Anticoagulation

Coagulation cascade - click for full-size

Heparin

Warnings

  • Thrombocytopenia occurs day 5-21
  • Can suppress aldosterone, causing hyperkalaemia
  • Reduce dose if GFR<30

Dosing

Initial bolus - 5000 units
Initial rate - 18U/kg/hour = 1.2 ml/hr for 70kg
APTT Action Rate change
1-1.2 Bolus 40u/kg Increase by 200u/hr
1.3-1.4 Increase by 1-200u/hr
1.5-2.5 No change
2.6-3.0 Reduce by 50u/hr
3.1-4.0 Reduce by 100u/hr
4.1-5.0 Stop for 30 mins Reduce rate by 200u/hr
>5.1 Stop for 60 mins Reduce rate by 2-300u/hr
Stop after therapeutic INR for two days

Warfarin

BCSH guidelines
SIGN guidelines

Warnings

  • No warfarin in pregnancy
  • Use 1 mg tablets only in impaired vision

Interactions

Class Substance Anticoagulant effect of warfarin
Antacids Cimetidine Antagonised
Omeprazole, esomeprazole, pantoprazole Possibly increased
Antibiotics Metronidazole, erythromycin Increased
Antifungals Increased by most, antagonised by griseofulvin
Antiepileptics Carbamazepine Increased
Phenytoin Possibly either
Foods Cranberry juice Increased
Supplements Gingko biloba, garlic, ginseng Various - also some antiplatelet activity
Hormones Corticosteroids Increased at high dose
Oestrogens Antagonised
Thyroxine Increased
Lipid-lowering Atorvastatin Antagonised transiently
Simvastatin, fluvastatin, rosuvastatin, fibrates, ezetimibe Increased


Starting warfarin

Slow anticoagulation is recommended for AF or other low-risk states: 1 mg/day, recheck INR after 1 week.

Warfarin dose reduced if:

  • Body weight <50 kg
  • Low serum albumin
  • Age >65
  • Raised baseline INR
  • Liver disease
  • Heart failure

Estimated warfarin maintenance dose

Or see warfarindosing.org

Age: Height (cm): Weight (kg):
Race: Caucasian Asian African
Enzyme inducers: (phenytoin, carbamazepine, rifampicin)
Amiodarone:
mg per day
Based on NEJM 2009; 360: 753
Day INR Dose
1 <1.4 10 mg
1.5-2.0 or >60 years 5 mg
>2.0 None
2 No test 10mg
5mg if INR>1.4 on day 1 or age>60)
3 <2.0 10mg
2.0-2.1 5mg
2.2-2.5 4mg
2.6-2.9 3mg
3.0-3.3 2mg
3.4-4.0 1mg
>4 None
4 <1.4 >8mg
1.4-1.5 8mg
1.6-1.7 7mg
1.8-1.9 6mg
2.0-2.3 5mg
2.4-3.0 4mg
3.1-4.0 3mg
4.1-4.5 Miss a day then 2mg
>4.5 Miss 2 days then 1mg

Duration of warfarin therapy

BCSH recommend:

  • Calf DVT - at least 6 weeks
  • Proximal DVT or PE with temporary risk factors & low risk of recurrence - at least 3 months
  • Proximal DVT or PE with permanent risk factors or high risk of recurrence - consider lifelong
  • Proximal DVT or PE unprovoked - at least 3 months but consider lifelong. Risk or recurrence is estimated at >9% which is above threshold where risk of warfarin is outweighed by benefit.


INR targets

  • AF - 2.5
  • 1st VTE event - 2.5
  • Recurrent VTE despite therapeutic warfarin - 3.5
  • Prosthetic valve - depends on type, see BCSH guideline.

Stopping warfarin

No need to taper off. For procedures:

  • Dental extraction - continue if INR<4
  • Endoscopy - continure if INR<3

Emergency reversal of anticoagulation

Major bleeding Stop warfarin
Give 5 mg intravenous or oral vitamin K
Give prothrombin complex (Octaplex) 50 U/kg
or fresh frozen plasma 15 ml/kg (less effective)
Non-major bleeding If clinically indicated - vitamin K 1-3mg IV
No bleeding If INR >8 - vitamin K 1-5mg orally