CLOTTING MECHANISM & BLEEDING DISORDERS

BY
FAMUREWA B. A B.Ch.D(Ife)
• OUTLINE
• INTRODUCTION
• PRINCIPAL ACTORS
• PHASES OF HAEMOSTASIS
• THE PRINCIPAL ACTORS
• PATHOPHYSIOLOGY
• NATURALLY OCCURING ANTICOAGULANTS
• BLEEDING DISORDERS
• CLASSIFICATION
• MANAGEMENT OF BLEEDING DISORDERS
• BIBLIOGRAPHY
• INTRODUCTION
Clotting mechanism was originally outlined by
Markowitz in 1903.
Cascade or “waterfall” theory was proposed in
1964.
Haemostasis is the process of clots formation in
walls of damaged blood vessels & preventing
blood loss while maintaining blood in fluid
state in the vascular system together with the
removal of clots as part of vascular
remodeling.
PRINCIPAL ACTORS
These are :
• Damaged blood vessels
• Blood Platelets
• Coagulation factors
Phases of Haemostasis:
• Vascular phase
• Platelets phase
• Coagulation phase
• Fibrinolytic phase
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
PLATELET PHASE
• Platelet exposure to subendothelial collagen
activates platelets
• ADP causes more platelets activation
• Platelets aggregation form temporary
haemostatic plug.
COAGULATION PHASE
A series of complex reaction leads to formation
of definitive plug (clots).
• Fundamental reaction is conversion of soluble
fibrinogen to insoluble fibrin.
• Coagulation factors are soluble plasma
proteins.
COAGULATION FACTORS
Factor I – Fibrinogen
Factor II – Prothrombin
Factor III – Tissue factor or thromboplastin
Factor IV – Calcium
Factor V – Proaccelerin
Factor VII – Proconvertin
Factor VIII – Antihaemophilic factor
Factor IX – Christmas factor
Factor X – Stuart prower factor
Factor XI – Plasma thromboplastin antecedent
Factor XII - Hageman factor
Factor IX – Christmas factor
Factor X – Stuart prower factor
Factor XI – Plasma thromboplastin antecedent
Factor XII - Hageman factor
Factor XIII – Fibrin-stabilizing factor
COAGULATION PHASE
• Coagulation proceeds by 2 separate pathways
(intrinsic & extrinsic) that converge by
activating a 3rd (common) pathway.
• Intrinsic Pathway a.k.a contact activation
pathway. 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.
Acute myeloid leukaemia
EXTRINSIC PATHWAY
• A.K.A tissue factor pathway. Is take about 20
seconds.
• Triggered by the release of tissue factor.
• TF binds to F VII in the presence of calcium
which activates Fs IX & X which links the 2
pathways.
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.
FIBRINOLYTIC PHASE
• A rate – limiting step in clotting after its
haemostatic function.
• Tissue Plasminogen activator (TPA) converts
plasminogen to plasmin.
• Plasmin degrades fibrin to fibrin degradation
product (FDP).
• TPA also degrades F V & F VIII.
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.
BLEEDING DISORDERS
• Any disorders arising from the 4 phases of
haemostasis.
• Classification
1. Vascular wall disorders
2. Platelet disorders
3. Coagulopathies
4. Fibrinolytic disorders
VASCULAR WALL DISORDERS
• Scurvy
• Syndromic disorders like
1. Cushing’s syndrome
2. Ehlers – Danlos syndrome
3. Rendu – Osler – Weber syndrome
PLATELET DISORDERS
• Congenital
Thrombocytopaenia e.g.
1. May – Hegglin anomaly
2. Wiskott – Aldrich syndrome
3. Neonatal alloimmune thrombocytopaenia

Thrombocytopathies e.g.
4. Glanzmann’s thrombasthenia
5. Platelet – type von Willebrand’s disease
6. Bernard – Soulier syndrome
PLATELET DISORDERS
• Acquired
Thrombocytopaenias 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
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
COAGULOPATHIES
• Congenital e.g.
1. Haemophilia A
2. Haemophili B(Xmas dx)
3. F XI defiency
4. F XII defiency
5. F X defiency
6. F V defiency
7. Fs XIII & I defiencies
8. Von Willebrand’s disease
COAGULOPATHIES
• Acquired
1. Drug/Anticoagulant related coagulopathies
e.g. Heparin, Coumarin (Warfarin & Dicumarol)
2. Disease related coagulopathies
• Liver disease
• Vit K defiency
• DIC
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
MANAGEMENT
• Detailed history
• Thorough clinical examination
• Relevant investigations
• Specific therapy
BIBLIOGRAPHY
Badoe EA et al. (2000) Principles and Practice of
Surgery.
Ganong WF (2003) Review of Medical Physiology
Greenberg MS, Glick M (2003) Burket’s Oral
Medicine.
Hoffrand AV et al. (2005) Postgraduate
Haematology.
www.manfred.mantz-online.de The blood
clotting cascade.
 PURPURA
• Oral cavity
HAEMOPHILIA