Reporting Standards for Endovascular Treatment of Lower Extremity Deep Vein Thrombosis

Risk Factors and Predisposing Conditions 

The conditions listed below represent independent risk factors for DVT and may influence its frequency of occurrence, clinical course, response to treatment, and likelihood of recurrence. In general, the presence of irreversible risk factors or idiopathic DVT confers a higher risk of recurrent DVT than reversible or time-limited risk factors.

1.Prior history of DVT. A prior episode of proved lower extremity DVT is a strong independent risk factor for a subsequent episode (13). Patients with residual venous thrombus on follow-up duplex US examination are at particularly high risk for recurrent VTE episodes (14). Knowledge of a history of prior DVT may influence the duration of anticoagulant therapy, indicate placement of an inferior vena cava (IVC) filter, or temper expectations for the results of endovascular therapy. For example, a population of acute iliofemoral DVT patients with a high incidence of prior DVT is expected to differ significantly from a population of patients without prior DVT with respect to the incidence and severity of PTS after catheter-directed thrombolysis.

2.Postoperative state and/or trauma. Major surgical procedures and bony fractures immobilize the patient and tilt the thrombolytic/hemostatic balance toward thrombosis. Patients particularly prone to DVT include those with pelvic and limb fractures and those undergoing neurosurgical, orthopedic, spinal, and major abdominal operations (15). DVT patient populations with a high incidence of recent surgery and/or trauma may be expected to have a higher incidence of bleeding complications with antithrombotic or fibrinolytic therapy.

3.Immobilization. Immobilization from illness or injury is a risk factor for DVT (16). The cause and duration of immobilization also influence the risk of DVT, with paraplegic patients being at particular risk (17).

4.Malignancy. The presence of malignancy is a major independent risk factor for DVT and recurrent VTE (18). Patients with widespread metastases and those with mucinous adenocarcinomas and other specific histologies are thought to be at particularly high risk. The presence of malignancy can significantly alter the type of anticoagulant therapy recommended, since low molecular weight heparins are associated with lower rates of recurrent VTE than vitamin K antagonists in cancer patients (19, 20). In addition, lower 2-year primary patency rates have been observed in cancer patients treated with endovascular therapy compared with patients with benign causes of DVT (21). Prevention of PTS may be less of a priority for cancer patients with short life expectancy, and this can mitigate against the use of aggressive endovascular DVT therapies.

5.Inherited or acquired coagulation abnormality. Hematologic abnormalities that predispose patients to primary or recurrent VTE include factor V Leiden mutation, prothrombin gene mutation, antithrombin III deficiency, protein C and protein S deficiencies, lupus anticoagulant, antiphospholipid antibody syndrome, hyperhomocystinemia, and plasma hyperviscosity states (22, 23, 24, 25, 26).

6.Pregnancy and postpartum state. Pregnant and postpartum women are at risk for DVT (27, 28). Pregnancy is a relative contraindication to thrombolysis.

7.Hormonal therapy. The use of hormonal therapy for contraception or other medical purposes is a risk factor for DVT (29). The type and duration of hormonal therapy also probably play a role in the development of thrombosis.

8.IVC filters. In patients with proximal DVT who receive concomitant anticoagulation, IVC filters reduce the early risk of PE but increase the rate of recurrent DVT (30). The presence of a filter may also increase the technical difficulty associated with endovascular treatment of IVC thrombosis (31).

9.Other factors. Extreme obesity, varicose veins, and congestive heart failure have been inconsistently identified as independent DVT risk factors (32).

A cumulative risk factor scoring system has been described but is not included in this document because its grading system does not accurately reflect the relative risk of DVT conferred by each individual risk factor and because it does not account for patients with idiopathic DVT (ie, no known risk factor) (3). Patients with idiopathic DVT have a higher risk of recurrent DVT than patients with time-limited risk factors.

Major Comorbidities 

The presence of major comorbidi-ties in a patient cohort may reduce the clinical success rate and increase the rate of complications with treatment. Conversely, exclusion of patient subsets due to comorbidity can bias DVT populations, and this should be borne in mind when comparing patient cohorts. For example, exclusion of PE patients from a DVT study might indicate better clinical status of the included patient population.

1.Bleeding risks. Bleeding complications in DVT patients may be caused by anticoagulant therapy, thrombolytic therapy, or endovascular procedure-related vascular trauma (33). Knowledge of the incidence of additional risk factors for bleeding in the population can therefore improve meaningful comparison of bleeding complication rates between studies. Such risk factors include active bleeding; previous or current intracranial disease; recent trauma, surgery, or percutaneous procedures; severe hepatic dysfunction; gastrointestinal bleeding history; and severe uncontrolled hypertension.

