BLEEDING DISORDERS

AND ITS MANAGEMENT

PRESENTED BY:
DR. MUKESH KUMAR
M.D.S. 1
ST
YEAR

GUIDED BY:
DR. RAJESH K. THAKUR
M.D.S.
CONTENTS
INTRODUCTION
PATHOPHYSIOLOGY
Basic Mechanisms of Hemostasis and Their
Interactions
Vascular Phase
Platelet Phase
Coagulation Phase
Fibrinolytic Phase
CLINICAL AND LABORATORY FINDINGS
Clinical Manifestations
Clinical Laboratory Tests
CLASSIFICATION OF BLEEDING
DISORDERS
Vessel Wall Disorders
Platelet Disorders
Coagulation Disorders
Fibrinolytic Disorders

IDENTIFICATION OF THE DENTAL
PATIENT WITH A BLEEDING DISORDER



MANAGEMENT
Platelet Disorders
Hemophilias A and B
Von Willebrands Disease
Disease-Related Coagulopathies
PROGNOSIS
ORAL HEALTH CONSIDERATIONS
Oral Findings
Dental Management
CONCLUSION
REFERENCES
INTRODUCTION
Dental health care workers are increasingly called
upon to provide quality dental care to individuals
whose bleeding and clotting mechanisms have been
altered by inherited or acquired diseases. This
provides an opportunity for the dentist who is trained
in the recognition of oral and systemic signs of
altered hemostasis to assist in the diagnosis of the
underlying condition. A number of dental procedures
result in the risk of bleeding that can have serious
consequences, such as severe hemorrhage or
possibly death, for the patient with a bleeding
disorder. Safe dental care may require consultation
with the patients physician, systemic management,
and dental treatment modifications.

BLOOD
It is a fluid, which circulates in the
vascular channels of human
body due to the pumping action
of heart. It consists of a liquid
portion PLASMA in which
various types of cells are
present .The cells are of 3
types.

1. Erythrocytes of Red Blood Cells.
normal count:
males:- 4.5-6.5 million / cu mm
females:- 4.0-5.6million / cu mm

2. Leucocytes or white blood cells.
TLC:- 4000- 11,000 / cu mm

3. Thrombocytes or platelets
Round or oval disc (2-4)
Normal 150,000- 350,000/cu mm
Half life- 8-12 days

PLASMA
Fluid part of blood. Relative
quantity of plasma and cells is
in ratio of 55:45.

COMPOSITION :
Plasma proteins (6.5 to 8
gm%).
Glucose (80-120 mg%).
Cholesterol & lipid (150-250
mg%).
Non protein nitrogenous
substance like urea, uric acid,
creatinine etc.
Hormones, enzymes etc.

Plasma proteins are of 3 types.

1. Albumin
2. Globulin
3. Fibrinogen


PATHOPHYSIOLOGY
OHemostasis means preventions of
blood loss.
OWhenever a vessel is ruptured,
hemostasis is achieved by different
mechanisms, including
Vascular phase
Platelet phase
Coagulation phase
Fibrinolytic phase

Vascular Phase

If the blood vessel is cut or
ruptured, the stimulus of the
traumatized vessel causes the
wall of the vessel to contract.
This reduces the flow of the
blood from the vessel rupture.
The contraction results from
nervous reflexes, local
myogenic spasm, and local
humoral factors from the
traumatized tissues and blood
platelets.

Platelet Phase
OPlatelet have many functional properties as
follows;
Actin and myosin molecules, similar to
those found in muscle cells, as well as
another contractile protein, thrombosthenin
Residuals of both the endoplasmic
reticulum and the Golgi apparatus
Mitochondria and enzymes systems that
are capable of forming adenosine
triphosphate and adenosine diphosphate

Enzymes systems that synthesize
prostaglandins
Fibrin stabilizing factor
Growth factor

OMechanism of the platelet plug
When platelet come in contact with a
damaged vascular surface, such as the
collagen fibers in the vascular wall or
damaged endothelial cells
They begin to swell; they assume
irregular forms with numerous
irradiating processes protruding from
their surfaces

Their contractile proteins contract
forcefully and cause the release of
granules containing multiple active
factors
They become sticky so that they stick
to the collagen fibers
They secrete large quantities of ADP
and their enzymes form thromboxane
A2
The ADP and thromboxane act on platelets
to activate them and the stickiness of these
additional platelets cause them to adhere to
the originally activated platelets.
Therefore at the site of damaged vascular
wall or extravascular tissues elicit a vicious
cycle of activation of increasing numbers of
platelets that attract more and more
additional platelets, thus forming a platelet
plug.
Coagulation Phase
OThe generation of thrombin
and fibrin the end product of
the third phase of hemostasis,
the coagulation phase.
OThis process involves multiple
proteins, many of which are
synthesized by the liver
(fibrinogen, prothrombin, V,
VII, IX, X, XI, XII, and XIII) and
are vitamin K dependent ( II,
VII, IX, X).

