#154 DVT and PE Master Class with Michael Streiff MD

June 10, 2019 | By Justin Berk

How to approach, diagnose and treat venous thromboembolism (VTE)

What do Judas Priest, surfing, and clots have in common? They are the passionate interests of expert Dr. Michael Streiff who guides us through the diagnosis and management of DVT and PE aka venous thromboembolism (VTE). By the end of the episode you will know how to catch a clot very Wells! We dive deep into the treatment options, literature, and some unique cases. ACP members can claim CME-MOC credit at https://acponline.org/curbsiders (CME goes live at 0900 ET on the episode’s release date).

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Credits

• Written and produced by (including CME questions): Justin Berk MD, MPH, MBA
• Cover art by: Kate Grant MBChB DipGUMed
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP; Stuart Brigham MD
• Edited by: Matthew Watto, MD, FACP
• Guest:  Michael Streiff MD

Time Stamps

• 00:00 Intro, disclaimer and guest bio
• 04:40 Guest one-liner, book and music recommendations, advice about rejection, how to think about studies
• 11:15 A case of DVT and some basic terminology
• 15:37 Which DVT risk factors are most important?
• 18:40 Use of the Wells score and D-dimer testing; should we use an age adjusted D-dimer; What about the YEARS criteria
• 22:55 Classifying DVT; determining need and duration of anticoagulation [distal (calf vein) DVT, proximal DVT]; brief discussion of IVC filters & catheter directed therapies
• 27:56 IVC filters for trauma
• 29:30 Upper extremity DVT
• 33:12 Proximal vs whole leg ultrasound for diagnosis of DVT
• 36:25 A case of pulmonary embolism; how to diagnose pulmonary embolism and a bit on V/Q scans
• 40:35 PESI score and HESTIA criteria
• 42:05 Summary of how to diagnose DVT and PE
• 43:34 Choice of initial anticoagulation
• 45:29 DOACs for cancer
• 48:14 DOACs for patients with very high or very low BMI
• 49:33 Why apixaban is Dr Streiff’s favorite DOAC?
• 51:20 Duration of therapy for DVT and PE
• 53:33 Unprovoked DVT and PE: Risk scoring models
• 57:52 Is thrombophilia workup necessary?
• 58:28 Antiphospholipid antibody syndrome
• 59:58 An extensive cancer workup is unnecessary
• 60:33 Subsegmental pulmonary embolism: To treat or not to treat
• 61:49 Apixaban dosing in CKD and ESRD
• 63:51 AUGUSTUS trial for dual versus triple therapy after ACS
• 64:52 Plug for National Blood Clot Alliance “Stop the Clot”; Anticoagulation Forum website; 2019 ASH guidelines are coming
• 66:35 Outro
• 68:00 Post credit scene

Persistence. If you have an article rejected 10 times, send it to an eleventh place.

Michael Streiff, MD offers advice on becoming a successful researcher

DVT and PE Pearls

Risk factors for VTE include recent surgery, hospitalization, OCPs, testosterone supplementation, pregnancy and obesity.

The DVT Wells Score is most validated and most commonly used clinical prediction tool for DVT, but it should only be used in the outpatient setting!

D-dimers can be age-adjusted to help reduce unnecessary ultrasound imaging (Schouten BMJ 2013).

Symptoms for PE can may be very mild: exertional dyspnea, mild back pain, or just feeling tired (PIOPED II Am J Med 2007).

V/Q scans are indeterminate for PE about 30% of the time (Sostman 2008).

The majority of VTE can be treated with direct oral anticoagulants (DOACs) including patients with cancer (SELECT-D, Hokusai cancer study).

Unprovoked upper extremity DVT warrants investigation for thoracic outlet syndrome.

Unprovoked VTE does not warrant cancer work-up (SOME Investigators NEJM 2015).

Female patients with first unprovoked VTE who want to discontinue anticoagulation, can be risk stratified using the HERDOO2 calculator (Rodger 2017).

