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210 Oscar Y. Moreno-Rocha, et al.
The use of bridging (temporary interruption and restarting of anticoagulation) during
surgical procedures has been controversial. Bridging has been found to be associated with no
decrease in thrombotic events but with a higher risk of bleeding and should only be used in
high-risk patients. Currently, bridging therapy is only recommended for patients with atrial
fibrillation and a recent stroke, atrial fibrillation and a high CHADS2 score,
within the past 3 months, or mechanical cardiac valves, especially mitral valves.
(5, 6)
a recent VTE
(79)
The availability of DOACs with short half-lives has decreased the need for heparin or LMWH-based
bridging. In most cases, DOACs only need to be stopped for 1 day for minor procedures and
2 days for major procedures and can be restarted as soon as it is safe from a surgical or procedural perspective. All patients taking anticoagulant medications should be monitored for
therapeutic efficacy (recurrence prevention), bleeding, the development of conditions that can
affect the half-life of the medications (renal failure, pregnancy, weight gain/loss), as well as for
adverse effects of the medications (such as skin necrosis, thrombocytopenia, or osteoporosis).
In patients with active cancer, using LMWH is superior to LMWH converted to warfarin
in patients with a renal clearance of ≥30 mL/min, and anticoagulation should be given for
a minimum of 6 months or until the cancer is no longer active. Edoxaban, rivaroxaban, or
apixaban are recommended in cancer patients with creatinine clearance is ≥30 mL/min in the
absence of strong pharmacological interactions or gastrointestinal absorption impairment.
Edoxaban and rivaroxaban should be used with caution in patients with a GI malignancy
due to an increased risk of GI bleeding.
(80)
Complications
Bleeding is the most common complication of anticoagulation. Tools available, such as the
HAS-BLED score, can help estimate a patient’s risk of bleeding while taking anticoagulant
medications.
(81–83)
Risk factors for bleeding while on anticoagulation include age >65 (1
point), age >75 (2 points), previous bleeding, cancer and metastatic cancer, renal or liver failure, thrombocytopenia, prior stroke, diabetes, anemia, concurrent antiplatelet therapy, poor
anticoagulant control, reduced functional capacity, recent surgery (within 3 months from
index event), frequent falls (two or more in the last year), alcohol abuse, and non-steroidal
anti-inflammatory drug use (NSAIDs).
(10, 84)
The presence of zero risk factors for major bleeding confers an absolute risk of 0.8% per year. Patients with one risk factor have a risk of 1.6%
per year, and those with two or more have a 6.5% risk or higher per year. Standard heparin
is associated with a bleeding rate of 10% over the first 5 days of treatment. Warfarin has
a major bleeding rate of 1–2% per year. DOACs may have a total bleeding rate of 5–10%,
although the risk of intracerebral bleeding appears to be lower than warfarin. However, the
DOACs have their own challenges, including difficulty reversing their anticoagulant effects
and difficulties with laboratory monitoring.
Heparin-induced thrombocytopenia (HIT) can occur in 0.6 to 30% of patients taking
heparin or LMWH, which is associated with high morbidity and mortality rates. Still, early
diagnosis and appropriate treatment can decrease these rates. HIT usually develops 3–14
days after starting unfractionated heparin, although it can occur earlier in patients who have
previously been exposed to heparin. Even small exposures to heparin, such as heparin coating on indwelling catheters, can cause HIT. This exposure leads to the formation of antibodies that bind to platelets and activate them, releasing procoagulant microparticles and
leading to increased thrombocytopenia and thrombosis. LMWHs have high cross-reactivity
with standard heparin antibodies. Both UFH and LMWH have been associated with HIT,
although the incidence and severity of thrombosis are lower with LMWH. The HIT diagnosis
might be suspected with a 50% or greater drop in platelet count below 100,000/uL or when
Contemporary and Evidence-Based Medical Therapy for VTE 211
thrombosis occurs during heparin or LMWH therapy. There are two laboratory tests for HIT.
The enzyme-linked immunosorbent assay (ELISA) can detect the anti-heparin antibody in
the plasma, but this test is highly sensitive but not very specific. The serotonin release assay
can be used as a confirmatory test and is more specific but less sensitive than the enzymelinked immunosorbent assay. Heparin must be discontinued, and oral anticoagulation should
not be started until an alternative anticoagulant has been established and the platelet count
has normalized. Argatroban is FDA-approved for prophylaxis and treatment of thrombosis
in patients with HIT and HITTS (heparin-induced thrombocytopenia and thrombosis syndrome).
(85, 86)
Non-FDA-approved alternatives include fondaparinux (Arixtra).
(10)
New Novel Therapies for VTE
The goals of treating DVT are to prevent the extension or recurrence of DVT, prevent PE,
and minimize the long-term effects of thrombosis, such as CVI. Standard anticoagulants can
achieve the first two goals but not the third. PTS can occur in up to 30–50% of patients
with DVT and even more frequently in patients with iliofemoral DVT. Reopening the vein
is thought to alleviate venous hypertension and prevent PTS, a concept known as the “open
vein hypothesis”.
thrombosis, including the fact that prolonged contact of the thrombus with the vein wall can
increase damage and that the thrombus can initiate an inflammatory response in the vein
wall that can lead to vein wall fibrosis and valvular dysfunction. The longer a thrombus is in
contact with a vein valve, the less likely it is to function correctly.
