Deep Vein Thrombosis and Pulmonary Embolism, an Updated Review

DR. NERVIK ROY, D.O.

INTERNAL MEDICINE, PGY-2AUGUST 3RD, 2019

Lecture Overview

u Case

u Review of Pathophysiology

u Approach

u Clinical Decision Makingu Treatmentu References

Points to Remember

u VTEs usually have an inciting event; if we can find the trigger, we can prevent further episodes.

u Risk stratification is useful to detect events if imaging modalities are not possible. u It can also aid us in our determination if the VTE event is severely life-threatening.

u VTEs without a trigger, due to underlying hypercoaguable states require life-long anticoagulation

u Many studies out showing superiority of DOACs/NOACs

Case Presentation

u 56 YO Caucasian Male comes with complaints of shortness of breath and unilateral (Left) leg pain for 4 days duration.

u SOB has been progressively worsening for 4 days; “described as cannot catch his breath”

u Left leg pain: patient initially noticed it 2 weeks ago as what he described as a “crampy” type of pain, located in the calf; however, it has been increased in intensity since 4-5 days ago.

u SOB Exacerbated with exertion; leg pain is constant.

u SOB Relief with rest; no improvement in LLE pain with NSAIDs/opoids

u No chest pain, dizziness, syncope/near syncope, hemoptysis, abdominal pain.

Case Presentation, cont.

u Generally unremarkable PMH, no medicines except as needed albuterol inhaler

u Very fit and active; goes mountain biking

u Relevant history: patient recently had a mountain biking accident and suffered many broken bones and pneumothorax u Hospitalized for 4 days

u Had chest tubes in place for 3 days, multiple rib fractures and lower extremity bruises

u Decreased activity, more opioid use since accident

Case Presentation, cont.

u Relevant Physical exam findings:u HR: 101, RR 18-20, BP 130s/80s, O2 sat: 91% on RAu Gen: Well-developed/nourished, middle-aged Caucasian male, siting up-

right in bed, mild CP distressu Resp: CTAB, no use of accessory muscles, normal AP diameter, no

wheezes, rhonchi, rales. Saturating 91% at rest, 88% after movementu CV: Tachycardic rate (100s), normal rhythm; no murmurs/gallops/rubsu MSK: LLE – swelling without pitting edema, approximately 1.5x size of the

RLE. Negative Homans sign. LLE is erythematous in coloration as compared to RLE.

u Based off of this history, and physical what we are most worried about is:

u Venous Thromboembolism Events!

What are VTEs?

Definitions/Pathophysiology

u Venous thromboembolism (VTE) is an umbrella term for any venous clot. u It includes deep vein thrombi (DVT) and pulmonary embolisms (PE). u DVTs are in the venous systems of the extremities

u Distal lower extremity DVT – includes the calf or peroneal veinsu Proximal lower extremity DVT – includes popliteal, femoral and iliac veins.

u These are often more dangerous as they have high propensity to eventually travel to the pulmonary arteries

u Upper extremity DVT – includes axillary and subclavian veins

u PE’s are in the pulmonary arteries and their branchesu Can use the term to include superficial venous thrombosis (which can progress to

DVTs) or other internal clots such as mesenteric clots or cerebral venous sinus thrombosis.

Side note:

u There are both Venous and Arterial types of thrombus, but these are different in composition and appearance.

u Arterial thrombus – typically composed of platelet aggregates (white thrombus).

u Venous thrombus – largely consists of fibrin and red blood cells (red thrombus).

u We will be exploring the “Red Thrombi” in this discussion.

Definitions/Pathophys, cont.

u A deep vein thrombus (DVT) can “grow up” to become a pulmonary embolism (PE), but is part of the same spectrum of venous thromboembolism.u This is why we fear extremity VTE events

u But why do we fear PEs?u PE’s cause an exponential increase in pulmonary vascular resistance.

u This in turn causes increased afterload in the RV

u Causes progressive RV failure which then causes LV failure

u The Left ventricle (LV) fails in sequence dropping cardiac output and thus shock and hemodynamic instability.

Definitions/Pathophys, cont.

Virchow’s Triad

Definitions/Pathophys, cont.

u Provoked*u Setting of OCTs, recent surgery, abrupt inactivity, steroid use

u Unprovoked**u Also consider in the category:

u Recurrent DVT/PE

u Provoked with minor, persistent, irreversible or multiple risk factors

How do we approach patient’s with VTE events?

