CLOTTING DISORDERS

Disorders of coagulation: Classified into:

A) Inherited: Hemophilia and Von Willebrand's disease.
B)Acquired: Liver diseases , Vit K deficiency, Anticoagulants,
Dysproteinemia, Disseminated intravascular coagulation (DIG).
Inherited Coagulation Disorders
Hemophilia A and B are both inherited as a sex linked recessive mechanism ,and occur
in males while Von Willebrand's disease affects both sexes.
Disease Deficient Factor
1. Hemophilia A VIII :C
2. Hemophilia B IX
3. Hemophilia C XI
4. Parahemophilia V
5. Von Willebrand's disease VIII :vWF

HEMOPHILIA A
(CLASSIC OR TRUE HEMOPHILIA)
Definition:
This is the most common type of hemophilia which occurs 10
times more than hemophilia B and 200 times more than any other
known type of hemophilia.
It is characterized by deficiency of factor VIII:C and
prolonged activated partial thromboplastin time (aPTT).
Etiology:
a. factor VIII :C deficiency is inherited in the majority of
hemophilias
b. 25% arise as spontaneous mutations.
C. acquired deficiency may be also due to unknown cause or
due to the development of factor VIII inhibitors antibody to
factor VIII:C in the blood after receiving many blood
transfusions.
Nature of factor VIII:-
1- The whole factor VIII (VIII:C/ vWF) is a complex protein
that circulates in plasma , consisting of small molecules with
coagulant activity (VIII:C) and a larger part von Willebrand's
factor (VlII:vWF) which is associated with platelet adhesion.
1
2- . VIII:vWF appears to stabilize factor VIILC.
Factor VIII:C VIIIrvWF

It is controlled by
* It is controlled by gene gene
located on short arm of X located on
chromosome. chromosome
* It is produced in the liver 12.
cells. * It is produced in
*It is able to correct the
coagulation endothelial cells.
abnormality in hemophilia. It is able to
correct
bleeding time
abnormality
in Von
Willebrand's
disease.

Ristocetin (antibiotic) induced platelets aggregation

(RIPA) : when adding ristocetin to platelet rich plasma
agglutination occur, abnormalities in vWF or in platelets
receptors (Bernard -Soulier syndrome) can make it
abnormal.
VIIIC/vWF : The form in which VIIIC and von
Willebrand's factor usually circulate in the plasma.
Classification of Hemophilia according to clinical and laboratory findings:
Severity VIII :C Signs &. Symptoms APTT
1. Severe Less than Severe hemoarthrosis Prolonge
1%
Spontaneous bleeding
2. l%-5% Spontaneous bleeding uncommon. Prolonge
Moderate
Serious bleeding from minimal
trauma.
3.Mild 5%-25% Spontaneous bleeding is rare. Variable
2
 Serious bleeding from surgery
or trauma.
4.SubcIini 25%-50% Diagnosis often missed. Normal
caI
Moderate bleeding from surgery
or trauma.

Normal value of VIII:C is from 50% - 150%

Bleeding character in hemophilia :bleeding stop immediately
after injury as a result of normal vascular and platelets response
but after an hour or more, intractable oozing or rapid blood loss
starts and persists.
The severity of bleeding depends on two main factors: a.
Level of factor VIII:C.
b.severity of trauma
Clinical Features of hemophilia:
General manifestations:
1) Bleeding after minimal injury or following circumcision,
tonsillectomy or dental extraction.
2) Hemorrhage under skin or in internal organs and joints and
may result in massive hematoma, permanent ankylosis and
erosion of the joint surface with severe pain.
3) Bleeding from the nose ,mouth,tonsillar area, urinary tract
and gastrointestinal tract.
Oral Manifestations:
1) Bleeding from any site of the oral cavity and sometime it
may cause respiratory obstruction if bleeding occurs e.g. in the
floor of the mouth.
2) Gingival bemorrhage may be massive and prolonged.
3) Bleeding associated with physiological eruption or
exfoliation of teeth..
4) Tooth extraction or minor surgical operation may lead to
severe hemorrhage, sometimes may be fatal.
Diagnosis:
1) Prolonged activated partial thromboplastin time (aPTT).
3
2) Normal prothrombin time (PT).
3) Normal bleeding time.
4) Reduced factor VI1I:C ;but normal VIII;vWF.
Treatment of Hemophilia A:
The bastic line of treatment qf hemophjiia A. B and C consist
of :
* replacement of the missing clotting factor ,
* rest and
* the use of antifinbrinolytic agents.
Treatmgnt of hemophilia will depend on :
1) Severity of the disease , level of factor VIII:C.
2) Severity of the trauma.
3) Presence or absence of VH1:C inhibitor antibody,
AvailablejjreparatiQns to raise VII1:C level ;
1. Factor VIII concentrates:
2. High purity factor VIII concentrate: .
3. Intermediate purity factor VIII concentrate: .
4. Cryoprecipitate :
It is obtained by allowing the frozen plasma from single
donation to melt at 4-8 C and removing the supernatant
(contain factor IX).
it contains factor VIIl:C,factor VIII:vWF and fibrinogen..
5. Desmopressin: stimulates immediate release of VIILC and
vWF from cell stores. Since it liberates plasminogen activator
from endotheliai cells, it should be followed immediately by
tranexamic acid to inhibit the enhanced fibrinolytic activity.
6. Tranexamie acid (Antifibrinolytic agent):It is
antifibrinolytic agents act by inhibiting the activation of
plasmin.
jrf preparation to raise VII1:C Jeyeh
a. Mild Hemophilia : Desmopressin is the agent of choice.
Cryoprecipitate or factor VIII concentrate is the second .
b. Severe Hemophilia: Best treated with factor VIII
concentrate.
Dental management of Hemophilia A
Prophylactic measures:-
1. Regular and meticulous dental care.
4
2. Fluoride application.
3. Dietary advice for sugar restriction.
4. Prevention of periodontal disease.
These measures reduce the need for extraction which may be a
major hazard in hemophilia.
Endodontics: Root canal treatment obviates the need for
extraction.
Reaming through the apex should be avoided.
Hemorrhage into the canal can be controlled by 1/1000
epinephrine on an endodontic paper point.
Pulpectomies in deciduous teeth usually is not associated with
undue bleeding.
Periodontal therapy: scaling can be performed (except in
severe hemophilia) under antifbrinolytic cover. Periodontal
surgery necessitates factor replacement.
Conservative dentistry: care should be considered to avoid soft
tissue trauma.
Rubber dam is useful to protect the mucosa from trauma.
Use the high speed vacuum aspirator and saliva ejector with
caution to avoid production of hematoma.
Use the matrix band with great caution to avoid tear in the
gingival tissues.
Use gingival retractor impregnated with epinephrine placed
in the gingival sulcus before any preparation at the gingival
margin of the tooth to avoid bleeding..
Hazard of Anaesthesia
Local and general anaesthesia are hazardous in the absence of
factor replacement. Conservative dental treatment may be
carried out without local anaesthesia.
a If the procedures are not tolerated , papillary or periodontal
infiltration is given and this is unlikely to cause serious
bleeding, since the tissues are firmly bound to the underlying
bone.
Topical application of 10% cocaine to the exposed pulp is
effective for vital- pulp extirpation.
Anaesthetic injection especially nerve block (inferior alveolar,
posterior superior alveolar and infraorbital) can be a hazard
5
particularly for severe hemophiliacs. The needle can tear the
wall of small blood vessels and a deep spreading hematoma
can threaten the air way.
a Although submucous infiltration is frequently given without
complication, the risk is still there and it may be safer as a
general policy to use nitrous oxide analgesia to avoid the use of
local anaesthetic.
Endotracheal intubation for general anaesthesia may cause
bleeding and is extremely dangerous in the absence of
replacement therapy.
Intramuscular injection should be avoided unless replacement
therapy is given ,a large hematoma may be produced.
Management of extraction:
1. Laboratory tests for hemoglobin estimation, blood grouping
and cross matching and factor VIILC assay to assess the severity
of the disease should be performed.
2. Factor VIII:C should be raised to 50%-70% before dental
extraction and raised to 100% for major surgery.
3. Postoperatively the patient should be hospitalized and factor
VIILC should be given intravenously twice a day for 7 days to
maintain its level at 50%.
4. Antibiotic should be given to avoid the risk of infection and
breakdown of blood clot e.g. oral penicillin for 10 days.
5. Aspirin should be avoided, it may cause gastric bleeding and
worsen the bleeding tendency by preventing platelets
aggregation.
Codeine and paracetamol are better alternatives.
6. Most of hemophilic patients are acutely anxious about dental
treatment, particularly the possibility of bleeding. Emotional
factors significantly influence fibrinolytic activity, reassure the
patient and the use of sedative may be helpful.
Local measures
1. Surgery should be carefully planned to avoid minimal trauma
to both bone and soft tissues.
2. Preoperative radiographs must be taken to show any
unsuspected disease which may add to the problem.
6
3. Suturing : It is desirable to stabilize gum flap and prevent
post operative disturbance of wound during eating, Non
resorbable and resorbable sutures are equally effective and
should be removed at 4-7 days .
Suturing may carry with it the risk of causing the blood to track
down toward the mediastinum and endanger the air way.
The postoperative bleeding, is an indication of inadequate
preoperative replacement therapy or the presence of factor
VIILC inhibitor antibody.
4. The lingual tissue in the lower molar regions should left
undisturbed since trauma may open up planes into which
hemorrhage can track and endanger the air way.
The buccal approach to lower third molar is thus preferred.
5. Packing of extraction socket is unnecessary if replacement
therapy has been adequate, however some advice to pack the
socket with oxidized cellulose soaked in tranexamic acid or
thrornbin.
6. Post operatively watch for hematoma formation, which may
manifest with swelling, dysphagia or hoarseness.

Hemophilia B ,Christmas Disease

The disease is identical to hemophilia A in both clinical
features and mode of inheritance but the deficiency is of factor
IX.
Factor IX is more stable than factor VIII, and is not present
in cryoprecipitate,
Coumarin anticoagulant as well as vit.K deficiency reduce
the level of factor IX. Treatment
Mild hemophilia B: fresh frozen plasma is adequate to control
bleeding.
Severe hemophilia B .'factor IX concentrate is available for IV
use one hour preoperatively.
As the half life of factor IX is often up to 18-24 hours,
replacement therapy can be given at longer interval than
hemophilia
7
 VON WILLEBRAND'S DISEASE
Definition
VWD is a hemorrhagic disorder usually transmitted as an
autosomal dominant trait affecting both males and females.
VWD is due to deficiency or abnormality of factor VIII:vWF
which is essential for platelets adhesion to damaged
subendothelium and also essential for stabilizing factor VIII:C in
the plasma.
VWD is classified into:
1. Type I: mild reduction of factor VIII:vWF,.
2. Type II; molecular defect of VHIrvWF,
3. Type HI: nearly no detectable level of factor VIII:vWF and
therefore factor VIII:C.
VWD is associated with:
a) Defective platelets function. (VWD type 1,11 &III) which
can be detected by:
i. Increased bleeding time.
ii. Defective platelets aggregation with restocetin.
b) Factor VIII:C deficiency which leads to increased aPTT .
(VWD type III).
Clinical Features:
The disease begins to express itself in infants and children
with symptoms of increased bleeding tendency with variable
degree of seventy.
The common bleeding pattern (into skin and mucous
membranes), causing
petechiae, epistaxis, menorrhagia and bleeding into
gastrointestinal tract. Gingival bleeding is more common
either spontaneously or after tooth brushing, Excessive
bleeding following minor trauma or dental extraction .
Hemarthrosis is rare.
Von Willebrand's disease is occasionally clinically identical to
hemophilia Pregnancy and contraceptive pills may cause
transient amelioration.
Treatment:

