Drugs Affecting Homeostasis and Thrombosis Flashcards
Which blood products can be used to help blood clot / prevent bleeding?
- Platelets - derived from blood donation
- Fresh frozen plasma - 200ml of plasma from blood donation. Contains coagulation factors in normal proportions. Dose = 15ml/Kg
- Cryoprecipitate - cooling of plasma to ~4℃ leaves behind a milky substance which contains concentrated fibrinogen, Von Willebrand factor and factors 8 and 9.
Describe the use of tranexamic acid.
- Helps blood clot and prevents bleeding.
- Anti-fibrinolytic drug
- Inhibits the activation of plasminogen to plasmin
- Oral or IV
- Used in trauma, bleeding, post operatively or post delivery.
- Clinical trial - effective only if given in first 3-4 hours. Did not cause an increase in thrombotic events.
Describe vitamin K-dependent clotting factors
What is the mechanism of action of warfarin?
Inhibits production of vitamin K in reduced form.
Compare and contrast the positive and negative aspects of warfarin use.
-
Positive aspects
- Established for decades
- Cheap
- Easily measurable effect
- Can be reversed with vitamin K or factor concentrate
-
Negative aspects
- Lots of drug interactions to enhance or inhibit its effect
- Slow onset - several days (3-6)
- Unpredictable dose need
- Needs regular blood testing
- Risk of bleeding
- Narrow ‘therapeutic window’
What are the drug interactions which increase the effect of warfarin?
- Amoxycillin - reduces absorption of gut vitamin K.
- Erythromycin, statins and acute alcohol intake - enzyme inhibition.
- Liver enzymes metabolise drugs so enzyme inhibition increase drug effect.
- Aspirin, clopidogrel, NSAIDs - increase bleeding risk; platelet function and GI mucosal damage.
What are the drug interactions which decrease the effect of warfarin?
- Rifampicin, carbamazepine, phenytoin, chronic alcohol intake - enzyme induction.
- Liver enzymes metabolise warfarin so increase in these enzymes decreases the effect of warfarin.
What are the indications for warfarin?
- Deep vein thrombosis (DVT) and pulmonary embolism (PE) - short- or long- term depending on whether recurrent and/or provoked.
- Prosthetic heart valve replacement.
- Atrial fibrillation to reduce stroke risk.
What are the factors to be aware of when prescribing warfarin to atrial fibrillation patients?
- Absolute and relative risk reduction (ie 2% vs. 50%).
- Balance of risks and benefits.
- Scoring risk of thrombosis (CHA2DS2-VASc) and bleeding (HAS-BLED).
What is the mechanism of action of direct oral anticoagulants (DOACs)?
- Xa inhibitors
- Prevent the activation of factor X (which allows prothrombin → thrombin) and therefore reduces clotting.
- Apixaban
- Rivaroxaban
- Edoxaban
-
Direct thrombin inhibitors
- Dabigatran
Compare and contrast use of Warfarin and DOACs.
- Favours Warfarin
- Favours DOACs
- Established drug
- Good trial evidence
- Cheap - but needs monitoring
- No monitoring needed
- Can be reversed
- Lower bleeding risk
- Effect can be easily measured
- As effective for stroke prevention
- Can be used with poor renal function
- Reversal agent for dabigatran
- Short half life
What is the mechanism of action of heparin?
Binds to and activates anti-thrombin, reducing Xa and thrombin generation.
What is heparin?
- Naturally occurring anticoagulant (discovered 1916).
- Can be extracted from lung and liver.
- Given as IV - unfractioned - half life <1 hour. Active the minute you give it and can be reversed by protamine.
- Or subcutaneously - low molecular weight - half life ~12 hours.
How is heparin monitored?
- IV heparin is monitored by APPT plasma testing and dose is adjusted.
-
Subcutaneous low molecular weight heparin (LMWH) such as dalteparin.
- Used as fixed dose for prophylaxis and weight adjusted dose for treatment.
- No routine monitoring unless poor renal function, extreme body weight or pregnancy. Anti-Xa level give measure of level of anticoagulation.
- Both used for treatment and prevention of DVT / PE.
- All patients on admission assessed for thromboembolism risk (VTE).
What are the adverse effects of heparin?
- Pain at the site of injection
- Increased bleeding risk
- Osteoporosis with prolonged use
- Heparin-induced thrombocytopaenia - antibody mediated, 5-10 days into treatment (antobodies latch onto platelets and cause significant drop in platelets)