THE CLOTTING MECHANISM
INTRINSIC MECHANISM

The intrinsic pathway is initiated when F XII
is activated by surface contact (e.g. with
collagen or subendothelium), and it involves
the interaction of F XI.
The next step of intrinsic coagulation, the
activation of F IX to F XIa.
Once activated, F IXa forms a complex with
F VIII, in a reaction that requires the
presence of both calcium ions and
phospholipids, which, in turn, converts FX to
an activated form F Xa.


EXTRINSIC MECHANISM

The extrinsic pathway is initiated by the
release of tissue thromboplastin, also
called tissue factor, and does not
require contact activation.
Tissue thromboplastin binds to F VII in
the presence of calcium, and this
complex is capable of activating F IX
and X, linking the intrinsic and extrinsic
pathways.


Fibrinolytic Phase
It is the major means of disposing of fibrin after its
hemostatic function has been fulfilled.


Hemostasis
Dependent upon:
*Vessel Wall Integrity
- Adequate Numbers of Platelets
4 Proper Functioning Platelets
^ Proper Function of Fibrinolytic
Pathway
^Adequate Levels of Clotting Factors


CLINICAL AND LABORATORY
FINDINGS
Clinical Manifestations
Clinical Laboratory Tests

Clinical Manifestations
Clinical manifestations of bleeding
disorders can involve various systems,
depending on the extent and type of
disease.
Individuals with mild disease may
present with no clinical signs, whereas
individuals with severe coagulopathies
may have definite stigmata.


When skin and mucosa are involved,
individuals may present with petechiae,
ecchymoses, spider angiomas,
hematomas, or jaundice.


Clinical Laboratory Tests
Common laboratory test that
help to identify deficiency
of required elements or
dysfunction of the phases
of coagulation.

PLATELET COUNT
BLEEDING TIME (BT)
PROTHROMBIN TIME
(PT)
PARTIAL
THROMBOPLASTIN
TIME (PTT)
THROMBIN TIME (TT)

PLATELET COUNT
The two clinical tests used to evaluate primary
hemostasis are the platelet count and bleeding time.

ONORMAL 100,000 - 400,000
CELLS/MM
3

< 100,000

Thrombocytopenia

50,000 - 100,000 Mild Thrombocytopenia

< 50,000 Severe Thrombocytopenia



BLEEDING TIME
It is the time taken from puncture of the
blood vessel to the stoppage of bleeding
PROVIDES ASSESSMENT
OF PLATELET COUNT
AND FUNCTION


NORMAL VALUE
2-6 MINUTES

PROTHROMBIN TIME
It is a test that measures how much time
blood takes to clot
Measures
Effectiveness of the
Extrinsic Pathway



NORMAL VALUE
10-15 SECS
PARTIAL THROMBOPLASTIN TIME

Measures
Effectiveness of the
Intrinsic
Pathway
Measures
coagulation
disorders.
NORMAL VALUE
25-40 SECS
THROMBIN TIME
Is a measure of the rate of conversion of fibrinogen
to fibrin

Time taken for
Thrombin to
Convert
Fibrinogen to
Fibrin
A Measure of
Fibrinolytic Pathway

NORMAL VALUE
9-13 SECS
CLASSIFICATION BLEEDING
DISEASES
Vessel Wall Disorders

Platelet Disorders

Coagulation Disorders

Fibrinolytic Disorders
Vascular component

Congenital
Hereditary haemorrhagic
telangiectasis
Ehlers-danlos disease


Acquired
Simple easy bruising
Senile purpura
The symptomatic vascular purpuras
Infections
Drugs
Cushings disease and
adrenocorticosteroid
administration
Scurvy
Dysproteinaemias
Henoch-Schoenlein syndrome
Miscellaneous disorders
Orthostatic purpura
Mechanical purpura
Auto-Erythrocyte sensitization
Systemis disorders



It is classified into 2 groups :

Quantitative defect.
O Thrombocytopenia
O Idiopathic
thrombocytopenic
purpura


Qualitative defect.

CONGENITAL
MEMBRANE RECEPTOR DEFECTS
Glanzmanns thrombasthenia
Bernard-soulier syndrome
Von-willebrand disease
ENZYME DEFECTS
Phospholipase deficiency
Cyclo-oxygenase deficiency
GRANUAL DEFECTS
Storage pool deficiency
Gray platelet syndrome
ACQUIRED
Stem cell disorders leukaemia
Drugs
Uraemia
Miscellaneous


HEMORRHAGIC DISORDER DUE TO PLATELET ABNORMALITIES

ACQUIRED
Vitamin K deficiency
Liver disease
Anti-coagulant drugs
Disseminated intravascular
coagulation
Massive transfusion of stored
blood


