Drugs affecting haemostasis and thrombosis Flashcards
To list the drugs used to modify blood coagulation
Tranexamic Acid
Warfarin
DOACs
Heparin
Aspirin
Clopidogrel
Thrombolytic drugs
Function of drugs used to modify blood coagulation
Drugs that :
- Help clot the blood
- Prevent/slow the clotting of blood
- Modify platelet function
- Help clot removal
Where are platelets derived from ?
Megakaryocytes in marrow
Fresh frozen plasma
Contains coagulation factors in normal proportions
Dose 15ml/kg
Cryoprecipitate
Pools of 5 donations using precipitate at 4C - concentrated fibrinogen, von willebrand factor and VIII
Specific coagulation factors
IX
VIII (donor derived or recombinant)
Fibrinogen
What is tranexamic acid ?
Anti-fibrinolytic drug (inhibits the process that dissolves clots)
Taken orally/IV
Describe the method of action of tranexamic acid
Inhibits the activation of plasminogen to plasmin
Used in trauma/GI bleeding/ post-op or delivery
Tranexamic acid
When is it effective ?
Effective if given within 3-4 hours
Method of action of warfarin
Inhibits the production of vitamin K in its reduced form.
Effect measured by prothrombin time - venous/capillary sample
Positive aspects of warfarin
Established for decades
Cheap
Easily measurable effects
Can be reversed with Vitamin K or factor concentrate
Negative aspects of warfarin
Lots of drug and food interactions to enhance or inhibit effect.
Slow onset- several days
Unpredictable dose needed
Needs regular blood testing
Risk of bleeding
Narrow therapeutic window
State the drugs that increase the effect of warfarin
Amoxycillin
Erythromycin, Statins
Aspirin, Clopidogrel, NSAID’s
Amoxycillin
(increase the effect of warfarin)
Reduces gut Vitamin K
Erythromycin, Statins, Acute Alcohol intake
(increase the effect of warfarin)
Enzyme Inhibition
Aspirin, Clopidogrel, NSAID’s
(increase the effect of warfarin)
Platelet function and GI mucosal damage
State the drugs that decrease the effect of warfarin
Rifampicin, Carbamazepine, Phenytoin, Chronic Alcohol intake
Rifampicin, Carbamazepine, Phenytoin, Chronic Alcohol intake
(decrease the effect of warfarin)
Enzyme induction
DOACs
Direct Oral AntiCoagulants
What are DOACs ?
Xa inhibitors
Direct thrombin inhibitors
Name some DOACs
Xa inhibitors
(Xa inhibitors)
Apixaban
Rivaroxaban
Edoxaban
Name some DOAC’s
Direct thrombin inhibitors
Dabigatran
State some points that favour warfarin
Established drug
Cheap- but needs monitoring
Can be reversed
Effect can be easily measured
Can be used with poor renal function
State some points that favour DOACs
No monitoring needed (except renal function)
Lower bleeding risk
As effective for stroke prevention
Reversible agents recently available (but expensive)
Short half life
State some key uses of oral anticoagulants
- Treatment of DVT and PE: short/long term depending on whether recurrent and/or provoked
- Arterial fibrillation to reduce stroke risk
State a use for warfarin ONLY
Prosthetic heart valve replacement (warfarin only)
State a use for DOACs ONLY
Prevention of DVT after planned hip and knee surgery
Stroke risk reduction in atrial fibrillation
Things to be aware of
Absolute and Relative risk reduction
Balance of risks and benefits
Risk score for thrombosis
State the stroke risk scoring system in AF
CHA2DS2 - VASc
CHA2DS2 - VASc
C - Congestive heart failure
H - Hypertension
A - Age >=75
D - Diabetes Mellitus
S - Prior stroke / thromboembolism
V - Vascular disease
A - Age 65-74
Sc - Sex category
What is the ORBIT score ?
For bleeding risk
When is the ORBIT scoring system used ?
Age >75
Renal Impairment
Co-prescription of anti-platelet drugs
Anaemia
Bleeding history
Mechanism of action of heparin
Binds to and activates anti-thrombin so reducing Xa and thrombin generation
Where is heparin found ?
Can be extracted from lung and liver
How is heparin given ?
IV infusion - immediate effects and wears off quickly
(un-fractioned half life <1 hour)
(LMW : half life approx 12hours )
How is heparin monitored ?
APPT plasma testing and dose adjusted
(IV heparin)
State a low molecular weight heparin
Dalteparin
Dalteparin
Used as a fixed dose for prophylaxis
No routine monitoring unless poor renal function, extreme body weight or pregnancy
Treatment and prevention of DVT/PE
What gives a measure of anti-coagulation ?
Anti-Xa levels
State some adverse side effects of heparin
Pain at site of injection
Increased bleeding risk
Osteoporosis with prolonged use
Heparin induced thrombocytopenia - antibody mediated 5-10 days into treatment
State the drugs to modify platelet function
Aspirin
Clopidogrel
Mechanism of action of aspirin
Causes irreversible inhibition of COX-1 so less thromboxane A2 production
Less platelet aggregation
Side effects of aspirin
Increases GI bleeding risk
Dyspepsia
Some effect in stroke prevention in AF
Uses of aspirin
Typically used after transient ischaemic heart attack or MI
Mechanism of action of clopidogrel
Inhibit ADP induced platelet aggregation
Used with aspirin to prevent recurrent myocardial infarction
Uses of clopidogrel
Used in ischaemic stroke and TIAs
Side effects of clopidogrel
Increased risk of :
- Dyspepsia
- GI bleeding
Duration of action of aspirin and clopidogrel
NO reversal agents, so effect will last the duration of platelet lifespan. (5-10 days )
What are thrombolytic drugs ?
Drugs to increase the activation of plasminogen to plasmin
Tissue plasminogen activators
Cause breakdown of fibrin and fibrinogen
Side effects of thrombolytic drugs
Increased bleeding risk in hours after dose
Alternative treatment to thrombolytic drugs
Stenting and Clot removal
