PP 5 Intro To Haemostasis Flashcards
What is haemostasis?
Stopping of blood flow
Maintains fluid stasis in vessels whilst permitting rapid clot formation
What are the 3 components of haemostasis?
Intact vascular wall
Platelets
Coagulation cascade - (anti)coagulation factors
Aim of haemostasis
Stop bleeding after trauma to blood vessel
- Make clot
- Control clotting
- Breakdown clot
Process of haemostasis
1- contraction of vessel wall
2- formation of platelet plug at site
3- formation of fibrin clot to stabilise
Vessel wall structure
Tunica intima - endothelium
Tunica media - smooth muscles
Tunica adventitia - comprised of fibroblasts + collagen
What happens to the vessel wall in haemostasis
- vasoconstriction- increased blood flow
- production of vWF
- exposure of collagen + tissue - initiates activation of clotting factor
What is vWF?
Von Willebrand factor
Von Willebran factor function
Platelet adherence
Carries + protects factor VIII
What are platelets made from?
Cytoplasm of megakaryocyte in bone marrow
Platelet life span
7-10 days
Describe platelets
Disc shaped
Anucleated
Platelet action at injury
Adhesion
Activation/secretion
Aggregation
Describe platelet adhesion
- After vessel wall damage - exposure of underlying tissues
- Platelets adhere to collagen via vWF
- vWF acts as a bridge between platelets + collagen
Describe platelet activation/secretion
- Platelets secrete granules containing ADP, thoromboxane etc..
- Granules get activated + activate other platelets
- Activation of clotting cascade
Describe platelet aggregation
- Cross linking of platelets to form platelet plug
- Provides some stability but friable
- Need to form clot - more stable
List mediating factors of platelet action + their functions
- fibrinogen- links platelets
- collagen- binds platelets
- ADP + thromboxane- causes interaction of platelets to make plug
- thrombin- converts fibrinogen to fibrin
- von Willebran factor- platelet adherence
- platelet receptors- glycoproteins complexes e.g. GP1, GPIIa/Ia - binding site for fibrinogen
Fibrinogen function in clotting cascade
Links platelets to from platelet plug
Collagen function in clotting cascade
Binds platelets
ADP + thromboxane function in clotting cascade
Cause interaction of platelets to make plug
Thrombin function in clotting cascade
Converts fibrinogen to fibrin
Von Willebrand factor function in clotting cascade
Platelet adherence
Carries factor VIII
What are tests for clotting defects performed on?
Platelet poor plasma
Test for clotting defects
APTT activated partial thromboplastin time
PT prothrombin time
TT thrombin time
What does APTT test?
Activated partial thromboplastin time
Intrinsic pathways
Factors VIII, IX, XI, VIII
What does PT test?
Prothrombin time
Tests extrinsic pathway
PET
What does TT test?
Thrombin time
Tests conversion of fibrinogen to fibrin by thrombin
What converts fibrinogen to fibrin?
Thrombin
What factors are in the common pathway?
What do deficiencies in them do?
Factors of 10
Factor V
Factor X
Prothrombin II
Fibrinogen I
Prolong APTT + PT
What do deficiencies in factors V, X thrombin + fibrinogen prolong?
Why?
APTT and PT
In the common pathway
Functions of natural anticoagulants
Stop over clotting
Breakdown clot
Natural anticoagulant examples
Antibthromin
Protein C + S
Function of anttithrombin
Inhibits action of thrombin
Explain the action of antithromin
- Activated by heparin on surface of endothelial cells
- Prevent spread of a clot by rapidly inactivating clotting factors - carried away in blood
Explain how protein C is activated
- thrombin binds to thrombomodulin
- this complex activates protein C
- activated protein C inactivates factor VIIIa + Va»_space; prevents prothrombin > thrombin
- protein S is a cofactor for APC
Function of activated protein C
Prevents prothrombin > thrombin
Function of tissue factor (extrinsic) pathway inhibitor
Opposes clot formation
Inhibits ability to generate Xa
What are the two pathways of the clotting cascade?
Contact activation (intrinsic) pathway
Tissue factor (extrinsic) pathway
What converts prothrombin to thrombin?
Factor Xa + Va
What is the intrinsic pathway measured by?
Activated partial thromboplastin time