Clinical Decision Making

Patients with the clinical exam findings described above and a history of one of the below risk factors:

Surgery within 6 – 12 weeks**

Active cancer

Recent Trauma

Recent hospitalization/immobility/nursing home admission

Recent initiation of OCPs

Excessive use of testosterone supplements

Pregnancy

Obesity

Clinical Decision Making, cont.

u Risk stratification for DVT and PE

u Some of our best tools in order for us to determine the likelihood that a patient has a VTE event is to use the patient’s history, Physical exam, labs, etc to formulate a probability that can guide decision making for treatment vs further testing vs continuing current management.

u This is because treatment of VTEs carries its own risks and thus, careful planning and judgement must be used to determine the need for treatment

u Wells Score, Geneva Score, Minaiti Score and Charlotte rule, of which the Modified Wells Score is the most widely used and accepted scoring system for DVTs

u For PEs: PE Wells Score, Geneva score are the most accepted

Risk stratification for DVT

Modified Wells Score Geneva Score

Risk stratification for DVT, cont.

u The DVT Wells Score is most validated and most commonly used. It has primarily been validated in the outpatient setting.

u BUT, it is not sufficient for the inpatient setting.u The Wells score performed only slightly better than chance for discrimination of

risk for DVT in hospitalized patients.

u It had a higher failure rate and a lower efficiency in the inpatient setting compared with that reported in the outpatient literature.

u Therefore, the Wells score risk stratification is not sufficient to rule out DVT or influence management decisions in the inpatient setting.

u Thus, we rely on Imaging to prove the presence or absence of DVT’s in the inpatient setting

Risk Stratification for PE

u When it comes to PE’s, there is a two-tiered approach in regards to risk-stratification that is recommended

u First, Determine the Liklihood that the patient has a PE with risk factors, clinical signs/symptoms using: u PE Wells Score

u the PERC rule

u or the Geneva score.

Wells Criteria (For PE) PERC Rule

Risk stratification of PE, cont.

u It is important to know that once a patient has been diagnosed with a PE, we must decide whether the patient has a potentially life-threatening PE

u This can found in PE’s causing “right-heart strain” u Can test for RHS using troponins, pro-BNPs, Echocardiograms (TTE)

u Trops and BNPs can be very sensitive

u Thus, we must Risk stratify by PESI scoring and/or Hestia criteria to determine disposition

Risk stratification of PE, cont.

PESI score

The PESI score

u Somewhat complex scoring system

u In general, with the PESI score:u The patient is High-Risk if hypotension present.

u Low if minimal symptoms, and lack of RV strain on imaging.

u Intermediate is where the waters get murkey

u Intermediate-low if less severe RV dysfunction and patient looks well.

u Intermediate-high if more severe RV strain, increase RV:LV diameter, patient “looks ill”, high clot burden

Simplified PESI score (sPESI)

u The PESI score has a large range of numbers, thus a Simplified PESI score can be used and is more helpful becauseu Fewer patients were classified as low risk by sPESI than PESI

u and the sPESI derivation cohort had patients with more comorbidities than the original

u sPESI: age >80; h/o cancer, CHF, chronic lung disease; HR >110 bpm; systolic BP <100 mmHg; SaO2 <90%.

u Zero = low risk. One or above = high risk.

Simplified PESI score (sPESI), cont.

MDCalc

Diagnosis?

Diagnostic tools

u DVT:u Venous US extremity with Doppler

u D-Dimer

u Negative D-Dimer can Rule Out DVT

u PE:u V/Q scan

u CT-Angio Chest

u D-Dimer

Diagnostic tools, cont.

u For PE, can also obtain:u EKG

u Tachycardia

u Demonstration of RHS: S1Q3T3; RBBB; RAD; RAE, etc

u Transthoracic Echocardiogramu Demonstrating RV wall hypokinesis, dilatation, RV systolic dysfunction

u ABG

u Chest X-Ray

Treatment Algorithm for DVT

M. Streiff, 2016

Treatment Algorithm for PE

M. Streiff, 2016

How do we Treat VTEs?

