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James Neuenschwander, MD, FACEPResearch Director Genesis HealthCare Emergency Department. Zanesville, OhioAdjunct Associate Professor The Ohio State University WexnerMedical Center. Columbus, OhioAtlantic City, NJ September 2017

Disclosures � Janssen Consultant and speaker bureau

Tattoo of the Year

Objectives � Identify the causes and risk factors of DVT/PE

� Present clinical work up and evaluation of DVT/PE

� Offer options for treatment and management of DVT/PE

Definitions� Venous Thromboembolism = Deep Venous

Thrombosis (DVT) and Pulmonary Embolism (PE)

Venous Thromboembolism (VTE)

� Unprovoked VTE implies that no identifiable provoking environmental event for VTE is evident

� Provoked VTE is one that is usually caused by a known event (eg, surgery, trauma, significant immobility)

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DVT� Proximal DVT is one that is located in the popliteal,

femoral, or iliac veins

DVT� Distal: does not have proximal component, is located

below the knee, and is confined to the calf veins (perineal, anterior tibial, and muscular veins

Risk Factors� Virchow’s Triad

� Inherited Thrombophilia

� Gender-Related Factors

� Acquired Risk Factors

Virchow’s Triad

� Blood flow alteration

� Vascular injury

� Blood constituent alteration

INHERITED THROMBOPHILIACommon inherited hypercoagulable states

� Factor V Leiden mutation

� Prothrombin gene mutation

� Protein S deficiency

� Protein C deficiency

� Antithrombin deficiency

Risk Factors: Gender� Pregnancy

� Oral Contraceptives: Risk increases within the first 6 to 12 months

� HRT: Approximately twofold increase in VTE risk, greatest in the first year of treatment

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Major Acquired Risk Factors• More than 48

hours of immobility in the preceding month

• Hospital admission in the past three months

Major Acquired Risk Factors

(Pt. 2)• Surgery in the past

three months

• Malignancy in the past three months

• Infection in the past three months

Other Acquired Risk Factors� Trauma

� IV Drug Use

� Glucocorticoids

� Tamoxifen

� Chronic Renal Disease

� Chronic Liver Disease

� Cardiovascular Disease

� Obesity

� Hypertension

� Smoking

� Age

� IBS

Why?� Why do supermarkets make the sick walk all the way

to the back of the store for their prescriptions while healthy people can buy cigarettes at the front?

DVT Presentation� Features are nonspecific and sometimes

asymptomatic.

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DVT Presentation (Symptoms)� Most Common Symptoms

� Leg swelling or edema

� Leg pain

� Leg warmth

DVT Presentation (Physical Exam)� Dilated superficial veins

� Unilateral edema or swelling with a difference in calf or thigh diameters

� Unilateral warmth, tenderness, erythema

� Pain and tenderness along the course of the involved major veins

� Local (eg, inguinal mass) or general signs of malignancy

DVT Presentation (Scoring)� Wells Score

� -2 to 8 Point Scale

� ≤ 0 = Low Probability

� 1-2 = Moderate Probability

� 3-8 = High Probability

DVT Diagnosis (D-Dimer)� Elevated in nearly all patients with acute DVT

(Sensitive)

� Found in many other conditions (Not Specific)

� Negative result (<500 ng/mL) useful for ruling out DVT in the right clinical situation

DVT Diagnosis (Ultrasonography)� Diagnostic test of choice for suspected DVT

DVT Diagnosis - rarely usedCT – Thrombus is usually identified on CT by demonstrating a filling defect with contrast-enhancement.

Venography Expensive, technically difficult to perform and interpret, and can lead to complications

MRI

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Why?� Is the person that invests your money called a broker?

DVT Treatment: Anticoagulation� Anticoagulation is the mainstay therapy

� Benefits vs Risk of bleeding

� Benefits - Prevention clot extension, PE, and improved mortality

� Risk of bleeding.

Traditional Therapy

� Low molecular weight heparin (LMWH) 1 mg/kg bid vs 1.5 mg/kg once daily

� Coumadin (Vitamin K antagonist) with bridging to INR of 2.0 to 3.0

� 3, 6, to 12 months

Cancer Patients and Pregnancy� LMWH

End stage renal disease and

mechanical valves� No DOAC with CrCl < 15 ml/min

� Recommendation vs Indication

� Valvular disease with native valves

Direct Oral AntiCoagulants (DOACS) � Rivaroxaban, Apixaban, Edoxaban Factor Xa inhibitors

� Rivaroxaban and Apixaban do not need LMWH bridging – but Edoxaban does

� Fast onset

� No need for routine monitoring

� Expense of the drug vs in patient stay?

