Consequences of anti-coagulant therapy (CH) Flashcards
What are anticoagulants?
Used for treating and preventing embolic events
What are the most common oral anticoagulants? (2)
- vitamin K antagonists e.g. warfarin
- DOACs e.g. apixaban, rivaroxaban, dabigatran
What is the most common parenteral (outside of GI tract) anticoagulant?
Heparin
What is vitamin K responsible for?
Production of factors 2, 7, 9, 10
Describe the mechanism of warfarin.
- block function of vitamin K epoxide reductase complex in liver –> depletion of reduced form of vitamin K = cofactor for gamma carboxylation of vitamin K dependent clotting factors
- inhibiting factors 2,7,9,10 and protein C and S (anticoagulant proteins)
How does warfarin affect PT and APTT?
- prolonged PT as it has the biggest effect on factor 7
- normal APTT
What are the indications for warfarin?
- prophylaxis of embolisation in rheumatic heart disease and AF
- prophylaxis after insertion of prosthetic heart valve
-
2nd line for prophylaxis and Rx of DVT and PE:
- 6wk for distal DVT
- 3m for provoked proximal DVT
- 6m for unprovoked proximal DVT
- long term if recurrent
- TIAs
What anticoagulant is given with warfarin if immediate effect is required (DVT/PE)?
Heparin is given concurrently
What are some side effects of warfarin?
- bleeding - advise about spontaneous bleeding, severe back pain
- rare - alopecia, N&V
- severe - skin necrosis or calciphylaxis
What is an advantage of warfarin?
Can be directly reversed by replacement of vitamin K
What are disadvantages of warfarin? (4)
- long half-life
- regular monitoring of PT and INR
- many drug-drug interactions
- not used in DVT and PE (2nd line)
What is the target INRs of patients on warfarin and what is the exception?
- target INR 2.5 except metallic mitral valve replacement (2.5-3.5)
- mitral valve replacement: 2.5-3.5
- VTE / AF / metallic aortic valve replacement: 2.0-3.0
- recurrent PEs: 3.5
What do we do if INR is raised significantly in a patient on warfarin?
Indicates high bleeding risk - warfarin reduced/withheld completely and vitamin K may be given and FFP
What do we do before emergency surgery with regards to warfarin?
- if surgery can wait: give IV 5mg vitamin K 6-8h before emergency surgery
- if surgery cannot wait: give 25-50 units/kg four-factor prothrombin complex
- planned surgery: warfarin stopped 5 days before, INR<1.5 to proceed
When is warfarin contraindicated? (6)
- pregnancy (risk of teratogenicity)
- haemorrhagic stroke
- significant bleeding
- hepatic / renal impairment
- within 72h of major surgery
- within 48h postpartum
How long before planned surgery must warfarin be stopped?
5 days
When can surgery go ahead in a patient on warfarin?
- when INR<1.5
- if INR>1.5 give oral vitamin K a day before surgery
What reduces warfarin activity? (1+5)
P450 inducers (think induce = reduce INR) - SCARS:
- Smoking
- Ciroc (alcohol)
- Anti-epileptics e.g. carbamazepine or phenytoin
- Rifampicin
- St John’s wart
What increases warfarin activity (1+4)
P450 inhibitors (think inhibit = increase INR) - ASS ZOLES:
- Antibiotics e.g. ciprofloxacin, isoniazid, clarithromycin, erythromycin
- SSRIs e.g. fluoxetine, sertraline
- Sodium valproate
- -Zoles e.g. omepraZole, ketoconaZole, fluconaZole
How do you manage major bleeding in an over-warfarinised patient?
- stop warfarin
- IV vitamin K 5mg (phytomenadione)
- prothrombin complex concentrates (if not available then FFP)
How do you manage INR>8 in an over-warfarinised patient?
- stop warfarin
- minor bleeding: IV vitamin K 1-3mg
- no bleeding: oral vitamin K 1-5mg
- repeat dose of vitamin K if INR still too high after 24h
- restart warfarin when INR<5
How do you manage INR 5-8 and minor bleeding in an over-warfarinised patient?
- stop warfarin
- give IV vitamin K 1-3mg
- restart warfarin when INR<5
How do you manage INR 5-8 and no bleeding in an over-warfarinised patient?
- withhold 1-2 doses of warfarin
- reduce subsequent maintenance dose
How do you manage patient if INR<2?
Up warfarin dose and start LMWH
What are some examples of DOACs?
- apixaban
- rivaroxaban
- edoxaban
- dabigatran
How do DOACs work?
- apiXaban and rivaroXaban = direct factor Xa inhibitor (hint X in middle of name suggests Xa inhibitor) –> prevents thrombin generation and thrombus development
- dabigatran = direct thrombin inhibitor
Why are DOACs preferred to warfarin?
Require less monitoring
Compare apixaban vs rivaroxaban vs dabigatran in terms of mechanism, excretion and reversal.
- mechanism: direct Xa inhibitor vs direct Xa inhibitor vs direct thrombin inhibitor
- excretion: liver vs faecal vs renal
- reversal: Andexanet alfa vs Andexanet alfa vs Idarucizumab
What are the indications for DOACs? (5)
- prevention of stroke and systemic embolism in adults with non-valvular AF and at least one risk factor
- PE & DVT - 3m (provoked), 6m (unprovoked or active cancer), high dose for first 7d
- prevention of VTE in adults who have undergone elective hip/knee replacement surgery
- prophylaxis of atherothrombotic events following ACS with elevated biomarkers - in combination with aspirin +/- clopidogrel
What are some side effects of DOACs?
- bleeding - advise patients about spontaneous bleeding or severe back pain (Andexanet alfa is a specific reversal agent for FXa inhibitors when life-threatening/uncontrolled bleeding)
- anaemia, bruising
- angioedema
When should DOAC dose be reduced?
- two of: 80+, <60kg, serum creatinine >133umol/L
- reduced if creatinine clearance 15-29mL/min
- stopped if creatinine clearance <15mL/min
What are some contraindications to DOACs? (5)
- liver disease associated with coagulopathy (elevated liver enzymes)
- prosthetic heart valve
- antiphospholipid syndrome
- active bleeding / high risk
- pregnant / breastfeeding
What drugs should you avoid if on DOAC?
Avoid NSAID, other anticoagulants, antiplatelets
How do we switch from a DOAC to warfarin?
Do not stop apixaban immediately
When do we stop a DOAC before surgery?
- minor bleeding risk - do not stop DOAC
- low bleeding risk - stop DOAC 24h before
- high bleeding risk - stop DOAC 48h before
How do we reverse apixaban/rivaroxaban (DOAC)?
Andexanet alfa
How do we reverse dabigatran (DOAC)?
Idarucizumab
What are the two types of heparin?
- short-acting: unfractionated heparin (standard)
- long-acting: LMWH e.g. enoxaparin, dalteparin
How is unfractionated heparin vs LMWH administered?
- unfractionated heparin: IV
- LMWH: subcutaneous
How is unfractionated heparin vs LMWH monitored?
- unfractionated heparin: APTT
- LMWH: via anti-factor Xa
Which type of heparin is usually preferable and why?
LMWH - preferred as lower risk of heparin-induced thrombocytopenia (occurs when heparin activates antithrombin III, which forms a complex that inhibits factor Xa)
How long before surgery must heparin be stopped?
May be stopped on day of surgery, since heparin has a much shorter half-life than warfarin
What is the reversal agent for heparin?
Protamine sulfate