Isolated subsegmental pulmonary embolism without DVT, underlying cancer, or other major risk factors can be followed with clinical surveillance i.e. no anticoagulation (VTE Guidelines Chest 2016)

DVT and PE Show Notes

Definitions

Venous thromboembolism is an umbrella term for any venous clot.  It includes deep venous clots (DVT) and pulmonary embolisms (PE). Others may also 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.

Distal lower extremity DVT – includes the calf or peroneal veins

Proximal lower extremity DVT – includes popliteal, femoral and iliac veins. These are often more dangerous.

Upper extremity DVT – includes axillary and subclavian veins

DOAC – Direct oral anticoagulant (eg rivaroxaban, apixaban, edoxaban, dabigatran). Formerly known as “NOACs” or “novel oral anticoagulants.”

The Diagnosis – DVT

Producer’s Note: Check out the JAMA Rational Clinical Exam article from 2006 on diagnosis of DVT.

Signs and Symptoms

A common description of DVT pain: A crampy calf pain that won’t go away. A leg cramp that won’t message out. Others may complain of leg distension/swelling or a pressure sensation. On exam: the patient may have change in color or size of the limb and may have edema in the ankles.

Risk factors for VTE: Surgery within 6 – 12 weeks is a strong risk factor as is cancer, recent hospitalization, recent initiation of OCPs, excessive use of testosterone supplements, pregnancy, and obesity.

Clinical Prediction Rules help establish pre-test probability. The DVT Wells Score is most validated and most commonly used. It has been validated in the outpatient setting. BUT, it is not sufficient for the inpatient setting (Silveira 2015).

Labs and Diagnostics

A negative D-dimer can rule out DVT (Wells NEJM 2003). You can also follow general diagnostic algorithms.

D-dimers should be age-adjusted to help reduce unnecessary ultrasound imaging. What’s the cut-off for a “positive” d-dimer? Use 500 mcg/L if under 50. If over 50, multiply the patient’s age by 10 (Schouten 2013).

The gold standard to confirm diagnosis is an ultrasound. Imaging can be a proximal leg ultrasound (i.e. only looking at popliteal and femoral veins) or a whole leg ultrasound which looks more distally including posterior tibial veins.

In Europe: the trend is to use more proximal ultrasound imaging with close follow-up (NICE  guideline) as there has been shown to be no outcome difference between proximal and whole leg ultrasound imaging. In the US: whole leg ultrasound is more commonly done (AHA guideline).

Expert Opinion: Whole leg ultrasound is recommended by Dr. Streiff: A symptomatic distal DVT would likely warrant treatment and it is difficult to get serial ultrasound imaging that may be required with proximal-only ultrasound imaging.

The Diagnosis of a PE

Producer’s Note: Check out the JAMA Rational Clinical Exam article from 2003 on diagnosis of PE

Signs and Symptoms

The signs and symptoms can sometimes be vague. Classic symptoms are pleuritic chest pain, shortness of breath or hemoptysis. Other symptoms may be very mild: exertional dyspnea, mild back pain, or just feeling tired (PIOPED II Am J Med 2007).

Labs and Diagnostics

A general approach is to ask about risk factors, calculate a PE Wells Score (or Geneva score), and look at d-dimer.

• The YEARS Algorithm can also be used to risk stratify based on d-dimer. The single study used a higher d-dimer cutoff of 1000 mcg/L if no hemoptysis, DVT, or high suspicion of PE.

V/Q Scans are rarely helpful in diagnosis of PE. They are indeterminate about 30% of the time. In pregnancy, CT may be less radiation than V/Q scan but both are probably safe. (In this population, you can also just use US to look for DVT to potentially start anticoagulation without additional imaging.)

The gold standard for diagnosis is a CT angiogram with PE protocol. CT can assess for location, clot burden, and may look for RV overload.

