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 Mller (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 2 3

Injury

autonomic nervous system serotonin Vasoconstriction

Vessel damage
Circulating platelets

Exposure of proteins, vonWillebrand Factor

Recruits

Factor VIII Collagen Other factors

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

COFACTORS Calcium and phospholipid Vitamin K

COAGULATION FACTORS
FACTOR
I (fibrinogen) II (prothrombin)

FUNCTION
Forms clot (fibrin) Its active form (IIa) activates I, V, VII, VIII, XI, XIII, protein C, platelets Co-factor of VIIa (formerly known as factor III) Required for coagulation factors to bind to phospholipid (formerly known as factor IV) Co-factor of X with which it forms the prothrombinase complex Unassigned old name of Factor Va Pro Convertin - Activates IX, X Co-factor of IX with which it forms the tenase complex Activates X: forms tenase complex with factor VIII Activates II: forms prothrombinase complex with factor V Activates IX Activates factor XI, VII and prekallikrein Crosslinks fibrin

Tissue factor Calcium V (proaccelerin, labile factor) VI VII (stable factor) VIII (Anti Hemophilic factor A) IX (Anti Hemophilic Factor B or Christmas factor) X (Stuart-Prower factor) XI (plasma thromboplastin antecedent) XII (Hageman factor) XIII (fibrin-stabilizing factor)

COFACTORS
FACTOR
von Willebrand factor prekallikrein (Fletcher Factor) high-molecular-weight kininogen (HMWK) (Fitzgerald Factor) fibronectin antithrombin III heparin cofactor II protein C protein S protein Z Protein Z-related protease inhibitor (ZPI)

FUNCTION
Binds to VIII, mediates platelet adhesion Activates XII and prekallikrein; cleaves HMWK Supports reciprocal activation of XII, XI, and prekallikrein Mediates cell adhesion Inhibits IIa, Xa, and other proteases; Inhibits IIa, cofactor for heparin and dermatan sulfate ("minor antithrombin") Inactivates Va and VIIIa Cofactor for activated protein C (APC, inactive when bound to C4b-binding protein) Mediates thrombin adhesion to phospholipids and stimulates degradation of factor X by ZPI Degrades factors X (in presence of protein Z) and XI (independently)

plasminogen
alpha 2-antiplasmin tissue plasminogen activator (tPA) urokinase plasminogen activator inhibitor-1 (PAI1) plasminogen activator inhibitor-2 (PAI2) Vitamin K

Converts to plasmin, lyses fibrin and other proteins

Inhibits plasmin Activates plasminogen Activates plasminogen Inactivates tPA & urokinase (endothelial PAI) Inactivates tPA & urokinase (placental PAI) Formation of clotting factors in liver

REGULATORS
1. 2. 3. 4. 5. Protein C Antithrombin Tissue factor pathway inhibitor (TFPI) Plasmin Prostacyclin (PGI2)

INTRAVASCULAR ANTICOAGULANTS
Endothelial surface factors Anti-thrombin action of Fibrin and antiThrombin 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