CONGENITAL
Haemophilias
Von willebrands disease
Other congenital deficiency
disorders
Fibrinogen deficiency
Prothrombin deficiency
Factor V deficiency
Factor VII deficiency
Factor X deficiency
Factor XI deficiency
Factor XII deficiency
Factor XIII deficiency

HEMORRHAGIC DISORDER DUE TO
COAGULATION ABNORMALITIES
THE SYMPTOMATIC VASCULAR
PURPURAS (Non
thrombocytopenic)

Aquired vascular disorder.
- The term symptomatic vascular purpura is used to describe the
purpura occurring in association with number of disorders.
- Alterations in capillaries resulting in capillary fragility.
- Some causes are
Infections

Cushings disease and corticosteroids administration

Scurvy

Dysproteinaemias

Henoch-Schoenlein syndrome
Scurvy:
Results from vit C deficiency

Clinical manifestations:.
Impairement in the synthesis of collagen & 0r antioxidant property of
vit C
Blood vessel fragility resulting in vascular purpura
Decreased immunocompetence
Delayed wound healing
Hemorrhage
Osteopororosis
Swollen joints



Oral manifestations:
+Interdental & marginal gingiva is bright red with swollen
smooth surface.
+In advance cases gingiva becomes boggy, ulcerates and
bleeds. In severe chronic cases, hemorrhage and
swelling of the periodontal membrane occurs, followed
by loss of bone, loosening of teeth & exfoliation.


Treatment:
+ Administration of vitamin C
+ Vitamin C intake normal:
infants- 35mg
adults- 60mg


(a) Upper and lower generalized gingivitis
characterized by haemorrhagic and
necrotic interdental papillae;

(b) hyperplastic haemorrhagic palatal
gingivitis associated with extensive
mucosal hemorrhage.
Scurvy
Hereditary hemorrhagic telangiectasis (rendu osler
weber disease)


Congenital haemorrhagic vascular disorder
Autosomal dominant disorder identified typically
by the triad of:
+ Telangiectasis
+ Recurrent epitaxis
+ Positive family history
Development of abnormal vasculature, defects
in endothelial cell junctions, endothelial cell
degeneration and weakness of perivascular
connective tissue dilatation of capillaries,
and arteriovenous malformation.
CLINICAL FEATURES


Most common sites are the skin and mucous membranes of
nose and mouth. May also occur in conjunctiva, bronchi,
gastrointestinal and renal tracts and in vagina.

The telangiectatic spots range in size from a pin point to lesions
upto several mm in diameter, vary in colour from purple to bright red
and they blanch on pressure.

The lesion tend to become more numerous and larger with
advancing age.

Bleeding may occur either spontaneously or following mild
trauma.
Epistaxis is the most common symptom.

lesions of oral cavity- gingiva, buccal mucosa, palate, floor of the
mouth and tongue.

Blanching round and
reticulated reddish-
purple plaques
Treatment :
Spontaneous hemorrhage may be controlled by
pressure packs.

The angiomatous and telangiectatic areas are
sometimes cauterized, treated with X-ray radiation or
surgically excised.

Epistaxis is usually the most common problem requiring
treatment.
Short terms measures includes nasal packing.

The main long term treatment is the administration of
larger dosages of oestrogen. (dose 0.25 mg per day
ethinyl oestradies.
Thrombocytopenic purpura:
Quantitative Platelet Defect
It can be
Primary- unknown cause (idiopathic
thrombocytopenic purpura)
Secondary- which may be due to wide variety of
situations
thrombotic thrombocytopenic purpura

SECONDARY THROMBOCYTOPENIA : is defined as
a decreasing in the peripheral blood platelet count
below the lower normal limit (<1,50,000 per cubic
mm).

Causes of thrombocytopenia


1. Impaired platelet production.
a. Generalised marrow failure
Aplastic anaemia
Leukaemia
Myelofibrosis
Megaloblastic anaemia
Marrow infiltrations
b. Selective suppression of platelet production
Drugs (quinine, sulpha drugs, rifampicin, anti metabolites)


2; Increased consumption or destruction of platelets.
Disseminated intravascular coagulation
Idiopathic thrombocytopenic purpura
Gram negative septicaemia
Viral infections

3; Splenic sequestration
Hypersplenism
Lymphoma
Liver disease
Peripheral smear of a patient reported to
have platelet counts of 10,000-
150,000/mL on various occasions. The
smear shows clumping of the platelets
and satellitism involving neutrophils and
platelets.
Investigations:
> 1,00,000 per cubic mm asymptomatic and bleeding time
remains normal.

between 50,000 to 1,00,000 per
cubic mm
prolong BT and bleeding occurs only
with severe trauma
< 50,000 counts easy bruising which is manifested by
purpura or bleeding with minor
trauma.

< 20,000 / cubic mm spontaneous bleeding such as
petechiae or may have internal
bleeding.