8
Treatment will depend on the severity of the bleeding and type
of VWD and the following drug or replacement therapy are
available
a) In mild -moderate VWD:
Desmopressin for minor surgery.
Fresh frozen plasma.
Cryoprecipitate.
b) In seyereJV WJ3: Factor VIII concentrate (for major
surgery).
N.B. Local hemostatic agents may be tried to control oral
bleeding.
LIVER DISEASES
In addition to vit. K dependent factors (II,VII, IX, & X) .the
liver synthesizes fibrinogen, prekallikrein, high molecular
weight kininogen, factors V,VIII, XI, XIII. plasminogen, a2
antitrypsin and antithrombin III.
In hepatocellular diseases (viral hepatitis, chronic hepatitis,
primary biliary cirrhosis and liver cirrhosis) there is impairment
of hepatic cells function. History of jaundice or heavy alcoholic
consumption may indicate significant liver disease.
The impairment of hepatic cell functions particularly in late liver
diseases is an important cause of bleeding disorder.
Liver disease may be associated with increased bleeding
tendency and this may be due to:
1. Reduced vit K absorption : absence of bile salts as in hepatic
jaundice leads to defective vit K absorption.
2. Reduced synthesis of coagulation factors due to severe
hepatocellular damage
3. Increased fibrinolysis* secondary to defective clearance of
plasminogen activator, leading to hyperplasmmemia producing
fibrinolysis.
4. Synthesis of abnormal fibrinosen molecules.
5. Thrombocytomniq .-chronic liver disease may be associated
with obstruction of portal circulation, leading to portal
hypertension with hypersplenism developing which leads to
increased platelets destruction. If the liver damage is not great
9
 enough , it does not affect coagulation phase , but affects
platelets phase.
6. Disseminqtedjnirgvascularcoasulation may occur in acute
liver disease.
Management:
1. Oral surgery should be deferred whenever possible .
Measurement of PT,aPTT and bleeding time should be screened.
2. if prothrombin time is increased:
* vit K IQrng is given parentrally daily for several days
preoperatively in an attempt to improve hemostatic functions.
*antifibrinolytic agent and fresh frozen plasma may however be
effective.
3. in emergency situations concentrate of factors II,VII,IX and
&X should be used, since it is useful in the treatment of
hypoprothrominemia induced by liver disease (as well as
induced by anticoagulant therapy).
Reye 's syndrome:
There is some evidence that the use of aspirin in children up to
the age of 15 years who have an upper respiratory tract infection
,chicken pox, influenza or other viral infection may develop
rarely liver damage (diffuse microvascular fatty infiltration) and
acute encephalopathy with cerebral edema. Therefore,
paracetamol in moderate dosage only is now the preferred
analgesic and antipyretic for children

VITAMIN K DEFICIENCY
Vit K is used by the liver for the synthesis of four clotting factors:
ILVIIJX & X .
Vit K is taken in with the diet (green leafy vegetables, casein,
various vegetable oils) and
from the synthesis by normal intestinal bacterial flora.
Humans have no significant storage reservoir for vit K.
poor dietary intake.
b. Malabsorption syndrome
Causes of vit K deficiency:
10
1. Inadequate supply- poor dietary intake
2. Poor absorption:
a. Obstructive jaundice b. Malabsorption syndrome
3. Failure of utilization:
a. Anticoagulant therapy b. Liver disease
4. Lack of vit K synthesis : prolonged use of broad spectrum
antibiotics.
General manifestation:
* Bruising * Gastro-intestinal bleeding
* Hematuria * Cerebral bleeding
Laboratory investigations:
* Prolonged PT.
* Prolonged PTT
a PTT become prolonged in severe and protracted vit K
deficiency. PTT may be normal because of longer half life of
factor IX & X.

Management:
* Vit K (phytomenadione) 10 mg intravenously daily for
several
days preoperatively to control minor bleeding.
PT shows some correction after 6 hrs & and return to normal
after 48 hrs. If patient has not been corrected by 48 hrs,
parenchyma! liver disease should be considered.
ANTICOAGULANTS
Anticoagulants are drugs used for prevention and treatment of
thrombosis e.g. deep venous thrombosis, myocardial infarction,
renal dialysis and cerebral thrombosis
Ajiticoagulant drugs include:
1) Oral anticoagulant.
2) Heparin (standard heparin and low molecular weight
heparin).
1) Oral anticoagulajitjjj e^g^cjimarin "warfarin"
Action:-

11
 Inhibition of the enzyme, " vitamin K epoxide reductase",
which under normal circumstances facilitates the reconstitution
of hepatic stores of vitamin K.
Coumarin leads to the inhibition of synthesis of biologically
active prothrombin (factor II) and factors Vll, IX and X.
Laboratory Findings:
Prolonged aPTT .
Prolonged PT (control 11-15 seconds)
Anticoagulant results in prolongation of PT up to 1.5 to 2.5
times the control and even up to 4.5 times the control in deep
venous thrombosis.
Management:
1. In minor oral surgery the PT should be within the normal
therapeutic range
(1.5 -2-5
times the normal).
2. The surgery should be atraumatic as possible.
3. If any sign of bleeding from extraction socket, use oxidized
cellulose, with sutures over the socket and pressure pack is
applied.
4. With the agreement of the physician .the anticoagulant may
be needed to be stopped (2-3 days) before major surgery or the
dose be reduced
5. In life threatening hemorrhage , gifve immediately vitamin K
5 mg by slow infusion and/or a concentrate of factors 1I,VH,
IX ,X or fresh frozen plasma.
2) Hepjmn:
Action: nrevgnt fibrin formation during the process of
coagulation through:
a. Inhibition of thrombin - fibrinogen reaction.fantithromin)
b. . inactivate factors IXa,Xa,Xla and XI la. Prevention of platelets aggregation (large dose)
Types Standard Low molecular weight
Heparin Heparin

Molecular 5000-35000 2000-8000

12
weight Produced by enzymatic or
Extracted from chemical
Origin liver degradation of standard
heparin
Half fife Short half life,
so Long half life; so given
given at 4-6 once daily by subcutaneous
hours injection
interval I.V.

Heparin Dicumarol
1. Animal origin. 1. Plant origin.
2. Rapid action (immediate) 2. Slow action (1-2 days).
3. Short duration.(hours - one 3. long duration (days)
day) 4. Given orally.
4. Given IV or SC. 5- Antidote is vit.K.
5. Antidote is l%Protamine 6. Mechanism of action:
sulphate. -Inhibition of factors II, VII,
6. Mechanism of action: IX & X In the
a. Antithrombin. liver..
b.AntipIatelets aggregation in
large dose.

Laboratory Findings:
Prolonged aPTT.
Prolonged PT.
Prolonged TT. Therapeutic dose maintains TT at 3-4
times the normal (10 -14 sec).
Management:
1. Surgery can be safely carried out , when the effect of heparin
has ceased.
2. In renal dialysis, surgery is better to be carried out ihe next
day as the effect of heparin ization have then ceased and there is
maximum benefit from dialysis.
13
Complications:
1. The main complication of treatment with heparin is bleeding.
This is managed by stopping heparin , occasionally it may be
necessary to neutralize heparin with protamine sulphate i.v.
2. Osteoporosis: on long term therapy.
3. Thrombocytopenia ?.(heparin induced platelets aggregation)

DISSEMINATED INRA VASCULAR

COAGULATION
(DIG)
DEFEBRINATION SYNDROME
Definition: It is uncommon, complex, process in which there is
widespread generationof fibrin within the blood vessels, due to
a; activation of extrinsic path-way by release of coagulant
material,
b.activation of the intrinsic pathway by diffuse endothelial
damage or
generalized platelet aggregation.
DIG maybe due to activation of blood coagulation by:
a.
Endothelial damage.
b. Endotoxin.
c. Immune
complex
Precipitating factors: including incompatible blood
transfusions, severe sepsis, obstetric complications, severe
trauma or burns and cancer (acute progranulocytic leukemia)
The possible effects of DIC include:-
1. Hernprrhagic jgndencjes as a result of;
a. Consumption of blood platelets.
b. Consumption of clotting factors.
c. Activation of fibrinolytic system.

14
2. Thrgmbotjc pjiejomenon plotting blood in the capillaries can
damage any organ e.g. kidney, liver, adrenals and brain.
3. Hemolysis of red_cells; microangiopathic hemolysis as a
result of mechanical damage by fibrin strands in small blood
vessels.
4. . Shock as a result of adrenal damage or obstruction of
pulmonary circulation by fibrin deposition.

Chapter 9
BLEEDING DISORDER
15
I) Platelets disorders
a. Thrombocytopenia
b. Thrombocytosis
c. latelets dysfunction and it includes;
i. Congenital ii. Acquired
Defect in adherence Myeloproliferative disease
Defect in release Uremia
Defect in aggregation Dysproteiemia
Drug -Aspirin

II) Vascular wall alteration:

Scurvy
Infection (measles,scarlet fever, endocarditis, malaria)
Allergy
Hereditary hemorrhagic telangiectasis
dishing syndrome
Platelets Disorders
* Platelets are produced as fragments of the cytoplasm of the
megakaryocytes in
the bone marrow.
* Life span : once released into the circulation , they have a
mean survival time
8-10 days.
* Count: The normal platelets count is 150,000-500,000 cubic
mm.
* The platelets membranes are rich in phospholipids (platelets
factor 3) responsible for:
1. Conversion of prothrombin to thrombin.
2. Production of arachidonic acid which changes into
thromboxane A2 & prostacycline in the presence of
cyclooxygenase enzyme.
- Thromboxane A2 induce platelets aggregation &
vasoconstriction.
- Prostacycline inhibits platelets aggregation & is potent
vasodilators.

16
3. Platelets membrane contains receptors for VonWillebrand
factor & fibrinogen which is important in platelete function.
4. Within the cell there are storage pools, that contain
adenosine diphosphate (ADP)
that favors platelet aggregation.
5. Serotonin (vasoconstrictor) is also produced by platelets.
* Platelets function
Help in stop bleeding by:
a. Aggregation & adherence to injured vessel toform primary
clot.
b. Help in clot formation..
-Help in clot retraction.by retractozyme produced by
the platlets

Disorders of the platelets are characterized by prolonged

bleeding time and classified into : -
1. Thronibocylopenia: a decreased number of circulating
platelets.
2. Ttirombocytosis:an increased number of circulating^plate!
ets.
3. Platelets dysfunction: normal number of platelets but fail to
function normally.
N.B. The platelets are responsible for the primary arrest of
bleeding at the site of vessel injury- Abnormalities in platelet's
number or function may result in easy bruising and spontaneous
bleeding from small vessels. I
General Manifestations: (easy bruising, purpura, epistaxix,
menorrhagia and abnormal bleeding following surgical
interferance.)-
1. The bleeding is mainly into the skin (purpura) . The term
purpura means reddish 10 purple .flal lesions caused by blood
vessels leaking into subcutaneous /issue. Purpura is classified
into petechiae which are small skin hemorrhages varying from
pinpoint size to 1-3 mm in diameter and which do not blanch on
pressure and ecchymosis which is larger than petechiae.

17
2. Bleeding from the mucous membrane of the nose (epistaxis )
and the mouth.
3. With severe deficiency there may be spontaneous bleeding
into CNS, GIT and genito-urinary tract.
Oral Manifestation : -

Submucosa! pelechiae and ecchymosis.

