Raising the Bar: Risk Stratifying VTE & Literature Update

Transcription

1 Raising the Bar: Risk Stratifying VTE & Literature Update Kelly Sawyer, MD, MS MCEP Assembly, July 2013 Disclosures No financial conflicts or disclosures However Take Home Points Risk Stratification is important, even for VTE admissions Understand what interventions your consultants and Institution offer You are your patient s best advocate Objectives Overview of VTE Treatment Guidelines/Controversies Risk Stratifying PE and DVT Patients Advocating for a multidisciplinary approach to VTE Guidelines ACEP updated 6 issues in 2011 Indications for thrombolytics AHA updated in 2011 Rx Sub/Massive PE, Iliofem DVT ACCP updated in 2012 (prior to FDA approval of Rivaroxaban) Focus: patient-centered treatment Epidemiology of VTE Increasing Incidence? Higher risk population? Poor risk assessments? Increasing Rate of Diagnosis? Annually > ,000 VTE events 1/3 of VTE deaths follow surgery ACEP Clinical Policy. Ann Em Med 2011; AHA Statement. Circ 2011; ACCP Guidelines. AT9, CHEST

2 Vulnerable Patients Unprovoked Age > History of prior VTE or thrombophilic disorder Obesity Cigarette Smoking Long Travel Unknown or unidentified predisposing factor Provoked Surgery / Trauma Prolonged Immobility Pregnancy / Hormones Comorbidities cancer Infection, Inflammation Sepsis, Central Access, IBD, Immune disorders CAD? VTE Recurrence Immobilization Justification for an aisle seat or upgrading to first class? Obesity is pandemic Dreaded Desk Work Winter = longer, sadder Mittal et al. JAPL, July Vol 59. 2

3 Pregnancy Inherent Hypercoagulable state Incidence: Post-partum period > last 20 weeks > first 20 weeks DVT: 80% in the LEFT leg High Risk = iliofemoral (64%) and isolated iliac vein (17%) among those with confirmed DVT OCP / HRT Especially after age 35 High & Low-dose estrogen Overall Risk Treating VTE in Pregnancy Traditional Treatment VTE Continue Treatment 6 wks postpartum or 3 months total, which ever comes last LMWH during gestation VKA, UFH, LMWH if lactating IV Heparin with Vit K Antagonist overlap N Engl J Med Nov 19;327(21): Anticoagulants Vit K Antagonists Warfarin (PO) Acenocoumarol (PO) Antithrombin Activators Heparin (PTT or ACT) LMWHs (anti Xa assay) Enoxaparin Dalteparin Fondaparinux (synthetic, SC) Direct Xa Inhibitors Rivaroxaban (Xarelto, PO) Apixaban (Eliquis, PO) Edoxaban Betrixaban (pending) Direct Thrombin Inhibitors Bivalirudin (reversible, IV) Argatroban (IV) Dabigatran (Pradaxa, PO) Thrombo- / Fibrino-lytics tpa /Alteplase (rt-pa) Tenecteplase / TNKase (rmt-pa) Reteplase (rmt-pa) Streptokinase Urokinase 3

4 Post-Thrombotic Syndrome Cluster of signs/symptoms, result of DVT Chronic swelling, pain Discomfort on walking Skin color change Venous insufficiency ulceration No good prediction tool however DVT: Diagnosis Pretest Probability should guide testing D-dimer? Imaging US CT Venography MRI Recommendations for evaluation of suspected first lower extremity DVT: patients with moderate pretest probability (PTP) for DVT. Use of whole-leg US. If whole-leg US shows only isolated calf vein DVT, treat, rather than using serial testing to rule out proximal extension only in patients with a high pretest probability or high risk of extension or severe symptoms. Bates S M et al. Chest 2012;141:e351S-e418S 2012 by American College of Chest Physicians 2012 by American College of Chest Physicians Bates S M et al. Chest 2012;141:e351S-e418S 4

5 LE DVT: Treatment Location determines risk, morbidity Sural V vs. Popliteal V vs. Femoral V Below Knee DVT - Risks for extension: positive D-dimer thrombosis that is extensive or close to the proximal veins (eg, > 5 cm in length, involves multiple veins, > 7 mm in maximum diameter) no reversible, provoking factor for DVT active cancer history of VTE inpatient status More Symptoms More reason to treat Provided there is no great risk for bleeding LE DVT: Treatment Early initiation of VKA (ie, same day as parenteral therapy is started) Continuation of parenteral anticoagulation for a minimum of 5 days and until the INR is 2.0 or above for at least 24 h (Grade 1B). DVT that involves the iliac and common femoral veins are at highest risk for PTS greatest potential to benefit from thrombus removal/lysis strategies LMWH or Fondaparinux > Heparin (Grade 2C) LMWH once/day ONLY IF twice the bid dose LE DVT: Intervention Most likely to benefit from Catheter Directed Thrombolysis iliofemoral DVT (eg, extensive clot, proximal) symptoms for < 14 days good functional status life expectancy of 1 year low risk of bleeding IVC Filter for DVT? For DVT: Only if anticoagulants are contraindicated Retrievable filters are often forgotten! 5

