Haemostasis Flashcards
Haemostasis what
arrest of blood loss from damaged vessels. Platelets aggregate become stabilized by fibrin and arrest bleeding from severed vessels
Thrombosis what does it cause
Formation of occlusive thrombi lead to MI, ischaemic stroke
Draw flow diagram for the vascular control of platelet function
ref. notes and include mediators
Process of platelet plug formation
damage to blood vessel->exposure of platelets to collagen and vWF in extracellular matrix and exposure to thrombin->platelets adhere and activate->release of mediators->vasoconstriction+aggregation of platelets->formation of soft platelet plug
Extrinsic and intrinsic pathway cascade draw flow chart
ref. notes 7a:TF, Va:Xa, (vwf:VIII), VIIIa:IXa, Va:Xa
What does thrombin activate
FV, VIII, IX, X takes place on activated platelets. Changes shape of platelet
Initiation where
TF-expressing cells in tissues after blood, with its clotting factors leak out of the blood vessels
3 categories leading to thrombosis
Stasis, vessel wall injury, hypercoagulability
Arterial thrombosis
white clots, usually associated with atherosclerosis, form at site of vascular injury, disturbed blood flow. Large platelet component. Antiplatelet drugs. MI and strokes
Venous thrombosis
stasis/turbulent flow of blood, vascular injury, hypercoagulability of blood. Platelet component, large fibrin component and RBC. Anticoagulants.Pulmonary embolism
what do you have to make sure when treating thrombosis
balance clot formation risk and risk of haemorrhage
Antiplatelet drug what does it do and example
limits growth/decreases risk of arterial thrombosis. aspirin, P2Y12 antagonists, GPIIb-IIIa antagonists
Aspirin what does it do
irreversible inhibition of COX-1 which prevents production of TXA2 (potent platelet agonist, vasoconstrictor, mitogen) but PGI2 production not affected because COX-2 can be produced. TXA2/PGI2 PGI2 action dominates
GPIIB-IIIa antagonist
Fab fragment (Abciximab, tirofiban), small molecule inhibitor (eptifibatide), use i.v. very potent block restenosis following angioplasty, inhibits aggregation. Major thrombocytopaenia risk
Anti platelet drug use
Mostly secondary prevention, block restenosis following angioplasty. But multiple pathways to platelet activation limit effect of specific inhibition. So sometimes dual therapy e.g. aspirin+clopidogrel
Anticoagulant and fibrinolytic therapy
Inhibit coagulation cascade, prevent propagation of blood clot but do not dissolve clot. Heparin, warfarin
What does intrinsic system comprise of
XII, XI, IX, VIII, X
What does intrinsic system comprise of
XII, XI, IX, VIII, X
What does thrombin accelerate
XI, VIII, XIII (fibrin stabilising factor), V,
What happens when thrombin+thrombomodulin
Protein C->Ca+protein S degrade Va and VIIIa
What happens when thrombin+thrombomodulin
Protein C->Ca+protein S degrade Va and VIIIa
How does fibrinogen turn into blood clot
Fibrinogen (thrombin)->fibrin monomers (Ca2+)->fibrin polymers(FXIII)->blood clot
What does heparin inhibit
Intrinsic system production of serine-protease factors (XIIa, XIa, IXa, Xa, thrombin) by direct method and potentiation of plasma serine-protease inhibitor and antithrombin III
Unfractioned heparin Pro+cons
Pro: effective, cheap, short half life, reversible with protamine
Con: continuous infusion, variable bioavailability, monitoring required, haemorrhage
Low molecular weight heparin pros+cons
Pro: bioavailability increase, T1/2 increase, risk of HIT decrease
Con: expensive, partial reversal with protamine, haemorrhage
Factor Xa inhibitor how administered
Injection (fondaparinux, indraparinux) act indirectly via antithrombin I.v or s.c. (100% bioavailability), more predictable PK than heparin), HIT rarely observed (does not bind to PF-4), superior to LMWH
Oral (rivaroxaban, apixaban) directly inhibit FXa, favourable safety does not require frequend blood monitoring
Thrombin inhibitor how administered
block active site of thrombin, both clot bound and free. i.v (hirudin, lepirudin, lepirudin, desirudin), = effective LMWH, used for anticoagulant therapy of patients with HIT
Oral (dabigatran) as erffective as warfarin, less chance of haemorrhage
How to prevent inappropriate clot formation
Endothelial cell NO and prostacyclin (inhibit platelet activation+aggregation), Tissue factor pathway inhibitor (inactivates and forms a complex with Factor Xa which inactivates TF-VIIa complex), APC (activated by thrombin-thrombomodulin with co-factor protein S inactivating Factor Va VIIIa), antithrombin (activated by heparan and heparin, inactivates thrombin, IXa, Xa, XIa and XIIa when not in clot or combined with prothrombinase
Draw out the relations between APC, fibrinolysis, plasmin
ref. notes
Draw flow chart fibrinolytic system
tPA- bound to fibrin->plasminogen->plasmin->clot breaks into soluble fragments.
Fibrinolytic purpose, risk, how administered, antidote, examples
activate plasminogen, high risk of haemorrhage, i.v infusion, severe haemorrhage treated with transexamic acid, streptokinase=bind and activate plasminogen-> plasmin, Alteplase=only activvate plasminogen bound to fibrin in thrombus
