Venous Thromboembolic Disease

Arun Jagannathan MDVascular and Interventional Radiology

Epidemiology of VTE●1% of US hospital admissions

●900k cases of VTE resulting in 60-300k patient deaths per year, mostly in untreated patients with dx made postmortem or not diagnosed and attributed to another etiology (MI, arrhythmia, etc.)

●⅔ assoc w/ hospitalization in prior 90 days

DVT Precipitating FactorsRudolf Virchow (1821-1902)

●German physician, anthropologist, pathologist

●Elucidated the mechanism of DVT -> PE in 1859

●Coined terms embolism and thrombosis

What is Virchow’s Triad?

HypercoagulabilityCauses?

Hemodynamic Changes (Stasis, Turbulence)Causes?

Endothelial Injury or DysfunctionCauses?

Nomenclature●Proximal DVT

○ Popliteal and higher

●Isolated Distal DVT○ Calf veins alone involved

Nomenclature●Unprovoked DVT

○ No identifiable cause or provoking event

●Provoked DVT○ Transient cause such as medication (i.e. HRT)

○ Persistent reversible condition

■ Pregnancy, curable malignancy, post op immobility

○ Persistent irreversible condition

■ Chronic heart failure, metastatic end-stage malignancy, thrombophilias, etc.

●Initial anticoagulation○ First few days up to 10 days

Nomenclature●Long-term anticoagulation

○ Given for finite time beyond initial, usually 3-6 months, up to 12 months

●Extended anticoagulation○ Indefinite

●New/Novel Anticoagulants○ Direct factor Xa and thrombin inhibitors

Patient History and PhysicalS/Sx of DVT?

Physical Exam findings?

Complete Thrombosis History●Time of onset

●Location of prior thromboses

●Results of objective diagnostic studies with past episodes

●Potential precipitating events○ Surgery

○ Hospitalization

○ Trauma

○ Pregnancy

○ Heart Failure

○ Immobility

○ OCP

Complete Thrombosis History●Comorbid disorders

○ Collagen-vascular disorders

○ Myeloproliferative disorders

○ Atherosclerotic disease

○ Nephrotic syndrome

○ Malignancy history

●Family History○ Well documented positive VTE history in one or more 1st degree relatives under

50 suggestive of hereditary defect and/or increased susceptibility for VTE

●Special Clinical Settings○ Recurrent unprovoked DVT in pt < 50 -> consider hypercoag state or IVC anomaly

○ Recurrent left LE DVT consider May-Thurner

Imaging Evaluation●Duplex US screening tool of choice for both LE DVT and UE DVT

○ False positive rate very low

○ PPV 94%

○ UE eval limited in proximal subclavian and BCVs as well as iliac veins

○ NOTE: evaluation of calf veins is MUCH more limited with regards to sensitivity than proximal LE evaluation

●CTV/MRV○ Useful in evaluation of central extension of DVT

○ Useful in evaluation of potential obstructing downstream mass lesions or other anatomic abnormalities

US for DVT

Repeat US if symptoms persist or worsen!●If initial study is negative and clinical suspicion is high, repeat study

day 5 to 7

●Calf vein US evaluation is very operator and body habitus dependent

What about all these Baker’s cysts on US?●Popliteal fossa (or Baker’s) cyst is fluid filled often palpable mass

●May represent true cyst vs herniation of fluid in joint

●May rupture into posterior calf resulting in pseudothrombophlebitis syndrome

●Can cause leg swelling via compression of pop vein and possibly even DVT

Anatomic Risk Factors●Paget-Schroetter or spontaneous upper extremity venous

thrombosis○ Underlying compression at thoracic outlet

○ Usually compression of subclavian vein between first rib and hypertrophied scalene or subclavius tendon

○ Typically young, healthy patients

■ Classically young throwing athlete

○ Sudden onset severe UE edema and pain after activity

○ Evaluate with CTV or MRV

Anatomic Risk Factors●Paget Schroetter Treatment

○ Acute less than two week duration

■ Thrombolysis

■ Anticoagulation

■ Evaluation for surgical decompression and venoplasty

○ Delayed presentation (> 2 weeks) with mild or intermittent symptoms

■ Anticoagulation trial alone

Anatomic Risk Factors●May-Thurner Syndrome

○ Compression of left common iliac vein between right common iliac artery and vertebral body

