Presented By:

Dr. Joseph John K. Pothanikat

Contents

• History

• Blood Coagulation

• Complex stages of coagulation

• Pathways of coagulation

• Implications of blood coagulation in clinical

practice.

• Management protocols for patients with

coagulation disorders.

• Bibliography

History

• Physiologist Johannes Müller (1801-1858) described fibrin

• fibrinogen, was thus named by Rudolf Virchow (1821-1902)

• A first clue as to the actual complexity of the system of coagulation

was the discovery of proaccelerin (initially and later called Factor V)

by Paul Owren (1905-1990) in 1947

• The usage of Roman numerals was agreed upon during annual

conferences (starting in 1955) of hemostasis experts. In 1962,

consensus was achieved on the numbering of factors I-XII

Blood

• Blood is a specialized bodily fluid that delivers necessary

substances to the body's cells

• 4 to 6 liters of blood.

• 38% to 48% is composed of the various blood cells, 52% to 62% of

the blood volume is plasma.

• The general functions of blood are:

– Transportation

– Regulation

– Protection

BLOOD CELLS• There are three kinds of blood cells

Red blood cells

White blood cells

• granular leukocytes

Neutrophils

Eosinophils

Basophils

• agranular leukocytes

Lymphocytes

Monocytes

Platelets

BLOOD COAGULATION

• Coagulation is a complex process by

which blood forms clots.

• This occur in mainly three phases.

1. The vascular phase

2. The platelet phase

3. The coagulation phase

VASCULAR PHASE

Injury

Vasoconstriction

Vasodilatation

PLATELET PHASE

1• Injury

2

• autonomic nervous system

• serotonin

3• Vasoconstriction

Vessel damage

Exposure of proteins, vonWillebrand Factor

RecruitsFactor VIII

Collagen

Other factors

Circulating platelets

Binds with collagen surface,

Glycoprotein Ia/IIa

Additional linkage by vWF

Activates platelets

Release of contents of granules

PLATELET PHASE

Vascular Damage

Platelet adhereance to subendothelial tissues

Platelet undergo chemical change

Formation of

PLATELET PLUG

THE COAGULATION PHASE

• Has two pathways which lead to fibrin formation.

1. The contact activation pathway (formerly known as the intrinsic pathway)

2. The tissue factor pathway (formerly known as the extrinsic pathway)

COFACTORS

• Calcium and phospholipid

• Vitamin K

COAGULATION FACTORS

FACTOR FUNCTION

I (fibrinogen) Forms clot (fibrin)

II (prothrombin) Its active form (IIa)

activates I, V, VII, VIII, XI, XIII, protein

C, platelets

Tissue factor Co-factor of VIIa (formerly known as factor III)

Calcium Required for coagulation factors to bind to

phospholipid (formerly known as factor IV)

V (proaccelerin, labile factor) Co-factor of X with which it forms

the prothrombinase complex

VI Unassigned – old name of Factor Va

VII (stable factor) Pro Convertin - Activates IX, X

VIII (Anti Hemophilic factor A) Co-factor of IX with which it forms

the tenase complex

IX (Anti Hemophilic Factor B or Christmas

factor)

Activates X: forms tenase complex with

factor VIII

X (Stuart-Prower factor) Activates II: forms prothrombinase complex

with factor V

XI (plasma thromboplastin antecedent) Activates IX

XII (Hageman factor) Activates factor XI, VII and prekallikrein

XIII (fibrin-stabilizing factor) Crosslinks fibrin

COFACTORSFACTOR FUNCTION

von Willebrand factor Binds to VIII, mediates platelet adhesion

prekallikrein (Fletcher Factor) Activates XII and prekallikrein; cleaves

HMWK

high-molecular-weight kininogen (HMWK)

(Fitzgerald Factor)

