Diagnosis and Treatment of VTE in the ER

UHN ER Conference Nov 3, 2015 Diagnosis and Treatment of VTE in the ER Bill Geerts Thromboembolism Program, Sunnybrook HSC Professor of Medicine, University of Toronto National Lead, VTE Prevention, Canadian Patient Safety Institute

Case: Dr. Sheryl M. 28 year old EM resident Previously healthy On birth control pill x 4 mos 1 week ago (on honeymoon): ankle fracture after a fall in Hawaii no surgery but plaster cast, crutches Return to Toronto 2 days later

Case: Dr. Sheryl M. Oct 27 ankle fracture in Hawaii Nov 2 - sudden onset of LEFT pleuritic chest pain and shortness of breath Today - to ER with worsening of chest pain O/E: P = 95 BP = 105/78 RR = 22 (splinting) SaO2 = 93% JVP = 1 cm > sternal angle Leg looks OK above the cast Routine lab tests: normal Chest x-ray: slight blunting RIGHT CPA

Case: Dr. Sheryl M. What would you do now? A.Do a formal pre-test probability assessment B. Obtain a D-dimer C. Arrange a Doppler ultrasound D.Arrange a nuclear medicine lung scan E. Arrange a CTPA F. Follow the local PE investigation algorithm

Case: Dr. Sheryl M. What would you do now? A.Do a formal pre-test probability assessment - no B. Obtain a D-dimer - no C. Arrange a Doppler ultrasound no or? D.Arrange a nuclear medicine lung scan E. Arrange a CTPA F. Follow the local PE investigation algorithm

Suspected PE Assess PTP Low or Intermediate (or PE Unlikely) High Age-adjusted D-dimer Negative Positive No imaging indicated Imaging indicated

PE Rule-Out Criteria in Patients with Low PTP (PERC) 8 Clinical characteristics Meets criterion Age <50 0 Initial HR <100 0 Initial SvO2 >94% on room air 0 No unilateral leg swelling 0 No hemoptysis 0 No surgery, trauma <4 wks 0 No history of VTE 0 No current estrogen use 0 PTP of PE <1% if score = 0 Kline J Thromb Haemost 2004;2:124716; J Thromb Haemost 2008;6:772

Suspected PE Assess PTP Low Intermediate High PERC >1 D-dimer 0 Negative Positive No PE work-up indicated No imaging indicated Imaging indicated Raja Ann Intern Med 2015;163(9):701

4-step process starting with 64 low-value items Common, high cost, low benefit, actionable 1. Do not order CT to Dx PE without 1 st stratifying for PE (pretest prob and D-dimer for low probability). 2. Do not order lumbar spine MR if no high-risk features. 3. Do not order CT of C spine after trauma for patients who do not meet NEXUS criteria or Canadian C-Spine Rule. 4. Do not order head CT with mild head injury unless patient meets New Orleans or Canadian CT Head criteria. 5. Do not order coag tests unless patient bleeding or has suspected coagulopathy or is taking anticoagulant. Schuur JAMA Intern Med 2014;174(4):509

To reduce: patient radiation exposure patient contrast exposure false positive tests and detection of small filling defects of uncertain clinical significance detection of incidental findings that require further imaging, etc. the huge inter-physician variability in rates of investigation and PE ER visit time for patients costs Why should formal algorithms be used to investigate patient with suspected PE?

Case: Dr. Sheryl M. PE after ankle # Would you admit her to hospital? A. Yes B. No C. I need more information to make this decision

Admission Criteria for Acute VTE PE: (~50% admitted at least overnight) Hemodynamically unstable thrombolysis Requires O 2 or parenteral narcotics Very high bleeding risk Severe renal dysfunction DVT: (<5% admitted) Very high bleeding risk Severe renal dysfunction Catheter thrombolysis

Case: Dr. Sheryl M. PE after ankle # Which of the following management options would you start? A. IV heparin warfarin B. full-dose SC LMWH warfarin C. full-dose SC LMWH with no warfarin D. rivaroxaban 15 mg PO BID E. apixaban 10 mg PO BID F. something else...

VTE Treatment with rivaroxaban R enox N=8,281 EINSTEIN-DVT and EINSTEIN-PE warfarin INR 2-3 rivaroxaban 15 mg BID x 3 wks 20 mg QD Recurrent VTE Major bleeding 5-10 d 3, 6 or 12 mos usual care DVT (N=3,449) PE (N=4,832) rivaroxaban usual care rivaroxaban 3.0% 2.1% 1.8% 2.1% 1.2% 0.8% 2.2% 1.1% P=0.003 Bauersachs NEJM 2010;363:2499 EINSTEIN-PE Investigators NEJM 2012;366:1287

Major bleeding (%) VTE or VTErelated death (%) Apixaban for VTE Treatment (AMPLIFY) RR = 0.84 [0.60-1.18] RR = 0.31 [0.17-0.55] Agnelli NEJM 2013;369:799