Oral hemorrhage at site of minor trauma.
Gingival bleeding - may be spontaneous or by the use of
tooth brush.
Hemorrhage into the dental papillae, producing gingival
enlargement.
The blood decomposes in the gingival sulcus or
pehodonta! pocket producing fetid odor and form good
media for bacterial growth, and fusospirochetal infection
may induce gingival tissue necrosis.
Pulp hemorrhage occasionally reported.
THROMBOCYTOFENTA
The normal number of platelets is 150 000-500 000/cubic
mm.
There area few clinical manifestations in the range of 50
000-150 000/cubic mm.
Minor spontaneous bleeding and -bleeding after surgery
is seen in the range of 20 000-50 000/cubic mm.
More serious bleeeding occurs as the platelets count falls
from 20 000/cubic mm to 0.
Etiology:
1. Idiopathic (ITP)
a. Increased platelets destruction
b. Decreased platelets production.
c.. Both
II. Secondary to :
A) Drug induced thromfaocytopenia:
i. Bone marrow depression e.g. cytotoxic drugs.
18
ii. Drug induced immune ihrombocylopema:,
B) Secondary to some diseases:
Bacterial or viral infection.(infectious mononucleosis)
Uremia, systemic lupus erythematosus.
Neoplasia of bone marrow or lyrnphoid tissues (leukemia,
lymphomas).
Radiotherapy.
Treatment:
The general line of treatment includes;
1. Remove the underlying cause if known.
2. Corticosteroids are useful in idiopathic
thrombocytopenic purpura (1TP) and in autoimmune drug
induced thrombocytopenia.
3. Spieneciomy (if there is increased platelets destruction-
normal megakaryocytes in bone marrow).
4. Platelets transfusions (for secondary ihrombocytopenia).
The platelets should be used within 6-24 hours after
collection and suitable preparation includes platelets rich
plasma and platelet rich concentrate.
5. Neumega is a new drug used to stimulate platelets in bone
marrow, it is JL-11.
Dental Implication :
Gingival bleeding can be controlled by the use of fibrin
foam, gef foam or absorbab;--. cellulose with thrombin -
20 vol. hydrogen peroxide should be tried , in many cases it
will control gingiv;il oozing.
Elective dental surgery should be deferred.
THROMBOCYTOSIS THROMBOCYTHEMIA
There is increased number of circulating platelets, the elevation
is in the range of 500 000-1000 000/cubic mm, but may be
higher.
Etiology:
1. Idiopathic:.
2. Secondary : may be secondary to ;
Spleenectomy
19
 Rheumatoid arthriti
Myeloproliferative disease (polycthemia vera,
chronic mefocytic leukemia)
Lung cancer
Thrombocytosis predisposes to both thrombosis and bleeding
tendancy, due to consumption of clotting factors.
Medical management:
Thrombocytosis is treated with :
32P-Labelled phosphorous.
Cytotoxic drugse
Corlicosteroids.
Anticoagulant drugs.
Dental Implication:
1. Dental treatment should be conservative, elective treatment
should be delayed.
2. If there is gingival bleeding associated with gingivitis or
periodontitis, only scaling is performed to one quadrant per visit
with extreme care to avoid inflicting trauma to the gingival
tissues.
3. Hydrogen peroxide ( 20 vol. ) and local hemostatic agents
should be tried to st gingival bleeding.
4. If extraction is unavoidable, pack the socket with gel-foam
which is usually sufficie to stop the bleeding.
5. The dental management is complicated by hemorrhage,
thrombosis and cytotox agents.
PLATELETS DYSFUNCTION
Platelets dysfunction is due to congenital or acquired disorders :
A. Congenital disorders
Patients often present with history of easy bruising, bleeding
following surgical procedures. Congenital disorder may be due
to ;
pistaxis. menorrhagia and abnorm
1. Defect ht adherence:

20
The glycoprotein (Ib) receptor for YIIhvWF is absent on the
platelet membrane Bernard -Soulier syndrome, (treatment:
platelets activating factor/ platelets transfusion)
von Willebrand's disease is clinically similar to platelets
disorders.
2. Defect in release: (storage pool disorder)
a. Quantitative deficiency of the storage pool: the platelets lack
the capacity to sto serotonin and ADP and consequently fail to
aggregate.
b. Failure to produce thfOttiboxane A2 and consequently the
platelets fail to aggregat
c. Sometimes the mechanism is unknown.
3. Defect in aggregation:
Galnzman's disases/ thrombo3sthenia : the platelets lack surface
glycoprotein reccpli (lib, Ilia) necessary for binding fibrinogen.
(treatment platelet transfusion)
Bernard-Soulier syndrome : platelets react normally to all
stimulants except ristocetin. Galnsman 's dixase : platelete
adhere normally &. aggerate with RisioceU'n but not with
coMagen.ADP OR epinephrin
B. Acquired disorders
The platelets dysfunction develops as an acquired phenomenon ,
the is generally prolonged, but the bleeding tendancy is fairly
mild and only I-IM when there is an associated reduction of
platelets count.

1. Meloproliferative diseases:
There is bleeding tendancy related to thrombocytosis per se thai
improv reduction of platelete count. In addition ihe platelets
may develop a variety and granular defects.
2. Uremia_j
Retained uremic toxins result in platelets abnormal aggregation
in respc, which is improved by hemodialysis.

21
3. Dysproteinemia:
Circulating paraproteins secondary io multiple myeloma are
associated with dysfunction, and interfere with the clotting
mechanism as well.
Treatment of the primary disease by chemotherapy or
plasniapht-rei. paraprotein level ,and improves platelets function
and clotting mechanism
4. Drugs
Aspirin inhibits the synthesis of both thromboxane A2 and
prosi1 irreversible acetylation of cycloxygenase, cyclo-
oxygenase converts araclv T prostaglandin. The later is
metabolized to TxA2 and Prostacycline. This <''.' -me life
span of platelets and is reversed only when the new platelets are
reit. :
Thromboxane A2 : synthesized by platelets from prostaglandins
and is m platelets aggregation and platelets release function and
is vasoconstrictor.
Prostacycline: formed from prostaglandins in the endothelium
of the waH
and veins. It is a potent vasodilator and potent inhibitor of
platelets
(opposite to TxA2).
Small (less than 300 mg ) oral doses of aspirin completely block
thror !'
production by platelets, while larger doses are apparently
required to block p-
production by endothelial cells. This is the rationale for low
dose aspirin
some thrombotic states.
High doses of aspirin are also given immediately after an acute
These doses may also inhibit the synthesis of pro thrombi it
therefore produce a second and different anticoagulant effect
Scurvy
-Vit C is necessary for hydroxyproline synethesis which is
essential
22
collagen. - Vit c deficiency defect in colloagen synthesis.
-Sources: fruits vegetables & milk

Clinical feature:
a. Petechial haernorrage that coalesce to form ecchymosis.
b. Haemorrage in muscles, joints: nailbeds. skin & gingiva.
c. Gingiva: swollen, friabile, bleeding, secondary infection &
loosen teeth.

-Daijy reguirernenl 45 mg. -Treatmeni: 1 g/day

HEREDITARY HEMORRHAGIC TELANGIECTASIA

Definition: HHT is transmitted as a non sex linked dominant
disorder, characterized by mucocutaneous lesions which are
multiple . superficial ,localized cherry red to purplish abnormal
vascular dilation of the terminal vessels (venules. arteriols &
capillaries)
Age: the lesions rarely develop before puberty but appear
progressively from the second or third decade. They appear to
increase in number and prominence as the patient ages as well as
bleeding episodes which tend to increase in frequency and
intensity.

Clinical features:
Site:
skin lesions :are common on face, neck and chest.
Subrnucosa ; mouth ,nose, pharynx and gastrointestinal tract.
Perioral skin, lips and nasal mucosa are the most common
sites.

Character:

23
 Epistaxis is the most common feature, followed by oral,
gastrointestinal and urogenital bleeding and hemoptysis.
These lesions blanch on pressure (contrary to petechia and
ecchymosis) and are nonpustulating.
Profuse oral hemorrhage either spontaneously ,or by trauma
or on the mere touch with cotton.
Skin lesions never bleed spontaneously.

N.B. Similar telangieclases of the skin and mucous membranes

may be associated with other diseases e.g. lupus erythematosus,
sarcoidosis, scleroderma ( progressive systemic sclerosis) and
CREST syndrome (Calcinosis cutis, Raynaud's phenomenon,
Esophageal dysfunction, Sclerodactyl and Telangiectasia).
Diagnosis: is reached through ;
a) Family history and history of epistaxis.
b) Clinical examination: presence of multiple telangectesies on
skin and mucous membranes.
c) Laboratory findings : normal bleeding time, coagulation
time, cloi retraction, platelets count and tourniquet test.
d) However, there is low hemoglobin content secondary to
continuous bleeding.

Pathologic Features :
The intrinsic lesions have been shown to be endothelial
discontinuity caused by degeneration or defective overlapping
at the endothelial junction.
Perivascular connective tissue abnormalities reduce the support
for tht, vessels, which also lack elastin and have inadequate
smooth muscle .
Dental aspect :
* Trauma should be avoided whenever possible.
* Lesions may occasionally interfere with periodontal therapy
or oral surgery and the bleeding can be treated by
electrocoagulation, laser therapy, cryotherapy or resell '-m.

24
* Escharotic agents such as silver nitrate, 50% trichloroacetic
acid and chromic acid are J effective on only small bleeding
points.
* Sclerosing agents such as morrhuate sodium can be used as
prophylaxis.
* Iron andfolate therapy may be required if there is chronic
anemia.
* /Von steroidal anti-inflammatory analgesics are
contraindicated because of 'he risk of gastrointestinal bleeding
and effects on platelets function.

DIAGNOSIS OF PATIENTS WITH BLEEDING

DISORDERS
An adequate history is the single most important part of the
evaluation of patients with (##) bleeding tendency, clinical
examination is also necessary, but the hematological teats are
needed to confirm the diagnosis

I. History
Any suggestion of a hemorrhagic tendency must be taken
seriously. The history should include.
1. Bleeding problem in relatives: may reveal hereditary
disease as hemophilias.
2, Bleeding problem following operation (e.g. tonsilectomy)
or after dental extinction. Pervious dental extraction provides
useful guide, but prolonged bleeding (I days, as an isolated
episode is usually the result of local factors, which are the
most common cause of excessive bleeding.

3. Bleeding problem following trauma : Small cuts in patient

with coagulation disorders may not cause excessive
immediate bleeding. Bleeding is usually delayed due to
vasoconsiriction, extra vascular pressure and platelets
plugging proceed normally. However. small cuts in patients

25
 with platelet or vascular deficiencies usually result in
immediate excessive bleeding.
4..Medication that may cause' bleeding problems:
a. Anticoagulants e.g. Heparin and coumarin. Heparin prevents
thrombin formation and in large dose inhibits platelets
aggregation. Cumarin: It antagonizes vit K, it depresses
clotting factors II. VII. IX and X in the liver.
b. History of Aspirin or Aspiring - containing drugs: the dose
and duration should be determined.
c. History of recent prolonged administration of broad
spectrum antibiotic therapy \\hich may disturb the intestinal
flora and interferes with vitamin K synthesis
d. Cytotoxic drugs

5. Presence of disease that may have associated bleeding

problems:
Biliary tract obstruction
Mai absorption
Leukemia
Parenchyma) liver disease
Hemophilia
Cancer, radiation therapy, anticancer chemotherapy.

6. History spontaneous bleeding from nose, mouth, gingiva,

ears, urinarytract, G.I.T., rectal, pulmonary or vaginal.

II. Clinical Examination

The skin and mucous membrances should be examined
for : petechia, ecchymosis, hematoma, angiomas and
jaundice.
The lymph node should be examined and the mobility of the
joint should be obsereved.
Platelets and vascular defect give rise to petechiae and
ecchymosis on the skin and mucous membranes

III. Screeing Laboratory Tests:

26
One or more or all the following laboratory test should be
ordered to confirm the diagnosis of the bleeding disorders:
Prothrombin time.
Thrombin time.
Partial thromboplastin time.
Tourniquet test.
Bleeding time.
Platelet count.
Determination of the level of clotting factors when indicated.

