coagulation Flashcards
what is haemostasis
arrest of blood loss from a damaged vessel at the site of injury
what is involved in the sequence of haemostasis
- vascular wall damage which exposes collagen and tissue factor
- primary haemostasis
- activation of blood clotting and formation of a stable clot
what is involved in primary haemostasis
local vasoconstriction
platelet adhesion, activation, and aggregation by fibrinogen
what do activated platelets release
thromboxane A2 (TXA2)
what does TXA2 bind to, what does this cause
- platelet GPCR TXA2 receptors (TP receptors) which causes mediator release
- vascular smooth muscle cell TXA2 receptors causing vasoconstriction
what mediators are released by TXA2 binding
5-HT (aka serotonin)
ADP
what does ADP bind to in primary haemostasis, what does this cause
platelet GPCR purine receptors (P2Y12)
binding causes: further platelets to be activated, aggregation of platelets into a ‘soft plug’, and exposure of acidic phospholipids on the platelet surface that initiates coagulation of blood and solid clot formation
describe the coagulation cascade
X is converted to Xa + Va (together known as prothrombinase) by IXa and VIIIa (together known as tenase). prothrombinase then converts II (prothrombin) to IIa (thrombin). thrombin then cleaves fibrinogen to form fibrin (solid clot)
what is thrombosis
pathological haemostasis, a haematological plug in the absence of bleeding
what is an arterial thrombus
mainly platelets in a fibrin mesh
what is an arterial thrombus also known as
a white thrombus
what does an arterial thrombus form if it detaches
an embolus which then lodges in an artery (causing stroke) or other organ
how is an arterial thrombus treated
antiplatelet drugs
what is a venous thrombus
white head, jelly-like red tail.. fibrin rich
what is a venous thrombus also known as
red thrombus
what does a venous thrombus form if it detaches
an embolus that usually lodges in the lung
how is a venous thrombus treated
anticoagulants
what drug works on factor X
warfarin
what drug works on factor II
warfarin
what drug works on factor Xa
orally active inhibitors
heparin/LWMH/fondaparinux
what drug works on factor IIa
orally active inhibitors
heparin/LWMH/fondaparinux
what is warfarin’s mechanism of action
inactivates factors II, VII, IX, and X
how is warfarin administered
orally
what is used to treat an warfarin overdose
vitamin K (as phytomenadione)
what is orally active inhibitor’s mechanism of action
directly inhibit thrombin or factor Xa
give an example of an orally active inhibitors
dabigatran (inhibits thrombin)
rivaroxaban (inhibits factor Xa)
what is the mechanism of action of heparin
inhibits factors Xa and IIa
what is the mechanism of low molecular weight heparin (LWMH)
inhibits factor Xa
what are the serine proteases in the coagulation cascade
VIIa
IXa
Xa
what does anti-thrombin III (ATIII) do
important inhibitor of coagulation as it neutralised ALL serine protease factors in the coagulation cascade
explain the link between heparin and ATIII
heparin binds to ATIII which increases its binding affinity especially for factors Xa and IIa which increases their rate of inactivation
how does heparin inactivate IIa
by binding to ATIII AND factor IIa
how does heparin inactivate Xa
by binding to ATIII
what are anticoagulants used to treat
AF
DVT
post-op thrombosis
patients with artificial heart valves
give examples of low molecular weight heparin (LMWH)
“-parin”
fondaparinux “-pariniux”
how is LMWH administered
subcutaneously (SC) = injection
how is heparin administered
IV = immediate onset of action SC = onset delayed by 1 hour
when is heparin preferred over LMWH, why?
renal failure
LMWH is excreted via the kidneys, heparin is not
what is given in if a heparin haemorrhage has occurred
protamine sulfate IV
what are anticoagulants used for
venous thrombosis
what are antiplatelets used for
arterial thrombosis
give examples of antiplatelets
aspirin
clopidogrel
tirofiban
what is the mechanism of action of clopidogrel
links to the P2Y12 receptor via disulphide bond producing irreversible inhibition
when would clopidogrel be used
most often given in patients intolerant to aspirin
what is the mechanism of action of aspirin
irreversibly blocks cycloxygenase (COX) in platelets preventing TXA2 synthesis
also blocks COX in endothelial cells inhibiting production of antithrombotic prostaglandin I2 (PGI2)
what cascade opposes the coagulation cascade
fibrinolytic cascade
describe the fibrinolytic cascade
plasminogen is converted to plasmin via endogenous tissue plasminogen activator (tPA). Plasmin then converts fibrin to fibrin fragments which are involved in clot lysis
where do fibrinolytic drugs act
act on the conversion on plasminogen to plasmin
give examples of fibrinolytic drugs
streptokinase
alteplase
duteplase
what is streptokinase
a protein extracted from strep cultures
when is streptokinase contraindicated
in a patient with a recent strep infection or an allergy
what are alteplase and duteplase
recombinant tissue plasminogen activators (rt-PAs)
how can haemorrhage caused by alteplase or duteplase be treated
oral tranexamic acid which inhibits plasminogen activation