○ Most common in women between 20 and 50

○ Consider as etiology in patient with unprovoked left iliofemoral DVT (propagating proximal to distal) or left LE chronic venous insufficiency

○ Evaluate with CTV/MRV (may overestimate)

Anatomic Risk Factors●May-Thurner Continued

○ Evaluate invasively using venography, IVUS, and pressure measurements

○ Treat with plasty/stent

Anatomic Risk Factors●IVC abnormalities

○ Agenesis

○ Hypoplasia or other malformation

○ Usually present with DVT in young patients that may be bilateral or recurrent with a clinical picture similar to inherited thrombophilias

Anatomic Risk Factors●Obstructing neoplastic mass lesion

Treatment of DVTUpdated ACCP 2016 Recommendations

●VTE -cancer: dabigatran/rivaroxiban/apixaban/edoxaban > VKA > LMWH

●VTE +cancer: LMWH > VKA and others

●Recurrent VTE on non-LMWH: LMWH

●Recurrent VTE on LMWH: Increase dose LMWH

Duration of Tx●Surgical or nonsurgical provoked DVT/PE: 3 months

●Unprovoked isolated distal or proximal DVT or PE: 3 months then reevaluate

●Second unprovoked VTE: indefinite anticoag with annual reassessment

●DVT/PE +cancer with low bleeding risk: indefinite anticoag with annual reassessment

Treatment of acute isolated distal DVT (calf)

●ACCP Guidelines 2016

●Unprovoked and without severe symptoms or risk factors for extension, serial imaging for 2 weeks over anticoag (US at 1 week and again 2 weeks)

●Unprovoked and with severe symptoms or risk factors for extension, suggest anticoagulation same as proximal DVT

●Provoked isolated distal DVT, suggest anticoagulation for 3 months

When CDT?●Patients with acute proximal LE DVT who attach a high value to

prevention of PTS and lower value to initial complexity, cost, and risk of bleeding with CDT

●Patients with acute proximal massive LE DVT resulting in phlegmasia

○ Phlegmasia abla dolens -> phelgmasia cerulea dolens -> venous gangrene

Phlegmasia Phlegmasia alba dolens

● Extensive acute LE DVT resulting in compromise of arterial inflow resulting in edema, pain, and white (alba) appearance of limb

Phlegmasia cerulea dolens

● Next stage where superficial venous drainage has also been compromised resulting in worsening pain, swelling and mottled purplish cyanotic (cerulean) appearance of extremity

● Emergent condition which may result in venous gangrene, compartment syndrome, circulatory collapse, shock and potentially death

Phlegmasia●Most common in 5th and 6th decades of life, higher in female and

males

●Malignancy in 20-40%

●Left > right involvement by 3-4x (May Thurner?)

Phlegmasia Treatment●Immediately begin IV UFH (not LMWH)

●Consult IR for Catheter directed thrombolysis/thrombectomy

Contraindications to Pharmacologic LysisAbsolute

● Intracranial tumor or recent intracranial or spinal surgery (< 2 months)

● History of hemorrhagic stroke

● History of ischemic stroke within 3 months

● Active bleeding or bleeding diathesis

Relative

● Severe uncontrolled HTN (>200 mmHg Sys or >110 Dia)

● Ischemic stroke older than 3 months

● Surgery within 10 days

● Pregnancy

DVT ThrombolysisSystemic

●Usually tPA (100mg IV over 2 hours)

●Reduced rates of PTS vs anticoag alone (43% vs 64%)

●Increased bleeding complications vs anticoag alone (9% vs 4%)

●Increased rates of complete clot lysis

●No difference in mortality or PE events

Catheter Directed Lysis (CDT)●Various methods of pharmacomechanical

thrombectomy/thrombolysis (discussed later)

●Can use much lower doses of lytics compared with systemic IV

●Lower rates of PTS (34% vs 70%) compared with anticoag alone

●No difference in nonfatal major bleeding (1.3% vs 0%)

