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