IV. Surgical Procedures:

Excessive bleeding following surgery may be the first clue
of underlying bleeding problem.

27
 Chapter 10
RED BLOOD CELL DISORDERS

RBC
Life span : 120 days
Cont:4.5 - 5 million / cubic mm.,males > females.
Hemoglobin: 13- 16 gm / dl in males.
13 - 14 gm / dl in females.
12 - 13 gm / dl in children.
RBC disorders; 1. Anemia 2. Polycythemia

ANEMIA

Anemia is defined as reduction in the oxygen carrying

capacity of the bload. It is usually related to decrease in the
number of circulating red blood cells and reduction of the
quantity of hemoglobin

Classification of Anemia: anemia may be classified

according to :
1) The size of RBCs into: normocytic, microcytic and
macrocytic anemia.
2)The hemoglobin concentration into : hypochromic and
normochromic anemia.
3) Etiology into: increase blood loss, increase red blood cell
destruction, decrease red
blood cell production or combination of above
where one of them
predominate.
There are ihree types of anemia:
MCV MCH MCHC Disease
1) Noj-rnocytic Normal Normal Normal a. Apfasdc
normochromic anemia b.
Sickle-cell
mem
2) Microcytic Decreas Decreas Decreas Iron
hypochromic e e e deficiency
28
 anemia
3) Macrocytic Increas Increas Normal a. Pernicious
normochromic e e anemia
b. Foliate
definition

MCV -= mean corpuscular volume = "80-

90 =Femtoliter"

MCH = mean corpuscular hemoglobin = "27-

32= picograms"
= Amount of Hb in single RBC

MCHC = mean corpuscular Hb concentration. = 34%

(3 1 -36 %)
= Average concentration ofHb in RBC

Hematocrit = percentage of blood occupied by RBCs

=45% in
males.36 % in female.
In hypochromic anemia MCHC is less than 30%.
In normochromic anemia MCHC = 30-36 %.

IRON DEFICIENCY ANEMIA

Iron deficiency anemia is microcytic hypochromic anemia
It is the most common type of anemia particularly in women of
child brearing age

Etiology:
1) Mainly due to blood loss .
2) Impaired iron absorption.
3) Inadequate iron intake
29
 4) Increased iron requirement .
Clinical features:
1) Features due to anemia
and tissue hypoxia
(in all animas )
a) Symptoms
General fatigue
Headache
Palpitation Angina of effort
Shortness of breath
b) Signs
*Pallor of skin, nail beds &
palpeberal conjunctiva.
* Tachycardia
* Cardiac murmurs?
decreased cardiac out put.
30
2) Features due to iron
depletion
Sparse hair
9 Brittle nails, with tendency to
crack and split.
Koilonychia: flattened or
spoon shaped and thinned
nails.
ORAL FEATURE
1) Pallor of oral mucosa.
2) Angular cheilitis in 15 % of
cases.
3) Glossitis: sore atrophic
tongue, in sever cases
atrophy of filliform and
fungifrom papillae and the
tongue appear red atrophic
with painful surface.
4) Sore mouth: sore atrophic
changes involve
other oral mucosa.
 5)Slow wound healing. ( in
iron store direct cause of
mucosal atrophy. The epithelial
Integrity
depend on adequate serum
iron level)

Laboratory Findings:
- Decreased hemoglobin less than 11 g/dl
of blood
- Decreased RBC count 3,000,000 -
4,000,000/mm3
- Decreased MCV, MCH & MCHC
- Many immature cells are seen in peripheral blood,
- RBC may be irregular in size (anisocytosis) or irregular in
shape (poikilocytosis).
- Decreased serum iron concentration and elevated total iron
binding capacity.
Serum iron
- Transferrin saturation =-------------------------------,= less than
10 % i.e. the serum
Total iron binding capacity
iron carrier,transferrin is<than 10 %,
The ratio in normal individuals is approximately 35 %.

Treatment:
The cause of iron deficiency should be identified and
eliminated.
Ferrous sulphate tablets (600 mg daily contain 120
mg ferrous iron) best absorbed when the patient is fasting. If
nausea, diarrhea or constipation occur, advice the patient to :
a, have the tablet with food.

31
 b. use other drug with low dose of iron e.g. ferrous
gluconate (600 mg daily contain 70 mg ferrous iron).
Parentral iron has no advantage and is useful mainly when
inflammatory bowel disease is aggravated by oral iron. Iron
stores are replaced quickly with parentral iron but hematological
response is not quicker. Oral iron may be given for 3 months or
more to replenish marrow iron stores. The response to iron
therapy can the monitored by increasing reticulocytic count and
Hb rises 1 gr/week.

Dental implication:
1- CBC with differential should be ordered for anemic patient
2- Avoid surgical procedures in severly anemic state because
of increased
bleeding & impaired wound healing. If hemoglobin below
10 g/dl, the
low oxygen tension affect rheologic interaction
between cellular
components of blood, mainly platelets & endothelium,
decreasing their
ability to clot effectively.
3- Avoid G.A if Hb < l0g/dl

PLUMMER-VINSON SYNDROME
PATTERSON-KELLEY SYNDROME

Plurnrner-Vinson syndrome is one manifestation of iron

deficiency anemia

Plummer-Vinson syndrome is characterized by :

1) Smooth red painful tongue with atrophy of filliform and later
by the fungiform papillae.
2) Atrophy of the mucosa of the mouth, pharynx and upper
esophagus.
32
3) Angular cheilitis , candidal infection,oral ulceration.
4) Dysphagia or feeling of food sticking in the throat.
. Dysphagia is due to muscular degeneration in the esophagus
and stenosis or webs of the esophageal mucosa.
The depletion of iron stores in the body may be the direct
cause of mucosal atrophy, since the integrity of the epithelium is
dependent upon adequate serum iron level. Patients with these
syndrome should be followed up closely for any oral or
pharyngeal changes that may be early indicator of carcinoma.

Skin: dry atrophic

brittle and spoon shaped finger nails.

Dental Implication

1. Periodic follow up ?

2 .Avoid GA ifHb is less than 10 g/dl

3 . Take care to avoid aspiration of materials during dental

treatment

PERNICIOUS ANEMIA ADDISONIAN ANEMIA

*PA is an autoimmune disease in which there is progressive

destruction 0/ the gastric fundic glands, leading to atrophic
gastritis, achlorhydria, loss a/production a/intrinsic factor and
vitamin B12 malabsorption.

"The disease is associated with autoantibody production against

their own parietal cells and intrinsic factor.

"The intrinsic factor is essential for absorption of Vit, B 12

which takes place in the ileum.

Vit B 12 is needed for

: 1. fatty acid metabolism,

2.DNA synthesis, thymidine synthesis and cell division. 3.Folic

33
acid metabolism.

4.Nervous tissue metabolism and maturation ofRBCs.

N.B: The metabolic relationship between Vit BIl and folate is

essential for DNA synthesis and their deficiency lead to
megaloblastic anemia.defective nuclear maturation of
RBC.

The RBC have small immature nuclei & large mature

cytoplasm.

Source of BI2:

1) Vit.B 12 is synthesized by the intestinal micro-organisms.

2) Animal source: meat, fish, egg and milk (but not in plant) and
IS not destroyed by cooking.

Pernicious anemia is the disease of middle age and over,

affecting both sexes and develop slowly because the liver stores
of Vit.B 12 are large (lasting 3 years) and ultimately lead to
macrocytic anemia, meglaoblastic changes in bone marrow. The
latter is due to delayed nuclear maturation ofRBC as result of
defective DNA synthesis.

Clinical Features:

1) Iusidious onset with progressive increasing sign and

symptoms of anemia.

2) Patient may have lemon yellow color which is due to both:

a. Pallor - feature due to anemia and tissue hypoxia.

b. Jaundice : feature of increased serum bilirubin due to

premature breakdown of newly formed RBC in the bone
marrow.

34
3- Neurological symptoms: develop in about 10% of cases and
causes diseases of brain, spinal cord and peripheral nerves. The
classical feature are those of polyneuropathy..

The patients are suffering symmetrical numbness or tingling of

the extremities, neuromuscular in coordination, muscular
weakness and ataxia.

Paraplegia, dementia and optic atrophy may occur.

4) Gastrointinal symptoms :constipation, or diarrhea, vague

epigastric pain and there is increased risk of stomach cancer.

Meg,r,lloblastc anemia are mainly due to deficiency in 812 &

folic acid which chiefly affect cells with rapid turn over e.g
hematopoietic cells, epithelial cells, GI mucosa & oral mucosa.

Oral Aspect:

1.Glossitjs. glossodynia & soreness atrophic tongue:

(burning of mouth can attributed to neuropathy.)

2. Pallor of the mucous membrane a/the entire oral cavity.

3. Aphthous ulceration may occur particularly on the tongue.

4. The patient can't tolerate to wear the denture due to changes

in oral mucosa.

5. Disturbance of taste sensation and a decrease in salivation,

eventually xerostomia, may result.

N.B Changes of the oral mucosa resembling pernicious anemia

may occur in such diseases as in folate deficiency,
ariboflavinosis, mal-absorption, and Sjogren syndrome.

35
Diagnosis:

(A)The diagnosis of PA could be suspected if the patient

complains of triad of symptoms:

a) Sore, painful atrophic tongue.

b) Generalized weakness

c) Numbness or tingling in the extremities.

(B) Hematological finding

* Decreased RBC count less than 1,OOO,OOO/ml with many

cells exhibiting macrocytosis, anisocytosis and poikilocytosis:

* Increase in MCV and MCH, and normal MCHe.

* Decreased leukocyte number and the polymorphs are

hypersegmented with 6 or

more lobes in the nucleus.

* Abnormally large platelets. Platelets number may decrease. ,.

Serum bilirubin can be increased.

* Serum folate is normal.

* All patients exhibits low serum Vit B12level, usually less than
100 pg/ml.

36
(C) Definitive diagnosis can be reached by:

1. Schilling test:

a) Radiolabelled Vito B12 (small measured dose) given orally.

b) Unlabelled Vit B 12 (large dose jgiven 1M 1 or 2 hour later.

c) Collect 24 hour urine.

d) Normal person can excrete> 15% radio labelled B 12 in PA it

is less than 15%in 24 hours.

e) Repeat with added oral intrinsic factor. In PA: excretion ofB

12 increases to normal, while in ileac disease: excretion ofB12
remains low.

2. Detection of serum antibody against

a) Parietal cells which are found in 90% of cases.

b) Gastric intrinsic factors are found in 60% of cases.

Treatment:

Patients are treated (for life) with LM. injection of hydroxy

cobalamine (1000 jlg), given as total dose of 5000-6000 jlg
over 3 weeks and then 1000 ug every three months.

N.B.:

The hematological changes of pernicious anemia may be

improved by oral folic acid therapy but will not stop the
progression of neurologic symptoms. It may aggravate
neuropathy. For this reason anaemic patients should never take
folic acid therapy without being first sure that their anemia is not
pernicious. folic acid improve Hb level but allow the neurologic
changes to progress.

37
 FOLATE DEFICIENCY ANEMIA
*It is a macrocytic normochromic anemia to deficiency of folic
acid.

* The effects offolate and Vit.B12 deficiency are similar, both

cause megaloblastic changes in the bone marrow and macrocytic
anemia.

*Unlike vit B 12 the body reserve of folate in the liver are low 6
- 10 mg and can be depleted within 4 months.

The main causes of folate deficiency are:

1) Poor intake.

2) Malabsorption: inflammatory bowel disease.

3) Increased demand: infancy, pregnancy, increased hemolysis.

