone marrow transplantation.

 Immunosuppressive drugs e.g. steroids and cyclosporine.

4. Follow-up
DENTAL MANAGEMENT
 Problems encountered are + their management:
 Increased bleeding tendency .. see later (clotting and
coagulation deficiency)

 Increased susceptibility to infection .. prophylactic

antibiotics are necessary with oral surgery

 Presence of anemia ..delayed wound healing (proper flap

design with minimal trauma as possible) (never go for
oral surgery if Hb is less than 7gm/dl)
 Precautions of steroid therapy (see dental manag. for
supplementary steroids schedule).
HEMOGLOBINOPATHIES
• Sickle Cell Anemia
• Thalassemia

Hemoglobinopathies = defects in the globin portion of

hemoglobin  abnormal hemoglobin carried by RBCs

 hemolytic anemia.
 SCHEME FOR SICKLE CELL
ANEMIA/THALASSEMIA
Sickle cell anemia: https://youtu.be/fIIJmg_1hv0 Thalassemia: https://youtu.be/oH6SMG3Ykjg

Scheme (detailed for)

Sickle cell diseases
and
Thalassemia
(see later)
 Basic knowledge
Hb = (Heme + globin)
 Heme part =
1 ferrous iron carried in a
porphyrin ring
 Globin part =
2α + 2βchains

Types of Hb:
In normal individuals most of
1- Adult Hb = "HbA" = 2α + 2βchains Hb is HbA and not more than
2- Fetal Hb = "HbF" = 2α + 2 γchains 1% is HbF.

3- Sickled Hb = "HbS”  amino acid abnormality where the

glutamic acid that is found in position 6 in βchain is replaced by
valine
 ANSWERS TO STUDENT’S QUESTIONS IN
BASIC SCIENCE OF BLOOD DISORDERS

• what is HbA2?and what is the difference between HgA and HgA2?

• HbA (⍺2β2) - HbA2 (⍺2𝛿2)
Normal adult Hb Sickle cell Sickle cell Thalassemia Thalassemia
(Normal Hb anemia trait (β) (major) minor
types in adults) Homozygous Heterozygous (Absence of β
chain)

HbA 97% HbSS: 80-90% HbSA: 60% HbF (⍺2ɣ2): HbA:

(defective β2) up to 90% considerable
amounts
HbA2 + HbF 3% HbF: 10-20 % Normal Hb HbA2 (⍺2𝛿2): HbF and HbA2:
types in the remainder remainder
adult: %
remainder
40%
SICKLE CELL DISEASE
read Hb beta gene
Sickle cell trait
(heterozygous=HbSA)
 patient does not display the
abnormal
severe symptoms of sickle-cell allele
normal allele
disease. 60% of Hb is HbS and
the remainder is HbA
Sickle cell anemia
(homozygous=HbSS) Hb beta gene
 patient displays severe symptoms
of sickle-cell disease. 80 - 90% of
Hb is HbS and the remainder is HbF
abnormal abnormal
(lack of HbA). allele allele
Note that: Both HbS and HbA with variable % are
expressed in those patient due to
“co-dominance”
SICKLE CELL DISEASE
read

Sickling is precipitated
by:
Hypoxia ( O2 tension )
as in high altitudes &
general anesthesia,
respiratory diseases. RBCs
 Infection destruction
 Dehydration =hemolytic
anemia

Sickle RBCs block

blood flow =
HbS RBCs become
ischemia -
molecules sickle shaped
infarction -
polymerize (rigid + inflexible)
thrombosis
Thalassemia (Greek thalassa = sea) is anemia originally found in
people living on the shores of the Mediterranean but is now known to
affect persons throughout the world.
There is deficient synthesis of either alpha or beta chain Hb.
Normally both chains are balanced.

