Chapter 2 - Bleeding Disorders Flashcards
What is haemostasis? and what does this process include?
Haemostasis is the body’s process to overcome blood loss after vascular damage.
To stop bleeding and vascular repair, the body forms a clot at the site of injury. This includes:
1) vasoconstriction - to reduce blood flow
2) activation of platelets through contact of site of endothelial damage - this forms a mechanical plug and activates the coagulation cascade
3) activation of blood coagulation factors - producing fibrin
platelet and fibrin aggregation forms the thrombus
The coagulation cascade is made up of 3 pathways. What are these three pathways?
1) Intrinsic pathway
2) Extrinsic pathway
3) Final common pathway
What is the intrinsic pathway?
Activation of Factor 12 (factor XII) by contact with ‘damaged’ surface leading to a series of reactions. Ultimately leading to the activation of factor 10 (factor X).
What is the extrinsic pathway?
Activation of ‘tissue factor’ - Factor VII released from damaged cells together with calcium ions leads to the activation of factor 10.
What is the ‘final common’ pathway?
Activated factor 10 from the intrinsic and extrinsic pathway contributes to the final common pathway.
Factor 10 helps to convert prothrombin into thrombin which in turn converts fibrinogen to activated fibrin.
When the process of haemostasis is disrupted, the body can react in two ways. What are these two ways?
Disruption may lead to:
1) Prothrombotic state - formation of clots much more readily
2) Antithrombotic state - excess bleeding
When considering anticoagulation two coagulation tests are performed. What are these?
PT - Prothrombin time (also known as INR)
APTT - Activated partial thromboplastin time
What is the significance of the coagulation PT test?
PT/ INR test evaluates the extrinsic and final common pathways - looking at how long it takes the blood to clot by determining the body’s ability to control prothrombin.
What is the significance of the APTT test?
APTT evaluates the intrinsic and final common pathways.
There are three main disease factors which contribute to thrombosis formation. What are they?
1) Abnormalities with blood flow - e.g AF,
2) Abnormalities of the surfaces in contact with the blood - e.g heart valve replacement (new prosthetic valve is replacing the damaged valve)
3) Abnormalities in clotting components - (seen in patients with cancer, elevated fibrinogen, raised platelets etc)
What is thromboembolism?
= Thrombosis (formation of a clot) + embolism (clot becoming lodged in the blood vessel)
formation of a clot, resulting in its main complication - embolism.
How may thromboembolism present?
DVT, PE or stroke
Venous thromboembolism (VTE) can present as DVT or PE.
What is the MOA of heparins?
1) Activate antithrombin - induces inactivation of thrombin
2) potentiates naturally occurring inhibitors of activated factor 10 (Xa)
How do antifibrinolytics work?
Inhibit fibrinolysis (breakdown of fibrin)
For the prevention or treatment of ischaemic neurological defects following subarachnoid haemorrage, which drug is the drug of choice and why?
Nimodipine (CCB)
Nimodipine increases cerebral perfusion, particularly in poorly perfused areas, by arterial dilatation, an effect which is proportionately greater in smaller than in larger vessels.
When managing thromboembolism in pregnancy, which antithrombotic agent is preferred and why?
Heparins because they do not cross the placenta
In general why are low molecular weight heparins preferred over unfractionated heparin?
Lower risk of osteoperosis and heparin-induced thrombocytopenia
If rapid reversal of the effects of heparin is required to manage a haemorrage, which agent can be given?
Protamine sulfate
What is recommended as long term treatment for someone who has had a TIA?
Initial - Aspirin 300mg
Long term: M/R dipyridamole in combination with aspirin
For a patient presenting with an acute ischaemic stroke, within 4.5hours of symptom onset, which antithrombotic agent is recommended?
Alteplase
When should treatment with aspirin be initiated after a stroke?
24hours after thrombolysis for 14 days
What should be given for the long term management following an ischaemic stroke?
clopidogrel 75mg recomended
How long does the antocoagulant effect with warfarin take to full develop?
48-72hours
if immediate antocoagulation is required, unfractionated/LMWH should be given concomitently
In a patient presenting with an NSTEMI, what is the duration that clopidogrel and aspirin should be given?
12 months (there is no evidence of benefit beyond 12 months)