4) Drugs: alcohol, barbiturates, phenytoin, methotrexate and oral

contraceptive.

The initial clinical presentation of folate and Vit.B12 deficiency

may be indistinguishable from each other. Contrary to Vit.B 12
deficiency, folate deficiency does not lead to neurological
manifestation

Folate deficiency anemia is characterized by:

a) Serum folate level low and serum Vit.B 12 is normal.

b) Schilling test is normal.

Treatment: Folic acid 5 mg/daily

38
 APLASTIC ANEMIA
Aplastic anemia is a rare bone marrow aplasia, causing
refractory normocytic normochromic anemia, leukopenia and
thrombocytopenia (pancytopenia).

Etiology may be attributed to:

1) Primary:

a) Congenital e.g. fanconi's anemia with features of skeletal,

renal and eNS abnormalities .:

b) Acquired: may be due to immune suppression of bone

marrow stem cells by T suppressors cells.

2) Seeondary to :

* Drugs: cytotoxic (busulphan) and noncytotoxic

(chloramphinicol) .

* Chemical: e.g. benzene.

* Ionizing radiation.

* Insecticides.

* Viral infection: vital hepatitis and measles.

* Thymoma.

Clinical manifestations

* Anemia, together with increased susceptibility to infection,

bleeding tendency and purpura which is often the first
manifestations.

* However the clinical manifestations depend on the severity of

pancytopenia.

39
*The oral manifestations include:

1. Pallor of the oral mucosa,

2. Minimal but persistent gingival bleeding,

3. Petechiae and ecchymosis and

4. Ulceration of the oral mucosa having little surrounding

erythema. The presence of severe ulcerative stomatitis is a
rather constant manifestation of aplastic anemia. Oral
manifestations of advanced cases appear similar to the oral
manifestations of acute leukemia.

Laboratory Findings:

The laboratory diagnosis is made on the bases of:

1. Pancytopenia.

2. Absence of reticulocytes.

3. Hypocellular or aplastic bone marrow with increased fat

spaces

Differential diagnosis:

Aplastic anemia should be differentiated from other causes

of pancytopenia.

Causes of pancytopenia:

1) Aplastic anemia

3) Hypersplenism

2) Megaloblastic anemia

4) systemic lupus erythematosus

5) Severe sepsis.
40
6) Bone marrow infiltration by :

Lymphomas.

Acute leukemia.

Myeloma.

Secondary carcinoma.

Treatment: The princip les of management include:

1) Eliminate the cause if possible.

2) Supportive treatment: this induce RBC, and platelets

transfusion and antibiotic therapy.

3) Bone narrow transplantation'.

4) Immunosuppressive drugs:

Antilymphocyte globulin . Steroids Cyclosporine

Dental Aspect of Aplastic Anemia:

Oral manifestation and management of aplastic anemia are

similar to those of acute leukemia in many respects:

* Increased bleeding tendency.

*Marked susceptibility to infection. " Presence of severe

anemia.

* Precaution to the effect of steroid therapy.

* Graft versus host disease consequent to bone marrow

transplant

(Lichenoid lesions & Sjogren Syndrome

41
 HEMOGLOBlNOPATHIES
Each hemoglobin molecule consists of two alpha and two
beta globin chains bound to a single heme moiety.

Heme contains one ferrous iron atom carried in a

porphyrin ring.

*Defecrs of the globin portion of hemoglobin induce the

erythrocytes to carry abnormal hemoglobin and the patient is
susceptible to hemolytic anemia.

*Adult hemoglobin, Hb A consist of two alpha and two beta

globin chains and is represented as a2~2.

*Fetal hemoglobin, HbJF, the beta chains replaced by two

gamma chain and IS represented as a2 y 2.

*Sickle cell disease: involve single amino acid abnormality, the

glutamic acid which is normally found in position 6 in beta
globin chain is replaced by valine.

*Thalcssemia: characterized by diminished synthesis of the

alpha or beta globin chains of hemoglobin.

N.B: - In normal person most of the hemoglobin is HbA.

- At birth about 80% hemoglobin is HbF.

- At six months HbP reduced to 5%.

- Adult life HbF is not more than 1 %.

42
Types of hemoglobin:

Hb Structure
Adult 1)Hb A 2 2 92%
2)Hb Alc 2 2 5%
B-NH It is glycosylated Hb
Glucose which is increased in
patient with uncontrolled
diabetes.
3)Hb A2 2 2 2%
Evelated in B thalassemia
4) Hb F 2 2 < 1%
Normal Hb of fetus
elevated in B thalassemia
Abnormal Hb s 2 2 Valine replace glutamic
chain acid in position 6 of B
chain
Struscture Hb C 2 2 Lysine replace glutamic
acid in position 6 ogf B
chain

ISICKLE CELL DISEASE II

Definition:

Sickle cell disease is hereditary disorder of hemolytic

anemia, characterized by appearance of numerous sickle shaped
red cells in the circulating blood

It is genetically determined hemolytic anemia caused by

mutation in Hbl3 polypeptide chain gene.

pathogenesis:

The basic defect is in the beta globin chains in which valine is

43
substituted for , acid on position 6. As a result of this, an
undesirable physical changes occur in the hemoglobin (HlrS). In
the presence of either deoxygenated state or acidosis, the HbS
molecules become insoluble and polymerize. The flexibility of
the red cells decreased become rigid and exhibit the
characteristic sickle shape.

This process is reversible initially but with repeated

sickling, the cell loose their flexibility remain deformed

Skilling is precipitated by:

* Infection. * Dehydration.

* Cold * Acidosis.

* Hypoxia (high altitude, general anesthesia).

In many cases the etiology is unknown.

Hb S release its oxygen contents to the tissues more easily than

Hb A, and these patient therefore feel well despite being anemic
except during crises or complication.

Sickiilffig an lead to:

1) Destruction of sickle cells (hemolysis) with features of

anemia.

2) Increased viscosity & clumping of cells in the

microcirculation. This leads to thrombosis .ischemia & infarct
Mutant

44
 gene

Abnormal polypeptide 'in Hb S

Lowered blood oxygen tension

Sickling

A) Increased viscosity & B)Destruction of

clumping of cells sickle cells

Ischaemia, thrombosis, infarction Anemia

Gut abdominal pain Heart failure

Spleen spleenic infarction Spleenomegaly

Extremities obone pain.tenderness Weakness

& osteomyelitis Lassitude

Brain cere bro- vascular Abnormal skull radiograph.

Accident

Kidney shematuria.renal failure

Lung opneumonia

Heart heart failure

Painful or infective crisis hematological crisis

Hemolync.aplastic.spienic sequestration crisis)

45
Sickle cell disease is classified into:

I) Homozygous state, sickle cell anemia .The patient

receives two abnormal alleles one from each parent -Jeading
to abnormalities of all chains of hemoglobin (MbSS).

2) Heterozygous state, "sickle cell trait" .The patient receives

an abnormal allele from one parent and a normal one from the
other(HbSA).

The sickle cell trait is less severe due to the presence of some
normal [3 chain.

The disease occur mainly in Africans (25% carry the gene), but
is also found m cast, India and southern Europe.

SICKLE CELL ANElVHA (HbSS)

Sickle cell anemia is a senous disease since 80-90% of Hb
is HbS and the is HbF.

Clinical feature:

The clinical manifestations are those mainly due to chronic

anemia which is punctuated by intermittent crise

1)Anemia : mild asymptomatic to severe hemolytic

anemia.icteric tinge in the sclera., patient is weak, short of
breath easily fatigued, and under developed.

2) Painful or infarctive crisis:

precipitating factors :fever, pregnancy, cold. dehydration,

psychic stress, hypoxia, acidosis and surgery,

46
clinical features:

1) Bone pain is the commonest feature.

2) Pain: abdomen, chest, spleen, liver.

3) Cerebral damage: hemiparesis, fits.

4) Dactylitis, and leg ulcers.

5) Kidney infarcts causing hematuria.

6)Penis infarcts causing priapism .. etc

The attack of painful crisis last from few hours to few days
and usually ssocrated with low grade fever.

3) Hematological crisis:

a) Hemolytic crisis:

The rate of RBC hemolysis accelerates

b)Aplastic crisis. bone marrow aplasia lasting 5 - 10 days

caused by parvovirus

c)Splenic Sequestration Crisis:

Sequestration of the sickled RBCs occur in all patients with

HbS.

In ealrly childhood, the spleen is enlarged with entrapment of

sickle cells. This can occur acutely in some cases and can be the
cause of infant death below one year.

47
In adults splenomegaly is. rare, due to repeated infraction and
fibrosis and functional aplasia occurs early childhood .. Splenic
function is lost and the patients are susceptible to infection. It is
best to regard these patients as moderately immune
compromised and at great risk for infectious disease.

4)Impaired growth

5) Skeletal deformities

6) susceptibility to infection.

Oral Manifestatious:

* The oral mucosa especially the soft palate is pale and has
yellowish tinge.

* Delayed eruption and enamel hypoplasia may be seen. @

*Maxillary over growth.

Radiographic changes:

1. The jaw boneshows both osteoporosis as well as areas of

osteosclerosis. The bone changes can be produced by two
opposing mechanisms:

*Since ftBCs have short life span of approximately 30 days

which is only one fourth of the normal red cell life span, this
leads to enormous stress placed upon the bone marrow to
produce more red cells. the hyperplastic bone marrow is evident
by osteoporosis.

*As a result of thrombosis occurring in the capillaries of the

bone marrow by sickled cells, thrombosis acts as a nidus for
calcification resulting in osteosclerosis.

There is osteoporosis and osteosclerosis affecting the mandible,

maxilla, skull, vertebrae and long bones
48
2. The trabecular pattern of alveolar bone tends to run
horizontally between the roots of teeth. (Ladder like effect).
Lamina dura appears dense and distinct.

3. Skull x rays::the diploe is thickened(due to bone marrow

erythroid hyperplasia) and the trabeculae are coarse and tend
to run perpendicular to the inner and outer table giving "hair
on end appearance". The frontal bossing is very prominent.

Laboratory Finding:

1) Normochromic normocytic anemia.

2) Sickling occurs after sealing fresh blood in a small chamber

of microscopic slide with a reducing agent for 1 hour
(sodium metabisulphite).

3) Sickling solubility test: a mixture of Hb S in reducing

solution (sodium dithionite) gives a turbid appearance
due to precipitation of Hb S, while Hb A, gives clear
solution.

4) Hemoglobin electrophoresis is more accurate methods for the

diagnosis. 80% - 90% is Hb S, the remainder is Hb F.

Management; (there is no treatment other than symptomatic

treatment) The precipitating factors for crises should be avoided.

-Notreatment is required for steady state of anemia.

-Acute attack require supportive therapy (IV fluid, oxygen,

antibiotic & narcotic analgesic)

-Folic acid given during pregnancy and those with severe

hemolysis.

-Blood transfusion is indicated during aplastic crisis were Hb

level is extremely low .

49
- Repeated blood transfusion should be avoided because

a, Its effect is transitory.

b. The patient may develop antibodies to the donors RBC.

c. Risk of transmission of viral hepatitis.

d. Risk of iron overload (hemosiderosis)

Dental Implication of sickle Cell Anemia:

1) Never anesthetize or operate on patient during sickle cell

crises, Elective surgery should be done when hemolysis is
minimum.

2)General anesthesia is hazardous in sickle cell anemia, because

of the severe anemia and because of the crises may develop. If
general anesthesia is required Hb should be at least 10 gldl and
select a phase when hemolysis is minimal. Partial exchange
transfusion with packed red cells and oral administration of folic
acid are valuable in correcting the anemia. avoid episodes of
hypoxia because cerebral or myocardial thrombosis can result.
(this is applied also for sickle cell trait)

3)Whenever possible, dental treatment should be carried out

under local anesthesia. However local infiltration or block
anesthesia is not without hazards, since the vasoconstrictor
content of the anesthetic solution can precipitate the crises.