●ATTRACT (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter Directed Thrombolysis) trial is a large randomized MCT (692 patients at 56 hospitals) of CDT in final follow-up phase of study

What is Post thrombotic Syndrome (PTS)?●Valve damage and incompetence

●Persistent venous obstruction (partial or complete)

●Increases vein and capillary pressures resulting in venous HTN

CEAP ClassificationClinical - C

●C0 - no visible disease

●C1 - telangiectasias/reticular veins

●C2 - varicose veins

●C3 - edema

●C4a - pigmentation or eczema

●C4b - lipodermatosclerosis

●C5 - healed venous ulcer

●C6 - active venous ulcer

CEAPEtiology - E

●Ec - congenital (Klippel-Trenaunay)

●Ep - primary (GSV/LSV reflux)

●Es - secondary (VTE, trauma)

CEAPAnatomy - A

●As - superficial

●Ad - deep

CEAPPathophysiology - P

●Pr - venous reflux (> 0.5s reverse flow on duplex US)

●Po - venous obstruction

●Pr,o - both

Measures of Clinical Severity●Venous clinical severity scale

●Venous disability score

●Venous segmental disease score

●Villalta scale○ Symptoms - pain, cramps, heaviness, paresthesias and pruritis

○ Signs - edema, induration, hyperpigmentation, redness, venous ectasia, pain

○ Assign points (none = 0, mild = 1, moderate = 2, severe = 3)

○ PTS not present: 0 to 4

○ Mild PTS: 5 to 9

○ Moderate PTS: 10 to 14

○ Severe PTS: > 15

Options for CDTAngioJet Thrombectomy

●Can be performed with limited or no tPA if needed

●Works best for acute thrombosis (less than 3-5d)

https://youtu.be/0QUUBZ6BxSo

https://vimeo.com/85367047

Options for CDTEKOS EkoSonic Endovascular System

https://www.btg-im.com/EKOS/US/Products/Technology#

Options for CDTBasic infusion catheters

●Cragg-McNamara

●Unifuse

Options for CDTAngioVac - The Big Gun

http://fast.wistia.net/embed/iframe/zncnq8a00p?popover=true

Complications from CDT●Bleeding risks are relatively low

●Observational study of 3649 pts with acute DVT treated with CDT plus anticoag or anticoag alone

○ Increased blood Tx in CDT patients (11% vs 7%)

○ Intracranial hemorrhage (0.9% vs 0.3%)

Caval InterruptionIVC Filters

IVC Filters●ACCP: Patients with Acute DVT/PE Tx’d with anticoagulants

recommend AGAINST routine use of IVC filter

When to filter?●Contraindication to anticoagulation

●Failure of anticoagulation

●Limited ability to tolerate additional PE burden○ Acute hemodynamically massive PE

○ Chronic thromboembolic pulmonary HTN

●Prophylactic placement (high risk spine injury or bariatric or spine surgery, other major traumas, major burn victims)

Complications of IVC Filters● Retrospective study of 80k noncancer patients in CA with no contraindication to

anticoag found 1 year incidence of DVT was 5.4% with filter vs 3.7% without

● Group of pts with active bleeding and filter had 32% reduction in adjusted risk of death at 30 days compared to no filter

● Other risks such as migration, fracture, erosion and perforation are uncommon with newest generation of filters

IVC Filter Retrieval● Always routinely reevaluate for potential filter retrieval

● The service that places the filter MUST maintain a registry of these patients

Double edged sword

Upper extremity DVT●Majority (70-80%) of both superficial and deep upper extremity

thrombosis secondary to intravenous catheters

●Superficial thrombophlebitis usually self limited with removal of device

●UE DVT contributes to 6% of PE

Upper extremity indwelling venous devices●Peripheral IV

●PICC

●Tunneled and nontunneled CVC

●Implantable ports

●Pacemakers

Risk factors for catheter related thrombosis●Previous DVT and other risk factors (malignancy,

hypercoagulability)

●Subclavian venipuncture

●Improper catheter tip position (not in SVC/RA)

●PICC○ Catheter diameter relative to vessel -> stasis and endothelial damage

○ Hospitalized patients 5-15% DVT rate

○ Ambulatory patients 2-5% DVT rate

Key Points for Central Venous Access●Appropriate device for type of access and duration needed