Leukemia:
Increased overproduction of WBCs
Appear in circulating blood in an immature form
Any of WBCs may be involved
lymphoid
myeloid
Etiology unknown but may be due to viral infections
(EB virus), chromosomal abnormality etc.
Acute- survival< 6months
chronic- over 1yr
subacute- b/w the two
CLASSIFICATION OF LEUKEMIA
Acute lymphocytic leukemia
Acute Lymphoblastic
Leukemia, or ALL)
is the most common type of
leukemia in young children.
This disease also affects
adults, especially those age
65yrs and older.

Anemia, thrombocytopenia.
Leukocyte count rises to
100,000 or more cell per cubic
mm.
Increase in lymphoid cells in
the differential count.
Acute myelogenous leukemia
(also known as Acute Myeloid
Leukemia, or AML)
occurs more commonly in
adults than in children
Predominant cell often
resembles the myeloblast.
Chronic lymphocytic leukemia
(CLL)
most often affects adults over
the age of 55. It sometimes
occurs in younger adults, but it
almost never affects children.

Anemia and thrombocytopenia.
WBC count> 500,000 cells
percubic mm
Differential count of lymphoid
cells elevated.
Chronic myelogenous
leukemia (CML)
A very small number of
children also develop this
disease.

_

Acute myelogenous leukemia
Leukemia Cell
GINGIVAL ENLARGEMENT
Clinical menifestations:
Damage to the bone marrow, by way of displacing
the normal bone marrow cells with higher numbers
immature white blood cells, results in a lack of blood
platelets, which are important in the blood clotting
process.
Patients with with leukemia may become bruised,
bleed excessively, or develop pinprick bleeds
(petechiae).
White blood cells, may be suppressed or
dysfunctional, putting the patient at the risk of
developing infections.
Finally, the red blood cell deficiency leads to
anemia, All symptoms may also be attributable to
other diseases; for diagnosis, blood tests and a
bone marrow biopsy are required.
Oral menifestations:
+ Gingivitis
+ Gingival hyperplasia(Such lesions may occur due to direct
leukaemic infiltration of tissues, or be secondary to
immunodeficiency, anemia and thrombocytopenia.)
+ Hemorrhage
+ Petechiae
+ Ulceration of the mucosa , rapid loosening of the teeth due to
necrosis of periodontal ligament.

Treatment:
Bone marrow transplant
Chemotherapeutic drugs
Radiation therapy
Corticosteroids etc
Aplastic anemia:
The term 'aplastic' means the marrow
suffers from an aplasia that renders it
unable to function properly
Typically, anemia refers to low red
blood cell counts, but aplastic anemia
patients have lower counts of all three
blood cell types: red blood cells, white
blood cells, and platelets
Causes:
One known cause is an autoimmune disorder, where the white
blood cells attack the bone marrow.
Exposure to radiation (radiation sickness)
Chemotherapy
Environmental toxins (insecticides, benzene, nitrogen
mustards)
Many different medications, including chloramphenicol
(Chloromycetin), phenylbutazone (Butazolidin), sulfonamides
(Gantanol and others), anticonvulsants, cimetidine (Tagamet)
and others
Certain viral infections, including viral hepatitis, parvovirus
B19, human immunodeficiency virus (HIV) and infectious
mononucleosis (Epstein-Barr viral infection)

Clinical features
Pale skin
Fatigue
Weakness
Dizziness
Light-headedness
Rapid pulse
Heart murmur
Bruising and tiny areas of bleeding in the skin
Abnormal bleeding from the gums, nose, vagina or
gastrointestinal tract, or blood in the urine
Infections

Treatment:
bone marrow transplant is the most effective therapy
Some patients will be treated with
immunosuppressive medications instead of bone
marrow transplantation. Like anti-thymocyte globulin
(Thymoglobulin), known as ATG; antilymphocyte
globulin (ALG); prednisone (Deltasone, Orasone,
Meticorten); and cyclosporine (Neoral,
Sandimmune, SangCya).
Blood-cell production also can be stimulated with
erythropoietin, granulocyte colony-stimulating factor
(G-CSF), granulocyte-macrophage colony-
stimulating factor (GM-CSF) or other hematopoietic
growth factor medications.
Megaloblastic anemia
Megaloblastic anemia is an anemia
(of macrocytic classification) which
results from a deficiency of vitamin B12
and folic acid.
It is characterized by many large
immature and dysfunctional red blood
cells (megaloblasts) in the bone
marrow
Causes:
nutritional defects (vitamin B12 is mainly
from animal sources, and vegans may
require supplementation)
chronic liver diseases
alcoholism
pregnancy
decreased production of intrinsic factor (this
disease entity is called pernicious anemia)
intestinal malabsorption (due to an enteritis,
celiac disease or other causes).
Folate and Vitamin B12 Interaction

Tetrahydrofolate is necessary for DNA synthesis
Cobalamin and folate are cofactors for
tetrahydrofolate production
Deficiency of either impairs cell division in the
bone marrow while RNA and protein synthesis
continues enlarged erythrocytes
Cobalamin deficiency impairs synthesis of S-
adenosylmethionine necessary for proper
nervous system functioning
Investigations:

