Bleeding disorders /certified fixed orthodontic courses by Indian dental academy

BLEEDING DISORDERS

INDIAN DENTAL ACADEMY
Leader in Continuing Dental Education
www.indiandentalacademy.com

INDEX
- PLATELETS:
FORMATION
MORPHOLOGY
FUNCTIONS

-HAEMOSTASIS:
VASCULAR SPASM
PLATELET PLUG FORMATION
COAGULATION

INHIBITORS OF COAGULATION

www.indiandentalacademy.com HAEMOSTASIS
DRUGS USED FOR OPPOSING

- THE LABORATORY TESTS FOR DIAGNOSIS OF
BLEEDING DISORDERS

- BLEEDING DISORDERS

- PERIODONTAL TREATMENT OF BLEEDING
DISORDERS

- REFERENCES


PLATELETS

• INTRODUCTION:

Platelets are tiny cells that congregate around
ruptures in bloodvessels to provide backbone of
clot.the platelets essentially form a temporary plug
to stop bleeding.active platelets also stimulate the
action of other coagulation proteins.


• FORMATION OF PLATELETS

MYELOID STEM CELLS


• Factors controlling thrombopoiesis:

1.Interleukins(IL): IL-3,IL-6,IL-11,colony stimulating
factors stimulate thrombopoiesis.

2.thrombopoietin(TPO): Produced by liver & kidney.It
helps the megakaryocyte to produce the platelets
rapidly.

3.TGFBeta: when excessive thrombopoiesis it is
released from platelets and depress the platelet
production.

• The life span of platelet is – 7 to 12 days
Most of the platelets are destroyed in
spleen.

• The normal platelet count is
150000 – 400000 / ul of blood


MORPHOLOGY
• SHAPE – disc shape ( inactive platelet)
spherical (active platelet)
• SIZE - 2-4 um in diameter
• Platelets exist in red bone marrow,blood &spleen
• Platelets have plasma membane , cytosol & no
nucleus.
• Plamamembrane has 2 layers
Outer glycocalyx layer:contains glycoproteins
Inner lipoprotein layer:contains phospholipids

PLATELET STRUCTURE


• The cytosol consists of
1.Granules:
-Alpha granules contain fibronectin, factor V, factor
VII, PF4, PDGF.
-Dense granules contain ADP, ATP, histamine&
Calcium
2.Tubules:
-Open tubules: Communicate with extracellular
fluid(ECF). During activation,ca++ from ECF enter
the inside of platelets via these tubules
-Dense tubules: donot communicate with the
exterior.They store ca++.

• 3.contractile elements:actin, myosin.

• 4.mitochondria & golgiapparatus


Functions of platelets

• Primary haemostasis – vascular spasm
platelet plug formation

• Secondary haemostasis (blood coagulation)


HEMOSTASIS
• 1.Vascular spasm

• 2.Platelet plug formation

• 3.Blood clotting or coagulation


• 1.Vascular spasm:


• 2.Platelet plug formation:

a) platelet adhesion.

b) plaetelet release reaction.

c) platelet aggregation & formation of
platelet plug.


* The substances involved in platelet plug formation:

• TXA2
• ATP
• ADP
• Ca++
• Serotonin
• Prostaglandin
• Fibrin stabilizing factor
• Lysozomes
• Platelet derived growth factor (PDGF)

a) Platelet adhesion


b)Platelet release reaction


c) platelet aggregation & formation of platelet
plug.


* 3.Blood clotting:

• Within the vessels blood is in liquid form.when it is
drawn from body it thickens and forms a gel.

• The gel separates from the liquid.This straw colored
liquid is called serum & the gel is called clot.

• The process of gel formation – clotting or
coagulation.


• Definition :

Blood clotting is an complex cascade of
enzymatic reactions in which each clotting factor
activates many molecules of the next one in a fixed
sequence.finally a large quantity of product (clot) is
formed.


• THE FACTORS INVOLVED IN CLOTTING:

-Clotting factors (CF)

-Ca++

-Enzymes synthesized by hepatocytes

-Molecules associated with platelets


Clotting factors


* Clotting can be divided into 3 stages.

• 1.Formation of prothrombinase by 2 pathways.
Extrinsic pathway
Intrinsic pathway

• 2.Prothrombinase converts prothrombin into
thrombin.

• 3.Thrombin converts fibrinogen into soluble
fibrin.Fibrinwww.indiandentalacademy.com
forms the clot.