After the diagnosis of a PE

After diagnosis, one must risk-stratify to determine if the PE is “Submassive” based on right-heart strain. Many send troponins and proBNP but Dr. Streiff warns that these can be very sensitive and are often elevated. Echocardiogram is also frequently used to monitor for right heart strain.

Risk stratification can also be done by PESI scoring and Hestia criteria to determine disposition. (See the previous Curbsider’s Episode with Owen Friedman: Episode #92: Pulmonary Embolism for the Internist)

Producer’s Note: Echocardiography in a hemodynamically stable patient with PE was recently discussed as a ‘Things We Do For No Reason.” (See previous guest @WrayCharles‘s Visual Abstract)

The Treatment for DVT and PE

Producer’s Note: For comprehensive discussion, please see JTT Guidance Statement, authored by our guest Dr. Streiff.

General Treatment

Gold standard treatment for VTE is anticoagulation. The majority of VTE can be treated with direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban.

Use heparin (or LMWH) if there is concern for clinical deterioration i.e. an intermediate to high risk Submassive PE. Rationale: Heparin is short acting if they need to have an intervention (i.e. thrombectomy or catheter directed thrombolysis).

The ATTRACT trial showed that among patients with proximal DVT, catheter-directed  thrombolysis did not result in lower post-thrombotic syndrome but did have a higher risk of bleeding. However, this intervention may still be indicated in cases like iliac compression syndrome or May Thurner syndrome. (Expert Opinion).

IVC filters have been shown to decrease pulmonary embolism in some cases but increase DVTs and have no mortality benefit. Dr Streiff highlights: they fracture, migrate, and cause recurrent clots.

There is no good data for prophylactic IVC filter placement in massive trauma patients. Instead, Dr. Streiff recommends using sequential compression devices (SCDs) and pharmacological prophylaxis early. Indications for IVC filter were not discussed but can be found here.

DOACs

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

• This includes the cancer patient population (SELECT-D, Hokusai cancer study) even with active chemotherapy
• Look out for drug interactions with azoles, rifampin, and a small number of chemotherapy agents
• Providers should be more wary with upper GI cancer due to increased bleeding rates

If a patient’s BMI is greater than 40, there is a reduced peak of DOACs. Blood volume goes up with body weight. In RE-LY study, dabigatran drug levels were lower in higher weights.

ISTH Guideline Summary on DOAC treatment: ”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.”

Expert Opinion: Apixaban is a Dr. Streiff favorite. Clotting is about the same as warfarin and bleeding rates are somewhat lower. Apixaban has a 12-hr half-life compared to rivaroxaban which is 5-9 hours. The thought is that apixaban will have fewer peaks and troughs and this is perhaps why it is associated less menorrhagia. “Though both are great.”

Treatment Duration

Treatment is 3 – 6 months if a trigger is identified (e.g. surgery, hospitalization, OCPs) and has been removed. This can be based on risk stratification.

If there is no identified trigger (i.e. an unprovoked clot) or there is an ongoing risk factor that is not removed (e.g. active malignancy), treatment duration is indefinite.  

For female patients with first unprovoked VTE that want to discontinue anticoagulation, they can be risk stratified using the HERDOO2 calculator. This has been well validated.

• If low risk, there is a  <3% of recurrence
• Men have twice the risk for recurrence so there is no true “low risk.” Expert Opinion: Treat indefinitely.  

Other models to risk stratify for discontinuation of anticoagulation include: Vienna (less validated), DASH Model (uses d-dimer, hormone use, age, gender). They can also be used for counseling and shared patient decision-making.

Isolated Calf DVT

Treatment of a calf vein DVT (or isolated distal deep vein thrombosis (IDDVT) is somewhat controversial. Expert opinion: Treat for 6 – 12 weeks, especially if symptomatic.

Expert Opinion: When doing a DVT ultrasound, make sure to visualize the top of the clot to ensure no May Thurner syndrome because this may change management (i.e. need for an iliac vein stent).

