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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