Clotting mechanism


Thrombin has 2 +ve feedback mechanisms


Clot retraction

• Clot retraction is the consolidation or tightening of the
fibrin clot.As the clot retracts it pulls the edges of the
damaged vessel close together.Fibroblasts from ruptured
area &new epithelial cells repair the vessel lining.

• Intra vascular clotting

*Clotting in an undamaged bloodvessels –
thrombosis.

*The clot – thrombus.

*A blood clot,bubble of air,fat from broken bones or
a piece of debris transported by the blood stream
-embolus


Inhibitors of coagulation

• Circulatory anti coagulants

• The fibrinolytic mechanism

• Tissue factor pathway inhibitor (TFPI)

• Thrombomodulin


• Role of Vitamin k

• Role of VWF

• Role of liver

• Role of bloodvessels


• Circulatory anticoagulants:

Antithrombin

Heparin

Protein C & protein S


CIRCULATORY ANTI COAGULANTS


• Fibrinolytic mechanism:


• Thrombomodulin


• TFPI :

After the onset of coagulation mechanism,
TFPI begins to be formed and inhibits the intrinsic
pathway.


• Role of vitamin K :

Vitamin K is required for synthesis of
factors II,VII,IX&X
Source of vitamin K:vegetables
Vitamin k is synthesized by intestinal
bacterial flora.
*Vitamin K deficiency:
-Vitamin K free nutrition
-Antibiotics like cephalosporins
-Newborns
-Obstructive jaundice

• Role of blood vessels:

-The subendothelium is highly thrombogenic.

-The contact of blood with subendothelium triggers
the formation of XIIa.

-Vascular endothelium synthesize PGI2 (prostacyclin)
opposes the action of TXA2 thus prevents the
platelet activation.


• Role of liver:

-Liver synthesizes prothrombin, fibrinogen, factors
V,VII,IX,X & XI.Thus the liver failure causes
failure of clot formation.

-Liver also synthesizes antithrombin III, heparin,
proteinsC & S.Thus liver failure also can cause
excessive clotting.


• Role of VWF:
- Synthesized by megakaryocytes & vascular endothelium.It
acts as a bridge between platelet & denuded endothelium.


* The drugs used for opposing haemostasis:

• 1.Anti thromboitics

• 2.Anti coagulants

• 3.Thrombolytic drugs


* 1.Anti thrombotics

• Eg:Aspirin
• Aspirin inhibits vasoconstriction & platelet
aggregation by blocking synthesis of TXA2.
• It reduces the chance of thrombus formation.
• Indications :
-Transient ischaemic attacks
-Myocardial infarction
-Angina pectoris
-Blockage of peripheral arteries

* 2.Anti coagulants:

• In vivo:
-Heparin :potentiates the action of anti thrombinIII
-Vitamin K antagonists :eg-warfarin
Blocks the synthesis of CF II,VII,IX,X.

-Indications: Deep venous thrombosis
Myocardial infarction
Pulmonary embolism


• In vitro: To prevent clotting in donated blood,
blood banks and laboratories often add a substance
which prevents coagulation by removing the
ionized calcium of blood citrate.

-Eg :
EDTA
CPD
Oxalates.


• 3.Thrombolytic drugs: These are injected into the
body to dissolve clots that have already formed to
restore circulation.

-The mechanism of action: activate plasminogen.

-Eg: Streptokinase
Tissue plasminogen activator
Urokinase

* The common laboratory tests for diagnosis of
bleeding disorders:

• 1.Bleeding time(BT)
• 2.Clotting time(CT)
• 3.Prothrombin time(PT)
• 4.Partial thromboplastin time(PTT)
• 5.Platelet count


BLEEDING DISORDERS


I) BLEEDING DISORDERS CAUSED BY VESSEL
WALL ABNORMALITIES

• Called non thrombocytopenic purpura.

• They induce small haemorrhages such as petchiae
and purpura in the skin,mucous
membranes,particularly in gingivae.

• The platelet count,BT,CT,PTT are normal.


CAUSES:

* 1.Infections: Meningococcemia
Septicaemia
Infective endocarditis.
Rickettsia
Measles

* 2.Drug reactions:The vascular injury is mediated by
drug induced Abs and deposition of immune
complexes in vessel walls leading to
hypersensitivity vasculitis.

• 3.Scurvy & Ehlers - Danlos Syndrome:

-Impaired formation of collagens causes
microvascular bleeding.

-Cushings syndrome-Protein wasting effects of
excessive corticosteroid production cause loss of
perivascular supporting tissues.

