Follow up - Aspiration Thrombectomy as the Sole Treatment for Acute and Sub-acute Deep Venous T

B. METHODS

3. Follow up

On follow-up there were 17 deaths unrelated to the procedure, 9 patients were lost to follow-up and 7 patients had less than one year of follow-up. The mean follow-up period in the remaining 75/108 (69%) patients was 45.3 months, range (12.6-77.3) months. Seventy five patients were assessed in the mid-term follow up (1-3 years after the procedure) and 52/108 (48%) patients remained in the long-term follow-up (>3 years after the procedure).

Follow-up was performed by CT venography at 6 months, 12 months and 24 months, as well as by telephone interviews. The patients’ symptoms on telephone interviews were assessed by the Post-Thrombotic Syndrome VEINES-QOL/Sym scales (Kahn et al., 2006). The results were analyzed in combination with a prospectively registered database.

17 III. RESULTS

Anatomical success was achieved in 92/108 (85%) patients after aspiration thrombectomy treatment of the thrombosed veins. In sixteen patients (15%) with residual thrombosis after thrombectomy (grade I to grade II lysis), additional thrombolysis was performed using urokinase (Vedantham et al, 2006). Seventy nine patients (73%) had residual venous stenoses post aspiration thrombectomy that were treated with stent placement and balloon angioplasty.

The amount of aspirated blood during the procedure ranged from 50 to 380 cc (mean, 158 cc) with decrease of mean hemoglobin level from 11.92.2 to 10.41.85 g/dL (mean, 1.5 g/dL). The mean hematocrit loss was 4.24. Total procedure time, excluding the time for urokinase infusion, ranged from 20-120 min (mean, 55.8 min). There was no major complication. No hemorrhagic complications occurred. There was no patient requiring transfusion. There was no patient mortality associated with the procedure and 30-day mortality rate was zero. Fever developed after the procedure in two patients, but subsided with antipyretics within 3 days.

On follow-up, 25 patients had recurrence of DVT and the findings were divided into mid-term follow-up and long-term follow-up categories. On mid-term follow-up, 61/75 patients (81.3%) had no recurrence of DVT and 14 patients (18.7%) demonstrated DVT recurrence. Fifty five patients (73.3%) were asymptomatic on mid-term follow-up and 20/75 (26.6%) had symptoms related to DVT. The most common risk factors associated with DVT recurrence were MTS and the presence of IVC filters. The details of the 14 patients with recurrence on mid-term follow up are shown in Table 7 below.

Table 7: Recurrence of DVT on mid-term follow-up (n=14).

Patient characteristic Number (n)

Sex (M/F) 11/3

DVT type (Sub-acute/ Acute) 5/9

Original side of DVT (Right/Left/Bilateral) 4/10/0

DVT recur side (Same/opposite/bilateral) 10/1/3

Anatomical extent of DVT (Iliofemoral/ Femoropopliteal) 14/0 Risk factors (single risk factor/two risk factors) 6/5

MTS 6

IVC filters 4

Post-operative/trauma 3

Malignancy 2

Pregnancy 1

Out of the 52 patients who remained during long-term follow-up, 41/52 (78.8%) had no recurrence of DVT and DVT recurrence was seen in 11/52 (21.1%). Thirty seven patients (71.1%) were asymptomatic on long-term follow-up and 15/52 (28.8%) were symptomatic.

The results are further elucidated in Table 8 below.

Table 8: DVT recurrence and symptoms recurrence on mid-term and long-term follow-up.

No DVT recurrence + symptomatic 13 10

DVT recurrence + asymptomatic 7 6

DVT recurrence + symptomatic 7 5

Out of the 11 cases of DVT recurrence on long-term follow-up, 4 were of sub-acute type and 7 were of acute type on initial presentation. The most common risk factors identified in DVT recurrence were MTS, IVC filters and post-operative state. Table 9 details the patient characteristics.

Table 9: Recurrence of DVT on long-term follow-up (n=11).