Imbalance of globin chain production lead to ppt. of globin chain

within the red cells precursors and resulting in **ineffective
erythropoiesis.
Ppt. of globin chain in mature red cells lead to **hemolysis
:Types of thalassemia

.Alpha thalassemia .1
Beta thalassemia: decrease or absent of .2
.- chain of globin

a)Homozygous Thalassemia
(Cooley’s Anemia, Mediterranean Anemia).

b)Heterozygous Thalassemia Minor

(or Trait).
 Shortened life
span to the ¼ of
normal
* infection
SICKLE CELL
ANEMIA Anemia: general + oral manifest.
Jaundice: yellow sclera

• Delayed eruption of
teeth
• Enamel hypoplasia
• Osteoporosis and osteosclerosis
Expansion of BM • Hair on end appearance of skull
spaces • Frontal bossing
• Maxillary overgrowth
• Ladder-like appearance of
alveolar bone – dense LD

Infarction • Teeth: (Atypical) odontalgia

(diagn. by exclusion)
• Pain in abdomen/chest/bone
• Kidney: hematuria
• Extremities: ulcers
• Osteomyelitis after oral surgey
 • Anemia: general + oral manifest.
THALASSEM • Jaundice: yellow skin/sclera
• Hemosiderosis: increase iron overload will
IA  increase susceptibility to infection
 parotid swelling
 Teeth: discoloration due to iron
deposition
Ashen-gray skin =
(pallor + jaundice + hemosiderosis)

Expansion of BM • Osteoporosis and osteosclerosis

spaces • Hair on end appearance of skull
• Frontal bossing
• Maxillary overgrowth
• Ladder-like appearance of alveolar bone
– dense LD

• Large head
• Short nose with depressed nasal bridge
Thalassemic face • Enlargement of the maxilla
• Forward drifting and spacing of maxillary
(Mongoloid features) incisors
• Anterior open bite
Lab. Sickle cell anemia
Invest.
• Normocytic normochromic anemia
• Increase RDW (reticulocytes increase to
compensate for lost RBCs)
• Increase serum bilirubin
• Decrease Haptoglobin (that bind free Hb
spilling into blood due to RBcs hemolysis)
• Electrophoresis: HBS predominant
• Sickling test: Sickling occurs after sealing
fresh blood in a small chamber of
microscopic slide with a reducing agent.
Thalassemia (major)
• Microcytic hypochromic anemia
• Increase RDW (reticulocytes increase to
compensate for lost RBCs)
• Increase serum bilirubin
• Decrease Haptoglobin (that bind free Hb spilling
into blood due to RBcs hemolysis)
• Electrophoresis: HBF predominant
• Increase serum iron
• Decrease serum folate
MANAGEMENT OF THE MEDICAL CONDITION: (SICKLE CELL ANEMIA)

1- If the case is steady: no treatment.

2- Avoid precipitating factors for crisis.

3- Acute attack: I.V. fluid, oxygen, antibiotic and analgesic.

4- Folic acid may be given during pregnancy and severe hemolysis.

5- Regular and repeated blood transfusion is given in severe anemia,

frequent crisis, before surgery and during pregnancy.

Repeated transfusion is used to

- Suppress production of HbS.

- To reduce circulating HbS to less than 20%.

 Management of the medical condition
(Thalassemia)
1.Regular blood transfusion

2. To decrease the iron overload:

• Iron chelating agent is given
• Ascorbic acid to increase urinary iron
excretion

4. Bone marrow transplant.

Note that: after BM transplantation graft versus host disease (GVHD)
might occur giving rise to oral lichenoid lesions of GVHD.
 Dental management

Problems encountered by dentist in:

