L9: Haemostasis Flashcards
What is haemostasis?
Process of stopping the flow of blood
Prevent bleeding
Prevent unnecessary coagulation, allow blood to flow
What are the basic steps involved?
Make a clot
Control clotting–> liquid to semisolid state
Break it down–> fibrinolysis
What is clotting?
The process whereby blood (normally a liquid) becomes a solid mass when it makes contact with connective tissue
What are the three steps of haemostasis?
1- Severed artery contracts, decrease pressure down stream
2- Primary haemostatic plug of activated platelets forms at hole in the vessel, sticks to injured tissue and CT outside, seconds to minutes
3- Secondary haemostatic plug forms, fibrin filaments stabilise the fragile platelet plug into a blood clot, 30 mins
What is essential for haemostasis?
Blood flow–> needs to keep moving, heart, valves, calf muscles have role
Blood vessels are important–> vasoconstriction ensures reduced blood flow
Platelets
Coagulation factors
Anticoagulation factors
What are the three main players in haemostasis?
Platelets
Process of blood clotting
Vascular wall
What are platelets?
Produced by megakaryocytes in bone marrow
Bud from cytoplasm
Normal platelet count is 150-400 x10^9/ L
Normal life span 7-10days
What activates platelets?
- Collagen cell surface
- ADP (released by activated platelets and injured RBC and amplifies there response)
- Thromboxane A2–> platelet aggregator
- Thrombin–> informs platelets that clotting sequence is activated
What do platelets do once they are activated?
- Stick to subendothelium (BM or collagen) specifically to Von Willebrand factor–> concentrated on surface
- Aggregate with other platelets
- Swell and change shape into sticky tiny spheres –> allow clotting components to assemble on surface
- Secrete factors that help form the platelet plug and aid clotting
(Adhere, activate, aggregation)
What factors mediate the platelet adhesion, activation and aggragation?
Plt receptors (glycoprotein complexes) Von Willebrand factors Fibrinogen Collagen ADP Thromboxane/arachidonic acid Thrombin
What is the process of blood clotting?
Fibrin needs activating -Intrinsic pathway--> Factors involved contained within the blood, triggered by negatively charged surface, no vessels need to be open for it to occur --> Factors, XII, XI, IX, VIII -Extrinsic pathway--> Needs tissue factor present outside the blood, triggered by thromboplastin released from damaged cells adjacent to area of haemorrhage --> Factor VII Converge on factor X--> Xa Prothrombin--> thrombin Thrombin activates fibrinogen --> fibrin
What role does the vascular wall pay in the clotting cascade?
Aterial media contracts–> subendothelium traps the platelets
Endothelium- balancing act between opposing and favouring clotting
- Plasminogen activator, von Willebrand factor and tissue factor–> activate
- Thrombomodulin –> Protein C opposes clotting
What laboratory tests are carried out to determine the effects of blood clotting?
Measure
- -> PT (Prothrombin time)–> extended problem with Extrinsic pathway or common pathway
- -> APTT (Activated partial thromboplastin time)–> extended problem with intrinsic pathway or common pathway
- -> Measure fibrinogen count–> measure amount of fibrinogen, problem with V or X
What is Von Willebrand Factor involved in?
Platelet adhesion to vessel wall
Platelet aggregation
Carries factor VIII
What factors oppose clotting?
Dilution of clotting factors
Anticoagulants–> oppose formation of fibrin
–> Protein C, Protein S and anti-thrombin
Fibrin degradation products also inhibit clotting
How does the clot evolve over time?
Platelets in clot die
Cling to fibrin, pull by actin-myosin (within platelets) contraction (clot retraction) to pull edges of wound together
Toughen the clot by squeezing out fluid
What is fibrinolysis?
Blood clot dissolved Hole in vessel repaired Macrophages recognise and break it down and it is destroyed by plasmin Fibrin--> fibrin degradation products Macrophages clear
How is plasmin produced?
Produced from inactive precursor plasminogen
Requires tissue plasminogen activator (tPA)
Urokinase (plasminogen activator) in urine
Streptokinase (plasminogen activator)–> not usually in body from streptococci–> antigenic so only used once
Why is the blood clotting cascade clinically relevant?
Problems with haemostasis:
- Bleeding disorders
- Arterial thrombotic disorders
- Venous thrombotic disorders
- Abnormal blood test results
- Drug therapy for pro- and anti- thrombotic purpose
Why do bleeding disorders occur?
Abnormality in vessel wall, platelets or coagulation factors
Inherited (haemophilia A or B) or acquired (liver disease, Vit K deficiency, Anticogaulants, Warfarin (inhibits vit K))
What are the signs and symptoms associated with coagulation factor disease?
Muscle haemotomas
Reccurrent haemotomas
Joint pain and deformity
Prolonged bleeding post dental extraction
Life threatening post op and post traumatic bleed
Intracerebral haemorrhage
What is haemophilia A?
X linked recessive
Lack of VIII
Mild/moderate/severe forms
Diagnose pre-natally or post birth if family history, presents in infancy if new mutation
Bleeding into muscle and joints and post-operatively
Treatment: Recombinant factor VIII or DDAVP
Normal bleeding time, platelet count, PT but prolonged ATTP
What is haemophilia B?
X linked recessive Factor IX deficiency Similar presentation to Haemophilia A Prolonges APTT Treatment: recombinant factor IX aka Christmas Disease (after person who first had it)
What is Von Willebrand disease?
Most common inherited bleeding disorder
Autosomal dominant
Carries factor VIII and mediates platelet adhesion to endothelium
Therefore prolonged bleeding time and ATTP time
Several genetic defects mild–> severe
Main due to reduction in vWB factor (other reduced activity)