●IJV > SCV > FV for CVC (lower thrombosis and infection rates)

●PICC is NOT first line access for emergent or routine inpatient treatment (obtain CVC)

●Use US guidance for CVC access if possible

●CKD/ESRD patients NO PICC, only peripheral IV below elbow (ideally dorsum of hand), CVC, or SBCC

Treatment of UE DVT●Same as LE DVT with regards to anticoagulation

●Catheter can be left in place with longer duration of anticoagulation for those with need for long term access (i.e. cancer patient with port)

●CDT reserved for severe central venous occlusion resulting in SVC syndrome

Important Take Home Points● Complete Thrombosis History is important

● US best screening tool for DVT eval, but know the limitations (calf veins, central chest and abdominopelvic veins)

● Recognize Phlegmasia, can progress rapidly!

○ Cyanotic and swollen extremity think phlegmasia cerulea dolens

○ Cyanotic WITHOUT edema think arterial occlusion

● Consider CDT in healthy active patients with acute proximal DVT to mitigate PTS

● IVC Filters are not benign leave and forget implants

● Appropriate use of upper extremity venous access catheters to limit burning bridges for future access (dialysis, etc.)

Part II: PE Evaluation and Treatment

Important FactorsTime of onset: acute, subacute, or chronic

Hemodynamically stable or not?

Anatomic location: saddle, lobar, segmental, subsegmental

Symptomatic or not?

CTA PE

CT Findings Suggesting Right Heart Strain

Stable patient?

Unstable patient?

Tweeners●Hemodynamically stable normotensive patients with intermediate-

risk submassive PE

●Anticoagulate and monitor closely for deterioration

●Example: Patient with large clot burden, severe RV dysfunction, high O2 requirement and severe tachycardia

What about subsegmental PE?●ACCP 2016 states patients with subsegmental PE and no proximal

DVT in legs who have low risk for recurrent VTE can be watched clinically without anticoagulation

●Can supplement surveillance with serial lower extremity DVT US

Systemic IV Thrombolysis●Hemodynamically unstable patients without high bleeding risk

●Select patients with submassive PE who are deteriorating after anticoagulation but not yet hypotensive

○ Deterioration may include worsening:

■ Symptoms

■ Vitals

■ TIssue Perfusion

■ Gas exchange

■ Cardiac biomarkers

PE CDT●Catheter Directed therapies include pharmacologic and mechanical

thrombolysis as well as thrombectomy

●Hemodynamically unstable patients or deteriorating submassive PE patients with high bleeding risk or who require rapid clot burden resolution

●Can be performed rapidly with lower doses of tPA (often 25 mg or less) compared with systemic (100 mg in standard weight patient)

Methods of PE CDT●Ultrasound-assisted thrombolysis

●Rheolytic thrombolysis

●Rotational embolectomy

●Suction embolectomy

●Thrombus fragmentation (Rotating pigtail catheter)

Risks of CDT●Bleeding

●Pulmonary artery perforation (very rare)

●AKI or severe bradycardia with rheolytic embolectomy

Surgical Embolectomy●Unstable patients for whom thrombolysis is contraindicated

●Embolus trapped in PFO or in RA or RV

●Only proximal emboli can be removed (RV, mPA, extrapulmonary PA)

How do we do it?●Saddle PE

○ Rotating pigtail fragmentation followed by bilateral infusion catheter placement (ultrasonic or regular)

●Peripheral PE○ If relatively evenly distributed and beyond lobar branches, not much benefit in

CDT over systemic IV

○ If relatively isolated or more proximal involvement from main branch or lobar branch, CDT bolus/drip

●Endpoint of treatment is based on combination of clinical picture and PA pressures (20-30 over 8-12 mmHg), no need to repeat venogram

○ Good, better, bust!

Final Points●PE CDT only indicated in unstable or deteriorating submassive PE

patients with high bleeding risk or requiring rapid clot dissolution

●Indications for surgical embolectomy: PFO/RA/RV thrombus or absolute contraindication for thrombolysis in unstable patient