Treatment of DVT/PE: 3 options 1 LMWH S/C warfarin (INR 2.0-3.0) 5-7 d 3 mosindefinite 2 LMWH S/C? pregnancy, uncontrolled adenocarcinoma, high bleeding risk 3 rivaroxaban (Xarelto ) 15 mg PO BID x 3 wks 20 mg daily apixaban (Eliquis ) 10 mg PO BID x 1 wk 5 mg BID

Case: Dr. Sheryl M. PE after ankle # Which of the following management options would you start? A. IV heparin warfarin - no B. full-dose SC LMWH warfarin -? C. full-dose SC LMWH, no warfarin - OK D. rivaroxaban 15 mg PO BID E. apixaban 10 mg PO BID F. something else...

What are contraindications to using rivaroxaban or apixaban? 1. 2. 3. 4.

What are contraindications to using rivaroxaban or apixaban? 1. High bleeding risk 2. Severe renal dysfunction (CrCl <30 ml/min) 3. Severe liver dysfunction 4. Pregnancy or breast feeding 5. Massive obesity -? dose 6. Mechanical heart valve 7. Likely poor compliance 8. Some other drugs: conazoles, HIV protease inhibitors, phenytoin, carbamazepine, rifampin 9. Unable to pay

What are the VTE treatment doses of rivaroxaban and apixaban?

What are the VTE treatment dose of rivaroxaban and apixaban? rivaroxaban (Xarelto) 15 mg PO BID x 3 weeks apixaban (Eliquis) 10 mg PO BID x 1 week 20 mg once daily 5 mg BID? >6 mos 2.5 mg BID

Starting a FXa Inhibitor for VTE 1. Is a FXaI appropriate? NOT: high bleeding risk, severe renal/liver dysfunction, pregnancy/breast feeding, massive obesity, MHV, poor compliance, some other drugs, unable to pay? Active cancer, APLA 2. Baseline CBC, egfr, LFTs 3. Stop antiplatelet agent unless essential 4. Education esp re compliance 5. Arrange periodic follow-up

Case: Dr. Sheryl M. PE after ankle # Would you investigate her for DVT? A.Yes B. No

Case: Dr. Sheryl M. PE after ankle # Would you investigate her for occult cancer? A. Yes B. No

Case: Dr. Sheryl M. PE after ankle # Would you investigate her for occult cancer? A. Yes B. No What if she was 74 and had unprovoked VTE?

Case: Dr. Sheryl M. PE after ankle # Would you investigate her for thrombophilia? A. Yes B. No C. It depends on...

Case: Dr. Sheryl M. PE after ankle # Would you advise discontinuation of the birth control pill? A. Yes B. No C. It depends on...

If the BCP might have been a triggering factor for the VTE DVT/PE BCP Anticoagulation

If the BCP might have been a triggering factor for the VTE DVT/PE BCP Anticoagulation BCP Anticoagulation

In Dr. S.M. s case... DVT/PE BCP Anticoagulation fracture long flight PE? clotting abnormality reduced mobility?bcp

Case: Dr. Sheryl M. PE after ankle # Which would you say to Sheryl? A. As you know, PE is pretty serious. It s fortunate you came to the ER today because this could have killed you. B. As you know, PE can be serious but, now that it s been diagnosed and you re starting treatment, you ll be just fine.

Case: Dr. Sheryl M. PE after ankle # What duration of anticoagulation would you advise? A.3 months B. 6 months C. 1 year D.Until the PE has resolved E. Indefinite

Treatment of VTE 10% Risk of Recurrent VTE Anticoagulation unprovoked active cancer ongoing risk factor major residual DVT post-thrombotic symptoms male provoked 0 VTE Time

Duration of Treatment for VTE Transient, reversed risk Unprovoked Continuing risk (unresolved cancer, AT deficiency, APLA) 3 mos indefinite* indefinite*

Duration of Treatment for VTE Transient, reversed risk Unprovoked Continuing risk (unresolved cancer, AT deficiency, APLA) 3 mos indefinite* indefinite* *Periodic reassessment re: 1) New patient risk factors for bleeding, thrombosis 2) New knowledge 3) Patient preference

For most patients like you... (with unprovoked VTE) <1%/yr 5-10%/yr Anticoagulants should be continued And we will reassess this decision together periodically

Case: Dr. Sheryl M. PE after ankle # What duration of anticoagulation would you advise? A.3 months B. 6 months C. 1 year D.Until the PE has resolved E. Indefinite

Suspected VTE in ER: Summary For investigation: use an evidence-informed diagnostic algorithm with formal PTP, ageadjusted D-dimer For?DVT: Proximal Doppler U/S For?PE: CTPA, V/Q, DUS For treatment: use an evidence-informed management algorithm 1. DOAC 2. LMWH 3. LMWH warfarin Massive DVT/PE: catheter thrombolysis