Haematology 7: Haemostasis Flashcards
Explain the mechanisms of normal haemeostasis
injury occurs –> vessel constricts –> unstable platelet plug forms –> plus is stabilized with fibrin –> dissolution of clot –> vessel repair
List the routinely available lab tests for investigating the coagulation cascade
- platelet count (monitor thrombocytopenia)
- bleeding time
- platelet aggregation (measures functional defect of platelets)
explain the mechanism of warfarin
- warfarin inhibits vitamin K
- gamma carboxylation = dependent on vitamin K in the liver
- so since warfarin –> inhibits vitamin K
- it stops gamma carboxylation (by inhibiting enzyme Vitamin K Epoxide Reductase)
- so it stops the ability of clotting factors to bind to surface of platelets
- hence reduces thrombin production
- warfarin uses = long term anticoagulation (e.g venous thrombosis, atrial fibrillation)
explain the mechanism of heparin
- Heparin potentiates action of anti thrombin
- antithrombin = main inhibitor of coagulation enzymes
- heparin = used for immediate anticoagulation (e.g in venous thrombosis / pulmonary embolism)
What are main antiplatelet agents currently used as anti thrombotic agents?
- COX-1 Inhibitor (e.g aspirin)
- ADP receptor antagonist (e.g clopidogrel, prasugrel)
- GDPIIb/IIIa antagonists (e.g abciximab,tirofiban, eptifibatide)
What is the normal range for platelet count?
150-350 x10^9 /L
If platelet count drops –>
If platelet count drops –> abnormal bleeding
What are the 2 main routes of coagulation?
- extrinsic
- intrinsic
List lab tests for blood coagulation
- APTT (activated partial thromboplastin time)
- PT (prothrombin time)
- TCT (thrombin clotting time)
What does APTT (activated partial thromboplastin time) measure?
APTT
- detects abnormalities in intrinsic + common pathways
- test measures clotting time
- used to monitor heparin therapy for thrombosis
What does PT (prothrombin time) measure?
PT
- detects abnormalities in the extrinsic + common pathways
- used to monitor warfarin treatment in thrombosis
What does TCT (thrombin clotting time) measure?
TCT
- not v important
- shows abnormality in fibrinogen –> fibrin conversion
APTT + PT = used together to screen causes of ________
APTT + PT = used together to screen causes of bleeding disorders
Why doesn’t blood clot completely when the cascade is activated?
- due to antithrombin
- antithrombin = plasma protein that can directly inhibit the clotting factors
Haemostasis definition:
- cellular + biochemical processes that enables both specific and regulated cessation of bleeding in response to vascular insult.
What is haemeostasis for?
to prevent blood loss from intact + injured vessels, and to enable tissue repair.
NOTE:
decrease in fibrinolytic factors = causes bleeding
increase in fibrinolytic factors = causes blood clotting
-
Note: Haemostatic plug formation = mainly important in small vessel
-
What are platelets derived from?
Megakaryocytes
What is the normal lifespan of platelets?
10 days
What is a key characteristic of the nucleus of the platelet?
- it is anuclear
Ultrastructure of platelets
- dense granules (containing ADP/ATP/Ca2+ etc.)
How is clotting factors recruited by the platelets?
through negative charge on the phospholipid membrane
What is meant by platelet activation?
conversion from a passive to an interactive cell
