Senior Academic Half Day 14 th January 2011

1. Senior Academic Half Day14th January 2011 Dr Oliver Chapman Consultant Haematologist, UHCW

2. Summary • Warfarin • Heparin • LMWH (enoxaparin) • Unfractionated • Novel anticoagulants • Quiz

4. Rationale Preventing harm from High Alert Medication- Anticoagulants The NHS Litigation Authority has reported that medication errors involving anticoagulants fall within the top ten causes of claims against NHS trusts Anticoagulants are one of the classes of medicines most frequently identified as causing preventable harm and admission to hospital (Pirmohamed M et al. 2004, Howard RL et al. 2007)

5. NPSA Risk Assessment Preventing harm from High Alert Medication- Anticoagulants • NPSA risk assessment 2006 found: • 120 deaths • 480 cases of serious harm • anticoagulants the second therapeutic group (after opiates) causing the most deaths and severe harm

7. Haemostasis - coagulation

8. Warfarin

10. NB If persisting risk factor eg paralysis, immobilised limb / cancer consider extending treatment duration – INDIVIDUALISED THERAPY (the future?)

11. CHADS2 score 0 – stroke risk <1%/yr • CHADS2 score 1 – stroke risk 2.5%/year • CHADS2 score 2 – stroke risk 4%/yr • CHADS2 score 3 – stroke risk 6%/yr • CHADS2 score 4 – stroke risk 8%/yr • CHADS2 score 6 – stroke risk 18%/yr • (cf warfarin fatal bleeding rate approximately 0.6% and 2% life threatening bleeding annually)

16. Starting warfarin • 2 regimes based on degree of urgency for therapeutic anticoagulation • Rapid anticoagulation in patients requiring heparin ie post thrombosis etc • Slow induction of anticoagulation in outpatients not requiring heparin ie prophylaxis eg AF

18. Why Warfarin and Heparin Need to overlap When Treating Acute Venous Thromboembolism • Pharmacokinetics of warfarin • 30 hour T1/2= 5 days to reach steady state • Time delay in achieving an antithrombotic effect based on the elimination half-lives of the vitamin K dependent clotting factors • (INR≠level of anticoagulation therapy during initiation of warfarin) • Protein C • Study evidence • 20 vs 6.7% incidence rethrombosis (Brandjes DPM, New Engl J Med 1992;327:1485-9)

19. Slow induction

20. Warfarin interactions

29. Warfarin Refer to elibrary trustwide guidelines “Warfarin Guideline”

31. Heparin - uses • Prophylaxis vs. Therapeutic • Therapeutic • Monitoring mandatory daily APTT-R + regular FBC with UFH/ intravenous heparin • Monitoring of LMWH generally not required

33. Dosing enoxaparin • Depends on indication (see below) • Treatment of VTE / peripheral vascular surgery: • Enoxaparin (ie clexane) should be administered subcutaneously as a single daily injection of 1.5 mg/kg (150 IU/kg). Treatment is usually prescribed for at least 5 days and until adequate oral anticoagulation is established. • Trust policy is to select the syringe strength which is appropriate to for the patient’s weight as per the following table (colour coded to correspond with the clexane syringe) :

34. Standard VTE dose 1.5 mg/kg – round to nearest syringe

35. Dosing enoxaparin 2 Treatment of unstable angina and non-Q-wave myocardial infarction: • Enoxaparin 1 mg/kg bd S/C injection. Treatment with enoxaparin in these patients should be prescribed for a minimum of 2 days and continued until clinical stabilisation. The usual duration of treatment is 2 to 8 days. 3 Treatment of acute ST-segment elevation myocardial infarction • The recommended dose of enoxaparin sodium for patients <75 years is a single IV bolus of 30mg plus a 1mg/kg SC dose followed by 1mg/kg administered SC bd (max 100mg for the first two doses only, followed by 1mg/kg dosing for the remaining doses).

36. Dosing enoxaparin • For treatment of acute ST-segment Elevation Myocardial Infarction in elderly patients 75 years of age, do not use an initial IV bolus. Initiate dosing with 0.75mg/kg SC bd (maximum 75mg for the first two doses only, followed by 0.75mg/kg dosing for the remaining doses).

37. Dosing enoxaparin 4 Prevention of extracorporeal thrombus formation during haemodialysis • An enoxaparin dose equivalent to 1 mg/kg introduced into the arterial line at the beginning of a dialysis session is usually sufficient for a 4 hour session. If fibrin rings are found, such as after a longer than normal session, a further dose of 0.5 to 1mg/kg may be given. For patients at a high risk of haemorrhage the dose should be reduced to 0.5 mg/kg for double vascular access or 0.75 mg/kg for single vascular access

38. Enoxaparin dose adjustments Dose adjustments A dose adjustment is required for patients with severe renal impairment (creatinine clearance < 30 ml/min), according to the following tables, since enoxaparin exposure is significantly increased in this patient population: Dosage adjustments for therapeutic dosage ranges Elderly patients

39. Dosage adjustments for prophylactic dosage ranges Standard dosingSevere renal impairment 40 mg once daily 20 mg once daily 20 mg once daily 20 mg once daily If treatment with enoxaparin is going to be prolonged eg >2 weeks in patients with renal failure (estimated creatinine clearance <30 ml/min) antiXa activity should be monitored on a single occasion after 7 days treatment (only repeat if significant change in renal function / dose adjustment previously required)

41. Anti Xa monitoring

43. Reversal

45. Therapeutic Heparin • LMWH is preferable in most situations • At least as effective as UFH in DVT and sub massive PE • Lower risk of bleeding (NB UFH often out of therapeutic range) • Lower risk of HITT • BUT difficulty with reversal – UFH preferred in some situations eg Pregnant patients with mechanical mitral valves who require surgery / patients with very high risk of haemorrhage

47. Heparin induced thrombocytopenia and thrombosis syndrome (HITTS)

50. Hirudin