The RBC are almost as large as
the lymphocyte. Note the
hypersegmented neurotrophil.
There are fewer RBCs.
Decreased red blood cell (RBC)
count and hemoglobin levels
The platelet count may be
reduced.
Neutrophil granulocytes may
show multisegmented nuclei
("senile neutrophil"). This is
thought to be due to decreased
production and a compensatory
prolonged lifespan for circulating
neutrophils
IDIOPATHIC THROMBOCYTOPENIC
PURPURA
Quantitative platelet defect

Synonyms - primary thrombocytopenic purpura
- essential thrombocytopenic purpura
- purpura hemorrhagica
- werlhofs disease
- auto-immune thrombocytopenia

Autoimmunity is thought to be one of the cause
+ Auto antibodies are formed against the membrane glycoprotein,
leading accelerated destruction and removal of platelets.
+ Some patient have absence of platelet stimulating or megakaryocyte
ripeneing factor.

Clinical manifestation
On the basis of duration of illness, ITP is classified into acute and
chronic forms.
+ Acute form is self limiting disorder observed frequently in children
recovering from a viral illness (eg- hepatitis) or an upper respiratory
tract infection.
+ Spontaneous appearance of purpuric or hemorrhagic lesions of the
skin
+ Epitaxis is common. Bleeding in urinary tract (hematuria), GIT
producing melena, intracranial hemmorhage
+ Many cases occur before 30yrs of age



Oral manifestations:
Profuse gingival hemorrhage (spontaneous)
Petechiae palate,oral mucosa, tongue
Tendency of excessive bleeding


One Plasmacytoid Lymphocyte. Idiopathic thrombocytopenic purpura
(ITP) blood - 100X , giant platelets
Purpura rash on the forearm
Multiple lesions on the face, lips and
tongue.
+Investigations:

BT is prolonged
Platelet count in blood film examination is decreased.
platelet count <60,000/cu mm.
coagulation time normal (failure of retraction)
torniquet test strongly positive (capillary fragility )
Bone marrow shows increase megakaryocytes indicating
peripheral destruction of platelet
Giant platelets in peripheral blood smear.


TREATMENT :

No specific treatment
+Trauma & agents likely to interfere with platelet
function ex- aspirin, alcohol must be forbidden.

+The main therapeutic measures are the
administration of corticosteroids and splenectomy .

+Persistent bleeding or internal. bleeding-platelet
transfusions
IV Immunoglobulin are indicated in selected cases.

DEFECTS IN PLATELET
ENZYMES

Qualitative platelet defect
Familial deficiency of the enzymes, cyclo-oxygenase and
thromboxane synthetase involved in the metabolism of arachidonic
acid and production of thromboxane A2.

The bleeding defect is mild and it is of clinical significance only in
the case of serious trauma or surgery.

BT is prolonged.

Platelet aggregation to ADP, collagen and arachidonic acid is
abnormal.

Platelet transfusion to cover trauma or surgery is usually the only
therapy required.

HEMOPHILIA ( bleeders disease, disease of
Hapsburgs, the disease of kings)
Congenital coagulation abnormality.
+Defect carried by X chromosome, and is transmitted as a
gender linked mendelian recessive trait ; thus hemophilia
occurs only in males.
+Heterozygous daughters carry the defect to half of their
sons and as a recessive trait to half of their daughters.

Three types :


Hemophilia A Plasma thromboplastinogen
(antihaemophilic globulin, AHG, factor
VIII), clot promoting factor
Hemophilia B/
Christmas disease
Plasma thromboplastin component
( PTC. Factor IX)
Hemophilia C Plasma thromboplastin antecedent
(PTA, factor XI)
CLINICAL FEATURES

Persistent bleeding ( spontaneous or mild trauma)
Usually present at birth (30-50%), but may not become clinically
apparent for years.
Hemophilia classified according to clinical severity as:










Haemophilia is characterized by bleeding into subcutaneous tissue,
muscle, weight bearing joints, internal organs etc. (hematomas)

Classification Factor activity % Cause of hemorrhage
Mild >5 Major trauma or surgery
Moderate 1-5 Mild to moderate trauma
Severe <1 Spontaneous, soft tissue
bleeding
In Hemophilia C, absence of bleeding into joints and
muscles
Haematuria is common.
The most feared site of bleeding is central nervous
system which is frequently fatal.