Upper extremity DVT

Distal upper extremity clots are less likely to need anticoagulation. Lines are risk factors. An unprovoked upper extremity DVT, warrants investigation for thoracic outlet syndrome, particularly if a gymnast or weightlifter. Similarly, if the patient is an older person with cancer, think about thoracic outlet syndrome secondary to cancer in the apex of the lung.

If an intravenous line is in place, treat for 3 months or until line is removed (Cohen ACP Hospitalist 2016). Example: If there is a PICC-associated clot, treat for 3 months, even after the line is pulled. (Expert Opinion: You can probably treat a shorter duration, but this is only based on observational data).

Expert Lightning Round: Questions and Answers

When should providers do a Thrombophilia work-up?

Only if concerned for antiphospholipid syndrome (APLS). If the patient has APLS, DOACs should not be used as they have a 5x higher recurrence when compared to warfarin (Pengo 2018). Instead, treat with warfarin. INR may also be misleading so it can be worthwhile to check a non-clot based assay (i.e. a chromogenic factor X) to ensure appropriate anticoagulation levels. Point-of-care INRs should also not be used in the presence of lupus anticoagulant (BUT, POC INRs are not affected antibodies to cardiolipin or beta 2 glycoprotein).

In patients with unprovoked VTE, should providers do an extensive cancer work-up?

Unprovoked VTE does not warrant cancer work-up. (SOME Trial shows it does not pick-up new cancers or affect outcomes). The recommendation is to ensure age-appropriate cancer screening is performed.

Should isolated subsegmental pulmonary embolisms be treated if incidentally found?

If the patient has underlying cancer, treat. If no cancer, look for DVTs and treat if those are present. If not, clinical surveillance only is recommended (CHEST Guidelines), but with the caveat that there is not great data and studies are pending.

Does apixaban need to be renally dosed in CKD?

A large observational study in Circulation 2018 showed CKD patients with atrial fibrillation did better with apixaban 5mg twice daily than 2.5mg twice daily. There was an associated decrease in VTE. Despite being renally excreted, apixaban levels looked to be safe with the higher dose.

Goals and Learning Objectives

Goal

Listeners will gain a broad understanding of the diagnosis and management strategies for venous thromboembolism.

Learning objectives

After listening to this episode listeners will…

1. Define basic terms include DVT, PE, VTE, and DOAC
2. Identify common signs and symptoms of DVT and how to use clinical prediction tools
3. Explain the role of d-dimer in ruling out DVT and PE
4. Use calculated criteria to risk stratify pulmonary embolism
5. Discuss the role of IVC filters and some of their adverse side effects
6. Determine the most common treatment for basic VTE and in special subpopulations such as patients with active cancer
7. Gain exposure to the difference in treatment durations for various types of venous thromboembolism

Disclosures

Dr Streiff reports research grants from Janssen, Boehringer/Ingelheim, Roche and consultantships with Janseen and Pfizer. The Curbsiders report no relevant financial disclosures for this episode.

Links

Referenced articles and supporting links embedded in text.

1. Judas Priest tour dates
2. The Lost Art of Healing by Bernard Lown MD
3. Streiff et al. “Guidance for the treatment of deep vein thrombosis and pulmonary embolism” Journal of Thrombosis and Thrombolysis. 2016.
4. SOME Trial (cancer work-up in new VTE): https://www.nejm.org/doi/full/10.1056/NEJMoa1506623
5. YEARS Study Algorithm to Dx PE: https://www.ncbi.nlm.nih.gov/pubmed/28549662
6. CHEST Guidelines for AC Therapy in VTE: https://www.ncbi.nlm.nih.gov/pubmed/26867832
7. ATS Reading list on PE: https://www.thoracic.org/professionals/career-development/residents-medical-students/ats-reading-list/adult/pulmonary-embolism.php
8. National Blood Clot Alliance “Stop The Clot” website
9. Anticoagulation Forum Website
10. ASH Guidelines (new ones coming soon)

Citation

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