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Doacs continued…� Drug-Drug interactions

� CYP3A4 and P-gp inhibitors. Ketoconazole. Itraconazole. Ritonavir. Clarithromycin.

� CYP3A4 and P-gp inducers. Rifampin. Carbamazepine. Phenytoin. St. John’s Wort.

� CrCl < 30 ml/min

Dabigatran (Thrombin Inhibitor)� LMWH or UFH for transition

DrugsTrade Name

Scientific Name

Bridging Dose Study

Coumadin Warfarin LMWH or UFH

Variable Numerous

Xarelto Rivaroxaban None 15 mg BID x 21 days,20 mg once daily

Einstein

Eliquis Apixaban None 10 mg BID x 7d, 5 mg bid

Amplify

Pradaxa Dabigatran LMWH or UFH

150 mg BID Re-Cover

DVT Treatment: Serial

Ultrasonography� Possible with some distal DVT, can possibly avoid

anticoagulation with serial surveillance

Contraindications to

anticoagulation� Active bleeding

� Severe bleeding diathesis

� Platelet count than 50,oo0 (can be lower based on the strength of the indication)

� Recent planned or emergent high bleeding-risk surgery procedure

� Major trauma

� History of ICH

Relative contraindications

� Recurrent GI bleed

� Intracranial or spinal tumors

� Platelet count less than 100,000

� Large AAA with concurrent HTN

� Stable aortic dissection

� Recent, planned, or emergent low bleeding-risk surgery/procedure

� Frequent falls

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DVT Treatment: Thrombolytic

Therapy/ Thrombectomy� Not usually indicated for DVT –can be used for

extensive ileofemoral. Ekos catheter

� Phlegmasia cerulea dolens: may be important for patients with PCD who have severe venous gangrene

When to stop before a procedure?Many cardiologists say if they will cath on Friday, hold Thursday night dose of DOAC

Roughly 36 to 48 hours based on the procedure

Why?� Didn’t Noah swat those 2 mosquitos?

Reversal � Warfarin

� Vitamin K: oral vs IV

� PCCC (factors II, VII, IX, X) or Recombinant factor VIIa

� FFP (15 ml/kg)

Reversal cont…� Dabigatran

� Idaruczumad (Praxbind)

� IV administration 5 gm

� Widely available?

� Can restart 24 hours after reversal agent

Reversal cont…� Rivaroxaban, Apixaban, Edoxaban, LMWH

� No specific antidote but date set in February 2018 for Portola – Will only be indicated for Rivaroxaban and Apixaban. LMWH?

� Can not use dialysis (protein binding)

� Vitamin K will not work

� Protamine will not work on DOACs but will for LMWH anf UFH

� PCCC (factors II, VII, IX, X)

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Adexanet Alfa� Decoy protein that binds factor Xa inhibitor with

stronger affinity than natural factor Xa

� Decision in Feb. 2018 by FDA

Obese patients� Data still out.

DVT Treatment: Inferior Vena Cava

Filter� Not routinely used

� Used in patients with absolute contraindication to anticoagulation

� Effective?

DVT Disposition� Discharge if:

� Hemodynamically stable

� Low risk of bleeding.

� No renal insuffiency

� Favorable situation (caregiver support, phone, understanding of conditions in which to return if things detoriate)

� NOT FOR: massive DVT to the iliofemoral, phlegmasiacerulean doleans)

Why?� Is the time with the slowest traffic called rush hour?

Pulmonary Embolism� Definition: obstruction of the pulmonary artery or

one of its branches by material (eg, thrombus, tumor, air, or fat) that originated elsewhere in the body

� Acute, Subacute, Chronic

� Massive: Hemodynamically unstable

� Submassive: Right ventricular strain

� Low risk: No right ventricular strain

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PE� Saddle, lobar, segmental, subsegmental

� Bilateral or unilateral

� Symptomatic or asymptomatic

PE Presentation� Wide variety of features (no symptoms to shock or

sudden death)

� Most common presenting symptom is dyspnea followed by chest pain and cough.