Oral manifestations:
+Gingival hemorrhage ( even in tooth eruption and
exfoliation)
+Mandibular pseudotumor (subperiosteal bleeding with
reactive bone formation)
+Bleeding during surgery

investigations
The normal factor VIII level is 50-100% and
is usually measured by CLOTTING ASSAY.
Normal haemostasis require 25% factor
activity, symptomatic patients have factor
VIII levels below 5%.
BT normal
Coagulation time
PT normal
aPTT
Functional assay of factor is useful in
diagnosing the disease.
Hematoma
Gingival bleeding following
Minor trauma
Bleeding into weight bearing joints
No known cure . Pts should be protected from traumatic injuries.
Hemophilia A
For Minor Dental Procedures a single infusion of factor VIII concentrate
coupled with 4-6 gm of D-aminocaproic acid (anti-fibrinolytic agent) four
times daily for 72-96 hrs after the dental procedure and antibiotic for same
duration.
For major dental procedure patient is hospitalized. Factor VIII
concentrate infusion started just prior to surgery and to be continued for a
minimum of 48-72 hrs. with an antibiotic administration.



Hemophilia B
Treatment is by infusion of factor IX concentrate.

Hemophilia B is the result of factor IX deficiency. It is managed by
replacement therapy with highly purified, virally inactivated factor IX
concentrates.
Prothrombin complex concentrates can also be used for factor IX
replacement.



TREATMENT
(Pseudohemophilia, Vascular hemophilia, Vascular purpura)

Most common congenital coagulation disorder occurring due to
qualitative or quantitative defect in the von-Willebrands factor.
The disease is mainly transmitted in an autosomal dominant
manner.

The von-Willebrands factor is a protein, synthesized by endothelial
cells and megakaryocytes. Due to deficiency of factor vWF, two
important abnormalities result.
1- PLATELET DYSFUNCTION normally the vWF forms a bridge
between platelets and endothelial wall component that is collagen
which allows the platelets to adhere to damaged vessel walls. Low
vWF leads to bleeding related to platelets dysfunction.
2- LOW LEVEL OF FACTOR VIII. The vWF acts as a carrier
protein for factor VIII and therefore its deficiency leads to secondary
reduction of factor VIII level.
von-WILLEBRANDS DISEASE (vWD):
Clinical manifestations:
+ Many children are asymptomatic
+ Excessive bleeding (spontaneous or minor trauma)
+ Common sites nose, skin, GIT, & severe menorrhagia
+ Bleeding tendency cyclic or sporadic.

Clinically these patients have a dual mechanism of bleeding due to
platelet dysfunction superficial bruising, epistaxis, gastrointestinal
haemorrhage.
defective coagulation mechanism similar to haemophilia leading to
spontaneous bleeding or following trauma or surgery

Oral manifestations:
Gingival bleeding
Bleeding during surgery


Management:
+ Transfusion of plasma or anti hemophilic
factor and by local control of hemostatsis.
+ Mild episodes of bleeding can be treated
with desmopression.
+ Serious or persistent bleeds, haemostasis
can be achieved with factor VIII concentrate.

Rare Coagulation Factor
Deficiencies
+ Congenital deficiencies in coagulation factors, other than
Factor VIII and Factor IX, are very rare. Factor XI deficiency in
the Ashkenazi Jewish population has a prevalence of 1 in
1,000; however, the prevalences of fibrinogen, prothrombin
and Factors V, VII, X and XIII deficiencies are in the order of
only 1 in 0.51 million.


+ These disorders are inherited as autosomal recessive traits
and manifest clinically in homozygotes or compound
heterozygotes. Although, with some exceptions, the bleeding
manifestations in these disorders are less severe than
hemophilia, patients may require coagulation factor
replacement before dental surgery. Specific factor
concentrates are available for some deficiencies (e.g., Factor
VII); fresh frozen plasma is used as the source for others (e.g.,
Factor V)


Liver disease
Aquired coagulation defect
Hepatitis (viral, toxic), cirrhosis -underlying
causes.
The proteins that initiate and maintain clotting of
blood are synthesized by the liver. A diseased
liver is unable to synthesize these proteins,
leading to a potential bleeding problem.
Synthesized in the liver factors II, VII, IX, X,
fibrinogen,
protein c & s(Anticoagulants)& protein Z (
activates thrombin)

The liver synthesizes bile acids and secretes them
into the small intestine where they play a critical role
in absorption of lipids. Vitamin K, as a fat-soluble
vitamin, requires proper lipid absorption for its own
absorption. Liver disease that results in decreased
bile salt synthesis leads to impaired vitamin K
absorption and deficiency.

Inadequate gamma-carboxylation of vitamin K-
dependent coagulation proteins ( Factors II
(prothrombin), VII, IX, and X, protein Z, protein C&S
)interferes with the coagulation cascade, and inhibits
blood clot formation
Lab-PT, PTT, BT

DISSEMINATED INTRAVASCULAR
COAGULATION


Acquired coagulation defect.
+ Also known as defibrination syndrome or consumption
coagulopathy.
+ It is a pathological process in the body where the blood starts to
coagulate throughout the whole body. This depletes the body of its
platelets and coagulation factors, and there is a paradoxically
increased risk of hemorrhage.
+ It may be acute, subacute or chronic characterized by thrombo
haemorrhagic manifestations.
+ It is usually a secondary complication of some systemic diseases
1. infections gram ve septicaemia, meningococcal
septicaemia, certain viral infections and malaria.
2. liberation of tissue factors retain dead foetus, massive
trauma and malignancies.
3. wide spread endothelial damage severe burns, acute
glomerulonephritis.