2.Pulmonary or cardiac disease. Preexisting pulmonary or cardiac disease can increase the clinical severity of any complications that are encountered and is an important indicator of the overall health of the patient population. The presence and severity of pulmonary hypertension and/or right heart dysfunction is particularly important. On the one hand, catheter manipulations may fragment thrombus and cause procedure-related PE. On the other hand, any pulmonary emboli may be dissolved by circulating thrombolytic agents.

3.Renal failure. Preexisting renal dysfunction can increase the rate of contrast-related renal failure after endovascular intervention and is an important indicator of the overall health of the patient population.

4.Active infection. Active bloodstream infection is a relative contraindication to some endovascular procedures. Because DVT patients commonly present with fever or leukocytosis, or both, the diagnosis of bloodstream infection should be based on positive blood cultures or septic hemodynamics.

5.Overall performance status. The use of standardized instruments to describe overall patient performance status (for example, ASA classification) may improve comparison of the relative overall health of different populations (34).

Details of Prior or Concomitant Treatment 

Accepted DVT treatments that can meaningfully affect evaluation of therapeutic interventions include bed rest with leg elevation, early ambulation protocols, compression stockings, anticoagulant therapy, antiplatelet therapy, surgical thrombectomy or bypass, endovascular thrombus removal methods, balloon angioplasty, stent placement, and IVC filter placement (19, 35, 36, 37).

Baseline Clinical Presentation of Venous Disease 

The pretreatment clinical status of venous disease in the population should be characterized in a manner that permits comparison between patient cohorts:

1.Acute DVT refers to venous thrombosis for which symptoms have been present for 14 days or less or for which imaging studies indicate that venous thrombosis occurred within the last 14 days (33). The primary symptoms of acute DVT are limb swelling and pain. Standardized measurement of limb circumferences at the same craniocaudal level can be used to quantify the degree of limb swelling. Pain can be graded using a number of validated pain scales (for example, the Visual Analog Scale) (38). Phlegmasia refers to a characteristic clinical picture in which DVT causes massive swelling of the entire extremity. Phlegmasia alba dolens is not associated with cyanosis. In contrast, phlegmasia cerulea dolens is associated with cyanosis and can lead to arterial insufficiency, compartmental compression syndrome (compartment syndrome), venous gangrene, and limb amputation (39).

2.Subacute DVT refers to venous thrombosis for which symptoms have been present for 15 to 28 days or for which imaging studies indicate that venous thrombosis occurred within this time interval. This designation, while not in common practice, is included because the expert committee members believed that a difference in endovascular treatment response rates exists between patients treated in this time window compared with patients treated earlier or later (33).

3.Chronic DVT refers to venous thrombosis for which symptoms have been present for more than 28 days or for which imaging findings document the presence of venous thrombosis more than 28 days before (33). Chronic venous disease may manifest with a broad range of symptoms that can vary in severity throughout the day. There are several methods by which the baseline clinical severity of chronic venous disease in a population can be described by physician assessment. First, the “C” (clinical) component of the CEAP system stratifies patients into six venous disease categories of increasing severity (Table 1) (6). Second, the Venous Clinical Severity Score (VCSS) is an excellent scoring system with which to follow the progress of chronic venous disease in individual patients and to compare patient cohorts (Table 2) (5). Although not completely validated for all DVT patient populations, the VCSS correlates well with CEAP class and with US findings of venous disease (40, 41, 42). Third, the Venous Disability Score is an easily applied scoring scheme in which venous disease severity is grossly categorized according to the degree to which it limits a patient's normal activities (Table 3) (40). Patient symptom self-assessment can also be extremely useful in describing disease severity and quality-of-life (QOL) in DVT populations. Symptom- or disease-specific QOL questionnaires that have been at least partially validated in venous disease populations include the CIVIQ, Villalta, Mathias, and VEINES-QOL/Sym questionnaires (Table 4 and Appendix 1) (43, 44, 45, 46, 47, 48, 49). General QOL measures have included the SF-36 and Nottingham Health Assessment (50, 51).

Table 2. Venous Clinical Severity Score

	Attribute	Absent = 0	Mild = 1	Moderate = 2	Severe = 3
	Pain	None	Occasional, not restricting activity or requiring analgesics	Daily, moderate activity limitation, occasional analgesics	Daily, severely limits activities, regular use of analgesics
	Varicose veins⁎	None	Few, scattered: branch VVs with competent GSV/LSV	Multiple: single segment GSV/LSV reflux	Extensive: multisegment GSV/LSV reflux
	Venous edema†	None	Evening ankle edema only	Afternoon edema above ankle	Morning edema above ankle requiring activity change, elevation
	Skin pigmentation	None, or focal, low intensity (tan)	Diffuse, but limited in area and old (brown)	Diffuse over gaiter distribution (lower third) or recent pigmentation (purple)	Wider distribution (above lower third) and recent pigmentation
	Inflammation	None	Mild cellulitis, limited or marginal area around ulcer	Moderate cellulitis, involves most of gaiter area	Severe cellulitis (lower third or above) or venous eczema
	Induration	None	Focal, circum-areolar (<5 cm)	Medial or lateral, less than lower third	Entire lower third or more
	Total number of ulcers‡	0	1	2–4	>4
	Active ulceration, duration	None	<3 months	>3 months, <1 year	Not healed >1 year
	Active ulcer, size	None	<2 cm diameter	2–4 cm diameter	>4 cm diameter
	Compressive therapy§	Not used or not compliant	Intermittent use of stockings	Wears elastic stockings most days	Full compliance stockings + elevation