4)Tourciquet should not be used, this may precipitate a crisis or

even may lead to loss ofthe limb.

5)Antibiotic should be given as a prophylactic cover in any

operation in sickle cell anemia (and sickle celltriat), since any
infection can precipitate a crises. Acute infection should be
treated immediately.

6)Always expect poor wound healing after extraction or surgery

in any patient with hemolytic anemia.
50
7)Cerebral or crdiac hypoxia may occur in these patients with
minor procedures.

8)Drugs which may cause respiratory depression should be

avoided including sedatives, it may lead to hypoxia.

9)Infarction in the bone may predispose to osteomyelitis

especially in the mandible.

10) Pain is usually of local dental origin but it may be caused by

infarction or osteomyelitis.

11) Pulpal symptoms are common m the absence of any obvious

dental disease. Pain should be controlled by paracetamol or
codeine rather than aspirin .Large dose of aspirin disturb the
acid base balance.

SICKLE CELL TRAIT (HbAS)

This occurs in heterozygous cases in whom 60'% of
hemoglobin lis HbS,the remainder is normal hemoglobin.

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 or unpressurized aircraft).

At times these patients may have renal complications

causing hematuria or splenic infarcts.

These patients have few problems in management, but if

general anesthesia is necessary full oxygen must be maintained.

Respiratory infection should be treated vigorously.

Sickle cell trait protects against Plasmodium falciparum

malaria.
51
Diagnosis is made by :

1) Positive sickling test.

2) Hb electrophoresis.

3) Blood count and film are normal.

THALASSEMIA
Thalassemia (Greek thalassa = sea) are anemia originally
found in people living on the shores of the Mediterranean but
are now known to affect persons throughout the

Thalassemia are groups of congenital disorders

characterized by deficient of either a or ~ chain of globin in Hb.
As a result RBC are microcytic

The unaffected chains is excessively produced and

precipitate within:

a.the red cell precursorsand resulting in ineffective

erythropoiesis.

b. or in mature red cellslead to hemolysis.

There are two types of thalassemia:

1)Alpha thalassemia which is mainly found in Asian and

caused by gene deletion.

2)Beta thalassermlia which prevalent over the world especially

among greek, Italian and Syrian and caused by point mutation.

52
 ALPHA THALASSEMIA
Alpha thalassemia characterized by deficiency of alpha
chain globin with production of abnormal hemoglobin. which
can not carry oxygen and biologically useless.

Clinical Features:

Alpha thalassemia have many subtypes of varying degree of

severity, among which are .the infants may die shortly after
birth. The infants are pale, edematous with very marked
hepatosplenomegaly. or the person suffer moderate anemia and
splenomegaly and they are not dependent on blood transfusion.

BETA THALASSEMIA
Beta thalassemia is classified into:

A)Homozygous Thalassemia (Cooley's Anemia, Mediterranean

Anemia)

B) Heterozygous Thalassemia Minor (or Trait)

(A) Homozygous Thalassemia, Cooley's Aemia,

Mediterranean Anemia
In homozygous 13 thalassemia no normal beta chains are
produced or its production is very reduced. 90 % is Hb F and
10 % is HbAl

53
Clinical Feature:

Cooley's anemia is the most serious type and characterized by:

1) Slow growth & development of children.

2)Ashen gray skin color due to combination pallor, jaundice &

hemosiderosis.

3)Recurrent bacterial infection.(increased availability of iron

for bacterial growth)

4)Extramedullary hemopoiesis with manifestation of hepato-

spleenomegaly.

5)Features of severe anemia.

6)Iron over load: in spite of anemia these patient become over

load with iron because of repeated blood transfusion
(transfusion hemosiderosis) with deposition of iron in heart,
liver, pancreas and skin.

Hepatic and pancreatic dysfunction, and cardiomyopathy will

develop by the time reach adolescence.

Oral muifestation

1) Oral mucosa appear pale with tinge becuase of chronic

jaundice,which is best seen at the junction of the hard and
soft palak and in the floor of the mouth.

2)Painful swelling of the parotid glands, possiblY caused iron

deposition.

3) Painful tongue as the patieots are susceptible to folate

deflCiency (as in other

chrome hemolytic anemia).

4) Hyperplasia of the bone marrow with manifestation of bone

54
expansion givin a rise to classical thalassemic faces, and the
patients has the following clinical presentation:

* The patient has a larae head and exhibit mongoloid feaunes, the
cheek bones

are prominent and the ~ose is short and having depressed bridge

* Enlargement of the maxilla.

* Delayed pneumatization of the sinuses.

* Forward drifting and spacing of maxillary incisors.

* Anterior open bite.

*Upper lip is retracted give the child chipmunk appearance.

5) Dentin & enamel contain excessive amount of iron (5 times

normal)with teeth discoloration.

6) Poor wound healing.

Radiographic Features: similar to sickle cell anemia.

Investigation:

1) MicrocYtic hypochromic anemia with low value MCV,

MCl1.,MCHC

2) Saturated iron binding capacity and high serum ferritin level

because of repeated blood transfusion.

3) Hb electrophoresis: Hb F up to 90% and remaining is flb A2

4) Decrease serum folate level due (0 utilization for

etythropoiesis

Management:

1) Reaular blood transfusion to keep Hb level above 10g/100 ml

55
of blood.

Blood transfusion is required every 4-6 weeks. .

2) Iron chelating agent is required treat iron overload

(transfusion hemosiderosis).

3) Bone marrow transplant has been used in the treatment of

beta thalassemia.

Dental implications

1. Avoid excessive b lee din g during surgery since the patient is

anemic.

2. Antibiotic is required to control infection.

3. Delayed wound healing is expected.

4.GA is difficult for intubation because of the enlarged maxilla,

The severe anemia and cardiomyopathy are additional problems

56
 (B) Heterozygous Thalassemia
Thalassemia Minor (or Trait)
It is common and usually asymptomatic, except for mild
hypochromic anemia may be aggravated by pregnancy or
intercurrent illness.

Thalassemia minor may be confused clinically and

hematologically with iron deficiency anemia.

The disease is benign and non progressive.

Laboratory Findings:

a) Microcytic hypochromic anemia with low MCV

,MCH,MCHC..

b) Serum ferritin, serum iron and iron store are normal .

c) Hb electrophoresis usually reveal Hb A2 and often HbF.

MbA is found in significant amount.

Treatment :

No therapy is indicated, however the patients should be

informed if they marry a person with the same defect, some of
their children may have thalassemia major.

GLUCOSE 6 PHOSPHATE DEHYDROGENASE

DEFICIENCY
* This is an erythrocyte metabolic defect, in the absence of
G6PD, the cannot manufacture glutathione-vreducing agent", so
cannot withstand oxidant compound and hemolysis occur due to
denaturing the hemoglobin.

57
* The life span of RBC is reduced to about 2/3 normal

*infection, diabetes and oxidant drugs may cause an acute

acceleration of RBC hemolysis.

*Metabolic acidosis can cause hemolysis and must be avoided

during general anesthesia.

* Dental infection should be dealt with without delay

*Avoid:

a) Analgesics: aspirin, phenacetin.

b) Antimalarial: quinine, chloroquine, suphasalasine.

C)Antibacterial:most sulphonamide,

dapsone,chloram phenicol.

d) Others :vit K e probenecid and - prilocaine

(may induce rnethaemoglobinaemia)

Blood transfusion may be life saving.

POLYTHYCEMIA, ERYTHROCYTOSIS
Polycythemia is defined as an increase in Hb, pCv and red cell
count.

Polycythemia can be divided into:

1) Relative (apparent) erythrocytosis

where the red cell volume is normal but there is decrease in the
plasma volume e.g. as in dehydration, burns, prolonged
vomiting or diarrhea, rapid diuresis in congestive heart failure,
postsurgical dehydration, diabetic ketosis etc .

58
 a. Decrease plasma volume.

b. N01111al RBC volume.

c. Increase Hb & packed cell

Hb rarely rise more than 25%

There is no detectable oral changes

2)Absolute erythrocytosis

where there is true increase in the red cell volume & classified
into:.

I. Secondary PoiycvthemU2 (Erythrocytosis):

a) RBC increased due to increase erthropoietin hormoneto

compensate for hypoxic state.

Erythrocytosis is due to: Lowered blood oxygen concentration

and is seen in :

i. People living at high altitude.(with low atmospheric pressure)

ill. Heart disease (congenital or failure)

iii, Chronic pulmonary disease (sillicosis - emphysema)

iv. Heavy smoking, can produce as much as 10%

carboxyhemoglobin i.e. reduce oxygen carrying capacity in the
blood.

v- Exogenous androgen administration.

b) Tumors which may release erythropoietin like substancee.g.

brain tumor, renal and lung carcinoma.

Complications :thrombosis, hemorrhage, and cardiac failure.

59
Treatment:1) Treat the cause when possible.

2) Venisection (phlebotomy) to reduce blood viscosity .

II. Primary, Idio1iJathk Polvcythemia Rubra Vera:

PRY is an uncommon disease affecting elderly patients and

has slight male predominance. The essential disturbance of PRV
include:

1) Increased number of RBCs (may reach 18 million/mm3).

2) Increased hemoglobin (18- 24 g/dl)

3) Bone replacement by erythropoietic tissue and myeloid

metaplasia in the liver and spleen.

4)Increased platelets count with platelets dysfunction in 50% of

cases.

5)Increased granular cell count in 70% of cases

6) Increased blood viscosity (mainly increased cell mass).

7)decrease serum iron, ferritin & ervthropuietin level,

Clinical Features:

The main clinical problem are due to

a) Increased blood volume.

b) Increased blood viscosity thrombosis

c) Bone marrow over activity.

1)Purplish - red skin color: face neck, ears, hands and feet.
(presence of deoxygenated blood in cutaneous vessels)

2)The superficial veins of the neck are dark and distended.

3) Splenomegaly in most patients (not a feature in 2ry

60
 polycythemia)

4) pain, 2ry to bone marrow hyperplasia.

5)The patient may complain of headache, tinnitus, numbness

and often is nervous.

6)Bleeding - bruising (petechiae & ecchymosis) or thrombosis

as a result of platelets dysfunction and increased blood viscosity.

Complication:

1) Thrombosis, hemorrhage and cardiac failure.

2) progression of the disease to acute leukemia or myelofibrosis.

Oral Feature and dental Aspect:

1. All oral mucosal surfaces are purplish red in color.

2. Petechiae and ecchymosis are common.

3. Gingival enlargement may be marked associated with

gingival bleeding.

4. Prominent sublingual varices ..

5. Infarcts may occur in smaller vessels because of increased

viscosity of the blood and may result in multiple ulcers on the
oral mucosa ..

The main dental management problemsare the tendency to

bleeding and thrombosis, sometimes may by fatal.

CBC should be ordered before dental treatment, no

treatment should be carried out unless Hb is below 16 g /dl &
hernatocrite below 47% and the patient's physician should be
consult

Medical treatment:

61
Treatment aimed to prevent complication, mainly thrombosis
and hemorrhage and this include:

1)Repeated venesection (phlebotomy)to reduce the red cell

mass and extend the survival time to more than 10 years.

2)Radiophosphorus (32p) is the simplest and most effective,

but it may increase the risk of development leukemia.

3) Cytotoxic drugs may be used to suppress marrow activity,

particularly controlling thrombocytosis.