6 LE DVT: Summary Early Ambulation (2C) Compression stockings to reduce PTS (2B)? Location, symptoms guide treatment call IR/Vascular for extensive proximal clot Treatment for 3 mo with VKA * to INR 2-3 **If cancer LMWH > VKA Pregnant LMWH *If not treating, instruct on f/u US in 5-7 days Compression Stockings Compression Stockings: ankle pressure of mmhg, lower pressure higher up the leg (eg, graduated pressure) Wear for 2 years, longer if helpful Compliance is problematic Evidence is uncertain SOX Trial UE DVT 5% to 10% of VTE involve the upper extremities 75% of UE DVT are secondary (eg, central line) If not catheter-related, often involves dominant arm Treatment: 3 months Lysis: severe symptoms, thrombus involving most of the subclavian & axillary veins, symptoms for < 14 days, good functional status, life expectancy of 1 year, and low risk for bleeding Complications UE DVT PE Recurrence PTS (20%) Different from LE, not related to venous HTN Sx: heaviness, limb fatigue with exertion Rx: compression bandages, sleeves Catheter-associated DVT: if functional & needed, leave in place, continue LMWH until removed Superficial Vein Thrombosis Associated with: chronic venous insufficiency, malignancy, pregnancy or estrogen therapy, obesity, long-distance travel, history of VTE may be unprovoked 2/3 s involve long/great saphenous v 6

7 SVT Risks Risks for complications: extensive SVT involvement above the knee, particularly if close to the saphenofemoral junction severe symptoms involvement of the greater saphenous vein history of VTE or SVT active cancer recent surgery Treating SVT Treat if at least 5 cm in length 45 days Monitor for concomitant DVT Consider IR/Vascular Intervention for complicated SVT Esp Greater Saphenous v PE: Statistics 5% die of initial PE or 2 nd PE w/in 7 days* *look for the DVT consider need for temporary IVCF Risk of dying of PE 70% if cardiopulmonary arrest occurs ( 1%) 30% if there is shock requiring inotropic support ( 5%) 2% in patients who are not hypotensive Treat While Waiting High clinical suspicion treatment with parenteral anticoagulants while awaiting the results of diagnostic tests (Grade 2C). Intermediate clinical suspicion treatment with parenteral anticoagulants if the results of diagnostic tests are expected to be delayed for more than 4 h (Grade 2C). Low clinical suspicion do not treat with parenteral anticoagulants while awaiting the results of diagnostic tests, provided test results are expected within 24 h (Grade 2C). Chronic Thromboembolic Pulmonary Hypertension 3% patients treated for PE 1/3 h/o VTE; 2/3 h/o PE or recurrent PE Underlying cardiopulmonary impairment Recurrent PE even more likely to be fatal Pulmonary vascular remodeling severe Pulmonary HTN R heart failure anticoagulate long term (1B) short term increased risk of death 7

8 Case 1 36 yo male with wheezing, sob for 2 weeks On antibiotics, steroids for 2 days Near syncope at work No risks for VTE; 3hr car ride, few wks ago Tachycardic, low 100s BP wnl SpO2 low 90s on 2L Case 1 cont Alert, mildly anxious appearing Bilateral wheezing on exam, no LE swelling Chest XRay Ddimer? Troponin? BNP? ECG Case 1 cont D-dimer 3800 Standing 3 hour repeat troponin Daytime Bedside Echo Bedside lower extremity doppler US Case 1 decisions 24 hours later Heparin only Catheter Directed tpa Systemic tpa Surgical Embolectomy Treat as outpatient with Rivaroxaban 8