Qualifying comments:

⁎ To ensure differentiation between the C1 and C2 CEAP classes, “varicose” veins must be >4 mm diameter to qualify for inclusion here. Occasional or mild edema and focal pigmentation over varicose veins does not qualify for inclusion under the two subsequent attributes. † Presumes venous origin by characteristic, eg brawny (not pitting or spongy) edema, with significant effect of standing/limb elevation and/or other clinical evidence of venous etiology, ie varicose veins, history of DVT. Edema must be regular finding, eg daily occurrence. ‡ Total number equals active and healed. § Sliding scale to adjust for background differences in use of compressive therapy.

Table 3. Venous Disability Score

	0 = Asymptomatic
	1 = Symptomatic but able to carry out usual activities⁎ without compressive therapy
	2 = Can carry out usual activities⁎ only with compression and/or limb elevation
	3 = Unable to carry out usual activities⁎ even with compression and/or limb elevation

⁎ Usual activities = patient's activities before onset of disability from venous disease.

Table 4. Selected Venous Disease Questionnaire Measures

	Measure	Type	Study	Intended Population
	Villalta Scale	Post-thrombotic symptoms	Villalta 1994 (43) Prandoni 1996 (18) Brandjes 1997 (35)	DVT
	CIVIQ	Disease-specific HRQOL	Launois 1996 (45) Ziegler 2001 (44)	CVD due to DVT or VR
	VEINES-QOL/Sym	Disease-specific HRQOL	Lamping 1998 (47) Kahn 2002 (87) Lamping 2003 (48) Kahn 2004 (49)	CVD due to DVT or VR
	Mathias Scale	Disease-specific HRQOL	Mathias 1999 (46) Comerota 2000 (91)	DVT

Note.—CVD = chronic venous disease; DVT = deep vein thrombosis; HRQOL = health-related quality-of-life; VR = primary venous reflux.

Venous gangrene is full-thickness skin necrosis caused by DVT. Blistering indicates partial thickness necrosis and is considered early venous gangrene (4).

4.Acute-on-chronic DVT refers to venous thrombosis that has both chronic (>28 d) and acute (≤14 d) components, as indicated by symptom history or imaging findings (33).

Pretreatment Anatomical/Physiologic Assessment 

The following categorization scheme should be consistently applied to describe the anatomical extent of DVT:

Proximal DVT refers to complete or partial thrombosis of the popliteal vein, femoral vein, deep femoral vein, common femoral vein, iliac vein, and/or IVC. Proximal DVT is often complicated by PE (19). Proximal DVT can be further subclassified as follows:

Femoropopliteal DVT refers to complete or partial thrombosis of the popliteal vein, femoral vein, and/or deep femoral vein.

Iliofemoral DVT refers to complete or partial thrombosis of any part of the iliac vein and/or the common femoral vein, with or without associated femoropopliteal DVT (33, 52). Published studies differ in terms of whether patients with common femoral vein thrombosis and a patent iliac vein are considered to have iliofemoral DVT. After consideration, the consensus opinion of the committee members is that by obstructing outflow from both the femoral and deep femoral veins, common femoral vein thrombosis produces a clinical picture that is essentially identical to iliac vein thrombosis. Therefore, the committee members do recommend that such patients be categorized as having iliofemoral DVT. Iliofemoral DVT carries a higher risk of recurrent VTE and possibly also a greater risk of PTS (52, 53).

Calf vein DVT refers to complete or partial thrombosis of one or more deep calf veins, including the anterior tibial veins, posterior tibial veins, peroneal veins, and deep muscular veins. Isolated calf vein DVT rarely leads to PE (19). When calf vein DVT propagates into the popliteal vein, it is considered proximal DVT.

Diagnostic venography represents the criterion standard imaging modality with which to confirm the presence and define the anatomical extent of DVT (54). The hallmark venographic finding of DVT is the visualization of intraluminal filling defects. Other findings may include abrupt cut-off of a vein, lack of opacification, and/or intraluminal septations or webs. In nearly all instances, when information from another diagnostic modality is not consistent with venography, the venographic result should be relied upon.