Treatment

u Once you have properly identified the risk of the patient, we can then determine the therapy modality

u Treatment of low or intermediate-low risk patients: Anticoagulation with parenteral agent, vitamin K antagonist with a parenteral anticoagulant bridge, or a direct acting oral anticoagulant (DOAC).

u Treatment of intermediate-high risk patients: Consider IV unfractionated heparin for easy on/off since these patients might need more advanced therapy if they become unstable or their symptoms fail to improve on anticoagulation.

u Treatment of high risk PE requires Advanced therapies for PE such as Systemic thrombolytics, catheter-directed thrombolytics, thrombectomy (either surgical or catheter directed) along with IV unfractionated heparin.

Treatment, cont.

u Gold standard treatment for VTE is anticoagulation.u The majority of VTE can be treated with DOACs – Direct oral anticoagulant

(Formerly known as “NOACs” or “novel oral anticoagulants.”)

u If for some reason a patient cannot tolerate a DOAC, Warfarin can be usedu Target INR 2.5 (between 2.0-3.0)

u If the patient is inpatient: Use heparin (or LMWH) if there is concern for clinical deterioration (an intermediate to high risk Submassive PE)*u For patients with known diagnosis of Cancer, can use Lovenox; use of N/DOAC

is still being studied.***

Treatment, cont.

u DOAC – Direct oral anticoagulant (Formerly known as “NOACs” or “novel oral anticoagulants.”) u rivaroxaban

u apixaban

u edoxaban

u dabigatran

Treatment, cont.

u DOACs (rivaroxaban, apixaban) are used for VTE if no concern for clinical deterioration.

u This includes the cancer patient population even with active chemotherapy

u Providers should be more wary with upper GI cancer due to increased bleeding rates

u If a patient’s BMI is greater than 40, there is a reduced peak of DOACs. Blood volume goes up with body weight. u Pending further evidence in patients at the extremes of weight (e.g., <50 kg, >120 kg or BMI ≥ 35

kg/m2) it is advisable to limit DOAC use to situations where vitamin K antagonists cannot be used.”

Treatment, cont.

u Another treatment modality is catheter-directed Thrombectomy and/or Thrombolysisu Reserved for extensive, large, massive or certain submassive VTEs causing

hemodynamic instability (as discussed earlier)

u Include Systemic TPA (alteplase), IR or interventional cardiology directed thrombectomy/thrombolysis

u In these cases, consider IV unfractionated heparin if there is doubt with obtaining thrombectomy or thrombolysis

Treatment, cont.

u IVC filters have been shown to decrease pulmonary embolism in some cases but increase DVTs **u Isn’t helpful as prophylaxis in massive trauma patients, either***

u Use of these devices should be limited to patients with acute VTE who cannot receive anticoagulation.

u When IVCF are inserted for other indications this should be after much thought and coupled with appropriate documentation.

Treatment, cont.

u Durationu Provoked: at least 3 months, duration can last for up to 12 months*

u Unprovoked: Life-long anticoagulation, along with Aspirin

u DOAC’s and Warfarin (target INR 2.5)

u For female patients with first unprovoked VTE that want to discontinue anticoagulation, they can be risk stratified using the HERDOO2 calculator.

u There are tools to risk stratify for duration of anticoagulation as well, but they are not well validated and further testing/revisions are still occuing

Side note

u If a patient has recurrent DVTs and the history does not point to a trigger, there may be an underlying hypercoaguability

u Such as:u Canceru APL syndromeu Activated Protein C resistance (Factor V Leiden) or Protein C Deficiency

u Protein S Deficiencyu Elevated Factor VIII

u Sticky Platelet syndrome*

u These patients will need LIFE-LONG anticoagulationu Studies have shown however, that with DOAC’s, there is more recurrence of VTE events as

compared to Warfarin**u Thus, these patients must be on Warfarin with Target INR 2.5

For inpatient…

u For our patients that are inpatient and have high-risk PE’s or are hemodynamically unstable and we want to eventually have a disposition plan, we must make sure that:u Patient is off supplemental oxygen or are at baseline oxygen requirement

(COPD on Home O2)

u HR and BP are stable.

u Symptoms have improved and patient can tolerate ambulation.

u Patients must be strongly encouraged to have consistent and regular follow-up with PCP/HC provider.

