Preventing Anticoagulation Errors with Clinical Dashboards

1. Preventing Anticoagulation Errors with Clinical Dashboards Dan Johnson, Pharm.D., BCPS August 3, 2011

2. Objectives • Describe the anticoagulant dashboards • Summarize the common anticoagulant drugs and their dashboard alerts • Discuss future directions in anticoagulant therapy and monitoring

3. Medication Errors with Anticoagulants • Significant potential for harm at normal doses • Minimal room for error with anticoagulants • Always read labels carefully • Monitoring is critical to prevent adverse events

4. Using Clinical Dashboards • What is a “dashboard” • Alert values for various drugs • Concurrent monitoring of target drugs • Focus on “at risk” patients when we cannot follow every patient • Resolve alerts and communicate information w. providers and other pharmacists

5. Anticoagulant Drugs • Heparinoids • Unfractionated heparin (UFH) • Enoxaparin (Lovenox®) • Coumarin derivatives • Warfarin (Coumadin®) • Direct Thrombin Inhibitors • Argatroban • Lepirudin (Refludan®) • Bivalirudin (Angiomax®) • Dabigatran (Pradaxa®) • Factor Xa Inhibitors • Fondaparinux (Arixtra®) • Rivaroxaban (Xarelto®)

6. Unfractionated Heparin • Indirectly inhibits thrombin by binding to antithrombin III • Large molecule with significant variability • Pharmacokinetics change based on dose • Half-life increases as dose increases • Where does heparin come from?

7. Pig Guts!!!

8. VUH Heparin Protocols • Three main protocols • Lower dose (ACS, atrial fibrillation, etc.) • Higher dose (DVT, PE, etc) • Custom • Nurses manage lower and higher dose protocols on implemented floors • Providers manage the custom protocol • Each protocol has limitations

9. Heparin Protocol-Items ordered

10. Higher Dose Heparin Protocol

11. Enoxaparin (Lovenox) • Shorter molecule of heparin • Low molecular weight heparin vs. UFH • Predictable pharmacokinetics • Does not vary by dose • Simple dosing • Administered subcutaneously • No monitoring required • Anti-Xa levels may be used in rare situations • 4 hours post dose, 0.6 to 1 for q12h treatment doses

12. Concerns with Enoxaparin • Adverse events similar to heparin • Bleeding • Thrombocytopenia • Lack of monitoring around invasive procedures • Epidural anesthesia • Black box warning • Dosing in obese patients • Renal dosing for CrCl<30 ml/min

13. Heparin-induced Thrombocytopenia (HIT) • HIT Type 1 (HAT) • Non-immune mediated • Usually do not drop platelets < 100,000 • HIT Type 2 (HITTS) • IgG antibody against heparin-PF4 complex • Onset 3-15 days after starting heparin • 50% drop in platelet count • Associated with thrombosis

14. Treatment and Diagnosis • Diagnosis • ≥ 50% drop in platelets • HIT antibody test • Serotonin release assay • Treatment • Remove all sources of heparin!!! • Heparin allergy • Alternative anticoagulant • Direct thrombin inhibitor • Fondaparinux

15. Heparin Dashboard

16. Alert Values for Heparin • Platelet drop • HIT positive • Old PTT/no PTT • CrCl< 30 ml/min • Infusion >2,500 units per hour

17. Evaluating a Dashboard Alert

18. Communicating Information Forward

19. Dashboard Functionality • Alerts are addressed by clinical pharmacists in each patient care area • Single pharmacist each daily responsible for final sign off • Clinical pharmacists & pharmacy residents have primary dashboard responsibilities

20. Warfarin (Coumadin) • Oral anticoagulant drug • Inhibits vitamin K dependent clotting factors • Dietary vitamin K • Where does warfarin come from? • Rat poison • Indicated for long term anticoagulation • Stroke prevention • DVT/PE • Mechanical heart valves

21. Good Old Warfarin • Slow onset (3-5 days) • Numerous drug interactions • Dietary concerns (Vit. K) • Unpredictable dosing • Frequent monitoring • Procedural bridging • Complicated patient counseling • Limited alternatives

22. Warfarin Monitoring • Signs of bleeding • Monitor CBC • Monitor INR for clinical efficacy and safety • Normal INR 1 • Therapeutic INR 2-3 for most • Bleeding risk increases as INR goes up • INR should increase by 0.2-0.3 per day • Dose changes by 10-20%

23. WarfarinDashboard Alerts • Rapid rise in INR (>0.4 in 24 hours) • High INR (INR >3) • Old INR/No INR

24. Warfarin Dashboard

25. Warfarin Patient Details

26. Challenges with Dashboard Monitoring • Staffing • Experience • Weekend/afterhours coverage • Practice variations • Developing quality alert values • Garbage in, garbage out • Alert frequency • Positive predictive value • Informatics resources

27. The Future of Anticoagulation • Oral direct thrombin inhibitors • Dabigatran (Pradaxa) • Oral Factor Xa inhibitors • Rivaroxaban • Apixiban • Betrixaban • Several potential benefits: • Less variability • Oral administration • No monitoring required

28. Dabigatran (Pradaxa) • Oral, fixed dose direct thrombin inhibitor • 150 mg twice a day • Predictable pharmacokinetics • Quick onset, relatively short duration • Limited drug interactions, no dietary concerns • No monitoring required

29. Dabigatran (Pradaxa®) • Oral direct thrombin inhibitor • Rapid onset • Short duration of action • Fixed dosing • No routine monitoring required • Limited drug interactions • No drug-food interactions

30. Concerns with Dabigatran • Renal clearance • Dose adjust for CrCl <30 ml/min • 75 mg BID • Do not give if CrCl <15 ml/min • Inability to monitor around invasive procedures • Capsules must be swallowed whole • No reversal agent • Cost

31. Why Use Dabigatran? • Indicated for non-valvularatrial fibrillation • Better than warfarin • Non-inferiority data in VTE • Inability to achieve stable INR on warfarin • Easier transition to oral anticoagulant therapy • Procedural bridging may be easier • Rapid onset compared to warfarin • Patient must be able to afford dabigatran

32. When to Avoid Dabigatran • Renal failure • Indications without data for dabigatran • Mechanical heart valves • VTE prophylaxis • Heparin-induced thrombocytopenia • Cost concerns with dabigatran • Stable warfarin patients? • Can pharmacogenomics make warfarin dosing easier/better?

33. Rivaroxaban (Xarelto) • Oral factor Xa inihibitor • FDA approved for ortho prophylaxis • 10 mg daily • Take with or without food • Substrate of CYP P450 3A4 and pGP • Avoid use if CrCl <30 ml/min • Half life 5-9 hours • Per tube administration may reduce bioavailability

34. Rivaroxaban Dosing • Ortho prophylaxis • 10 mg once daily starting 6 to 10 hours after surgery • Only FDA approval at this point • DVT/PE • 15 mg BID for 3 weeks followed by 20 mg daily • Atrial fibrillation • 20 mg once daily, 15 mg daily for moderate renal impairment

35. Future Directions • Improve dashboard functionality • New alerts (old drugs and new) • Newer monitoring systems (Sentri7) • Utilize new anticoagulants in appropriate patients • Clinical pharmacist focusing on only anticoagulation • Inpatient anticoagulation service

36. Questions?