Ideally, each patient being considered for endovascular therapy should undergo baseline venographic characterization of the entire venous system of the limb from calf through IVC. This provides the most accurate determination of the baseline extent of thrombosis, which is necessary for meaningful evaluation of several major DVT outcomes such as the incidences of progressive DVT and recurrent VTE. However, it is recognized that this may be difficult to achieve in actual clinical practice. Many experienced interventionalists do not routinely image or treat thrombus that extends below the popliteal vein, and the quality of calf venography can vary somewhat with operator experience. It is recognized that calf venography may not be clinically warranted in certain situations, for example, when iliocaval DVT is present but does not extend into the femoral vein. In clinical trials, patients may be randomized to a control arm in which endovascular therapy is not given, and it may not be deemed ethical to subject these patients to invasive veno-graphic testing.

In these situations, compression duplex sonography can be relied on to evaluate the femoropopliteal and common femoral veins with extremely high accuracy (55, 56, 57). The hallmark finding of DVT on duplex sonography is venous noncompressibility. Other findings may include visualized intraluminal material, absence of flow on augmentation, lack of respiratory variation, and incomplete color filling.

The calf veins and iliocaval venous system pose a greater challenge to clinical DVT research efforts. Although clinical treatment decisions can be reliably based on noninvasive imaging in the overwhelming majority of DVT patients, the much greater detail needed to accurately assess anatomical outcomes in clinical research studies is often difficult to obtain. Duplex sonography has only 70% to 85% accuracy for calf vein thrombosis but is nevertheless the best available noninvasive modality with which to characterize its extent (54, 58, 59). Duplex sonography of the iliac vein may be limited by poor venous visualization owing to its deep position in the pelvis, although it can be diagnostic in many instances. A well-opacified contrast-enhanced CT scan or MR imaging scan is likely to be accurate in diagnosing iliac vein DVT when venography cannot be performed (60, 61). However, it must be noted that CT and MR imaging have not undergone rigorous validation studies for DVT diagnosis. For these reasons, venographic definition of the complete anatomical extent of DVT should be sought whenever possible. When this is not possible, reliance on a combination of duplex ultrasound (calf veins) and CT scanning or MR imaging (iliocaval veins) is recommended.

Partial physiologic evaluation of the venous system can be performed in several ways: a) Endovascular catheter access permits the acquisition of direct venous pressure measurements to characterize venographically identified abnormalities. The limited available evidence suggests that a resting mean pressure gradient of 2 mm Hg or less is normal and that a gradient of 5 mm Hg or greater indicates hemodynamically significant stenosis (62, 63, 64); b) Duplex sonography can diagnose venous reflux and estimate flow velocities; and c) plethysmography can determine the postexercise venous refill time and thereby estimate the volume of venous reflux, with some limitations (65).

The Venous Segmental Disease Score (VSDS) incorporates the “A” (anatomical) and “P” (physiologic) parts of the CEAP system into a 10-point reflux scale and a 10-point obstruction scale (Table 5) (43). The VSDS correlates well with the CEAP system and can be used to score the combined results of imaging and physiologic testing (45).

Table 5. Venous Segmental Disease Score⁎

	Reflux	Obstruction (or Excised/ligated)
	1/2 Lesser saphenous
	1 Greater saphenous	1 Greater saphenous (only if from groin to below knee)
	1/2 Perforators, thigh
	1 Perforators, calf
	2 Calf veins, multiple (PT alone = 1)	1 Calf veins, multiple
	2 Popliteal vein	2 Popliteal vein
	1 Superficial femoral vein	1 Superficial femoral vein
	1 Profunda femoris vein	1 Profunda femoris vein
	1 Common femoral vein and above†	2 Common femoral vein
		1 Iliac vein
		1 IVC
	10 = Maximum reflux score‡	10 = Maximum obstruction score‡

Qualifying comments: Reflux means that all the valves in that segment are incompetent. Obstruction means there is total occlusion at some point in the segment or greater than 50% narrowing of at least half of the segment. Most segments are assigned one point, but some segments have been weighted more or less to fit with their perceived significance, eg increasing points for common femoral or popliteal obstruction and for popliteal and multiple calf vein reflux and decreasing points for lesser saphenous or thigh perforator reflux. Points can be assigned for both obstruction and reflux in the same segment. This will be uncommon but can occur in some post-thrombotic states, potentially giving secondary venous insufficiency higher severity scores than primary disease.

⁎ Based on presence of venous segmental reflux or obstruction as assessed by appropriate venous imaging, duplex US or venogram. † Normally there are no valves above the common femoral vein. ‡ Not all of the 11 segments listed can be involved in reflux or obstruction.

Recommendations for Reporting 

Basic demographic description must be provided, including age, gender, and affected limb (right, left, or both) for all patients in each treatment group. For studies including patients with IVC involvement, both the number of patients and the number of symptomatic limbs must be stated. For categorical variables (ie, gender), the proportions of subjects in each category must be reported. For continuous variables (ie, age), the mean or median (nonparametric variables), SD or SEM, and range must be reported. The study inclusion and exclusion criteria must be explicitly stated, and the method of assigning treatments to subjects must be described. When possible, patient selection should be stratified by anatomical DVT extent, symptom duration, and clinical severity.

