Haemostasis Flashcards
Summarise the mechanisms of normal haemostasis
Vessel constriction
Platelet plug formation
Plug stabilisation with fibrin
Dissolution of clot
What clotting factors are synthesised by the vascular endothelium?
PGI2
Thrombomodulin
vWF
Plasminogen activators
How many platelets are produced by each megakaryocte?
about 4000
What is the lifespan of a platelet?
10 days
Where are 1/3 of platelets stored?
Spleen
What receptors are present on the platelet surface?
Thrombin
Glycoprotein
Recall the types of granule present in platelets and the composition of each type
Dense: ADP, ATP, serotonin, Ca++
Alpha: vWF and Factor V
Glycogen
Describe the cytoskeleton of platelets
Actomyosin, microtubules
Recall the 2 mechanisms by which a platelet can adhere to the endothelium
Direct binding to Gp1a
Binding to Gp1b which binds vWF
What happens when a platelet adheres to the endothelium?
GpIIa and GpIIb activated on platelet surface
ADP and TXA2 are released
Thrombin activates coagulation
How are the platelets aggregated when the plug forms?
Fibrinogen AND Ca++ connects platelets via GpIIa and GpIIb
Recall the mechanism of PG metabolism that leads to PGI2 and TXA2 production
- Membrane phospholipid converted to arachdionic acid via phospholipase
- Conversion to endoperoxidases (eg PGH2) via COX1
- Converted to PGI2/ TXA2 via synthetases
Where are most coagulation factors synthesised?
Liver
Where is vWF synthesised?
Vascular endothelium
What clotting factors are synthesised in megakaryocytes?
Factor V and vWF
Recall the successive activation of factors in the coagulation cascade
12 11 9 10 prothrombin fibrinogen
Which coagulation factors are activated by tissue factor? What is the cofactor in each case?
9 (8a)
10 (calcium)
Recall the mechanism of fibrinolysis
Plasminogen and tPA simultaneously encounter a fibrin clot
Plasminogen converted to plasmin
Plasmin degrades fibrin producing FDP
What is an elevated FDP indicative of?
DIC
What are the main inhibitory mechanisms in the clotting cascade?
Antithrombin III
Protein C with protein S
Where in the coagulation cascade does anti-thrombin have inhibitory action?
9a
10a
thrombin
What is the other name for factor IIa?
Thrombin
What is a normal platelet count?
150-400 x 10^9
What platelet count would cause common spontaneous bleeding?
<40 x 10^9
Recall 3 clinical features of AI thrombocytopenia
Purpura
Multiple bruises
Eccymoses
What are the 3 main tests for coagulation?
APTT (activated partial thromboplastin time)
PT (prothrombin time)
TCT (thrombin clotting time)
Describe the function and use of APTT
Initiates coagulation through factor XII therefore detects abnormalities in intrinsic and common pathways
What abnormalities can be detected by PT
Extrinsic and common pathway faults
What test is used to test for haemophilia?
TCT
What coagulation test is used to monitor heparin therapy?
APTT
What coagulation test is used to monitor warfarin therapy?
PT
Which enzyme is inhibited by warfarin and why does this inhibit coagulant?
Vit K epoxide
clotting factors are reacted with vit K in liver
Recall the mechanism of action of heparin
Accelerates antithrombin action
Recall the 3 classes of antiplatelet agent
ADP receptor agonists
COX antagonist
GpIIa/GpIIb antagonists
