Clotting and Drug Mechanisms ☺️

Question 1

Primary haemostasis

Answer 1

Vessel wall damage => reflex VC

• endothelium constantly produce prostacyclin to prevent platelets from activating
• prostacyclin release interrupted when damaged

Collagen + vWF revealed to platelets => adhere and activated => aggregation (ADP), VC (seretonin, thromboxane
Form plug via fibrinogen receptors activated by ADP

Question 2

Antiplatelet drug target sites

-examples

Answer 2

Aspirin

• COX1 inh => inh thromboxane formation
• CO2 inh => inh inflammatory, analgesia at higher doses

Clopidogrel, prasugrel, ticagrelor
P2Y12 => inh ADP and prevent aggregation

Specialist use
GP2b3a => inh

Question 3

Secondary hemostasis

• extrinsic pathway = outside vessels
• instrinsic pathway

Answer 3

Blood, factors leaks out of vessels
TF found on damaged cells
-TF + 7 => 10 => 2 thrombin => 1 via activated platelet

Thrombin triggers intrinsic and activates more platelets
12 => 11 => 9 => 8 => 5 => 10 => 2 => 1

APC => degrades 5, 8

Question 4

Breakdown of clots

Answer 4

tPA binds to fibrin => plasminogen -> plasmin => clot breaks down

Question 5

Anticoagulant drug target sites

Answer 5

Heparin (IV) - antithrombin activator => inactivates Xa, thrombin

Fondaparinux - sim to heparin

Warfarin - 1(0)972 production slowed

DOAC

Question 6

Fibrinolytics
-drug target sites

Antifibrinolytics
-drug target sites

Answer 6

Lyse arterial thrombus (PE, stroke within 4.5hrs of onset)
Streptokinase - binds, activates plasminogen
Alteplase - binds to fibrin+plasminogen

Tranexemic acid - inh plasminogen

Question 7

Antiplatelet use

-post ACS

Answer 7

High dose (often in ambulance) followed by maintenance
1ST LINE - Aspirin 300mg STAT => 75mg OD
2ND LINE - any others

NSTEMI => Clopidogrel 300-600mg STAT => 75mg OD
Prasugrel 60mg STAT => 10mg OD
Ticagrelor 180mg STAT => 90mg BD

Question 8

Differences between clopidogrel, prasugrel, ticagrelor

Answer 8

Clopidogrel

• irreversible prodrug
• lowest bleeding risk

Prasugrel

• irreversible prodrug
• highest bleeding risk

Ticagrelor

• reversible active
• mid bleeding risk

Question 9

Contraindications to AP

Relative bleeding risks

Answer 9

CI

• active bleed
• GI ulcer

Aspirin has greater GI bleed risk

Dual AP => high risk
Triple therapy (Dual + AC) => greatest risk

Question 10

GI protection with DAPT

Answer 10

1st line - ranitidine 300mg OD
-150mg BD in eGFR U60

Clopidogrel - PPI (pantoprazole in clopidogrel - has lowest risk of CYP interaction)
-omeprazole interacts with clopidogrel metabolism (CYP)

Question 11

When to use triple therapy

Answer 11

When they have indications for both AC and AP use

Question 12

Warfarin indications

Answer 12

Prophylaxis of

• embolus in rheumatic HD, AF
• prosthetic heart valve
• VTE
• APS clots

Treat

• VTE
• TIA

Question 13

Properties of warfarin

• onset
• INR based on indications
• duration of dosing

Answer 13

Slow onset => peaks at 3-4 days
-needs bridging therapy
Variable dosing based in INR
Affected by lifestyle factors, illness

INR ranges
AF, DVT, PE, TIA - 2-3
Mechanical prosthetic valve - depends on type (2.5-4)

Test

• once stable - every 3 months
• new - daily and increase gap

Duration

• lifelong for lifelong indications
• PE+DVT - 3-6 months

Question 14

DOACs

• MOI
• half life, speed of action

Answer 14

Apixaban, rivaroxaban, edoxaban - direct Xa inh
Dabigatran - direct thrombin inh

Short T1/2
Immediate action, rapid peak
No bridging needed

Rivaroxaban with food

Dose depends on liver, renal, platelets, weight

Prevent
-stroke in non valve AF

Manage
-acute VTE, long term/post hip knee replacement prophylaxis

No monitoring needed

Question 15

AF dosing

Answer 15

May take dose down based on age, weight, renal function
Calculate with Cockroft Gault equation
-actual BW