Heamostasis and thrombosis Flashcards
What is a two level wells score? And a D-Dimer test?
A scoring system that measures chances of DVT-it isnt a clinical investigation but a survey that checks how likely they are to have it
D-dimer test-check how well the fibrin is coagulation/working
What are the factor presents in initial stages of thrombus formation on the molecular level?
Mostly theories-but good ideas exist
Inital stages-
Tissue factor exist on blood cells (not erythrocytes)-TF presenting cells => activate the Prothrombinase complex (FX and FV)
Prothrombinase activates-> activates prothrombin to Thrombin (FIIa) –initiation phase of the 3 stage coagulation
Antithrombin (AT-III) inactivates FIIa and FXa
How can anticoagulants target the main players of the initial phase of thrombus formation? Which coagulants do what
Anticoagulants-used here as a term to describe drug that treat thrombosis
Dabigatran-inhibits FIIa - direct acting oral coagulant (novel)
Rivaroxiban-inhbits FXa-oral
(oral matters because easy to give + compliance)
Increase activity of AT
Heparin-activates AT (IV infusion)
Low molecular weight heparin (eg: Dalteparin)-activate AT (Subcutaneous)
Act fast
Warfarin-Vitamin K antagonist-inhbits the factor used to generate FII/VII/XI/X
Onset is slow-good prophylaxis
Which drugs would you want to give to a patient with recently diagnosed DVT?
Once diagnosed-
Low molecular weight heparins - give immediately (and works fast)-
Then maintenance treatmant with oral anticoagulant (tends to be rivaroxiban and warfarin)
=> but in many cases, the danger isnt the DVT but the thrombus detatching and causing PE (doesnt always happen but can)
What is the pharmacological treatment given for a patient when a DVT has become a PE?
PE is a lot more serious but treatment is quite similar
Once diagnosed- give Heparin or Low molecular weight Heparin . for immediate action (in hospital setting)
And maintenance treatment with oral anticoagulants
What increases the likely hood of thrombus formation?
Virchows triad
1) Rate of blood flow (higher better)-so when immobilised-leg blood flow is reduced
2) Consistency of blood (balance of coagulant and anticoagulation factors)-usually more genetic
3) Blood vessel wall integrity (damaged endothelial)-likely when surgery and/or hypertension
What are the anti-coagulants used as anti-platelet therapy? What is one important use of them?
Aspirin and Clopidogel
Used in treatment of white thrombus (tend to be in artery)-important in NSTEMI (also used in STEMI) (red thrombus tend to be in veins)
What are the main players in the amplification stage of thrombus formation at the cellular stage?
Initial stage ends with FIIa
This tends to activate platelets - (changes shape, becomes sticky and attatches to other platelets) => platelets move to thrombus and start blocking
how does platelets activate?
Platelets have Ca stores
And have proteases activated receptors on surface (activated by FIIa)-causes release of Ca => causes release of ADP from dense granules out of cell (and cause stellar appearance of platelet)
ADP activates P2Y12 receptors on other platelets (paracrine/autocrine)-activates platelets and aggregation
Activation activates COX-(liberate Arachidonic acid)-COX generate TXA2
Glycoprotein GpIIb/IIIa also plays role in their aggregation-activated by TXA2
What are the main mechanism of action of the main anti-coagulant drugs?
Clopidogel-P2Y12 receptor antagonist-oral
Aspirin-Oral-irreversible COX-1 inhibitor (lower dose prefered)-stops from GpIIb/IIIa activation to stop aggregation
Abciximab-monoclonal AB that targets GpIIb/IIIa and inhbits it- limited used (only by specialists)
Why cant you just give anti-coagulants in stroke?
because stroke symptoms can come from an occlusion stroke (use anti-coagulants then) or a hemmorghaghic stroke- (need the exact opposite/drainage
What are the main treatment options of ischeamic strokes? Why is it different from MI?
Thrombolytic therapy-destroy the clot
tPA (eg: Alterplase)
In stroke-the thrombus is often formed within the heart and embolise up-so not “vein” or “artery” // white/red thrombus- its neither
Also lodged in lumen, not wall/deeper
only way is to get rid of clot using blood factors
Anticoagulants here wont reduce size of clot-only prevent it from growing
What are the main players of the propagation stage of thrombus formation at a cellular phase?
Activated platelets-cause large scales thrombin production-large thrombin production causes net like structures to clot the bleeding
Anticoagulants here wont reduce size of clot-only prevent it from growing
Will be broken down with plasmin - protease that degrades fibrin
tissue Plasminogen activator (tPA)-activates plasmin-degrades the clot very fast
(can work too well and give excessive bleeding-high risk)
What is the main thrombolytic?
Recombinant tPA-Alterpase-activate plasminogen to plasmin- that will degrade the clot very fast
they are very efficient-can be too efficient and has high risk of causing excessive bleeding=> why really only used in emergencies (eg: ischeamic stroke)
Summarise when to use anti-coagulants, anti-platelets and thrombolytics? (give exemples of each)
Anticoagulants-in clots formed in veins (red thrombus) -rivaroxiban, warfarin, heparin)
Anti-platelets-in clots formed in Arteries (clopidogel, Aspirin, Abciximab)
Thrombolytics-when neither (Formed in heart) and need emergency removal (Alterpase (recombinant tPA))
