Preventing Anticoagulation Errors with Clinical Dashboards

Dan Johnson, Pharm.D., BCPSAugust 3, 2011

Objectives

• Describe the anticoagulant dashboards• Summarize the common anticoagulant drugs

and their dashboard alerts• Discuss future directions in anticoagulant

therapy and monitoring

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

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

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®)

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?

Pig Guts!!!

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

Heparin Protocol-Items ordered

Higher Dose Heparin Protocol

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

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

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

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

Heparin Dashboard

Alert Values for Heparin

• Platelet drop• HIT positive• Old PTT/no PTT• CrCl< 30 ml/min• Infusion >2,500 units per hour

Evaluating a Dashboard Alert

Communicating Information Forward

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

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

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

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%

Warfarin Dashboard Alerts

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

Warfarin Dashboard

Warfarin Patient Details

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

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

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

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

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

Why Use Dabigatran?

• Indicated for non-valvular atrial 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

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?

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

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

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

Questions?