Supports reciprocal activation of XII, XI, and

prekallikrein

fibronectin Mediates cell adhesion

antithrombin III Inhibits IIa, Xa, and other proteases;

heparin cofactor II Inhibits IIa, cofactor for heparin and dermatan

sulfate ("minor antithrombin")

protein C Inactivates Va and VIIIa

protein S Cofactor for activated protein C (APC, inactive

when bound to C4b-binding protein)

protein Z Mediates thrombin adhesion to phospholipids

and stimulates degradation of factor X by ZPI

Protein Z-related protease inhibitor (ZPI) Degrades factors X (in presence of protein Z)

and XI (independently)

plasminogen Converts to plasmin, lyses fibrin and other

proteins

alpha 2-antiplasmin Inhibits plasmin

tissue plasminogen activator (tPA) Activates plasminogen

urokinase Activates plasminogen

plasminogen activator inhibitor-1 (PAI1) Inactivates tPA & urokinase (endothelial PAI)

plasminogen activator inhibitor-2 (PAI2) Inactivates tPA & urokinase (placental PAI)

Vitamin K Formation of clotting factors in liver

REGULATORS

1. Protein C

2. Antithrombin

3. Tissue factor pathway inhibitor (TFPI)

4. Plasmin

5. Prostacyclin (PGI2)

INTRAVASCULAR ANTICOAGULANTS

• Endothelial surface factors

• Anti-thrombin action of Fibrin and anti-

Thrombin III

• Heparin

THE IMPLICATIONS OF BLOOD COAGULATION

• Tourniquet test

• Bleeding time

• Clotting time

• Prothrombin time

• Partial thromboplastin time

• International normalized ratio

TOURNIQUET TEST

• Also known as a RUMPEL-LEEDE CAPILLARY-FRAGILITY TEST

or simply a CAPILLARY FRAGILITY TEST

• Normal value: <10 petechiae

BLEEDING TIME• IVY METHOD

A standard-sized incision is made around 10 mm long and 1 mm deep. The time

from when the incision is made until all bleeding has stopped is measured and is

called the bleeding time. Every 30 seconds, filter paper or a paper towel is used to

draw off the blood

• Less than 9 and a half minutes.

• DUKE METHOD

About 3-4 mm deep pricked with a special needle or lancet,

preferably on the earlobe or fingertip,

then wipes the blood every 30 seconds with a filter paper.

. 1-3 minutes

CLOTTING TIME

• Collect blood in a chemically clean glass test tube and then to tip the tube

back and forth approximately every 30 seconds until the bood has clotted.

• Normal: 6 to 10 minutes

PROTHROMBIN TIME

• Gives an indication of the total quantity of

prothrombin in the blood.

• Blood removed from the patient is immediately oxalated.

• Later, a large excess of calcium ion and tissue thromboplastin

is suddenly mixed with the oxalated

blood.

• The calcium nullifies the effect of the oxalate, and the tissue

thrombo­plastin activates the prothrombin-to-thrombin reaction by means of

the extrinsic clotting pathway.

• The time required for coagulation to take place is known as the prothrombin

time.

• Normal value: Approximately 2 seconds.

PARTIAL THROMBOPLASTIN TIME

(KAOLIN CEPHALIN CLOTTING

TIME )

• indicator measuring the efficacy of both the Intrinsic and the

common coagulation pathways.

• Also used to monitor the treatment effects with heparin.

• Normal value: Between 25 & 39 sec.

• Prolonged APTT may indicate:

1. Use of heparin (or contamination of the sample)

2. Coagulation factor deficiency (e.g. hemophilia)

INTERNATIONAL NORMALIZED RATIO

• Each manufacturer assigns an ISI value (International Sensitivity

Index) for any tissue factor they manufacture.

• The ISI value indicates how a particular batch of tissue factor

compares to an internationally standardized sample.

• Usually ISI varies between 1.0 and 2.0.

• A high INR level such as INR=5 indicates that there is a high chance

of bleeding, whereas if the INR=0.5 then there is a high chance of

having a clot.

PLATELET FUNCTION ANALYZER 100

(PFA-100)

• An invitro system for the detection of platelet dysfunction

• Consists of a microprocessor-controlled instrument and a disposable

test cartridge that contains a biologically active membrane.

• The presence of epinephrine and the high shear rates generated

under standardized flow conditions result in platelet attachment,

activation, and aggregation, which slowly build to a stable platelet

plug of the aperture.

• The time required to attain full occlusion of the aperture is reported

as "closure time" (normal < 175 seconds).

