1B anticoagulant therapy Flashcards
What are some therapeutic indications for anticoagulation?
-
Venous thrombosis
- Initial treatment to minimise clot extension/embolisation (< 3 months)
- Long term treatment to reduce risk of recurrence
-
Atrial fibrillation
- 800 per 100 000 population potentially eligible in 1 year
- To reduce risk of embolic stroke
- Mechanical prosthetic heart valve
What are preventative indications for anticoagulation (thromboprophylaxis)?
e.g. Following surgery, during hospital admission, during pregnancy
What is heparin?
- Naturally occurring glycosaminoglycan
- Produced by mast cells of most species
- Porcine products used in UK
Describe the lengths of heparin chains
Varying number of saccharides in chains: differing lengths:
- Long chains: unfractionated (UFH)
- IV administration
- short half-life
- Low molecular weight (LMWH): subcutaneous administration
What does unfractionated heparin do?
Enhancement of antithrombin
- Inactivation of thrombin (Hep binds AT + thrombin)
- Inactivation of FXa (Hep binds AT only)
- Inactivation of FIXa, FXIa, FXIIa)
What does LMWH do?
- Contain pentasaccharide sequence for binding AT
- Predictable dose response in most cases so does not require monitoring (cf UFH)
Describe the effect of unfractionated heparin on APTT
Describe the effect of LMWH on APTT
How does warfarin work?
Warfarin blocks the recycling of Vit K.
It is a vitamin K antagonist (competes with Vit K) that works by interfering with protein (gamma) carboxylation.
It therefore reduces synthesis of functional factors II, VII, IX and X by the liver, inducing an anticoagulated state slowly.
Why does warfarin administration require monitoring?
- Narrow therapeutic index
- Many dietary, physiological and drug interactions
How are the effects of warfarin reversed?
- Reversed slowly by Vit K administration: takes several hours to work
- Reversed rapidly by infusion of coagulation factors:
- PCC
- FFP
Describe the depletion of coagulation factors upon warfarin administration
What are the side-effects of warfarin?
- Bleeding
- Minor 5%pa
- Major 0.9-3.0%pa
- Fatal 0.25%pa
- Skin necrosis
- Purple toe syndrome
- Embryopathy: chondrodysplasia punctata
What is skin necrosis?
Severe protein C deficiency
- 2-3 days after starting Warfarin
- Thrombosis predominantly in adipose tissues
What is purple toe syndrome?
Disrupted atheromatous plaques bleed
- Cholesterol emboli lodge in extremities
What is chondrodysplasia punctata?
Early fusion of epiphyses
- Warfarin is teratogenic in 1st trimester
How is warfarin monitored?
INR (International Normalised Ratio)
Target INR usually 2-3
- ISI = International Sensitivity Index
- Indicates sensitivity of particular thromboplastin for warfarin
- Unanticoagulated normal INR = 1.0
Describe the incidence of bleeding related to INR
What can cause resistance to warfarin?
- Lack of patient compliance
- Measure warfarin levels
- Proteins induced by Vitamin K (PIVKA)
- Diet, increased Vit K intake
- Increased metabolism Cyt P450 (CYP2C9)
- Reduced binding (VKORC1)
List four examples of DOACs and where they affect the coagulation pathway
Compare warfarin and DOACs
What is given for venous thrombosis initial treatment to minimise clot extension/embolisation (<3 months)?
DOAC or LMWH for first few days followed by DOAC or warfarin
What is given for long term treatment to reduce risk of recurrence of venous thrombosis?
DOAC or warfarin
What is given to reduce risk of embolic stroke from A.Fib?
DOAC or warfarin
What is given for mechanical prosthetic heart valve?
Warfarin (DOACs not effective and should be avoided)
What is different about the dosage when using anticoagulant for thromboprophylaxis?
Lower doses used
What is given as thromboprophylaxis following surgery?
LMWH or DOAC
What is given as thromboprophylaxis during hospital admission?
DOACs not effective for use as medical thromboprophylaxis
What is given as thromboprophylaxis during pregnancy?
LMWH (DOACs not safe in pregnancy)