The proportion of patients presenting with DVT, PE, both DVT and PE, or neither must be stated for the entire population and for each treatment group. Authors must indicate how the presence of DVT or PE was established. Description of how many episodes of proved PE were symptomatic versus asymptomatic is highly recommended.

The proportion of patients with each of the following risk factors should be stated for the patient population and for each treatment group: prior DVT history, recent (<1 mo) major surgery or percutaneous procedures, recent (< 1 mo) trauma or immobilization, presence of malignancy, known inherited or acquired coagulation abnormality, pregnancy or post-partum state, hormonal therapy, or the presence of an IVC filter. Inclusion of information pertaining to the type and timing of recent surgery, type and extent of malignancy, type of coagulation disorder, type of hormonal therapy, and presence of paraplegia in the patient population is highly recommended. The proportion of patients with additional risk factors for major bleeding (especially intracranial disease, liver disease, and gastrointestinal bleeding history), cardiopulmonary disease (particularly pulmonary hypertension), renal dysfunction, or infective conditions must be specified. Inclusion of information pertaining to the severity of these conditions is highly recommended. The thresholds for study inclusion with regard to acceptable hematocrit, platelet count, international normalized ratio (INR), and partial thromboplastin time (PTT) must be stated. If therapeutic interventions (ie, vitamin K administration, transfusion) were allowed to bring these parameters within the acceptable range, this should be stated.

The proportion of patients who received ongoing or previous DVT or PE treatment using any of the following methods must be stated: bed rest with leg elevation; early ambulation protocol; compression stockings (specifying the stocking type, length, amount of compression, and compliance level is highly recommended); anticoagulant therapy (specifying the agent, duration of therapy, and target INR or PTT if applicable is required); surgical or endovascular procedures (specifying the procedure type and extent is required); and/or IVC filter placement (specifying the type is required, providing the duration of implantation and timing of removal are recommended).

The baseline clinical presentation of venous disease in the population must be described. The proportion of patients with acute, subacute, and chronic DVT in the patient population and in each treatment group must be specified. For patients with acute DVT, the number of patients with limb swelling and/or pain must be specified. The use of standardized leg circumference measurements and validated pain scales are highly recommended in describing acute symptom severity. The number of patients with phlegmasia cerulea dolens, compartmental compression syndrome, or signs of arterial insufficiency must be indicated. For studies evaluating treatment of chronic venous disease, the mean or median CEAP clinical class, VCSS, Venous Disability Score, or venous disease-specific patient self-assessment questionnaire score of the population must be provided; reporting of more than one of these parameters is highly recommended. The use of a general health-related QOL patient self-assessment instrument is also recommended.

The baseline anatomical extent of thrombosis and the imaging methods of diagnosis must be specified. The proportion of patients with calf vein DVT, femoropopliteal DVT, iliofemoral DVT, infrarenal IVC involvement, and suprarenal IVC involvement must be reported. Baseline bilateral duplex US evaluation for the presence of venous reflux is also highly recommended for all patients.

Venous Access 

Endovascular DVT interventions require catheter access in at least one part of the venous system. Access may be obtained in open surgical fashion (using a surgical cutdown and/or venotomy) or in percutaneous fashion. When percutaneous deep venous access is obtained, US guidance is commonly used. Fluoroscopy can also be used either in conjunction with US or as the sole imaging modality.

Venous access can be antegrade (in the direction of normal venous flow) or retrograde (against the direction of normal venous flow). For the treatment of lower extremity DVT, ante-grade access is commonly obtained in the popliteal vein, posterior tibial vein, soleal vein, anterior tibial vein, and/or peroneal vein (1, 66). When using ante-grade access, a site is ideally chosen below the caudal extent of the thrombus. Retrograde access is commonly obtained from the internal jugular vein, although other major deep veins can also be used. Common femoral vein access can be antegrade or retrograde and can be obtained in the affected ipsilateral limb or in the contralateral limb. For example, the use of right common femoral vein access to treat a left iliofemoral DVT would be classified as retrograde contralateral.

Transluminal Thrombus Removal Methods 

The following sections describe the most common methods of performing transluminal removal of thrombus from the deep venous system:

Pharmacologic thrombolysis refers to administration of drugs with thrombolytic activity. When reporting the results of pharmacologic thrombolysis, the thrombolytic infusion time is the total time during which the drug was infused. Treatment time is the total time from the start of the first thrombolysis procedure or the initial drug administration (whichever was first) to termination of the final follow-up procedure or of the infusion (whichever was last). Pharmacologic thrombolysis is subdivided according to the thrombolytic agent delivery method:

Systemic thrombolysis refers to pharmacologic thrombolytic agent delivery through an intravenous line, which is located distant from the affected extremity (8, 67). The drug can be administered as a bolus (single dose) or as a continuous infusion.