• 4.Amyloid infiltration of blood vessels:

Systemic amyloidosis associated with
perivascular deposition of amyloid and consequent
weakening blood vessel walls.


5.Henoch-Schonlein purpura: (senile purpura)
- Systemic hypersensitivity disease characterized
by a purpuric rash, ployarthralgia,acute
glomerulonephritis


* 6.Heriditary haemorrhagic telangiectasia:
• is an autosomal dominant disorder
characterized by dilated,tortuous blood vessels that
have thin walls and hence bleed readily.most
commonly occurs under the mucous membranes of
the nose,tongue,mouth,eyes,GIT.


• II.BLEEDING DISORDERS DUE TO FAULT OF
PLATELETS:

A.Related to reduced platelet number
(thrombocytopenic purpura)

B.Related to defect in platelet function


A.Related to reduced platelet number:
(Thrombocytopenic purpura)

• Platelet count is < 100000/ul.
• post traumatic bleeding is aggravated-when platelet
count is 20000-50000/ul.
• BT is prolonged.
• PT,PTT – normal.
• The common sites involved are:
-skin
-Mucous membrane of GIT &
genito urinary tract

CAUSES:
1.Decreased production of platelets
- Generalized diseases of bonemarrow
a) Aplastic anaemia
b) Leukaemia
- Selective impairment of platelet production
a) Drug induced : Alcohol,thiazides,cytotoxicdrugs.
b) Infections: measles,HIV.
- Infective Megakaryopoiesis
a) Megaloblastic anaemia
b) Myelodisplastic syndrome
c) Paroxysmal nocturnal haemoglobinuria.

2.Sequestration:
- Spleen normally sequesters
30-40% of platelets.
-In case of hypersplenism or
splenomegaly it sequesters 90% of all platelets.
-Treatment: splenectomy

3.Dilutional:
-Massive transfusions may produce
thrombocytopenia.Blood stored for longer than
24hrs contains virtually no viable
platelets.Thus,plasma volume &RBC are
reconstitued by transfusion,but the number of
circulating platelets is reduced.

4.Decreased platelet survival:

i)Immunologic destuction:

a.Auto immune: Idiopathicthrombocytopenic purpura
Systemic lupus erythematosis.
b.Iso immune: Post transfusion
Neonatal
c.Drug associated:heparin,quinidine,sulfa compounds.
d.Infections: Infectious mononucleosis
HIV
Cytomegalovirus.

ii)Non immunologic destruction:

Disseminated intravascular coagulation(DIC)
Thrombotic thrombocytopenic purpura
Giant haemangiomas
Microangiopathic haemolytic anaemias


i)Immune thrombocytopenic purpura(ITP):

• Primary ITP – Acute
Chronic (common)

• Secondary ITP – Systemic lupus erythomatosis
AIDS
Viral infections
Drug therapy


PRIMARY ITP: CHRONIC:

• Most common
• Cause:the formation of auto Abs against platelet membrane
glycoproteins,most often IIb-IIIa or Ib-IX
• Prevalence: F:M=3:1
• Age : <40yrs
• C/F: -Insidious in onset.
-Bleeding into skin,mucousal surface
-Petechiae prominent in the dependent areas where the
capillary pressure is high.Petechiae become confluent &
give rise to ecchymosis.
-Long history of easy bruising ,epitaxis,bleeding gums.

• The disease may be manifested first by malena,haematuria
and increased menstrual flow.

• Subarachnoid haemorrhage & intracerebral haemorrhage
very rarely seen.

• Diagnosis:
-Decreased platelet count
-Normal or Megakaryocytes in bone marrow.
-Prolonged BT

* Treatment:Glucocorticoids & splenectomy

ACUTE ITP:

• Occurs in children

• M:F=1:1

• C/F:
-Abrupt in onset
-The interval between infection & onset is 2wks
-Usually selflimited and resolves spontaneously within
6months.
-20% of children may develop chronic ITP.

*Treatment:corticosteroid therapy

Secondary ITP:

• Drug induced:Heparin
Quinidine
Sulfa compounds
-Heparin induced : occurs in 5% of cases receiving
heparin.
Two types: TypeI-occurs rapidly after onset of
therapy

TypeII-5-14 days after onset of
therapy. www.indiandentalacademy.com

• HIV associated thrombocytopenia:

CD4, the receptor for HIV on T cells demonstrated
on megakaryocytes,making it possible for these cells
to be infected by HIV.Infected megakaryocytes
undergo apoptosis causing impaired platelet
production.


• Non immunologic thrombocytopenia

-Cause:by mechanical injury.