With the previous comments in mind, alternative forms of therapy with improved efficacy
and decreased bleeding are needed to address these limitations. Factor XII and XI have been
identified as potential targets for such agents.
itate and augment thrombosis, have also been studied as potential biomarkers for thrombosis
and as targets for agents to limit thrombosis and subsequent vein wall fibrosis that leads to
PTS. Inhibition of P-selectin and E-selectin has been shown to decrease thrombosis and vein
wall fibrosis without increasing bleeding in multiple different animal models (and E-selectin
inhibition in two patients with calf vein thrombosis).
area of future study for treating VTE, either as a standalone therapy or as an adjunct to
standard anticoagulation. Additionally, novel therapies to enhance fibrinolysis and decrease
inflammation in PE and DVT patients are under development. These novel VTE therapies
offer opportunities for improving treatment outcomes.
ment (specifically in the treatment of PE) is the use of PE response teams (PERTs), which have
become common. They allow for a coordinated and rapid treatment of PE by a multidisciplinary group of providers, such as non-invasive clinicians, emergency physicians, clinical
pharmacists, endovascular proceduralists, and cardiac, thoracic, and vascular surgeons. The
effectiveness of the PERT team for the treatment of PE is an area of active investigation.
(87)
There is evidence to support more aggressive treatments for extensive
(10)
(88)
Selectins, a family of glycoproteins that facil-
(86)
Selectin inhibition is a promising
(89–99)
Finally, another new develop-
(10)
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Chapter 21
Endovascular Management of Deep Venous Thrombosis
Tyler Callese, Savannah Fletcher,Aniket Joglekar,
Lucas Cusumano, John Moriarty, and Justin McWilliams
INTRODUCTION
Endovascular treatment of deep venous thrombosis (DVT) is largely based on the “open vein
hypothesis,” which suggests that the proactive removal of thrombus improves flow within
the deep venous system, prevents chronic venous hypertension, venous reflux and decreases
the risk of post-thrombotic syndrome (PTS).
anticoagulation and compression stockings, is effective at preventing thrombus propagation
and decreasing risk of pulmonary embolism, in almost half of all patients it does not restore
baseline quality of life or prevent PTS.
(2)
Catheter-directed therapies are effective at rapidly removing thrombus and restoring inline flow with randomized trials supporting the implementation of these techniques in certain
populations. Patient selection and procedure technique depend on the location, extent, etiology, and clinical presentation of DVT. This chapter reviews methods of endovascular thrombus removal and management recommendations based on clinical presentation.
(1)
While conservative management, including
ENDOVASCULAR TECHNIQUES AND DEVICES
Catheter-Directed Thrombolysis
Catheter-directed thrombolysis (CDT) most commonly involves straight, multiple side-hole
infusion catheters (Table21.1), which are placed across the thrombosed segment for direct
administration of fibrinolytic agents into the thrombus.
nase, streptokinase, reteplase, tenecteplase, and tissue plasminogen activator (tPA).
requires lower doses of lytic agents compared to systemic thrombolysis, minimizing the risk
of systemic bleeding.
(4)
Contraindications to thrombolytic agents include recent or active
hemorrhagic event (cerebral, gastrointestinal, trauma, etc.) or major surgery.
In the first stage of CDT, infusion catheters are placed across the thrombus and lytic agents
are administered for 12 to 36hours.
(5)
tPA is commonly used and generally administered
at 0.01 mg/kg/hr mg/hr up to a max dose of 20 mg/24hours or fixed dose of 0.25–1 mg/
(12)
h r.
Systemic anticoagulation is held during thrombolysis, but subtherapeutic (300–500
Units/hour) unfractionated heparin is typically administered through the sheath side-arm(s)
to prevent additional thrombus formation.
(13)
Patients are monitored closely in the intensive
care unit or specialty surgical ward for evidence of complications associated with bleeding.
In the second stage, venography is performed to evaluate for thrombus resolution and any
underlying anatomy and pathology that may indicate adjunctive procedures, such as venoplasty and stenting.
(14)
There is no consensus regarding the necessity of, or a standardized
protocol for, fibrinogen monitoring during thrombolysis and significant practice variability
(15)
exists.
(3)
Fibrinolytic agents include uroki-
(2, 4)
(5)
CDT
(5)
DOI: 10.1201/9781003316626-24 217
Table 21.1 Endovascular Devices for Deep Venous Thrombosis Interventions
218 Tyler Callese, et al.
Manufacturer Device Name Size (Fr) Device Components
Angiodynamics AlphaVac System 25 22 Fr funnel-tip catheter (20- or 180-degree tip)
Argon Medical
Devices, Inc.
