clotting mechanisms & bleeding disorders

8/7/2019 Clotting Mechanisms & Bleeding Disorders

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CLOTTING MECHANISM & BLEEDING DISORDERSBY

FAMUREWA B. A B.Ch.D(Ife)


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OUTLINE

INTRODUCTION PRINCIPAL ACTORS

PHASES OF HAEMOSTASIS

THE PRINCIPAL ACTORS PATHOPHYSIOLOGY

NATURALLY OCCURING ANTICOAGULANTS

BLEEDING DISORDERS

CLASSIFICATION

MANAGEMENT OF BLEEDING DISORDERS

BIBLIOGRAPHY


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INTRODUCTION

Clotting mechanism was originally outlined byMarkowitz in 1903.

Cascade or waterfall theory was proposed in1964.

Haemostasis is the process of clots formation inwalls of damaged blood vessels & preventingblood loss while maintaining blood in fluidstate in the vascular system together with the

removal of clots as part of vascularremodeling.


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PRINCIPAL ACTORS

These are : Damaged blood vessels

Blood Platelets

Coagulation factors


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Phases of Haemostasis:

Vascular phase

Platelets phase

Coagulation phase

Fibrinolytic phase


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Pathophysiology putting them together

VASCULAR PHASE Vasoconstriction of vessels

Moderate size vessels Neurogenic from

tunica media Vasoactive amines are said to be responssible

e.g. Serotonin etc. and thromboxane


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PLATELET PHASE

Platelet exposure to subendothelial collagenactivates platelets

ADP causes more platelets activation

Platelets aggregation form temporaryhaemostatic plug.


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COAGULATION PHASE

A series of complex reaction leads to formationof definitive plug (clots).

Fundamental reaction is conversion of soluble

fibrinogen to insoluble fibrin.

Coagulation factors are soluble plasma

proteins.


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COAGULATION FACTORS

Factor I Fibrinogen

Factor II Prothrombin

Factor III Tissue factor or thromboplastin

Factor IV Calcium

Factor V ProaccelerinFactor VII Proconvertin

Factor VIII Antihaemophilic factor

Factor IX Christmas factor

Factor X Stuart prower factorFactor XI Plasma thromboplastin antecedent

Factor XII - Hageman factor


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Factor IX Christmas factor

Factor X Stuart prower factorFactor XI Plasma thromboplastin antecedent

Factor XII - Hageman factor

Factor XIII Fibrin-stabilizing factor


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COAGULATION PHASE

Coagulation proceeds by 2 separate pathways(intrinsic & extrinsic) that converge by

activating a 3rd (common) pathway.

Intrinsic Pathway a.k.a contact activationpathway. It takes 5 to 10 mins

In Vivo When blood is exposed to collagen

fibres beneath the endothelin the pathway is

activated.

In Vitro Blood is exposed to electro-ve

charged wettable surfaces e.g. glass.


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Acute myeloid leukaemia


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EXTRINSIC PATHWAY

A.K.A tissue factor pathway. Is take about 20seconds.

Triggered by the release of tissue factor.

TF binds to F VII in the presence of calciumwhich activates Fs IX & X which links the 2

pathways.


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COMMON PATHWAY

Activation of F X begins this pathway.

F Xa convert FII to thrombin in the presence of

Ca, phosphoipid & FV

Thrombin converts F I to fibrin (monomer).

Fibrin is polymerized to form a gel & cross

linked via F XIII.


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FIBRINOLYTIC PHASE

A rate limiting step in clotting after itshaemostatic function.

Tissue Plasminogen activator (TPA) converts

plasminogen to plasmin.

Plasmin degrades fibrin to fibrin degradation

product (FDP).

TPA also degrades F V & F VIII.


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NATURALLY OCCURING ANTICOAGULANTS

2 major groups, Viz: Inhibitors of serine proteases of coagulation

cascade (Serpines) & tissue factors pathway

inhibitors (TFPI)

Protein C pathway Inhibitors of F Va & VIIIa.


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BLEEDING DISORDERS

Any disorders arising from the 4 phases ofhaemostasis.

Classification

1. Vascular wall disorders2. Platelet disorders

3. Coagulopathies

4. Fibrinolytic disorders


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VASCULAR WALL DISORDERS

Scurvy Syndromic disorders like

1. Cushings syndrome

2. Ehlers Danlos syndrome3. Rendu Osler Weber syndrome


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PLATELET DISORDERS

Congenital

Thrombocytopaenia e.g.

1. May Hegglin anomaly

2. Wiskott Aldrich syndrome

3. Neonatal alloimmune thrombocytopaenia

Thrombocytopathies e.g.

1. Glanzmanns thrombasthenia

2. Platelet type von Willebrands disease

3. Bernard Soulier syndrome


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PLATELET DISORDERS

AcquiredThrombocytopaenias e.g.

1. Autoimmune or idiopathic

thrombocytopaenia purpura (ITP)2. Thrombotic thrombocypaenia purpura (TTP)

3. Cytotoxic chemotherapy

4. Drug induced (quinine, quinidine etc.5. Leukaemia

6. Aplastic anaemia


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Acquired platelet disorders

7. Myelodysplasia

8. Systemic lupus erythematosus

9. Infection HIV, Malaria, Mononucleosis

10. Disseminated intravascular coagulation (DIC)

Thrombocytopathies e.g.1. Drug induced (Aspirin, NSAIDs, Penicillin,

Cephalosporins)

2. Uraemia

3. Alcohol dependency

4. Myeloma

5. Acquired platelet type von W disease


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COAGULOPATHIES

Congenital e.g.1. Haemophilia A

2. Haemophili B(Xmas dx)

3. F XI defiency4. F XII defiency

5. F X defiency

6. F V defiency7. Fs XIII & I defiencies

8. Von Willebrands disease


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COAGULOPATHIES

Acquired1. Drug/Anticoagulant related coagulopathies

e.g. Heparin, Coumarin (Warfarin & Dicumarol)

2. Disease related coagulopathies Liver disease

Vit K defiency

DIC


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FIBRINOLYTIC DISORDERS

These could result in haemorrhage or

excessive clotting & thrombosis

They are classified as

1. Primary fibrinolysis which result in bleeding

2. Secondary fibrinolysis which results in

thrombosis. This is seen in

DIC

Dialysis patient with CRF


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MANAGEMENT

Detailed history Thorough clinical examination

Relevant investigations

Specific therapy


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BIBLIOGRAPHY

Badoe EA et al. (2000) Principles and Practice ofSurgery.

Ganong WF (2003) Review of Medical Physiology

Greenberg MS, Glick M (2003) Burkets Oral

Medicine.

Hoffrand AV et al. (2005) Postgraduate

Haematology.

www.manfred.mantz-online.de The blood

clotting cascade.


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PURPURA

Oral cavity


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HAEMOPHILIA

clotting mechanisms & bleeding disorders

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