62
 Chapter 11
WHITE BLOOD CELL DISORDERS
White Blood Cell Disorders:

a) Leukocytosis

b) Leukopenia

c) Myeloproliferative disease.

i. Acute myeloid leukemia

ii. Chronic myeloid leukemia

d) Lyrnphoproliferative diseases:

i. Acute lymphoblastic leukemia

ii. Chronic lymphocytic leukemia

iii. Multiple myeloma

iv. Lymphoma (Hodjkin's and non-Hodjkin's)

The white blood cells are classified into:

1) Granular cells:

a. Neutrophils

b. Eosinophils

c. Basophils

2) Non-granular:

a. Lymphocytes (Tcell 80 % & B cel/5-15 %)

b. Monocytes
63
 The peripheral blood contains approximately 4000-11000/
whitecell/mm3. and the differential WBC include:

Band : : 0 - 200/mm3

Segmented neutrophils : 3000 - 6000/mm3. 60-70 % -Band cell is indented

nucleus more than it's
Lymphocytes :1500 - 4000/mm3. 25-.35 % half in the greatest
diameter.

Monocytes : 200 - 900/mm3. 2-6 % -It is immediate

precursor of mature
Eosinophils : 100 - 70G/mm3. 1-2 % neutrophils.

Basophils :20 - 150G/mm3. 0-1 %

- The granulocytes and monocytes are produced by bone

marrow, while the lymphocyte are produced by lymph nodes.

- Neutrophils are the first line of defense against bacterial

invasion of the mucous membranes and the skin via their
chemotaxis, phagocytosis and bactericidal action. This function
is aided by immunoglobulin and complement

- Monocytcs are immature cells in the blood stream but once

they reach the tissues they become mature phagocytes

(marophages) "

- Eosinophils may phagocytose foreign substances but cannot

kill bacteria

- Basophils migrate to tissues and act as mast cells in allergic

reactions.

- Lymphocytes T & B are involved in cellular and humoral

immunity.

64
Definition of Terms:

- Leukocytosis (granulocytosis): is the increase in number of

white blood cells more than 11000/mm3.

- Leukemoid reaction: persistent elevation of white blood eel!

count with absolute

count remaining above 30,000/mm3, (e.g. viral infection). The

cells He mature but occasional cell less mature than band or
juvenile neutrophils. Bone marrow biopsy is required to
differentiate leukemoid reaction from leukemia. Large amount
ofleukocyte alkaline phosphatase are found in normal
neutrophils.

- Leukopenia: decrease in the number of circulating WBe

usually to less than 4000/mm3.

- Granulocytopenia (neutropenia): decrease in granulocytes

chiefly as a result of decrease of neutrophils.

- Agranulocytosis : no neutrophils are detected in the peripheral

circulation.

65
 Agnmuliocytos
No neutrophils are found in
peripheral circulation
Etiology:
1- Idiopathic
2- Secondary to : drugs,
irradiation, severe infection
Cyclic Neutro enia
Periodic or cyclic decrease of
I circulation circulating
neutrophils secondary to
I bone marrow maturation arrest.
Neutropenic episodes :
occur every.

3-4weeks and last for a few

days (3-5)

66
Clinical Features: Clinical Features:

*Adults - more in women. * Affects both sexes; more in

*High fever, chills, fatigue, sore *infants and children.

throat.
* Fever, malaise, sore mouth and
* Infection is chaJ.-acteristic
feature, affecting: throat + regional lymphadenitis.

mouth, G.l.T.,G.U.T., R.T. and (similar to but milder than

skin.
agranulocytosis)

Infection is not significant

because of:

* Shorter duration of
neutropenia.

* Compensatory increase of
monocytes which prevents spread
of bacterial infection

Oral features: Oral features:

* Painful necrotizing oral (1) During neutropenic episode:

ulceration ( particularly: gingiva-
palatej'The ulcers: large, deep, a) Severe gingivitis
irregular, with no inflammatory
b) Stomatitis with oral ulceration
reaction at the margins. They are
both are due to bacterial
covered by greyish or black
invasion. These return to
pseudomembrane.
normal when neutrophilic
Secondary fusospirochaetal count returns to normal.
67
infection .with foul odor.
*Regional lymphadenopathy
(common)
Lab. Findings:
*Peripheral blood smear:
(1) absence of granulocytes
(2) Total W.B.Cs .. 2000 / cu mm
*Bone marrow: normal but
granulocytes are absent.
Treatment:
* Eliminate cause.
Management:
* Parental antibiotics.
*Keep mouth and skin as clean
as possible by:
. (1 )Chlorhexidine mouwash
68
(2) Repeated gingivitis may
progress to periodontitis or
rapidly progressive periodontitis.
(3) There may be isolated major
aphthouslike ulcers [ patient with
such ulcers,
I cyclic neutropenia should be
ruled out]
Lab, Findings:
Periodic decrease in circulating
neutrophils.
Management:
* Maintain good oral hygein
* Periodic recall for
. periodontal
treatment.
(2) Tropical antibiotic

No dental surgery should be

performed

MULTIPLE MYELOMA
Definition:

It is disseminated plasma cell neoplasm in the bone

marrow producing abnormal monoclonal immunoglobulin (IgG-
less commonly IgA). This paraprotein can be the blood and
urine (by electrophoretic pattern) and in urine (Bence Johns
Protein). Look page 382

The neoplastic plasma cells lead to:

1) Bone marrow infiltration resulting in anemia,

thrombocytopenia and neutropenia.

2)Bone destruction causing fractures, vertebral collapse and

hypercalcemia.

3) Renal impairment secondary to :

a) Deposition oflight chains of the paraprotein in renal tubules.

b)Hypercalcemia.

c) Hyperuricemia.

d) Invasion of the kidney by neoplastic cells.

4) The paraprotein bind with clotting factors, render them

inactive and may lead to

liability to bleeding. The paraprotein also increase the blood

viscosity. The paraprotein coat the platelets resulting in
69
defective platelets function.

5) there is reduction the normal immunoglobulin level, which

contribute to recurrent

Clinical Features:

1)Multiple myeloma is the disease of middle age or elderly with

slight predilection for males.

2) The clinical features are bone pain, spontaneous pathological

fracture, anemia, excessive bleeding tendency, neurological
lesions as paraesthesia, weakness and visual disturbance.

Oral manifestations may be the first sign of the disease and

characterized by:

*- Pain in the jaw or teeth, caused by bone destruction from:

Direct infiltration by tumor cells

Indirect from osteoclast activity factors secreted by tumor cells.

More common in mandible due to higher content of red marrow.

*- Paresthesia (mental).

*- Mobility or migration ofthe teeth.

* Intraoral hemorrhage.

*- Increased susceptibility to infection.

*-Soft tissue masses of plasma cells.

*- Pathological fracture of mandible is rare.

*Amyloid deposition of the tongue (macroglossia).

70
Laboratory Features :

HematologicaL:

_ Normochromic anemia - Neutropenia

- Thrombocytopenia - E.S.R. raised

Biochemical:

_ Hypergammaglobulinemia monoclonal IgG (lgA less often)

_ Hypercalcemia _ Bence Jones Proteinuria

N.B. : The paraproteinemia may be associated with excretion of

IgG light chain in the urine ..

This paraprotein can be detected in the blood and urine (by

their electrophoretic pattern) and in urine (Bence Jones Protein).

Radiological:

_ Generalized osteoporosis _ Punched out radiolucency.

Diagnosis:

1) Protein electrophoresis : characteristically show monoclonal

band ( serum and urine)

2) Urine: for assessment of light chain excretion.

3) Detection of plasma cell neoplasia by bone marrow biopsy.

4) X-ilay: Generalized osteoporosis or punched out osteolytic

lesion (skull).

Dental management complicated by:

71
 1) Hemorrhage resulting from

Thrombcytopenia
Abnormal platelets function
Abnormal coagulation
Hyperiscosity

2) If surgery is necessary blood investigation should be

performed:

1. Platelets count

2. Bleeding time

3. PTT

4. PT

3) Increased susceptibility for infection due to:

* Neutropenia

* Abnormal immunoglobulin

* Bone marrow failure

* Cancer chemotherapy

4)Renal failure, anemia & chemotherapy may complicate dental

management

72
Treatment: .
Bone pain helped by radiotherapy. Renal impairment
require dialysis. Anemia
should be corrected and infection should be controlled.

Chemotherapy is generally used for the treatment of multiple

myeloma. The prognosis is variable but the survival of treated
patients averages 2 years.

INFECTIOUS MONONUCLEOSIS.
(GLANDULAR FEVER)

Glandular fever occurs predominantly in children and adults as a

result of
Epstein barr Virus. EBV. is found in the saliva during the
infection and for several months thereafter. Glandular fever is
called also kissing: disease because of occurrence in younger
age group (commonly seen in college campuses, nurses and
physician) and is probably spread by means of saliva,' in other
words the infection appears. to be spread
by closed oral contact..

Pathogenesis: .

Following infection of oro-pharyngeal epithelium, EBV spread

to subjacent B lymphocytes in the lymphoid tissues. Activation
of Tc lymphocytes by EBV antigen result in the appearance of
atypical T- lymphocytes in the peripheral blood. Tc cells appear
to specifically recognize virus infected B lymphocytes. B
lymphocytes are stimulated with the production of heterophil
antibodies.

Clinical Features:
Infectious mononucleosis is protean in its manifestation but the
typical clinical features include:
1) Fever, headache and malaise.

73
2) Generalized lymphadenopathy particularly the posterior deep
cervical.

3) Spleenomegaly.

4) Oro-pharyngeal features:
a. Sore throat with exudates on the tonsils.
b. Petechiae at the junction of hard and soft palate.
c. Pharyngeal edema which may threaten the air way

Dental Aspect:

Infectious mononucleosis is an important cause of enlarged

cervical lymph nodes. Tonsillar exudate (to be distinguished
from diphtheria), petechiae at the junction of the hard and soft
palate, gingivitis, mucosal and gingival ulceration may be
common finding. EBV may cause sialadenitis.

Diagnosis:
1 ) Relative and absolute lymphocytosis is diagnostic feature,
at least 10% of lymphocytes are atypical because they are larger(
more cytoplasm) and have nucleoli in their nuclei and persist for
weeks or months follow disappearance of the clinical features .

2 ) Heterophil antibodies (IgM) detected by :

a) Paul Bunnel test: Heterophil antibodies can be detected by

agglutination of sheep erythrocytes.
b) Monospot test: rapid method to demonstrate heterophil
antibodies to horse erythrocytes, by detecting agglutination
on a glass slide.

The titre of heterophil antibodies develop by 1-2 weeks of the

illness and disappear over 3-6 months.

3) EBV antibodies is detected against viral capsid llntigen.

74
EBV antibodies are produced early in the disease and persist for
many years.

N.R.: Occasionally there is mild neutropenia or

thrombocytopenia.

Treatment:
a) Mainly symptomatic, during fever and malaise, bed rest is
advised, analgesic
and antipyretic drugs are prescribed.

b) Systemic corticosteroid is required if there is severe

laryngeal edema, which hazards air way.

c) Flagyl prescribed to reduce sore throat.

d) Antiseptic mouth wash for gingivitis and stomatitis.

LEUKEMIAS II
Definition: Leukemias are neoplastic proliferation of WBC
(lymphoid, monocytic or myeloid stem cells) and characterized
by the presence of immature cells in the peripheral circulation
and bone marrow (in high percentage).