CLINICAL FEATURES

Skin and mucus membrane bleeding and hemorrhage from multiple
sites that is surgical incisions, vein puncture, catheter sites.

DIC may appear that develops suddenly and usually causes
bleeding, which may be very severe.. Bleeding may occur at the site
of an intravenous injection or in the brain, digestive tract, skin,
muscles, or cavities of the body.
LABORATORY FINDINGS

DIC results in lower fibrinogen (as it has all been converted to fibrin),
A more specific test is for "fibrin split products" (FSPs) or "fibrin
degradation products" (FDPs) which are produced when fibrin
undergoes degradation when blood clots are dissolved by
fibrinolysis. Platelet count is low. Prothrombin time is prolonged.
Thrombin time is prolonged.

DIC kidney
DIC - Gangrene in patient
with meningococcal sepsis
MANAGEMENT

Treatment is aimed at treating the underlying cause DIC and taking
measures to control the major symptoms.
Aggressive antibiotic therapy is recommended for infections.

Factors such as acidosis, dehydrations, hypoxia and renal failure
should be corrected accordingly.
Patients with bleeding should receive (i) fresh frozen plasma and
cryoprecipitate to replace depleted clotting factor. (ii) Platelet
concentrate to correct thrombocytopenia.
The use of heparin is controversial. It is used in those patients who
have thrombosis or those rare patients who continue to bleed despite
vigorous treatment with plasma and platelets.

Anticoagulant drugs:

Aspirin therapy
Irreversible inhibitor cyclooxygenase
1. decreasing platelet release and aggregation owing
to blockage of thromboxane A2 generation by
platelets.
2. Short effect on endothelial synthesis of prostacyclin
(inhibits plt. aggregation).
Net result inhibition of plt aggregation.
The effect lasts 9 days.


Ticlopidine, Clopidogrel

Inhibits ADP activation pathway of platelets
aggregation inhibited.
No effect on prostaglandins.
ADP released by injured tissue, red blood
cells and platelets.
Indicated for reduction of cardiovascular
events following MI, CVA, unstable angina
pectoris, stent implantation.




Coumarin therapy -warfarin
-vitamin K antagonist (oral anticoagulants).
V k is coupled in gamma-carboxilation reaction of factors
II (prothrombin), VII, IX, X, and protein C. Coumarin
competes Vk.
-1-3 days from peak plasma concentration and maximum
anticoagulant effect.

For adjustments: takes 2-3 days for reduction (when
needed) to be reflected. Or small dose of subcutaneous
Vk.
Patient should be evaluated before possible bleeding
causing procedure.
Local agents should be used in case of excessive post
operative bleeding.


Heparin therapy
Short acting anticoagulant (t1\2- 4 hr).

Extrarenal metabolism.
Binds to endothelial surface and to various
plasma proteins.
Activity depends upon antithrombin III (ATIII)
Which inhibit clotting factor proteases IXa,
Xa, XI, XII, IIa(thrombin).
Heparin enhances ATIII reaction 1000-fold.






CONCLUSION
O Management of the patient with a bleeding disorder must be
based on a complete understanding of the disease. The dentist
should consult with the patient's primary physician or
hematologist to discuss
O The severity of the disease;
O The dental and oral/maxillofacial procedures planned and
nature of the bleeding risk;
O The patient's response to previous dental treatment, surgery,
and trauma;
O The patient's response to various modes of systemic therapy,
O There should be inclusion of blood component replacement
therapies.
O With appropriate management strategies, nearly all bleeding
disorder patients can benefit from the full range of dental
procedures available to establish and maintain good oral
health.

References
Textbook of medical physiology by
Arthur C. Guyton
Burkits oral medicine by Malcolm A.
Lynch
Textbook of oral pathology by William
G. Shafers
Text book of physiology by Ganong

ORAL SURGERY
If the procedure has limited invasiveness
and the patient has a mild bleeding disorder,
only slight or no modification will be required.
The patients physician should be consulted
before invasive treatment is undertaken.
In patients with drug-induced
coagulopathies, drugs may be stopped or
the doses modified.
For irreversible coagulopathies, replacement
of missing factors may be necessary.


Pain Control

Nerve-block anesthetic injections are contraindicated unless there is no
better alternative and prophylaxis is provided, (risk of hematoma
formation. Extravasation of blood in the oropharyngeal area by an inferior
alveolar block or in the pterygoid plexus can produce gross swelling,
pain, dysphasia, respiratory obstruction and risk of death from asphyxia.)

The commonly used blocks require minimum clotting factor levels of 20%
to 30%.


