Coagulation Flashcards
What is coagulation?
Formation of a fibrin strong, insoluble clot or thrombus. This reinforces the platelet plug and may trap blood cells, white/red thrombus.
-The coagulation cascade occurs, which is a complex enzyme cascade, the last stage includes the conversion of soluble fibrinogen to insoluble fibrin.
What is the role of thrombin?
-Thrombin cleaves fibrinogen, producing fragments that polymerise to form insoluble fibrin (insoluble mesh)
-Fibrin links are strengthened by activation of factor XIII
-Platelet activation
-Cell proliferation
-Regulation of smooth muscle contraction
What is the role of the liver in coagulation?
-Synthesises clotting factors
-Vitamin K (phytomenadine)
*Lipid soluble
*Needed to make factor II, VII, IX, X
*Dietary source
*Synthesis in the GIT
*Synthesises bile salts - vitamin k absorption
What drugs can be used to prevent thrombosis of white thrombi?
Aspirin
What drugs can be used to prevent or treat red thrombi?
-Injectable anticoagulants - heparin and thrombin inhibitors - immediate action
-Oral anticoagulants - warfarin (take several days to work)
If a pt has venous thrombosis and are started on warfarin what should they be given until warfarin takes action?
Injectable anticoagulant
What factors does warfarin act on?
7,9,10
What is the simple MOA of heparin?
Activate antithrombin 3
-Inactivates thrombin and Xa and other SER proteases
-Changes conformation of ATIII
-Accelerates rate of action of ATIII (thrombin inhibition)
What does inhibiting a single molecule of Xa do?
Help to prevent the formation of hundreds of thrombin molecules
What are the two types of heparin?
-Unfractionated (UFH)
-Low molecule weight heparins (LMWH)
What is the issue with unfractionated heparin?
It is all the heparin together, not as predictable and only used within the hosptial
What is the benefit from using LMWH?
It is purified from unfractionated heparin, it inhibits 10a and is therefore more specific and predictable
-Can be used at home
-Less side effects
-Reduced frequency of dosing
Does heparin act quickly or slowly?
QUICK! - Short half-life- acts immediately
t1/2 40-90 mins
What is the MOA of warfarin?
It inhibits vitamin K reductase, and is a competitive inhibitor.
-Reduces synthesis of coag factors 2,7,10.
What effect does inhibiting vitamin k have?
It takes time to work, all people need different doses.
-It indirectly works on clotting therefore has no effect on pre-existing clots, only those that form after the effect of the factors decline.
