Haemostasis Flashcards
Primary Haemostasis- Platelets basic structure and how they’re made
platelets are non-nucleated made by fragmentation of megakaryocyte cytoplasm. They become rounded and have spinucles when they are activated
Primary Haemostasis- Adhesion, describe the direct adhesion, where the platelets attach to and how
platelets stick directly to injured endothelium via GPIa receptor to collagen
Primary Haemostasis- Adhesion, indirect adhesion, what is involved and how it happens. Discuss VWF
adhesion occurs via VWF which binds to GPIb receptor. Von Willebrand factor is a GP made by endothelial cells and it mediates adhesion and aggregation, carrier for factor VIII
Primary Haemostasis- Platelet release action, what is released and how
platelet membrane is invaginated to form a surface connected canalicular system in which granules (a-granules/dense granules), ADP, fibrinogen and VWF are released
Primary Haemostasis- Thromboxane A2, what it is and how it’s made
Thromboxane A2 is used is platelet aggregation and is a prostaglandin made from arachidonic acid(cyclo-oxeganse)—->cyclic endoperoxides—->TA2(T synthetase)/prostacyclin PGI2 (prostacyclin synthetase) which is a powerful vasodilator and suppresses platelet activation
Primary Haemostasis- Platelet Aggregation, what molécules and chemicals cause aggregation
release of ADP and TA2 bind respectively to P2Y12 and TA2 receptor, this is positive feedback and activates platelets. This activation causes confrontational change in GPIIb receptor to allow fibrinogen to bind. This causes further activation of platelets and fibrinogen links platelets together to form plug
Primary Haemostasis- Anti-platelet drugs
Aspirin- blocks action of cyclo-oxygenase, reducing platelet aggreg, non nuclear platelet cannot make more COX but endothelial cells can so PGI2 is still made
Clopidogrel- blocks P2Y12 so ADP can’t bind
Secondary Haemostasis- Where are clotting factors made, how are they activated and why is this needed
- clotting factors made in liver except VWF and VIII.
- factors II, VII, IX, X rely on vitK for carboxylation of their glutamic acid residues, essential for function.
- coagulation is multi step, in each stage a inactive zymogen turn into active CF by exposure of AS, factor V and VIII are co factors, CF work on phospholipid surface of platelets, Ca2+ needed for binding of CF to phospholipid
Secondary Haemostasis- talk about initiation phase of clotting
Tissue factor (TF) is exposed on site of injury, it binds to VIIa, activating IX to IXa and X to Xa, leading to activation of prothrombin (II) to an initial small amount of thrombin (IIa)
Secondary Haemostasis- discuss amplification phase of clotting
small amount of thrombin mediates activation of co-factor V and VIII, factor XI and platelets
Secondary Haemostasis- discuss propagation phase of clotting
factor XI converts more factor IX to IXa which along with VIIIa, amplifies conversion of X to Xa=rapid burst in thrombin generation, this cleaves circulating soluble fibrinogen to insoluble fibrin clot
Anti-Coagulation: what proteins are involved in this process and how are they activated
proteinC, proteinS and antithrombin.
- thrombin binds to thrombomodulin on endothelial cell surface leading to activation of proteinC=APC, this inactives V and VIII, in presence of co-factor protein S.
- thrombin and factor Xa are inactivated by antithrombin
Anti-Coagulation drugs- heparin, warfarin, and direct oral anticoagulants
Heparin- works indirectly by potentiating action of antithrombin by wrapping of longer heparin chains around T and AT
Warfarin- VitK antagonist that interferes with protein carboxylation on factors II, VII, IX, X, tablet, effect needs to be monitored, several days to take effect
DOAC’s- directly inhibit thrombin or factor Xa