PE Presentation (Symptoms)� Most Common Symptoms

� Dyspnea at rest or with exertion (73 percent)

� Pleuritic pain (66 percent)

� Cough (37 percent)

� Orthopnea (28 percent)

� Calf or thigh pain and/or swelling (44 percent)

� Wheezing (21 percent)

� Hemoptysis (13 percent)

PE Presentation (Physical Exam)� Common Physical

Examination Findings

� Tachypnea (54 percent)

� Calf or thigh swelling, erythema, edema, tenderness, palpable cords (47 percent)

� Tachycardia (24 percent)

� Rales (18 percent)

� Decreased breath sounds (17 percent)

� An accentuated pulmonic component of the second heart sound (15 percent)

� Jugular venousdistension (14 percent)

� Fever, mimicking pneumonia (3 percent)

PE Presentation (Scoring)� PERC (Pulmonary Embolism Rule Out Criteria)

� Age <50 years

� Heart rate <100 bpm

� Oxyhemoglobin saturation ≥95%

� No hemoptysis

� No estrogen use

� No prior DVT or PE

� No unilateral leg swelling

� No surgery/trauma requiring hospitalization within the prior four weeks

PE Diagnosis (D-Dimer)� Most useful in excluding PE in low risk patients

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PE Diagnosis (CT)� CTPA scan is the imaging modality of choice for

suspected PE

� Most sensitive and specific modality

PE Diagnosis (VQ Scan)� Modality of choice with patients that should not be

exposed to radiation or dye

� Less conclusive than CT, more inconclusive scans

PE Diagnosis (Radiography)� Not typically used to diagnose

� Hampton’s Hump

� Westmark’s Sign

PE Treatment: Initial Approach� Initial approach for patients with suspected PE should

focus upon stabilization

� Risk stratification is crucial (Hemodynamically stable/unstable)

PE Treatment: Initial Approach if

Unstable� Restore perfusion with IVF and vasopressors

� Stabilize airway

� UFH

PE Treatment: Definitive Approach

for Unstable Patients� Thrombolytic therapy is indicated in most

hemodynamically unstable patients, provided there is no contraindication

� Embolectomy indicated in those for whom thrombolytic therapy is either contraindicated or unsuccessful

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PE Treatment: Definitive Approach

for Stable Patients� If low bleed risks, anticoagulation is indicated

� For those with contraindications or a high bleeding risk, placement of an inferior vena cava (IVC) filter should be performed

DrugsTrade Name

Scientific Name

Bridging Dose Study

Coumadin Warfarin LMWH or UFH

Variable Numerous

Xarelto Rivaroxaban None 15 mg BID x 21 days,20 mg once daily

Einstein

Eliquis Apixaban None 10 mg BID x 7d, 5 mg bid

Amplify

Pradaxa Dabigatran LMWH or UFH

150 mg BID Re-Cover

PE Disposition� Discharge if HESTIA or PESI criteria met?

Weeda et al. on Reduced PE LOS

with rivaroxaban� 624 patients chart review

� Decreased LOS/Cost

� No Readmission Changes

� No Bleeds

Nguyen et al: Observation Not For

Sick People� PE still a serious disease

� According to IMPACT, ~46% of observation stay patients were at higher-risk for early post-PE mortality

Objectives � Identify the causes and risk factors of DVT/PE

� Present clinical work up and evaluation of DVT/PE

� Offer options for treatment and management of DVT/PE

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Questions??? References� UpToDate:� Overview of the causes of venous thrombosis - Authors: Kenneth A

Bauer, MD, Gregory YH Lip, MD, FRCPE, FESC, FACC� Clinical presentation and diagnosis of the nonpregnant adult with

suspected deep vein thrombosis of the lower extremity - Authors: Clive Kearon, MB, MRCP(I), FRCP(C), PhD, Kenneth A Bauer, MD

� Overview of the treatment of lower extremity deep vein thrombosis (DVT) – Authors: Gregory YH Lip, MD, FRCPE, FESC, FACC, Russell D Hull, MBBS, MSc

� Clinical presentation, evaluation, and diagnosis of the nonpregnantadult with suspected acute pulmonary embolism – Authors: B Taylor Thompson, MD, Christopher Kabrhel, MD, MPH

� Treatment, prognosis, and follow-up of acute pulmonary embolism in adults – Author: Victor F Tapson, MD