Haemostasis and Thrombosis

Question 1

What is the initially series of events in thrombosis

Answer 1

Tissue factor production
TF activates FX and V – prothrombinase complex
Activates FII to FIIa

(Antithrombin III produced – inactivates IIa and Xa, to try and rate limit)

Question 2

What drugs target the earliest stages of thrombosis?

Answer 2

Dabigatran 
Rivaroxaban
Heparin 
Low molecular weight heparin (E.g Dalteparin) 
Warfarin

Question 3

How does dabigatran work?

Answer 3

Oral FIIa inhibitor (can cause serious GI bleeding leading to death so isn’t really used)

Question 4

How does rivaroxaban work?

Answer 4

Oral FXa inhibitor, may also cause GI bleeding but lower risk than a FIIa inhibitor

(Apixaban also used in this way)

Question 5

How do heparin and low molecular weight heparins work?

Answer 5

Activates AT-III (usually given IV, can be SC)

Low weight heparins have same effect but are normally delivered SC not IV and may also interact with FXa directly

Question 6

How does warfarin work?

Answer 6

Vitamin K antagonist, prevents production of FXa and FII among others as they are vitamin K dependant

Question 7

What is the basic treatment guideline for DVT?

Answer 7

Use the drugs targeting early stages of thrombosis

Parenteral used acute, oral used for long term maintenance. Generally warfarin used but sometimes rivaroxaban used instead. Warfarin cheaper but has more side effects and interactions. Rivaroxaban carries risk in internal bleeding.

Question 8

What is the basic treatment guideline for PE?

Answer 8

Same as DVT, however heparin now also indicated due to the increased risk.

Question 9

What is Virchow’s Triad?

Answer 9

Thrombosis factors (NOTE: NOT LITERAL CLOTTING FACTORS)

Rate of blood flow, consistency of blood (constituency of coagulants and anticoagulants), blood vessel wall integrity.

(These Generally, applies to veins not arteries)

Question 10

What are NSTEMIs and STEMIs?

Answer 10

NSTEMI – Non-ST elevated MI, presents with shortness of breath, dizziness and chest pain. No ECG change but elevated troponin. Caused by partial occlusion due to white thrombus

STEMI - ST elevated MI, same symptoms - more severe and ECG changes seen. Caused by full occlusion due to white thrombus

Question 11

How are platelets involved in thrombosis?

Answer 11

Thrombosis amplication – Thrombin activates platelets, they become sticky and stellate due to binding to Protease-activated receptor (PAR) on its surface.

Cause Ca2+ release from stores – Ca2+ exocytosis of ADP from dense granules

ADP binds to P2Y12 on platelets – activates COX and liberates AA to generate TXa2 from AA (arachidonic acid)

TXA2 activation leads to expression of GPIIb/IIIa integrin receptors on platelet surface – involved in further aggregation

Question 12

What drugs target platelet aggregation?

Answer 12

Clopidogrel
Aspirin
Abciximab

Question 13

How does clopidogrel work?

Answer 13

P2Y12 antagonist (oral), prevent ADP binding

Question 14

How does Aspirin work?

Answer 14

Irreversible COX-1 inhibitor (oral) - note, this is the only irreversible one

Question 15

How does Abciximab work?

Answer 15

IV, SC monoclonal antibody antagonist against GPIIb/IIIa used only by specialists, third line treatment

Question 16

Why are CT scans done in suspected strokes?

Answer 16

To determine if ischaemic or haemorrhagic - Treating a haemorrhagic stroke as if it were ischaemic will kill the patient so you have to know before beginning treatment

Question 17

What drugs are used only in severe situations such as stroke and STEMIs? Why?

Answer 17

Thrombolytics, these are the only class of drug that break down pre-existing clots but are extremely dangerous and carry large risk of internal bleeding so must only be used when benefit to patient would be greater than risk.

Question 18

What is an example of a thrombolytic drug?

Answer 18

Alteplase IV - a recombinant tissue type plasminogen activator (rt-PA)

Plasmin dissolves stable fibrin clots