Page 2376 - Hematology_ Basic Principles and Practice ( PDFDrive )

2118 Part XII Hemostasis and Thrombosis

in major economic costs to patients and society because of the direct Limitations of this study are its modest sample size, geographical
medical costs of caring for its clinical sequelae (e.g., venous ulcers) limitation to four treatment centers in Southern Norway, and pos-
and the indirect costs of work disability. sibly reduced relevance to clinical practice in the United States and
The pathogenesis of PTS is complex and incompletely understood. other countries due to the lack of use of thrombectomy devices and
Inflammatory mediators, growth factors, extracellular matrix compo- limited use of stents.
nents, blood-borne elements, and endothelial cell factors contribute Contemporary methods of PCDT have been integrated into
to the inflammatory response to DVT, which influences thrombus pivotal multicenter randomized trials, including the ongoing
resolution, organization, and subsequent venous wall injury. Even National Institutes of Health–sponsored Acute Venous Thrombosis:
with anticoagulant therapy, incomplete clearance of thrombus is Thrombus Removal with Adjunctive Catheter-Directed Throm-
common, and residual thrombus often blocks venous blood flow. In bolysis (ATTRACT) trial, which completed patient enrollment in
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addition, venous valves may be damaged, resulting in valvular reflux. December 2014. Patient follow-up is ongoing and the results should
The combination of valvular reflux and obstruction causes ambula- be available soon.
tory venous hypertension, which leads to edema, tissue hypoxia and
injury, progressive calf pump dysfunction, subcutaneous fibrosis, and
skin ulceration. Therefore, it is logical to postulate that rapid throm- Acute Iliofemoral DVT as a High-Risk Condition
bus elimination and restoration of deep venous flow may prevent
these untoward physiologic effects and preserve long-term venous It is important for physicians to recognize the range of clinical
function. presentations of proximal DVT. The extent of thrombosis is an
In support of this “open vein hypothesis” are studies that have important predictor of clinical course and long-term outcome with
observed a strong correlation between the amount of residual anticoagulant therapy. In particular, with femoral vein thrombosis,
thrombus after a course of anticoagulant therapy and the subsequent the primary collateral route by which blood leaves the limb (and
incidence of recurrent venous thromboembolism. Moreover, data by which the venous obstruction is decompressed) is via the deep
from a number of small randomized trials suggest that systemic (profunda) femoral vein, which empties into the common femoral
thrombolysis and contemporary surgical venous thrombectomy are vein in the groin. Consequently, thrombosis above the entry point
associated with improved long-term venous patency, preservation of the deep femoral vein (i.e., in or above the common femoral
of venous valvular function, and reduced PTS compared with vein) causes more severe outflow obstruction, which often results in
anticoagulation alone. However, these studies are small and all have more leg swelling and pain, and a higher incidence of late clinical
methodologic limitations. For patients with DVT, CDT is performed sequelae.
using the same procedures as those used for arterial thrombosis. Iliofemoral DVT is defined as DVT involving the iliac vein and/
Ultrasound-guided access to an extremity vein, usually the popliteal or common femoral vein, with or without involvement of other lower
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vein for the lower extremity, is obtained. A venogram is performed extremity veins. Although physicians typically classify DVT as either
and the CDT or PCDT methods described previously are used to distal or proximal because the risk of PE is higher with proximal
remove the thrombus. After clot lysis, venography is performed to DVT, patients with iliofemoral DVT have poorer clinical outcomes
evaluate the underlying vein. Any residual stenosis is then treated than patients with less extensive proximal DVT. Involvement of the
with angioplasty or stenting. In general, the use of stents after DVT common femoral vein and/or iliac vein portends a much higher risk
thrombolysis is optimally limited to the iliac vein, although it is of recurrent VTE and more severe PTS than those with less extensive
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sometimes necessary to extend contiguous stents into the common DVT. Hence, it is important to view iliofemoral DVT as a high-risk
femoral vein. Patients with femoral vein stenosis, or isolated common condition and to ensure the utilization of evidence-based PTS pre-
femoral vein lesions that do not extend into the iliac vein, are best vention measures, especially therapeutic anticoagulation of appropri-
treated with angioplasty. Axillosubclavian vein thrombosis of known ate intensity and duration. These patients are readily identified
cause (e.g., previous central venous catheter) is amenable to balloon because they usually present with swelling of the entire limb and most
angioplasty if there is underlying stenosis. In patients with primary have compression ultrasound evidence of thrombus in the common
axillosubclavian vein thrombosis (“effort thrombosis”), stenosis of femoral vein.
the subclavian vein is typically identified and is best treated with Patients with acute (symptom duration ≤14 days) iliofemoral
surgical thoracic outlet decompression rather than aggressive balloon DVT who are not at increased risk for bleeding are the best candidates
angioplasty or stenting. With rare exceptions, stent placement in the for CDT and PCDT. 1,18,25 There are no well-designed prospective
subclavian vein is contraindicated because of the high frequency of studies of CDT for treatment of upper-extremity DVT; generally,
stent fractures. such treatment is restricted to symptomatic patients with axillosub-
In a historic 473-patient multicenter registry, the use of CDT clavian vein thrombosis of recent onset, often in the context of a
resulted in successful clot lysis in more than 80% of patients with combined interventional-surgical strategy (i.e., for Paget-Schroetter
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acute proximal DVT. However, major bleeding was observed in syndrome).
11.4% of patients, mostly access site bleeding. Intracranial bleeding
was observed in 0.4% of patients and fatal PE occurred in 0.2% of
patients. Summary: Indications and Contraindications
In 2012, the first rigorously designed multicenter randomized for CDT in DVT
controlled trial was published describing long-term outcomes with
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adjunctive CDT. In this Norwegian study, 209 patients with acute The lack of data to establish the utility and proper indications for
iliac or femoral DVT were randomized to receive standard anticoagu- CDT in DVT patients does not absolve physicians of their respon-
lant therapy with or without the addition of infusion-only CDT. This sibility to ensure that the long-term risks of PTS are carefully con-
study demonstrated a 26% relative risk reduction (55.6% vs. 41.1%, sidered when crafting an individualized treatment strategy for DVT
p = 0.04) in the occurrence of PTS over 2 years of follow-up. Major patients. The strategy should incorporate a high degree of confidence
bleeding occurred in 3% of patients, resulting in one blood transfu- in anticoagulation drugs; a familiarity with the available (albeit
sion and one surgical intervention. There were no intracranial bleeds. imperfect) data that suggest that CDT is reasonable for selected DVT
Adjunctive CDT was associated with a small QOL benefit and patients; and an individualized assessment of the clinical DVT sever-
reduced job absenteeism over the first 6 months of follow-up; ity, extent of thrombosis, comorbidities, and personal preferences of
however, QOL was not different at 24 months follow-up. Overall, the patient.
these findings suggest that endovascular thrombolysis may indeed Patients who do not meet a clinical threshold justifying the use of
improve long-term outcomes, but they are not entirely clear as to CDT include those with asymptomatic DVT or DVT isolated to the
whether the degree of benefit is likely to be sufficient to justify the calf (because the risk of PTS is relatively low in these groups), and
attendant risks and costs in large populations of DVT patients. patients with chronic femoropopliteal DVT (because studies have