Flow-directed thrombolysis refers to pharmacologic thrombolytic agent delivery through a pedal intravenous line placed within the affected extremity, with or without the use of tourniquets to intermittently compress the saphenous system to direct the drug into the deep venous system. The drug can be administered as a bolus or as a continuous infusion (68). Use of the term locoregional thrombolysis is discouraged, since this may be confused with intrathrombus thrombolysis.

Catheter-directedintrathrombusthrombolysis (CDT) refers to pharmacologic thrombolytic agent delivery through an infusion catheter or wire that is embedded within the thrombosed vein being treated (1, 69). Multi-side-hole catheters are most commonly used for this purpose. The drug can be administered as a single or periodic bolus or as a continuous infusion (70). A lacing dose, in which a catheter is used to disperse a bolus dose of the thrombolytic drug throughout the thrombus, can also be given (71).

Mechanical thrombectomy refers to use of catheter-based mechanical devices that contribute to thrombus removal via fine (microscopic) thrombus fragmentation, maceration, or aspiration. When performed percutaneously, the term percutaneous mechanical thrombectomy (PMT) is used (2).

Pharmacomechanical thrombolysis refers to thrombus dissolution via any simultaneous use of pharmacologic thrombolysis and mechanical thrombectomy. Several specific methods may fall under this definition: a) Pulse-spray pharmacomechanical thrombolysis refers to a specific technique in which a thrombolytic drug is periodically forcefully injected into the thrombus using a multi-side-hole catheter (72). This technique is clearly distinguished from lacing, in which an intrathrombus bolus dose is given without any intended mechanical effect. b) Because fine thrombus maceration may enhance pharmacologic clot dissolution and vice versa, the use of any mechanical thrombectomy method while a pharmacologic thrombolytic drug is circulating constitutes a form of pharmacomechanical thrombolysis (73).

Adjunctive Mechanical Thrombus Removal Techniques 

The following techniques are mechanical in nature but are not classified as mechanical thrombectomy methods because they do not produce fine (microscopic) maceration of thrombus.

Aspiration thrombectomy refers to the use of a syringe to aspirate thrombus from the clotted vein via a catheter or sheath (74).

Balloon thrombectomy refers to the use of catheter-mounted balloons (for example, a Fogarty balloon) to mobilize or extract thrombus.

Balloon maceration refers to the use of an angioplasty balloon to produce gross thrombus fragmentation or maceration. This is commonly done to enhance the rate of clot dissolution during pharmacologic thrombolysis.

Concomitant Medical Therapy 

Supplemental antithrombotic therapy can be given during thrombolysis to augment the thrombolytic effect or to prevent new thrombus formation, or both. Parenteral agents that have been used include unfractionated heparin and glycoprotein IIb/IIIa inhibitors (75). Therapeutic-level heparin administration refers to the intravascular use of unfractionated heparin to raise the PTT to 1.5 to 2.5 times the control level. Subtherapeutic heparin refers to the intravascular use of unfractionated heparin at lower doses to prevent peri-catheter thrombosis (PTT <1.5 times control).

Balloon Angioplasty, Stent Placement, and Inferior Vena Cava Filter Placement 

When thrombus removal is completed or nearly completed, repeat venography is typically performed to evaluate for any venous stenoses that might have contributed to the initial thrombotic episode. At this point, balloon angioplasty may be used to dilate a visualized venous stenosis. This term should be used only when an angioplasty balloon is used with the specific intent of enlarging the venous lumen (unlike balloon maceration in which the specific intent is to increase the surface area of residual thrombus). Stent placement refers to use of a metallic endoprosthesis to enlarge and maintain the venous lumen. The timing of stent placement with respect to clot removal merits description, since stents can be used either for treatment of stenosis or to exclude residual thrombus from the vein lumen and thereby shorten the thrombolytic infusion time (76). IVC filter placement can also be employed to prevent PE either before or after endovascular thrombus removal methods are employed. Retrievable or permanent filters can be used.

Adjunctive Surgical Therapies 

Arteriovenous fistula creation can be performed to improve flow and thereby maintain early patency after endovascular or surgical venous recanalization (21). In most cases, the fistula is taken down after a defined period of time.

Surgical thrombectomy refers to the use of open surgical techniques, including venotomy, to remove thrombus from the deep veins of the body (77, 78).

Venous bypass refers to the surgical placement of a native or prosthetic conduit to bypass a segment of venous occlusion.

Recommendations for Reporting 

When describing transluminal thrombus removal methodology, authors must clearly state what treatment was originally intended and what treatment was actually administered. This will facilitate intention-to-treat analysis of the data. For example, if the originally intended protocol for using a mechanical thrombectomy device to treat a DVT cohort did not include subsequent pharmacologic thrombolysis, this should be clearly stated. In that situation, patients who receive subsequent pharmacologic thrombolysis for residual thrombus should be reported as having failed stand-alone mechanical thrombectomy. In contrast, if the original treatment protocol was written to include mechanical thrombectomy followed by pharmacologic thrombolysis, then treatment success or failure can be assigned based on the results of treatment with the entire protocol (ie, both modalities in sequence).