IMPORTANT BLEEDING DISORDERS

PURPURA

• Platelet Count <60,000 cells/ Cumm

• Bleeding time is prolonged.

von Willebrand Disease

• Bleeding time is prolonged

• Clotting time is normal

• Prothombin time is normal

• Depressed levels of factor VIII

Aldrich Syndrome

• Prolong Bleeding time

• Considerable anisocytosis

Thrombocytopathic purpura

• Bleeding time is either prolonged or normal

• Prothrombin time is normal

• Normal capillary plugging is impaired

IMPORTANT CLOTTING DISORDERS

Hemophilia A

• Clotting time is prolonged

• Bleeding time & Prothrombin time is normal

• partial thromboplastin time may be prolonged

Hemophilia B

• The only difference between hemophilia A is in the Prothrombin

consumption time & the partial thromboplastin time

Factor v deficiency or Parahemophilia

• Clotting time, Prothrombin time are prolonged.

• Bleeding time is normal

• Reduction in plasma proaccelerin

HEMOPHILIA A

• Hereditary disorder.

• Cause could be deficiency of factor VIII or antihemophilic

factor.

CLINICAL FEATURES:

• Prolonged bleeding after tooth extraction

• Major site involved; frenum of lip and tongue.

HEMATOLOGICAL FINDING:

• Clotting time is prolonged, but, bleeding time, platelet

count and prothrombin time are normal.

• The prothrombin consumption time and partial

thromboplastin time is prolonged.

MANAGEMENT:• Aim is to rise the factor VIII level.

• Replacement therapy with plasma & cryoprecipitate.

• FactorVIII concentrates.

• Intra ligamentary injections

HEMOPHILIA B

• Hereditary deficiency of factor IX or functionally defective

factor IX.

• very rare, compared to hemophilia A.

• Clinical features are same as hemophilia.

TREATMENT

• Managed with factor IX con­centrates.

• 80 units/kg are necessary to achieve a 100% level.

• Associated with risk of thrombosis with repeated use.

FACTOR V DEFICIENCY

(Parahemophilia)• Rare hemorrhagic disorder.

• Clinically similar to hemophilia.

• Deficiency of factor V or proaccelerin.

Clinical features:

• Spontaneous epistaxis

• Cutaneous ecchymosis and hamartomas are frequently

seen

• Spontaneous gingival bleeding.

• prolonged bleeding after extraction of tooth is observed.

Laboratory findings:

• Both clotting and prothrombin time are prolonged.

• Bleeding time is normal.

• Reduction in plasma proaccelerin.

MANAGEMENT

• Transfusion and freshly frozen plasma are given when

there is excessive hemorrhage.

DENTAL MANAGEMENT OF PLATELET DIS­ORDERS

• Caution ! For patients with platelet counts lower than 50,000/mm3.

• Analgesics containing acetaminophen and/or codeine should be

prescribed and antibiotics should be taken for oral infections

• If the gingival tissue bleeds easily, tooth brushing should be

re­stricted.

• Oral antimicrobial rinses can be prescribed to limit oral inflammation.

• Bleeding is controlled using local hemostatic tech­niques

Dental Management of Patients with Acquired

Coagulation Disorders

• As a general rule, anticoagulant drugs should not be with­drawn in

conjunction with oral surgery.

• the drug substituted with coumarin.

• PT level should be ad­justed to 1.5 to 2 times the reference value

when bleeding is anticipated or local anes­thesia is required.

• Infiltration injections are given in lieu of nerve block anesthesia

GUIDELINES TO BE FOLLOWED IN THE MANAGEMENT

OF PATIENTS WITH COAGULATION DISORDERS

• STRESS-REDUCTION GUIDELINES

• CHAIR POSITION GUIDELINES

• ANESTHESIA GUIDELINES

• ANALGESIA GUIDELINES

• ANTIBIOTIC GUIDELINES

DRUG ADVERSE EFFECTS AND INTERACTIONS

GUIDELINES

1. Nitrous oxide

2. Analgesics

3. long-term steroid therapy

Bibliography

• Essentials of Anatomy and Physiology, 5 th edition, Valerie & Tina

• Essentials of Physiology, Gyton.

• Textbook of Oral medicine, Ghom.

• Pharmacology & Therapeutics For Dentistry, 4 th Edition, John.

• Medical Emergencies in dental office, 6th edition, Malamed.

• Current Medical Diagnosis & Treatment, LANGE, 2004

• www.wikipedia.org