Boston Scientific
Corporation
Inari Medical FlowTriever System 16,20,24 Mechanical
Medtronic Cragg-McNamara Valved
Penumbra, Inc Indigo System 3,5,6,7,8,12,16 Penumbra Engine aspiration source
Cleaner 15 7 Handheld battery-driven motor with atraumatic
Cleaner XT 6
AngioJet ZelanteDVT 8 AngioJet Ultra Console (monitors and energizes
AngioJet Solent Omni 6
AngioJet Solent Proxi 6
Ekos+ Endovascular
System
ClotTriever System 13, 16 ClotTriever catheter
Infusion Catheter
8 Ultrasound-
4, 5 Single-use single lumen catheter with variable
Aspiration handle
250 cc waste canister
sinusoidal wire tip
pump)
Optional Clothunter device compatible with
ZelanteDVT device facilitates wall-to-wall contact
Ekos Control Unit CU 4.0 (current generation) able
to control two Ekos+ catheters
Single-use 7.8 Fr catheter with ultrasonic core and
varying infusion lengths (8–20cm)
Triever Aspiration catheter
Optional Intri24 introducer sheath
Optional Protrieve introducer sheath
Optional FlowTriever nitinol disk for clot disruption
FlowSaver blood salvage system
Optional ClotTriever sheath
Optional Protrieve sheath
infusion lengths (5–50cm)
Standard intravenous hospital infusion pump.
Engine aspiration canister
Intelligent Aspiration Tubing
Aspiration catheter
Optional Separator wire
Mechanism of
Action
Mechanical
Aspiration
Thrombectomy
Mechanical
Thrombectomy
Rheolytic
Thrombectomy
Assisted
Thrombolysis
Aspiration
Thrombectomy
Mechanical
Thrombectomy
Catheter-Directed
Thrombolysis
Mechanical
Aspiration
Thrombectomy
Relevant Clinical
Trials
ATTRACT (6)
PEARL IRegistry
(7)
PEARL II Registry
(8)
CAVA (9)
ACCESS PTS (10)
PEERLESS
(NCT05111613)
CLOUT (11)
DEFIANCE
(NCT05701917)
BOLT
(NCT05003843)
Endovascular Management of Deep Venous Thrombosis 219
Ultrasound-Assisted Thrombolysis
Ultrasound-assisted thrombolysis (USAT) combines CDT with intravascular ultrasound
(16, 17)
energy to simultaneously fragment and dissolve thrombus.
The EkoSonic endovascular
system (Ekos) utilizes an infusion catheter containing a core wire that emits pulsed high frequency, low intensity ultrasound waves to theoretically increase thrombus permeability to the
(18)
thrombolytic agent, reduce infusion times, and decrease thrombolytic dose.
While USAT is
associated with high rates of substantial lysis (>50%), it does not demonstrate improvements
in clinical outcomes and is associated with much higher costs than conventional CDT.
(19, 20)
Mechanical Thrombectomy
Mechanical thrombectomy (MT) involves physical fragmentation of thrombus (Table21.1)
and may be performed concomitantly with thrombolysis administration.
device (Argon Medical) is low profile (6–7 F) and handheld with a rotating atraumatic sinu-
(22)
soidal vortex wire that macerates the thrombus.
There are currently several devices on the
market with a similar mechanism.
The ClotTriever (Inari Medical) is a novel large-bore mechanical thrombectomy device
(11 F device requiring a 13–16 F sheath) and contains a nitinol coring element and braided
collection bag designed to core and extract thrombus (Table21.1).
(21)
The Cleaner
Mechanical Aspiration Thrombectomy
Mechanical aspiration thrombectomy (MAT) involves aspiration of thrombus with or without fragmentation (Table21.1).
The AlphaVac (Angiodynamics) is a large-bore aspiration thrombectomy device with
an angled cannula tip and negative pressure generated by a handle-actuated syringe
(Table21.1).
right atrial thrombus.
The Triever device (Inari Medical) is a large-bore aspiration catheter available in multiple
sizes (Table21.1).
be performed through this device with the FlowTriever nitinol disk catheter, which engages
and fragments thrombus facilitating retrieval through the Triever catheter.
The Indigo system (Penumbra) is a family of mechanical aspiration catheters that use
computer-aided aspiration for thrombectomy (Table21.1).
wide array of sizes and lengths allowing use throughout the vascular system. Negative pressure is supplied via the Penumbra ENGINE, which senses when the aspiration catheter is
in freely flowing blood or thrombus. Intermittent aspiration is initiated when thrombus is
detected (Figure21.1). Aspirated material is collected in a canister attached to the ENGINE.
Thrombus can be manipulated by advancing the separator wire (Penumbra) through the
aspiration catheter helping to clear the catheter tip.
Large-bore aspiration catheters are efficient at removing thrombus within larger vessels
(e.g., iliofemoral and caval thrombus); however, their use requires the consideration of sheath
size and operative blood loss.
required, although many physicians are increasing their comfort with large-bore popliteal
vein access. With sheath sizes greater than 12 Fr, a venous access site closure technique, such
as a preclose technique or retention suture, should be considered.
(22)
This device is targeted for larger thrombus including iliocaval thrombus and
(23)
(22)
Negative pressure is created by an attached syringe. Adjunctive MT can
(22)
Catheters are available in a
(2)
Common femoral vein or internal jugular vein access is often
(24)