The clinical setting in which patients received treatment (ie, outpatient, standard inpatient hospital bed, intermediate-care unit, or intensive care unit) must be specified.

The specific vein or veins accessed for endovascular DVT treatment must be indicated. Authors must state whether access was obtained percutaneously or via open surgery and whether the access was directed ante-grade or retrograde. If imaging guidance was used, the specific modality must be indicated. Inclusion of how frequently antegrade venous access sites were below the caudal extent of thrombus is required.

The primary method of thrombus removal must be specified (pharmacologic thrombolysis, mechanical thrombectomy, pharmacomechanical thrombolysis, aspiration thrombectomy, balloon thrombectomy, or balloon maceration), and the chronological order in which the methods were used must be reported.

For studies evaluating pharmacologic thrombolysis, the thrombolytic agent, manufacturer, bolus dose (if given), initial hourly infusion dosage and solution concentration, total dose administered, thrombolytic infusion time, hematologic monitoring protocol, and parameters used for adjusting the dose must be specified. For studies including patients with IVC thrombosis or bilateral DVT, doses and infusion times for that patient subset must be reported separately and should be calculated per patient and per treated (symptomatic) limb. The route of drug administration (systemic, flow-directed, or catheter-directed intrathrombus) must be specified. For patients undergoing catheter-directed intrathrombus thrombolysis, the type of catheter (multi-side-hole vs. end-hole) catheter used to administer the drug must be specified. If a lacing dose was given, this must be specified. If flow-directed thrombolysis was performed, description of the tourniquet system (type, manufacturer, and method of use) is highly recommended. If balloon maceration or other methods to grossly macerate thrombus were used, the protocol for use must be described as well.

For studies evaluating mechanical thrombectomy, the device name, manufacturer, and model must be stated. The exact method of device use must be specified, especially for devices that can be used in multiple modes. For example, when describing use of the Angiojet, authors must state whether it was used with the effluent lumen open or occluded. Inclusion of the total device activation time is highly recommended.

For studies evaluating pharmaco-mechanical thrombolysis, the timing of drug administration and mechanical thrombectomy device usage must be clearly indicated. If pulse-spray pharmacomechanical thrombolysis was used, this must be clearly stated.

If aspiration thrombectomy, balloon thrombectomy, or balloon maceration was used, the catheter system utilized must be specified along with the protocol for use.

The specific protocol for use of balloon angioplasty, stent placement, or IVC filter placement should be standardized within the protocol and must be described with reference to the timing and results of the transluminal thrombus removal methods. If balloon angioplasty was used, the specific vessel dilated and balloon diameter must be specified. Inclusion of the inflation pressure and duration of inflation is recommended. If stenting was performed, the vessel treated, stent type, manufacturer, size, and diameter to which the stent was dilated must be provided. If IVC filters were placed, the type, indication, timing of placement with respect to endovascular DVT treatment, intended duration (temporary vs. permanent), and timing of removal must be indicated. The type and extent of any adjunctive surgical methods used must be described.

The use of any concomitant medical therapy that may affect the coagulation pathway or platelet function must be described. If heparin was given, the dose, route of administration (ie, peripheral intravenous line vs. angio-graphic sheath), intended level of anticoagulation (therapeutic-level vs. subtherapeutic), and target PTT must be provided. The protocol used to monitor the level of anticoagulation must be described. If a vitamin K antagonist was used, the target INR must be described. Brief description of the protocols for periprocedure management and long-term use of anticoagulant and antiplatelet agents is also required.

Assessment of Treatment Safety 

Deep venous thrombosis therapies have varying complication profiles. For treatments involving any pharmacologic agent, major or minor allergic reactions may be observed. Any invasive therapy can produce an infectious complication, and those that require conscious sedation or general anesthesia carry risks of cardiorespiratory compromise. Major bleeding, defined as intracranial bleeding or bleeding severe enough to result in death, surgery, cessation of therapy, or blood transfusion, is an important safety outcome of all DVT therapies involving antithrombotic agents (8). Minor bleeding is defined as less severe bleeding manageable with local compression, sheath upsizing, or dose alterations of a pharmacologic thrombolytic agent, anticoagulant, or antiplatelet drug (8). Renal failure, defined as a 20% or greater increase in serum creatinine level, can complicate any procedure in which iodinated contrast is used (80). Angioplasty and stenting procedures may be complicated by venous rupture and/or stent malposition or migration; these events may have no consequence or may cause significant problems such as bleeding or contralateral DVT. Symptomatic or asymptomatic PE can be caused by the underlying VTE disease process or by thrombus manipulation. Methemoglobinuria is an expected effect of many mechanical thrombectomy devices and is not a complication except when associated with renal failure or hemolysis, which is significant enough to result in death, surgery, cessation of therapy, or blood trans-fusion.

