haemostasis Flashcards
the vessel wall is lined by endothelium which in normal conditions prevent what?
platelet adhesion and thrombus formation
injury to vessels causes
reflex vasoconstriction
endothelial damage results in
loss of antithrombic properties, activation of platelets and coagulation and inhibition of fibrinolysis
3 steps that occur to platelets after endothelial damage is?
- platelet adhesion
- platelet activation
- platelet aggregation
platelet adhesion - escaping platelets come into contact w and adhere to?
collagen and subendothelial bound VWF
-> glycoprotein lb does this
-> activates platelet prostaglandin synthesis
in response to platelet prostaglandin synthesis - platelet dense bodies release what?
- ADP
- serotonin
- and other factors
platelet activation - release of ADP leads to a conformational change in fibrinogen receptor, on surface of adherent platelets, allowing it to bind to?
fibrinogen
fibrinogen is what?
- a dimer
as fibrinogen is a dimer it can form a direct bridge between platelets thus causing?
platelet aggregation
-> and a platelet plug is formed
what is haemostasis?
- arrest of bleeding and maintenance of vascular patency
release of serotonin and TXA2 from platelets cause what?
vasoconstriction of vessels
release of what induces platelet aggregation and formation of a platelet plug?
- ADP
coagulation pathway is stimulated and leads to formation of?
- fibrin
fibrin strands are cross linked by factor?
XIII
what does cross-linked fibrin do?
- stabilizes haemostatic plug by binding platelets and red cells
coagulation involves a series of enzymatic reactions that lead to conversion of soluble plasma fibrinogen to
- fibrin based clot
fibrinogen and prothrombin are referred to what factors respectively?
- I and II
factors are synthesised in what part of the body?
- liver
what are 2 co-factors?
- V and VIII
coagulation pathway is composed of 3 pathways which are?
- intrinsic and extrinsic pathways and common pathways
secondary haemostasis refers to?
- stabilisation of activated platelets due to actions of strands of fibrin - these generate a ‘stable mesh’ the main component in a thrombus (clot)
fibrin is converted from its precursor fibrinogen by ?
thrombin
- and is end product of chain of reactions that make up the coagulation cascade
extrinsic pathway is initiated by ?
- tissue factor
where is tissue factor found?
- expressed on surface of many cells outside blood vessels
- when endothelium is damaged, TF, comes into contact w blood and combines w factor VII to form a complex -> Xa triggering common pathway
TF combines w factor VII to form a complex activating what factor?
- Xa -> thus triggering common pathway
common pathway begins w activation of?
- factor X
via either extrinsic or intrinsic pathway - final stage of coagulation cascade
what is final stage of coagulation cascade?
- formation of thrombin and fibrin
factor Xa combines w ? to convert prothrombin into thrombin
- factor V, platelet membrane phospholipids and Ca2+ ions
thrombin converts fibrinogen into?
- fibrin strands which form an important structural component of a thrombus
thrombin activates many parts of the coagulation cascade via positive feedback loop through what pathway?
- intrinsic pathway
the intrinsic pathway can be activated by?
- surface contact - when damage to vascular endothelium leads to exposure of clotting factors -> negatively charged subendothelial
- also within blood vessels, thrombin generated from prev activation of extrinisic pathway also activates intrinsic pathway
instrinic pathway also leads to amplification of what substance?
- thrombin - creating positive feedback loop
intrinsic pathway: surface contact activates?
- factor XII
intrinsic pathway: factor XIIa activates factor?
- factor XI
intrinsic pathway: factor XIa combines w factor VIIIa, platelet membrane phospholipid and Ca2+ ions to activate?
- factor X
intrinsic pathway: factor Xa activates common pathway generating more?
- thrombin
function of thrombin?
- fibrin generation
- intrinsic pathway activation: thrombin initiates intrinsic pathway
- factor XIII activation - XIIIa (fibrin stabilising factor) - cross-links fibrin - to generate fibrin mesh - surrounding platelets and stopping bleeding
- platelet activation
- regulation of clot formation
what initiates common pathway?
- factor Xa
components of extrinsic pathway?
- TF
- factor VII (7)
components of intrinsic pathway?
- factor XII (12)
- factor XI (11)
- factor IX (9)
- factor VIII (8)
- platelet membrane phospholipids
- Ca2+ ions
components of final common pathway?
- factor X (10)
- factor V (5)
- prothrombin
- platelet membrane phospholipids
- Ca2+ ions
- fibrinogen
what are some proteins that inhibit coagulation cascade when enough thrombin has been produced?
- protein C
- protein S
- antithrombin
- tissue factor pathway inhibitor
protein C is produced in response to thrombin binding to?
- thrombomodulin on vascular endothelium
thrombin + thrombomodulin (receptor) leads to activation of?
- protein S
-> protein S breaks down factors Va (5) and VIIIa (8) in neg feedback loop
antithrombin is produced where and what is its function?
- produced by liver and destroys factors XIa (11), Xa (10) and thrombin
heparin and fondaparinux enhance natural effects of what protein?
- antithrombin
TFPI (tissue factor pathway inhibitor) binds to and inactivates?
- factor VIIa (7)
- factor Xa (10)
warfarin is a vit K antagonist which prevents synthesis of?
- vit k dependent clotting factors - II (2 - prothrombin), VII (7), IX (9), and X (10)
LMWH is prescribed alongside warfarin when tx is initiated why?
- as vit K is also required for synthesis of natural anticoagulants protein C and protein S so warfarin may inhibit their production initially
when can LMWH be stopped?
- once INR is at target range
PT time measures time taken for fibrin to form via what pathway?
- extrinsic pathway
PT - 9-12 secs
Activated thromboplastin time measures time taken for fibrin to form via which pathway?
- intrinsic pathway
APTT - 23-38 secs
measuring 12, 11, 9, 8, 10, 5, prothrombin and fibrinogen
causes of prolonged PT > 12 secs
- DIC
- Vit K deficiency
- chronic liver disease
INR monitors levels of anticoagulation in patients on which drug?
- warfarin
causes of prolonged APTT > 38 secs?
- DIC
- clotting factor deficiencies - haemophilia A or B
- lupus anticoagulant
- Von Willebrand’s disease
lupus anticoagulant can prolong APTT test but do not increase what?
- tendency of a patient to bleed
dysfunction of coagulation cascade can be caused by what medical conditions?
- haemophilia - A (8), B (9), C (11)
- chronic liver disease
- factor V leiden
extrinsic and intrinsic pathway both result in activation of factor ?
- X - which leads to conversion of prothrombin to thrombin
thrombin, converts fibrinogen -> fubrin and triggers activation of factor ?
- XIII (8) to cross link fibrin strands and stabilise clot
stable clot is formed by ?
- activated platelets, fibrin and factor XIIIa