Sickle cell anemia:
• Anemia; delayed wound healing, oral lesions causing burning sensation of oral mucosa.
• (Atypical) odontalgia due to
•infarction of bone (mandible)  osteomyelitis
•infarction of pulp  pulpal necrosis
Thalassemia:
• Anemia; delayed wound healing, oral lesions causing burning sensation of oral mucosa.
• Increase susceptibility to infection due to iron overloa d
1-Patient education: avoid spicy food, vinegar, excessive salty food. Inform the patient that the oral condition
becomes better with control of anemic state.
2- Drugs/precaution during dental treatment:
 Oral surgery:
• For both diseases:
• oral surgery not performed unless level of Hb reaches 7 gm/dl
• if general anesthesia is needed… a specialist must be present.
• proper flap design of oral surgery and minimal trauma to augment wound healing
• antibiotics as prophylaxis in any operation (since infection may precipitate sickling in Sickle cell
anemia, iron overload that enhance bacterial growth in thalassemia)
• never anaesthetize or operate on patient during crisis.
• avoid vasoconstrictor in local anesthesia as it may precipitate crisis.
• avoid drugs which may cause respiratory depression & lead to hypoxia (e.g. Sedatives).
 Sickle cell anemia: Manage pain caused by infarction e.g. pulpal pain (do endodontic treatment)
 symptomatic treatment of intraoral manifestation:
• “burning sensation” (Tantum Verde q.d.s. 10 min. before eating and at bedtime)
• for angular cheilitis: combined antifungal/antibiotic treatment is preferable such as quadriderm
cream.
4- Follow-up: maintain optimum oral hygiene
 SICKLE CELL TRAIT (HbAS)
 This occurs in heterozygous (Hb.SA) patients
60% is HbS,
40% is HbA.

 The patient is asymptomatic and lives normal life unaffected by

his abnormal hemoglobin.
 Sickle cell crises can be caused by reduced oxygen tension
(general anesthesia, high altitude).

 At times these patients may have renal complications causing

hematuria or splenic infarcts.
 Thalassemia minor
(or trait)

(microcytic hypochromic anemia)

It is common and usually asymptomatic, except for mild
hypochromic anemia, which may be aggravated by pregnancy
or recurrent illness.
Lab finding
micro-hypochromic anemia,
normal serum iron and iron store
Hb electrophoresis.: HbA2 –Hb F –HbA (in significant
amount)
Treatment: no therapy indicated but if they marry person with
the same defect ,.. … Thala. major
 In all hemolytic anemia there is:
I. Anemia  pallor of nail beds, palpebral conjunctiva &
oral mucosa especially soft palate, tongue & sublingual
tissues +floor of mouthy .

2. Jaundice:  secondary to RBC destruction 

hyperbilirubinaemia, can be detected first in sclera, but
skin, soft palate & tissue of floor of mouth become icteric
as serum bilirubin increase

3. Bone marrow hyperplasia to compensate

increase RBC destruction.
(listen to the voice over and be ready
with your questions next lecture)

Glucose 6 phosphate
dehydrogenase deficiency
(G6PD)-Scheme with
Illustrations
 GLUCOSE 6 PHOSPHATE
DEHYDROGENASE DEFICIENCY

 This is an erythrocyte metabolic defect, in the absence of

G6PD, the RBC cannot manufacture glutathione “ a
reducing agent”, so RBC cannot withstand oxidant
compound and hemolysis occur due to denaturing the
hemoglobin.
 There is no anemia and no clinical features
of pallor and jaundice.
• Drugs, Infection and diabetes can cause an acute
acceleration of RBC hemolysis.
Student’s questions regarding G6PD deficiency, 
-what does “offending oxidant drugs” mean and how do they accelerate hemolysis? 
-why is there no anemia, pallor, or jaundice in this case even though hemolysis of rbcs
takes place? 
- https://youtu.be/VoBysmk6Qiw

- And here is a general explanation:

Offending oxidant drugs are those drugs
that result in generation of free radicals in
RBCs. Those free radicals are normally
removed in RBCs so not to harm cell itself.
In case of glucose 6 ph dehydrogenase def.,
RBCs are not capable to do that and free
radicals pile up and end by causing early
destruction of RBCs than usual (after about
2 months)

- Dentist: take care of Ibuprofen and aspirin

prescription in such patients
Dental considerations:
1) Avoid offending oxidant drugs which include:
a. Analgesics: aspirin, phenacetin.

b. Antimalaria: quinine, chloroquine, sulphasalasine.

c.Antibacterial : most sulphonamide, dapson,
chloramphenicol.
d. Others: vit K , probenecid, Fava beans ‫قول‬WW‫=( ب‬Favism)
2) Infection should be treated.

3) Blood transfusion may be life saving.

There are three types of anemia:
MCHC MCH MCV Types of anemia

Normal Normal Normal 1) Normocytic normochromic

Decrease Decrease Decrease 2) Microcytic hypochromic

Normal Increase Increase 3) Macrocytic normochromic