Any adverse event occurring during the time period beginning with the initial diagnostic venogram to 24 hours after the termination of therapy (including removal of venous access) must be considered procedure-related. Adverse events that are detected later than 24 hours can also be procedure-related, such as renal failure. The use of 30-day mortality rates is encouraged to enable comparison with other treatment methods.

Assessment of Treatment Efficacy 

Although outcomes such as PE and PE-related death can be evaluated with short follow-up intervals, the time course for meaningful evaluation of the progression of chronic venous disease is significantly longer. Therefore, clinical follow-up should be graded as short-term (<1 y), mid-term (1–3 y), or long-term (>3 y).

Pulmonary Embolism and Late Pulmonary Dysfunction 

Anticoagulant therapy drastically reduces the incidences of PE and PE-related death (19). In surviving patients, late complications of PE may include pulmonary arterial hypertension, chronic pulmonary thromboembolic disease, cor pulmonale, and various pulmonary function abnormalities. These problems can lead to death or QOL impairment and are therefore extremely important to quantify using objective means. Pulmonary function parameters of interest include right heart and pulmonary arterial pressure estimation using direct manometry or echocardiography, pulmonary vascular resistance, diffusion capacity, and pulmonary capillary blood volume.

Early and Late Limb Status 

Immediate Venous Patency 

Immediate post-treatment venography is commonly performed in DVT patients undergoing endovascular intervention. Anatomical success can be defined in one of two ways, and preferably both: a) successful restoration of antegrade in-line flow in the treated vein with elimination of any underlying obstructive lesion (81). This is generally assessed on the final procedural venogram (ie, after adjunctive endovascular therapies are completed). Unfortunately, the degree of residual venous diameter narrowing needed to produce flow limitation and symptoms have not been characterized in the venous system. b) For studies evaluating transluminal thrombus removal methods, estimation of the degree of thrombolysis can be also be performed. This should be assessed on the venogram obtained after thrombus removal but before stent placement because stents can exclude residual thrombus and confer a venographically normal appearance even when residual thrombus is present, confounding accurate assessment of the thrombus removal methods. Venographic scoring systems that have been used in prior DVT studies include the Marder scale, SVS scale, and the Venous Registry Index (4, 12, 82) (Table 6). These scales can be used to classify patients as showing minimal or no thrombolysis (grade I, < 50% thrombus removal), partial thrombolysis (grade II, 50 –95% thrombus removal), or complete thrombolysis (grade III, 95–100% thrombus removal).

Table 6. Venographic Scoring Systems⁎

	A. Marder Scoring System (different segments have differing maximum point values)
	VENOUS SEGMENTS	POINTS	CRITERIA FOR SCORING SEGMENTS
	Iliac	6
	Common femoral	4	Count full points for complete occlusion
	Femoral	10	Proportionally lower for partial occlusions
	Popliteal	4	No points for patent vein
	Anterior tibials (paired)	4 (2 each)
	Posterior tibials (paired)	6 (3 each)
	Peroneals (paired)	6 (3 each)
	Total Score Possible:	40
	B. SVS Scoring System (each segment is worth 3 points)
	VENOUS SEGMENTS	POINTS	CRITERIA FOR SCORING SEGMENTS
	Tibial-soleal veins	3
	Popliteal vein	3	0 = patent
	Femoral vein	3	1 = subsegmental, nonocclusive thrombus
	Common femoral vein	3	2 = subsegmental, occlusive thrombus
	Iliac vein	3	3 = occlusive thrombus throughout segment
	Inferior vena cava	3
	Greater saphenous/branches	3
	Lesser saphenous/branches	3
	Total Score Possible:	24
	C. Venous Registry Index (each segment is worth 2 points)
	VENOUS SEGMENTS	POINTS	CRITERIA FOR SCORING SEGMENTS
	Inferior vena cava	2
	Common iliac vein	2	0 = completely free of thrombus
	External iliac vein	2	1 = partially occluded
	Common femoral vein	2	2 = completely occluded
	Proximal half of femoral vein	2
	Distal half of femoral vein	2
	Popliteal vein	2
	Total Score Possible:	14

⁎ For each scoring system, the total thrombus score for a limb is the sum of the individual scores assigned to each venous segment. The maximum point value for each segment differs somewhat among the three scales, as do the criteria for scoring each segment.

Assessment of Resource Utilization 

Analysis of treatment expenses has traditionally been based on charges rather than costs to the hospital. Unfortunately, charges are arbitrary and true costs are often difficult to obtain (87). In addition, costs can vary depending on which party is incurring them (88, 89). A rigorous analysis of DVT treatment costs should include the cost of all procedures, devices, and medications given; the cost of any in-patient treatment or intensive care unit care; the costs of immediate and long-term complications; and the costs of long-term monitoring and treatment.