Classification:
Leukemia is classified according to :
1) Speed of evolution into acute and chronic leukemia

2 ) According to the individual cell:

a) Myeloid (myelogenous, myelocytic) leukemia involving

granulocytic series.
b) Monocytic leukemia involving monocytic series.
c) Lymphoid (lymphogenous, lymphocytic) leukemia,
involving lymphocytic series.
3) According to the number of circulating leukemic cells:
75
a) Aleukemic leukemia:
Normal number of WBc. in peripheral circulation
No immature celIs in peripheral circulation.
Bone marrow crowded with immature WBc.

b) Subleukemic leukemia:
Normal number of WBC.
Immature cells are present in peripheral circulation.

c) Leukemic Leukemia:
Increased number of WBC in peripheral circulation. .
Immature cells are present in peripheral ciq:ulation

Etiology: exactly unknown, it may be due to:

I) Genetic factor: Chromosomal abnonnalities e.g. philadelphia

chromosome have been associated in 95% of cases of chronic
myeloid leukemia. It results from translocation of genetic
material from chromosome 22 to chromosome 9.

2) Environmental Factors:

a) Radiation (radiotherapy, radiation of atomic bombs).

b) Drugs: cytotoxic drugs.
c) Chemicals: benzene compound used in industry.

3) Viral factors: Human T leukemia virus (HTL V)

Clinical Features:
Acute leukemia affects mainly children and young adult, while
chronic leukemia affects adult of middle age and older. There is
some exception to this rule. Most of acute heukemia in adults
are acute monocytic leukemia. All acute leukemia has the same
clinical features and also all chronic leukemia exhibit to a great
extent similar clinical presentation. Leukemia cannot be
differentiated without hematological studies.
Generally the signs and symptoms of leukemia are due to:
76
l)Suppression of the bone marrow by leukemic cells which may
result in:

a) Anemia:
b) Thrombocytopenia:
c) Impaired normal function of neutrophils:

Impaired function of immune system (B or T lymphocyte).

2) Infiltration of leukemic cells in various organs and tissues:

77
 Acute leukemia Chronic leukemia
Fate Survival less than six months Survival over one year
Age Children Young adults Adults older age group
Cell type Lymphoblastic Myeloid- Myeloid Lymphatic
Monocytic
Begins abruptly with fever
Clinical . . Insidious onset.
and
Features headache. . May be asymptomatic & discovered during
Signs of routine blood
.
anemia. examination.
. Signs ofthromboc)10penia. . The patient appears in good health.
. Recurrent infectIOn? T-13 cell . .The patient may exhibit signs of anemia or
suppression neutropema thrombocytopenia or weight lqss .
Generalized
.
Lymphadenopathy
Cellular Occur only when. disease has Cellular infiltration is
infiltration longer common
in tissues and duration:
organs Lymph node enlargement, hepato -Enlargement ofliver - Enlargement oflymph
splenomegaJly, CNS infiltration and spleen nodes (may cause
(parasthesia, obstruction of intestine
paralysis) or
gall bladder -7 jaundice
-Skin lesions are
-May undergo blast
common: .
*petechaie,
crisis (acute myeloid
*ecchymosis,
*leukemids appear in
leukemia) inducing
the
lymph node form of:
enlargement and
- Papules.
skin
Infiltration - pustules.
- Bullae.
- Pigmentation.
- Itching ,burning.
- H.Z lesions
Lab findings:
Subnormal, raised normal or
1. W.B.C Raised Raised
reduced
Decreased
2. R.B.C Low or normal Low or normal
(anemia)
3. Platelets Decreased (thromboc)10penia) Low ,normal or raised Low or normal
4.
a. Peripheral
a. Blast cells. a. More diffrentiated leukemic cells
blood
b. Bone marrow b. Increased ceJlularitY,1 % of b. 1 Cellularity. .
aspirate immature ceJls
78
 *Serum
* Phildelphia
immunoglobulin:
chromosome presence low
5. T-B *B-Iymphocytes 90%
T-B Lymphocytes
lymphocytes do
not carry out normal
immune function:do not
transform into plasma
cells
when exposed to
antigen
*Hypogamma-
globulinemia.
*The abnormal
immunoglobulin cause
hemolytic anemia and
thrombocytopenia
I *The normal

immunoglobulin is low
*T-cells, 5% affecte9

79
Oral manifestation
Oral manifestations of acute and chronic leukemias are the
same, generally chronic leukemias are less severe.

Oral manifestations are due to:

I. Bone marrow suppression (anemia and thrombocytopenia)

2. Leukemic cellular infiltration in various tissues and organs

which impairs their function.

3. Impaired function of immature granulocytes, B-T

lymphocytes and neutropenia.

4. The use of anticancer drugs.

.
Incidence of oral lesions
Acute Lymphatic Myeloid Monocytic
Leukemia 20% 40% 80%
.
Chronic leukemia 12% 12%

Oral and Paraoral Manifestations Underlying Mechanism

I-pallor of oral mucosa Anemia
Atrophy of tongue coating .-
2. Oral and gingival bleeding Thrombocytopenia,
DIC
Impaired liver function
Infiltration of the gingiva by
3. Gingival enlargement
immature
Leukemic cells
- Thrombosis and infarction in
small gingival
blood vessels
- State of vit C deficiency
- Local irritating factors

80
4. Infection: *CandidaJ - Impaired T cell function
* Bacterial - Impaired B cell function and
neutropenia
5. Teeth: extrusion and rapid Joss of
- Infiltration of leukemia cells in
teeth
periodontal ligament leading to
necrosis
6. Xerostomia: enlargement of -Infiltration of Leukemic cells in
parotid gland parotid glands

-Infiltration of leukemic cells in

7. LymPhadenopathy:
lymph nodes or lymphoid tissues
*cervicallymph adenopathy may be
an early manifestalion of leukemia

*May be associated with enlargement

of palatine and pharyngeal tonsils

Infiltration of leukemic cells in

8. Trigeminal neuralgia - mental
5th Cranial nerve
Eraesthesia
- Infiltration of leukemic cells in
9. Bell's palsy
7th cranial nerve.

81
Dental Implications:

The main dental management problems in acute and chronic

leukemia are:

1) Oral infection
2) Bleeding
3) Anemia.
4) Susceptibility to hepatitis or HIV infection.

Acute leukemia has additional problems of:

a) Disseminated intravascular coagulation.
b) Complication of bone marrow transplantation.

The dental surgeon should recognize carefully the followin_

1) Leukemic patients have a tendency towards ulceration. post-
operative hemorrhage and delayed wound healing.

Every effort should be done for very conservative dental

therapy, while avoiding oral surgical procedures. Ifthe latter is
inevitable the patient should bc hospitalized.

2) Since leukemic patients are at great risk of infection, oral

hygiene should be encouraged with regular 0.2% chlorhexidine
mouth rinse. Antifungal and antiviral drugs can be prescribed as
prophylactic.

3) Patients with signs and symptoms of acute leukemia:

a. Should receive only palliative emergency dental care e.g.
symptomatic treatment for oral ulcers, and antibiotics for
infection, analgesics for pain. In acute dental pain adequate
drainage should be gained by opening wide the pulp chamber to
permit drainage.
82
b. No surgery should be performed in acute leukemia except in
emergencies because of the risk of hemorrhage and infection
(osteomyelitis and septicemia). The patients should be
hospitalized, given platelets or blood transfusion and antibiotic
should continue until wound has healed.

c. In spontaneous gingival bleeding, remove gross local factors

and place absorbable gelatin sponges subgingivally saturated
topically with thrombin solution and maintain them under
pressure. If the local measures fail, refer the patient to the
hospital for blood transfusion or platelets transfusion.

4) Patients with chronic leukemia:

a) The infection is less problematic in patients with chronic

leukemia, than those with acute leukemia. This is because the
cells are more mature and functional in chronic leukemia.
However, in later stages, infection becomes a
serious complication.

b) With special consideration ,patients who are in a state of

remission can receive most of the indicated dental treatment. For
periodontal and surgical procedures, bleeding time should be
undertaken beforehand, if bleeding time is prolonged, delay
dental treatment or obtain platelet replacement through
consultation with the patient's physician.

83
c) Operative procedures should be performed with strict asepsis
and as atraumatically as possible with the use of synthetic
absorbable suture materials.

d) Aspirin should be avoided since it may interfere with

hemostasis.

Lymphomas
Lymphomas are group of solid malignant tumors with wide
spectrum of clinical and pathological effects. Lymphomas
originate in lymph nodes and lymphoid tissues in any part of the
body.

Classification of lymphoma:
Lymphomas are classified according to hist8pathological
features into:

1. Hodgkin's disease:
a) Lymphocyte predominant (best prognosis) Younger patients
b) Nodular sclerosis.
c) Mixed cellular.
d) Lymphocyte depleted (worst prognosis). Older patients,

2. Non Hodgkin's lymphoma:

a) Nodular
b) Diffuse (including Burkett's lymphoma)

Hodgkin's Disease
Hodgkin's disease is a malignant neoplasm of lymphoid tissues
of unknown etiology.

A) It begins in younger patients, 20-30 years of age as

asymptomatic enlargement of peripheral lymph nodes, most
commonly the cervical (60-70%) .The lymph
node is enlarged ,discrete, rubbery and not tender on palpation.
B) In older patients: systemic symptoms may precede
lymphadenopathy. Systemic symptoms include pain, remittent
84
- fever, night sweats, weight loss, malaise, bone pain and
pruritis. The enlarged lymph nodes can cause symptoms by
pressure on other organs or ducts

- Enlargement of mediastinal nodes causes dysphagia and

retroperitoneal nodes cause urinary obstruction.

- Further progression of the disease leads to invasion of bone

marrow, spleen, skin, liver, lung and spinal chord.

- Alcoholic drinks may cause pain in the affected lymph nodes.

- Anemia is common, late in the disease.
- Cellular immunity is impaired with loss of T-c-ell function that
worsens as the disease progresses, so fungal and viral infections
are common and may disseminate

Treatment:
Chemotherapy and radiotherapy or combination used for
treatment may suppress neutrophils and antibody function for
years, increasing the patient's susceptibility to bacterial
infection.

Diagnosis
Definite diagnosis is mainly reached by biopsy. The presence of
characteristic Reed Sternberg cells is diagnostic which is
described as having mirror image nuclei with owl eye nucleoli.
In addition to Reed Sternberg cells, there are large numbers
of small lymphocytes and histocytes.

Non Hodgkin's Lymphomas

NHL are malignant neoplasms, that arise from cells of lyffiph
nodes, seen in patients over 40 years and are classified into
nodular and diffuse and generally have poor prognosis.
NHL appear to be of B-cell or T cell origin.

85
The most common presentation is painless enlargement of
lymph nodes, the cervical being common and is the first sign.

Extranodal involvement does occur at any site where lymphoid

tissues are present and this was found to be more common than
in Hodgkin's disease. There is marked predilection for
such site as gastrointestinal tract and CNS. NHL frequently
involves Waldever's ring, mesenteric lymph nodes, bone
marrow, liver, spleen and skin. The manifestations depend on
the site of involvement and the result of pressure of enlarged
lymph nodes or infiltration

Treatment:
Since early dissemination of NHL is common, NHL is treated
with multiple chemotherapy. Radiotherapy may be useful in the
initial stage.

Dental aspects and management problems of lymphomas:

- Painless enlargement of cervical lymph nodes may be the

initial manifestation of the disease.
- Extranodal involvement of Waldeyer's ring (palatine,
pharyngeal and lingual tonsils) is more common in NHL than
Hodgkin's disease. Non tender enlargement of the tonsillar
tissue in adult should be referred to otolaryngologist for
evaluation.

- Hodgkin's disease rarely affects the mouth.

- NHL may reveal soft tissue swelling in pharynx, palate,
tongue, gingiva or lips. The jawbones may be involved (Burkitt's
lymphoma) and the teeth may become loose.

- Oral infection with viruses, fungi or bacteria may occur as a

result of depressed T or B cell function. '

- Oral ulceration may be induced secondary to cytotoxic drugs.

86
- Anemia and bleeding tendencies are due to malignant cell
infiltration of bone marrow and or the effect of cytotoxic drugs.

87