Lecture 2: Haemostasis Flashcards
What does von willebrand factor do?
Secreted by the endothelium when it is injured
How many platelets come from a single megakaryocyte?
4000
How big are platelets?
3uM by 0.5uM
What happens when platelets are activated?
exocytosis, change of shape, increased respiratory rate
Adhesion- to exposed collagen
Activation- exocytosis of dense granules, serotonin, ADP and Ca
Aggregation- stimulated by ADP by fibrinogen (blocked by prasugrel)
How are platelets activated?
Extracellular ADP –> activation of P2Y receptor –> cation flow
Platelets release thromboxane A2 (vasoconstrictor)
ADP is positive feedback
What is the difference between plasma and serum?
Plasma is the fluid portion of blood, whereas serum is the fluid remaining after clotting
Overview intrinsic vs extrinsic cascades
Extrinsic- tissue factor pathway- requires TF to occur- initiation of coagulation
Intrinsic- contact activation- all factors are already in place- amplification of the process through positive feedback
What factors activate thrombin?
Xa and Va
How is factor X activated to Xa?
Extrinsic Xase (TF and factor VIIa)
Intrinsic Xase (factor VIIIa and factor IXa)
Thrombin
What are the prothrombin group factors?
Factors II, VII, IX, X
These are enzymes, vitamin K needed for synthesis, require Ca for activation, stable
What are the thrombin group factors?
Factors I, V and VIII
Thrombin activates them, V and VIII are co-factors, factor I is fibrinogen, increased in inflammation, pregnancy and with oral contraceptives
What is plasmin?
Lyses fibrin - stops/destroys clots
Starts as inactive plasminogen (made by liver)
Requires tissue Plasminogen activator (tPA) to mature - tPA is on the surface of endothelial cells
What is protein C?
Coagulation inhibitor
Starts as inactive enzyme, made in the liver, activated on the surface of endothelial cells
Inactivates factor Va and VIIIa
Works with co-factor protein S to inactivate Va
What is antithrombin III?
Peptide made in the liver
Blocks the activity of thrombin (and of Xa and IXa)
Heparin –> increases ATIII activity
Overview of vitamin K deficiency
Results in clotting insufficiency
Rare bc vit K made by bacteria of large intestine and in leafy green vegetables
Caused by GI disease or no fat absorption: liver disease –> no bile salts
Warfarin prevents recycling of vit K
What causes haemophilia A?
Lack of factor VIII
haemophilia B - lack of factor IX
What are the anti-platelets?
Prevent clotting in the arteries
Asprin: COX inhibitor, blocks formations of thromboxane A2 in platelets, lengthens bleeding time, doesn’t increase coagulation time
ADP inhibitors: prasugrel/clopidogrel
What are the anti-coagulants?
Prevent clotting in the veins
Heparins: inhibit coagulation (with ATIII) by inhibiting factor Xa
NOACs: dabigatran (thrombin inhibitor) and rivaroxaban (factor Xa inhibitor)
Warfarin: vitamin K antagonist, slow onset, requires monitoring
What are the fibrinolytics?
Clotting in arteries (high pressure)
tPA, streptokinase, urokinase