Anesthetic infiltration and intraligamentary anesthesia are potential
alternatives

An anesthetic with a vasoconstrictor should be used when possible.

Alternative techniques,:-
including sedation with diazepam or nitrous oxideoxygen analgesia,
Patients undergoing extensive treatment requiring factor replacement
may be treated under general anesthesia in a hospital operating room.
Surgical procedures carry the highest risk of bleeding, and
safety precautions are needed.

For coagulopathies-
The patients hematologist should be consulted before
planning, and patients with severe disease should be treated in
speciality centres.

Transfusion of appropriate factors to 50% to 100% of normal
levels is recommended when a single bolus infusion is used in
an outpatient setting.

In patients with hemophilia, additional postoperative factor
maintenance may be required after extensive surgeries. This
can be done with factor infusion, DDAVP, cryoprecipitate or
fresh frozen plasma depending on the patients condition.

Local hemostatic agents and techniques such as
pressure, surgical packs, sutures and surgical stents
may be used individually or in combination and may
assist in the local delivery of hemostatic agents,
such as topical thrombin and vasoconstrictors.

use of vasoconstrictors because of the risk of
rebound vasodilatation, which may increase late
bleeding risk.

The use of absorbable hemostatic materials may
favour clot formation and stability. However, these
materials also carry a risk of infection and may delay
healing; (avoided in immunosuppressed patients.)

Management of patients with platelet disorders,
who require dental procedures

Drugs:
The patients physician should be consulted
before any decision is made to modify the
patients drug regimen.

If ASA has to be withdrawn, this should be done
at least 10 days before surgery. In most cases,
ASA therapy does not need to be stopped, and
local hemostatic measures are sufficient to
control bleeding.

Similarly, other antiplatelet drugs, such as
clopidogrel and dipyridamole, usually do not
need to be stopped.


For patients taking warfarin, their international normalized ratio (INR)
should be measured before a surgical procedure. The normal
therapeutic range is 2.03.0. According to current
recommendations, most oral surgical procedures can be performed
without altering the warfarin dose if the INR is less than 3.0. If INR
values are greater than 3.0, physician referral is suggested.

It is important to consider the risk of reducing the level of
anticoagulation in patients on warfarin due to the risk of a
thromboembolic event.

Patients taking heparin are often those who are on hemodialysis due
to end-stage renal disease. Heparin has a short half-life (about 5
hours) and patients can often be treated safely on the days between
dialysis.

Periodontal therapy:
Periodontal health is of critical importance in patients with bleeding
disorders as inflamed and hyperemic gingival tissues are at
increased risk of bleeding. (Periodontitis may cause tooth mobility
and warrant extraction,)

Patients with coagulopathies may neglect their oral health due to
fear of bleeding during tooth brushing and flossing, which leads to
increased gingivitis, periodontitis and caries.

Periodontal probing, supragingival scaling and polishing can be
done normally without the risk of significant bleeding.

Factor replacement is seldom needed for subgingival scaling and
root planing if these procedures are done carefully. Ultrasonic
instrumentation may result in less tissue trauma.
For severely inflamed tissues, initial treatment with
chlorhexidine mouthwashes and gross debridement is
recommended to reduce tissue inflammation before deep
scaling.

Factor replacement may be required before extensive
periodontal surgery and use of nerve blocks.

Periodontal packing materials and custom vinyl mouthguards
(stents) are used to aid in hemostasis and protect the surgical
site, but these can be dislodged by severe hemorrhage or
subperiosteal hematoma formation. Antifibrinolytic agents may
be incorporated into periodontal dressings for enhanced effect.

Post-treatment antifibrinolytic mouthwashes are usually
effective in controlling protracted bleeding.


Restorative and Endodontic Procedures

General restorative procedures do not pose a significant risk of
bleeding.
Care should be taken to avoid injuring the gingiva while placing
rubber dam clamps, matrices and wedges. A rubber dam
should be used to prevent laceration of soft tissues by the
cutting instruments.
Saliva ejectors and high-speed suction can injure the mucosa
in the floor of the mouth and cause hematoma or ecchymosis;
thus, they should be used carefully.
Endodontic therapy is preferred over extraction whenever
possible in these patients.
Endodontic therapy does not usually pose any significant risk
of bleeding and can be performed routinely. Endodontic
surgical procedures may require factor replacement therapy.


Prosthodontic Procedures
These procedures do not usually involve a considerable
risk of bleeding. Trauma should be minimized by careful
post-insertion adjustments.
Oral tissue should be handled delicately during the
various clinical stages of prosthesis fabrication to reduce
the risk of ecchymosis.
Careful adjustment of prostheses is needed to reduce
trauma to soft tissue.

Orthodontic Procedures
Orthodontic therapy can be carried out without bleeding
complications, although care should be taken that
appliances do not impinge on soft tissues and emphasis
should be put on excellent, atraumatic oral hygiene.