Eg:Thrombotic microangiopathies-thrombotic
thrombocytopenic purpura
Haemolytic-uremic syndrome


• B.Bleeding disorders related to defective platelet
function:

1.Congenital

2.Acquired


1.Congenital
• On the basis of specific functional abnormality

a)Defect in platelet adhesion to sub endothelial
matrix.eg:Bernard-Soulier syndrome.
Platelet membrane glycoprotein is a receptor for
VWF and is essential for platelet adhesion.

b)Defect in platelet aggregation
Eg:Glanzmann’s thrombasthenia.
Platelets fail to aggregate in response to
ADP,collagen,thrombin,fail to form glycoprotein
complex which forms bridges between platelets.

c)Disorders of platelet secretion:

Eg: storage pool disorders.

-Characterized by normal initial aggregation with
collagen ADP, but the secretion of
TXA2,prostaglandins, & granule bound ADP are
impaired.


2.Acquired:

a)Ingestion of aspirin & other NSAIDS which increase
BT.

b)Uremia: Impaired platelet function


• III)BLEEDING DISORDERS RELATED TO
ABNORMALITIES IN CLOTTING FACTORS:
(FAULT IN SECONDARY HAEMOSTASIS)

-The Bleeding is manifested by large post traumatic
ecchymosis or haematomas

-Prolonged BT

-Bleeding into GIT,UT & joints.


• Two types

1.Congenital:deficiency of fac VIII-haemophilia A
deficiency of fac IX- haemophilia B

2.Acquired: DIC
VitaminK deficiency
Liver disorders


• Haemophilia A :

-Most common heriditary disorder.

-Caused by reduction in amount or activity of fac VIII.

-It is inherited as an X-linked recessive trait.

-Occurs in males & homozygous females.

-30% of pts-no family history.caused by new
mutations.

-The severity correlates with the level of fac VIII
activity.
• <1% of normal activity – severe
• 2-5% of normal activity- moderate
• 6-50% of normal activity- mild
-C/F:Easy bruising & massive haemorrhage after
truama or operative procedures.spontaneous
haemorrhages occurs in regions of body normallly
subject to trauma,particularly in joints(haem
arthroses)
-Normal BT,platelet count & PT but prolonged PTT.
-Treatment:Recombinant fac VIII

• Haemophilia B (Christmas disease):

-It is inherited as an X linked recessive trait.

-Caused by a wide sprectrum of mutations involving-
the fac IX gene.

-Clinically indistinguishable from haemophilia A.

-14% of pts fac IX is present but non functional.

-Prolonged PTT,normal PT& BT.
-Treatment: Recombinant fac IX.

• VONWILLEBRAND DISEASE

• Caused by an inherited defect in involving platelet adhesion.

• C/F:Spontaneous bleeding from mucous
membranes,excessive bleeding from wounds,menorrhagia.

• Prolonged BT,normal platelet count.

• Types:Type1
Type2
Type3

Type 1&3 are associated with a reduced quantity of
circulating VWF.
• Type1:mild&autosomal dominant.
• Type3:severe&autosomal recessive
haemarthroses is common
Severe deficiency of VWF has a marked effect on
stability of fac VIII.
• Type 2 is characterized by qualitative defects in
VWF.
-Because of mutations the VWF is abnormal.
C/F:mild to www.indiandentalacademy.com
moderate bleeding.

• Patients with Vonwillebrands disease have a
compound defect involving platelet function &
coagulation pathway.


* Acquired haemophilia

• Disseminated intravascular clotting:

• It occurs as a secondary complication in a vareity of
diseases.

• It results from pathologic activation of the extrinsic and/or
intrinsic pathways or impairment of clot inhibiting
influences.

• The mechanisms trigger DIC
- release of TF into the circulation
- wide spread of injury to endothilial cells.

Release of TF into the circulation
Causes
 Obstetrics complications.
- retained dead foetus
- septic abortion
- amniotic fluid embolism
- toximia

 neoplasms - adenocarcinoma, leukemia

 infections – gm-ve species,
malaria,
histoplasmosis
aspergillosis

wide spread of injury to endothelial cells

Endothelial injury
↓
release TF
↓
promotes platelet aggregation
↓
activates intrinsic pathway

• Consequence of DIC

widespread deposition of fibrin
↓
ischemia
↓
microangiopathic haemolytic anaemia.


