18: Haemostasis + Thrombosis Flashcards
What is a D-Dimer test?
When is it perfomed?
What are the consequences?
Test the break down products of Fibrin –> performed when susprected of thrombosis
•Positive D-dimer test - diagnosis of deep-vein thrombosis (DVT) –> interim treatment with parenteral anticoagulant
What is the Wellls score?
A score to determine someones likelyhood of having a thrombosis
What happens in the initiation stage of blood coagulation?
Oervall: there is a small scale thrombin production
- Tissue factor (III + VII) activates FX and FV. Together they form the prothrombinase complex
- Prothrombinase Complex (Xa+Va) activate prothrombin to Thrombin (II –> IIa)
Regulation occurs via Antithrombin
- inhibits IIa and Xa
What happens in the amplification state of blood coagulation?
Platelet activation & aggregation
FIIa activates the Platelets
What happens to the platelets during platelet activation? (overwiew)
2.Activated platelet
- Changes shape
- Becomes ‘sticky’ and attaches other platelets
Explain the process of platelet activation on a cellular level
Everything due to activation of PAR by Thrombin:
- ADP release
- Thrombin binds to protease-activated receptor (PAR) on platelet surface.
- PAR activation –> rise in intracellular Ca2+
- Ca2+ rise –> exocytosis of adenosine diphosphate (ADP) from dense granules
- ADP activates P2Y12 receptors–> platelet activation/ aggregation
- COX-activation
- PAR activation –> liberates arachidonic acid (AA)
- Cyclo-oxygenase (COX) generates thromboxane A2 (TXA2) from AA
- Glycoprotein IIb/IIIa receptor (GPIIb/IIIa)
- TXA2 activation –> expression of GPIIb/IIIa integrin receptor on platelet surface
- GPIIb/IIIa - involved in platelet aggregation
What happens when Thrombin binds to the PAR on platelets?
PAR= protease-activated receptor
leading to
- intracellular Ca2+ release
- triggers release of ADP
- Freeing of Arachidonic Acid
- Production of TxA2 by COX
What is the effect of ADP release from the platelet?
ADP activates P2Y12 receptors leading to platelet activation/ aggregation
What is the effects of COX activation in the plateley by thrombin binding to PAR?
- PAR activation –> liberates arachidonic acid (AA)
- Cyclo-oxygenase (COX) generates thromboxane A2 (TXA2) from AA
- TXA2 activation –> expression of GPIIb/IIIa integrin receptor on platelet surface
- GPIIb/IIIa - involved in platelet aggregation
What is the effect of TXA2 in the platelet?
- TXA2 activation ® expression of GPIIb/IIIa integrin receptor on platelet surface
- GPIIb/IIIa - involved in platelet aggregation
What are anticoagulants?
Drugs that directly target the initiation stage of blood coagulation
(Also used as expression for all anti-thrombosis/haemostasis drugs)
Name some direct-acting anti-coagulants and their MOA
- Dabigatran (oral)
- FIIa inhibitor
- Rivaroxaban
- FXa inhibitor
Which Drug inhibits FIIa?
Dabigatran
Which drug inhibits coagulation Factor Xa?
Rivaroxaban
What is the MOA of Dabigatran?
It is a FIIa inhibitor
What is the MOA of Rivaroxaban?
FXa inhibitor
What is the MOA of Heparin?
What is its ROA?
IV, SC
–> enhances the activity of Antithrombin II (indirectly decreases the acitvity of FII+ FX
Which drugs increae the activity of Anti-thrombin?
Heparin and low-molecular weight heparins (e.g. Dalteparin)
What is the MOA of LMWHs?
Low molecular weight heparins
- activate anti-thrombin III –> decrease activity of FX
- (also have some effect but overall less effect on IIa)
What is the MOA of Warfarin?
What is its ROA?
Oral administration
It is a Vit K antatgonist
- Vit K is needed for generation of FII, VII, IX and X
How do you treat a DVT?
Why?
- Immediate treatment with parenternal anticoagulants (e.g. Deltaparin)
- Maintainance with oral anticoagulants (Warfarin and Rivaroxaban)
–> Because it is a Red thrombus –> treatments are more effective
What is a red thrombus in compariston for a white thrombus?
Red thrombus–> mainly venous, coagulatied blood
White thrombus –> mainly arterial and have a high content of foam cells
What kind of treatments would you use to treat a reed vein thrombus?
Anti-coagulants like
- Heparin
- Dabigatran
- Rivaroxaban
- warfarin
–> All are prophylactic
What kind of drugs would you use to treat a white thrombus?
Anti-platelets like
- Clopidogrel
- Aspirin
- Abciximab
–> As prophylaxis!
What is the Difference between a STEMI and a NSTEMI?
How would they differn in the treatment?
The ST elevation on an ECG but often:
- STEMI: full occlustion of a Coronary artery
- NSTEMI: partial occlustion of a coronary artery
STEMI: Anti-platelet and thormbolysis
NSTEMI: Anti-platelet
What is the Virchows triad?
RISK FACTORS that make you more suspectible to DVT+ PE
- SLow rate of blood flow
- Imbalance between pro-coagulation & anticoagulation factors
- Damage to epithelial wall
What is the MAO of clopidogrel?
What is the ROA?
ROA: oral
- it is a ADP receptor (P2Y12) receptor antagonist
- –> prevents platelet activation + aggregation
Which drug is an P2Y12 receptor antagoinst?
Clopidogrel
What is the MOA and ROA of Aspirin?
ROA: oral
Irreversible COX-1 inhibitor –> Inhibit production of TXA2
NB: High doses no more effective BUT more side-effects
Which drug is an irreversible COX-1 inhibtor?
Aspirin
What is the MOA and ROA of Abciximab?
ROA: IV, SC
3.Prevent platelet aggregation, GP IIb, IIIa inhibition –> too effective
Limited use AND only by specialists
What are the commonly used Anti-platlet drugs?
- Aspirin–> COX-1 inhibitor
- Clopidogrel –> P2Y12 antagonsit
What happens during the Propagation stage of haemostasis?
Formation of a Fibrin Mesh
- IIa –> activates Fibrinogen into Fibrin (I –> Ia)
Explain the process of Thrombolysis
Thrombolysis can remove a pre-formed cloth:
- acitvation of plasminogen into plasmin (that degrades fibrin)
Explain the MOA and ROA of Alteplase
Thrombolytic drug:
IV administration
recombinant tissue type plasminogen activator (rt-PA)
acitivation of plasminogen into plasmin –> fibrin degradation
Which drug is a recombinant tissue type plasminogen activator (rt-PA)?
Alteplase