9 % Mortality 8/6/2013 massive vs submassive PE Controversial both definition & treatment Blood Pressure = stability Lack of high risk features On-going study for decades All others are low risk PE Risk Stratifying PE Cardiac biomarkers (troponin, BNP) RV Micro-infarction increased mortality Assessment of right ventricular size and function RV dilation, hypokinesis RV diameter 90% of the LV diameter on CT scan - independent risk factor for death and nonfatal complications Combination identifies the highest risk patients RV Dysfunction & Mortality RV Dysfunction 20.9% Normal RV Function 14.8% Days from Diagnosis Goldhaber et al. Lancet 1999: 353. Thrombolytics for PE Infusion Strategy (rtpa) Short infusion times reduce bleeding risks, achieve more rapid clot lysis Typical: 100mg over 2 hr T ½ 5-10 minutes Thrombolytics Major contraindications Relative contraindications Structural intracranial disease Systolic BP > 180 mm Hg Previous intracranial hemorrhage Diastolic BP > 110 mm Hg Ischemic stroke within 3 mo Recent bleeding (non-intracranial) Active bleeding Recent surgery Recent invasive procedure Recent brain or spinal surgery Ischemic stroke more that 3 mo previously Recent head trauma with fracture or Anticoagulation (eg, VKA therapy) brain injury Traumatic cardiopulmonary resuscitation Bleeding diathesis Pericarditis or pericardial fluid Diabetic retinopathy Pregnancy Age > 75 y Low body weight (eg, < 60 kg) Female sex Black race 9

10 Risk of Bleeding Major vs Minor Bleeding Intracranial Bleeding Symptomatic Intracranial Bleeding General: Risk of ICH ~2-3% Risk of major bleeding varies from 5-20% PEITHO Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury Large, multicenter Trial; finished in Europe; results presented at ACC 2013 Results 1006 patients with PE, normal BP, evidence of RV dysfunction & injury Decreased short term all-cause mortality & hemodynamic collapse Increased ICH, especially if >75 yo PEITHO Investigators. Am Heart J Randomized Trial of Tenecteplase to Treat Severe Submassive Pulmonary Embolism Multicenter randomized double blind, placebo controlled trial. SBP >90 mmhg with RV hypokinesis OR hypoxemia <95 OR abnormal biomarker Tenecteplase + Enoxaparin (40 subjects) VS Placebo + Enoxaparin (43 subjects) 3 mo follow up for patient-oriented wellness & RV functional outcome Case 2 72 yo female with sudden onset SOB, chest pressure Presents at night PMH: remote colon ca Tachycardic initially, SpO2 low 90s BP wnl J Am Coll Cardiol. 2013;61 10

11 Remember Case 2 cont Quick bedside echo Chest Xray Ddimer? Troponin? BNP? CT Chest CT Head too? Case 2 cont Standing 3 hour troponin resulted Full vs Half Dose tpa Treatment Options? Heparin Only Catheter Directed Lytics Systemic thrombolytics Surgical Embolectomy Treat as outpatient with Rivaroxaban 118 patients: Massive PE with instability or massive PE with RV dysfunction Death 6% vs 2%, Major Bleeding 10% vs 3%, No fatal recurrent PEs MOPETT Half tpa vs No tpa 121 patients 61 half dose t-pa and modified anticoagulant dosing 60 anticoagulant alone Results (pub 2013): Safe, Effective; Reduced PA pressures quickly Shorter LOS Reduced rates of recurrent PE and Pulm HTN Moderate PE, not based on biomarkers or Echo No bleeding in either group; Follow up at 28 months: 55% reduction in RVSP Case 3 60 yo male, COPD Presents for SOB O2 sat 80s in triage Tachycardic Denies LE symptoms Stabilized for CT 11

12 Case 3 cont PE: Further Intervention Short term CCU Admission BIPAP overnight Remains hypotensive, mildly hypoxic Escalation of care? What are your options? If lytics are contraindicated, lytics fail, or shock continues & death is seemingly imminent: Catheter-based Thrombolysis Surgical Embolectomy Severely ill with persistent DVT, may need temporary IVCF ECMO Case 4 35 yo female brought to ED at night Sudden SOB Unable to assess due to distress Unknown PMH Post-op boot on LLE Indications: VV Reversible Respiratory Failure VA Reversible Cardiogenic Shock Case 4 cont Intubated Mild improvement in SpO2 Never achieved ROSC 12

13 Thrombolytics for Cardiac Arrest, presumed due to PE Imminent or cardiac arrest bolus dosing is indicated ie. 50mg push t-pa (or TNKase), possibly repeat 50mg after 15 minutes Case 5 30 yo female, collapses in the hospital Intermittently responsive, speaking Pale, diaphoretic Brought to you in the ED No vitals obtained by EMS Case 5 cont Vitals are dismal ECG Intubate? Trop, BNP, Lactate CPB Treatment Options Case 5 cont Post-cardiac resuscitation / surgery care novel ideas? Outcome 13

14 PE in General Stable, small PE s without risk factors treat like DVT LMWH or Fondaparinux > Heparin Early administration of VKA to INR 2-3 for 3 months Early discharge home treat at home? Novel Treatments Treat at home? Lancet 2011 Advocating for Patients with VTE Several Treatment options: Which is best vs available? Require timely intervention & Reassessment Failed treatment requires plan B often upstairs! Medical & Surgical patients Increased risk post-discharge High morbidity & mortality Predictors of Mortality Lactate PESI Score 14

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