Side note

u When using DOACs, it is imperative that a comprehensive medication reconciliation is performed.

u This is due to drug interactions with: u -Azoles

u -Rifampin

u -Chemotherapy agents

Back to the initial case:

u 56 YO Caucasian Male comes with complaints of shortness of breath and unilateral (Left) leg pain for 4 days duration; found to have LLE DVT as well as small, Bilateral PE’s

u Patient was seen in the ED, started on IV Heparin

u Patient’s symptoms were stable, O2 saturation at >95%, BP stable

u After overnight stay, patient was discharged with Oral Anticoagulation using a DOAC (Apixaban).

u Followed up with myself after 2 weeks, doing well

u Will keep patient on DOAC for approximately 4-5 months due to the patient having many work-travel plans; follow-up to determine if it is appropriate to discontinue

References

u 1. Risk Factors for Deep Vein Thrombosis and Pulmonary Embolism: A Population-Based Case-Control Study. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ. Arch Intern Med.2000;160(6):809–815. doi:10.1001/archinte.160.6.809

u 2. Eight-year follow-up of patients with permanent vena cava filters in the prevention of pulmonary embolism: the PREPIC (Prévention du Risque d’Embolie Pulmonaire par Interruption Cave) randomized study. Decousus, H. Circulation. 2005; 112: 416–422

u 3. Association Between Inferior Vena Cava Filter Insertion in Trauma Patients and In-Hospital and Overall Mortality. Sarosiek S, Rybin D, Weinberg J, Burke PA, Kasotakis G, Sloan JM. JAMA Surg. 2017;152(1):75–81. doi:10.1001/jamasurg.2016.3091

u 4. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. Allison E. Burnett, Charles E. Mahan, Sara R. Vazquez, Lynn B. Oertel, David A. Garcia, and Jack Ansell. J ThrombThrombolysis. 2016; 41: 206–232. 2016 Jan 16. doi: 10.1007/s11239-015-1310-7

u 5. Allison E. Burnett, Charles E. Mahan, Sara R. Vazquez, Lynn B. Oertel, David A. Garcia, Jack Ansell, J ThrombThrombolysis. 2016; 41: 206–232. Published online 2016 Jan 16. doi: 10.1007/s11239-015-1310-7

References, cont.

u 6. Comparison of the diagnostic performance of the original and modified Wells score in inpatients and outpatients with suspected deep vein thrombosis. Engelberger, Rolf P. et al. Thrombosis Research, Volume 127, Issue 6, 535 – 539.

u 7. Tapson VF. Acute pulmonary embolism. N Engl J Med 2008;358:1037–1052.

u 8. Fuster V, Moreno PR, Fayad ZA et al. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol2005;46:937–954

u 9. Merli GJ. Pathophysiology of venous thrombosis, thrombophilia, and the diagnosis of deep vein thrombosis-pulmonary embolism in the elderly. Clin Geriatr Med 2006;22:75–92, viii-ix.

u 10. Jerjes-Sanchez C. Venous and arterial thrombosis: a continuous spectrum of the same disease? Eur Heart J 2005;26:3–4.

u 11. Weinberg I, Abtahian F, Debiasi R, et al. Effect of delayed inferior vena cava filter retrieval after early initiation of anticoagulation. Am J Cardiol 2014;113:389-94.

u 12. Lip GYH, Blann AD. Thrombogenesis and fibrinolysis in acute coronary syndromes. Important facets of a prothrombotic or hypercoagulable state? J Am Coll Cardiol 2000;36:2044–2046.

u 13. Thomas RH. Hypercoagulability Syndromes. Arch Intern Med. 2001;161(20):2433–2439. doi:10.1001/archinte.161.20.2433

References, cont.

u 14. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Vittorio Pengo, et all. Blood 2018 132:1365-1371; doi: https://doi.org/10.1182/blood-2018-04-848333

u 15. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Jiménez D, et all. Arch Intern Med. 2010 Aug 9;170(15):1383-9. doi: 10.1001/archinternmed.2010.199.

u 16. Streiff, Michael. Guest/expert. “#153 DVT and PE Master Class with Michael Streiff MD”. The Curbsiders Internal Medicine Podcast https://thecurbsiders.com. June 10, 2019.

u 17. https://www.stoptheclot.org

u 18. MDCalc.com

u 19. UpToDate.com

Thank you, NOMA!