Anticoagulation

Question 1

What are Antiplatelet Drugs ?

Answer 1

Inhibit platelet function therefore primary haemostasis

Generally used to treat arterial disease and arterial thrombosis

Question 2

What are arterial thrombuses and their treatment ?

Answer 2

High pressure system can cause atherosclerosis plaque to rupture
-Since plaque thrombus is platelet rich aspirin and other anti-platelet drugs are used
-modify risk factors for atherosclerosis also advised

Question 3

Give examples of antiplatelet drugs

Answer 3

Aspirin
Clopidogrel
Prasugel
Ticagrelor
Abciximab
Tirofiban

Also vWF inhibitors

Question 4

How does aspirin work ?

Answer 4

Inhibits COX-1 so decreased thromboxane production
-Affects platelets for the life span of the platelet
-Used for Stroke, ACS, IHD, PVD
-Major side effect is bleeding, particularly GI
-Avoid in children due to Reye’s Disease

Anti-platelet

Question 5

Give examples of P2Y12 Receptor antagonists

Answer 5

Irreversibly - Clopidogrel, Prasugel
Reversibly – Ticagrelor

Anti-platelet

Question 6

What do P2Y12 Receptor antagonists do ?

Answer 6

Antagonists block the g-coupled protein receptor for GCPR for ADP
-ADP binding decreases cAMP levels; Leads to activation of Glycoprotein (GP) IIb-IIIareceptors
-Commonly used in Stroke or IHD, often in combination with aspirin (“dual antiplatelet”)
-Metabolism by CYP enzymes and can affect efficacy; genetic testing

Blocking the P2Y₁₂ receptor directly causes antiplatelet effects.

Question 7

Give examples of GP IIb-IIIa inhibitors

Answer 7

-Potent antiplatelet agents
-Intravenous administration
-Typically in angioplasty

e.g. Abciximab (Can cause very severe thrombocytopenia) and Tirofiban

Question 8

What is Glannzmans Thromboasethenia ?

Answer 8

Rare genetic disorder affecting GPIIb-IIIa receptors; Severe bleeding disorder
-Loss of one of the two integrins

Question 9

What are GP IIb-IIIareceptors

Answer 9

Glycoprotein IIb-IIIa receptors
-Facilitate platelet aggregation via fibrinogen binding

Question 10

How are the function of antiplatelets reversed ?

Answer 10

No specific antidotes; Stop antiplatelet agent
Tranexamic acid in some situations

(Some evidence that donor platelet replace cooked from aspirin platelets)

Question 11

What is Von Willebrand Disease ?

Answer 11

Deficiency of vWF

Treatments:
Can replace vWF with recombinant or plasma derived vWF
DDAVP (synthetic desmopressin) increased secretion of vWF stores from endothelial cells

Question 12

What are Anticoagulants ?

Answer 12

Medication that inhibit fibrin clot formation
-Generally used to treat venous thrombosis and AF (atrial fibrilation)

Question 13

What is Venous thrombosis ?

Answer 13

Occurs in Low pressure system

Virchow’s triad; Stasis, vessel wall, hypercoaguability make them more likely

Treatment – heparin/warfarin/new oral anticoagulants

Stasis can be from placenta pressur

Question 14

What is Unfractionated heparin ?

Answer 14

Potentiates the effects of Antihrombin; Inhibits thrombin and FXa
-Mixture of glycosaminoglycans of various molecular weights (5000– 250000 Daltons)
-Needs a lot of monitoring during treatment

Anticoaglant

1 unit of heparin is the amount of the preparation required to keep 1ml of cat’s blood liquid for 24 hours at 0oC

Question 15

How is unfractioned herparin reversed (e.g. if causing bleeding) ?

Answer 15

Short half life; stopping infusion and supportive measures are often sufficient
Protamine can be used but seldom is

Question 16

What is low molecular weight heparin ?

Answer 16

-2000 – 8000 Daltons
-Subcutaneous administration; Once or twice daily
-Longer half life than UFH
-Lower risk of Heparin Induced Thrombocytopenia

Question 17

How is low molecular weight herparin reversed (e.g. if causing bleeding) ?

Answer 17

Protamine offers partial reversal

Question 18

What is a side effect of heparin use ?

Answer 18

Heparin induced thrombocytopenia (HIT)
-Reduces platelets but remaining ones are hyperactive so is a thrombotic condition (Concern is thrombosis not bleeding)

Treatment
-Stop Heparin
-Need alternative anticoagulation
-Avoid future heparin exposure

Question 19

What are common examples of anticoagulants ?

Answer 19

Heparin and warfarin

Question 20

What is warfarin ?

Answer 20

An anticoagulant
Inhibits VKOR
-Decreases carboxylation and activation of Factors II,VII,IX & X; vitamin K is a co-factor of this
-Used to treat strokes and AF
-Once daily dosing, monitored by INR

Low vit K causes bleeding

Question 21

What is INR ?

Answer 21

Measure of length of time for blood to clot

INR = International normalised ratio
PT = prothrombin time
ISI = International Sensitivity Index

Question 22

How is Warfarin reveresed (i.e. if bleeding) ?

Answer 22

Warfarin has a bleeding risk
Give them vitamin K; Oral or IV
-Allows synthesis of new coagulation factors
-Slow action; Minimum time to effect 6 hours & more likely 12-24

Give them PCC
-Contains FII, FVII, FIX & FX; Rapid reversal of anticoagulation
-Short half life
-Thrombotic Risk in 1-2% of patients

Are often used together

Question 23

What are Direct Oral Anticoagulants ?

Answer 23

Have replaced heparin/warfarin for most things
-Targeted treatments
-No need for monitoring; Single dose
-Less interactions; Effective and likely safer
-Typically renally excreted; Issue for CKD

Question 24

How is bleeding from a direct oral anticoagulant treated ?

Answer 24

Andexanet-Alfa
-Recombinant modified FXa

Idarucizumab
-Used for dabigatran, a direct thrombin inhibitor

Question 25

What is Tranexamic Acid

Answer 25

Widely used antifibrinolytic -Used to treat heavy periods and post-partum bleeding