Haemostatic failure

consumption of platelets and CF,
↓
activation of plasminogen
↓
plasmin→ fibrinolysis → inhibition of thrombin
↓ platelet aggregation
proteolysis of clotting factors ↓
↓ bleeding
bleeding

SPONTANEOUS BRUISING IN
HAEMOPHILIA


PERIODONTAL TREATMENT OF
HAEMORRHAGIC DISORDES
• Identification of the pt via the health history,clinical
examination and lab tests.

1.H/O bleeding after previous surgery or trauma.

2.Past & present drug history.

3.H/O bleeding problems among relatives.

4.Illness associated with potential bleeding problems.

• Clinical examination :

Ecchymosis
Jaundice
Spider telangiectasia
Haemarthrosis
Petechiae
Haemorrhage vesicles
Spontaneous gingival bleeding
Gingival hyperplasia

• LABORATORY TESTS :

BT
CT
PT
PTT
Complete bloodcell count
Torniquet test


* Haemophilia A:

• To prevent surgical haemorrhage fac VIII levels of atleast
30% are needed.

• Parentral 1-deamino-8-D-arginine vasopressin (DDAVP)
can be used to raise fac VIII levels in mild to moderate
haemophilia.

• In severe case preoperative infusion of fac VIII or
cryoprecipitate form is recommended.

• Advantage of DDAVP:Avoids the risk of viral disease
transmission from fac VIII infusion.

* Haemophilia B:

• To prevent surgical haemorrhage fac VIII levels of
atleast 30%-50% are needed.

• Purified prothrombin complex concentrates or fac
IX concentrates can be used to raise fac IX levels .

• Mild-DDAVP before periodontal surgery or
toothextraction.

• Severe-preoperative infusion of
www.indiandentalacademy.com fac IX or
cryoprecipitate form.

• Probing scaling and prophylaxis – without medical
modification.

• More invasive treatment such as block local
anesthesia,root planning or surgery – prior physician
consultation.

• Local haemostatic measures:to enhance clot
formation.
Pressure packs
Electro cautery
Splints&dressings

• Anti haemostatic agents:may be placed over surgical sites or
extraction sockets.
-Oxidized cellulose
-Gel foam
-Surgicel
-Avitene
-Purified bovine collagen.
• Anti fibrinolytic agents:
-Epsilon-aminocaproic acid(EACA)-systemically
-Amicar systemically
-Tranexamic acid-systemically, also available in a
mouthrinse.
-100mg / kg – preoperatively
continued towww.indiandentalacademy.comat a dose 50mg/kg
8-10 days postoperatively
qid.

• TREATMENT OF LIVER DISEASES OPPOSING
HAEMOSTASIS

-physician consultation
-Lab tests
-Conservative,non surgical periodontal therapy
-If surgery is required may require hospitalization
-Platelet count should be >80000/mm3
-PT <2.5


* TREATMENT IN PTS TAKING ANTI COAGULANT
THERAPY

• The effectiveness of anticoagulant therapy is
monitored by PT.

• The recommended INR-2to3.

-INR < 3- infiltration anesthesia,scaling &
rootplaning.
-INR < 2-block anesthesia, minor surgery & simple
extractions.
-INR <1.5-complex surgeries,multiple extractions.

• Physician consultation to determine the degree of
required anticoagulation & dicontinuation of the
drug until the desired PT is achieved.May be
discontinued for 2-3 days.

• The pts taking aspirin <325 mg / day – discontinued
for atleast 7-10 days before periodontal therapy in
consultation with physician.

• NSAIDS like ibuprofen – the effect is
transitory,lasting only a short time after the last drug
dose. www.indiandentalacademy.com

*Thrombocytopenic purpura

• Removal of local irritants to reduce the inflammation & to
avoid the aggressive therapy.

• Oral hygiene instructions & frequent recall visits.

• Platelet count < 60000/mm3-scaling &rootplaning is safe.

• Platelet count >80000/mm3-surgical procedures safely can
be performed.
• Platelet transfusion may be required before surgery.
• Atraumatic surgical techniques&local haemostatic measures

* Non thrombocytopenic purpura

• Surgical therapy should be avoided unless
qualitative & quantitative platelet problems are
resolved.

• Local haemostatic pressure&atraumatic technique
should be applied.


REFERENCES

1.Concise medical physiology-Choudhuri
2.Principles of anatomy&physiology-Tortora
3.Pathologic basis of disease-Robbins
4.Clinical periodontology-Carranza
5.Management of dental pts with bleeding
disorders:Review and Update
(Oral surg Oral med Oral pathol 1988;66:297-303.
6.Haematology text book-Martin & Peter

THANK YOU


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