Pathomechanism of bleeding and

its relation to dentistry

Dr. Ákos Zsembery Department of Oral Biology,

Semmelweis University

May 2, 2016

Hemostasis

The objects of the complex hemostatic process are:

• To maintain the composition and fluidity of the blood within

the blood vessels,

• To seal leaks in the blood vessels and stem or stop blood

loss,

• To restore normal vascular structure or effectively repair by

scar tissue.

The three cornerstones of hemostasis are:

• Vascular system

• Coagulation system

• Fibrinolytic system

Hemostasis

There are four steps

• Vasoconstriction - decreasing blood flow (within seconds)

• Thrombocyte-plug formation

interaction between vessel wall, platelets and adhesive proteins

→ platelet clot

primary hemostasis (3-5 minutes)

• Coagulation - plug extended

consolidation of the platelet thrombus → insoluble fibrin net

coagulation factors and inhibitors

secondary hemostasis (10-30 minutes)

• Fibrinolysis

clot lysis → clot is dissolved (with repair process: days to weeks)

fibrinolytic activators and inhibitors

Vessel wall

Vessel wall damage

Primary hemostasis

Platelet adhesion

Primary hemostasis

Platelet activation

Activation of the platelets

Primary hemostasis

Platelet aggregation

Primary hemostasis - summary

Assays for primary hemostasis

The coagulation theories

•The classical or four-factor theory (Morawitz 1904)

•The waterfall or cascade theory (Macfarlane 1964;

Davie and Ratnoff 1964)

•The autocatalytic theory (Seegers and Barthels 1969)

•The revised coagulation theory (Broze 1995)

•The cell-based model (Hoffman 1998) - overlapping stages are

proposed:

Initiation

Amplification

Propagation

Stabilization

Coagulation

Coagulation factors

Inhibitors

Main assays for coagulation

Fibrinolysis

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Main assays for fibrinolysis

Hemostatic balance

The 5 signs describe the most prominent

symptoms resulting from coagulation disorders

Easy bruising Hematoma or bruising after injection,

with induration large hematoma from minor injuries

Frequent or prolonged Spontaneous nosebleeds resist for 10min

nosebleeds or require medical attention

Heavy menstrual Heavy menses needing to change a pad

bleeding or a tampon more than hourly

Prolonged bleeding Recurring bleeding following surgical

after surgery or delivery procedures, such as tonsillectomy

Prolonged or mucosal Heavy, prolonged, recurrent intra- or

bleeding post- extraction bleeding requiring

after dental work medical attention

Hereditary disorders of platelet function

• Caused by a congenital quantitative or qualitative defects of

VWF (the most common congenital bleeding disorder),

• Typically manifests in a mucocutaneous bleeding tendency

(petechiae, superficial ecchymosis, epistaxis, menorrhagia

and bleeding after tooth extraction),

• Diagnosis based on

Clinical features

History

Laboratory tests

Von Willebrand Disease (VWD)

Classification of von Willebrand’s disease

• Prolonged APTT

• Prolonged PFA-100® test result or prolonged bleeding time

• Screening tests for VWD:

VWF ristocetin cofactor activity (VWF:RCo)

VWF antigen (VWF:Ag)

• For subtype classification specialized assays are required

(VWF collagen binding assay, F VIII-binding capacity,

ristocetin-induced platelet aggregation, VWF multimeric

structure analysis by gel-electrophoresis and platelet VWF

content)

Laboratory testing for VWD

Standardized bleeding time - PFA-100

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Acquired platelet defects

Hemophilia – when the hemostatic

balance tilts to hypocoagulability

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An inherited bleeding disorder caused by very low concentration of a

specific coagulation factor.

The most common inherited bleeding disorder is vWD; together with

hemophilia A and B, it accounts for > 95 % of all hemophilia cases.

Hemophilia A and B cannot be distinguished clinically; diagnosis must

be confirmed by specific factor assays.

The bleeding tendency is related to the measured factor concentration:

Severe hemophilia: < 1 % (<1 IU/ml)

➔ spontaneous bleeding (into joints or muscules)

Moderate hemophilia: 1-5 %

➔ bleeding after minor injuries

Mild hemophilia: 5-40 %

➔ bleeding after surgery,

dental extraction, or accidents

Hemophilia

• Hemophilia A and B are X-linked disorders, limited to males.

• The factor concentration in carriers is about half of the normal

• Female carriers with low levels of F VIII or F IX, predispose

them to excessive bleeding

• Mutation analysis provides predictive information regarding

severity of hemophilia and the risk to develop inhibitory

antibodies.

Hemophilia A and hemophilia B

Coagulation screening assays in the diagnosis of

coagulopathy

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Thrombosis

Possible outcomes of venous thrombosis

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Anti-platelet drugs

ASA

• Acetylates COX, blocking TxA2 release from activated platelet

• Irreversible inhibition (7-10 days)

NSAID

• Inhibit COX

• Reversible inhibition

ADP antagonist (clopidrogel, ticlopidin)

Phophodiesterase inhibitor (dipyridamole)

Different forms of heparin

Oral drug-induced coagulopathies (OAT)

• Warfarin, dicumarol

• Vitamin K antagonist, inhibiting the modification of the

clotting factor zymogen II, VII, IX, X

• Ca++-dependent binding to phospholipid is damaged

• Long-term therapy increases risk of bleeding, relative to the

intensity of therapy

• Anticoagulant effect is monitored by PT (INR)

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Fibrinolysis