Patient characteristic Number (n)

Sex (M/F) 8/3

DVT type (Sub-acute/ Acute) 4/7

Original side of DVT (Right/Left/Bilateral) 3/8/0

DVT recur side (Same/opposite/bilateral) 9/0/2

Anatomical extent of DVT (Iliofemoral/ Femoropopliteal) 8/3 Risk factors (single risk factor/two risk factors) 4/4

MTS 5

IVC filters 3

Post-operative/trauma 3

Malignancy 1

Pregnancy 0

On follow-up of the 79 patients with stents, there were 14 deaths unrelated to the procedure and 12 patients were lost to up. In the remaining 53 patients, mean follow-up period was 1359 days (range 383 -2356) days and 35 patients remained during long-term follow-up. DVT recurrence was seen in a total of 10/53 (18.9%) patients, out of which 9 had intra-stent thrombi of the stented veins with 7 occlusions of the stents that required re-interventions. A total of 7/53 (13.2%) stents were found to be collapsed. Four of the stent collapses were between 50-75% of luminal diameter and occurred without recurrence of any DVT, due to wedging of the stent between the left common iliac artery and the spine. The remaining 3 stent collapses occurred in a background of DVT recurrence and were between 25-50% of the stent lumen.

Among the 10 patients with DVT recurrence in the stented group, 5 patients had a single risk factor for DVT recurrence and 5 had two risk factors present. The most common risk factors were identified to be May Thurner syndrome- 6 patients and inlaying IVC filters-3 patients. The other risk factors found were 2 malignancies, 2 operative statuses, 1 post-partum period and one case of idiopathic DVT. Table 10 depicts the characteristics of the stented patients in whom DVT recurrence occurred.

Table 10: Recurrence of DVT in stented group (n=10).

Patient characteristic Number (n)

Sex (M/F) 6/4

DVT type (Sub-acute/ Acute) 5/5

Original side of DVT (Right/Left/Bilateral) 2/8/0

DVT recur side (Same/opposite/bilateral) 8/1/1

Anatomical extent of DVT (Iliofemoral/ Femoropopliteal) 10/0

MTS 6

Risk factors (single risk factor/two risk factors) 5/5

Four out of 108 patients underwent pulmonary CT angiography before the procedure and pulmonary thromboembolisms were detected in 3 of them, 2 of which resolved after treatment and one patient was lost to follow-up. After the procedure, 45/108 (41.6%) of the patients underwent pulmonary CT angiography to rule out pulmonary thromboembolism.

Nineteen patients had a pulmonary thromboembolism post aspiration thrombectomy and 26 patients did not demonstrate any pulmonary thromboembolism on pulmonary CT angiography. All of the pulmonary thromboembolisms detected were asymptomatic and resolved spontaneously with conservative treatment. During the mid-term follow-up, one of the patients who initially demonstrated PTE post procedure had recurrence of DVT, whereas in the long-term follow-up group 4/ 11 (36%) patients with DVT recurrence had PTE post aspiration thrombectomy.

Fig. 3. May Thurner syndrome with DVT. This 31 year old male patient presented with pain and swelling of his left lower extremity of 15 days duration. CT venography revealed MTS and left sided DVT extending from the external iliac vein up to the popliteal vein.

Figure A shows the features of the May Thurner syndrome. The white arrow denotes the right common iliac artery that is compressing the left common iliac vein against the lumbar vertebra. Figure B shows DVT in the left external iliac vein and figure C shows the DVT extending up to the left popliteal vein.

Fig. 4. Treatment and recurrence. Post aspiration thrombectomy venography (figure A) revealed venous stenosis at the left common iliac vein which was treated with stent placement and balloon dilatation. Three years later in 2010, the patient presented with stent collapse between the right common iliac artery and the lumbar vertebra (figure C), along with recurrence of DVT as seen in figure D.

IV. DISCUSSION

Deep vein thrombosis causes considerable morbidity due to its recurrent nature and long term sequelae such as the post-thrombotic syndrome (PTS). Post-thrombotic syndrome often leads to severe clinical disability, quality of life (QOL) impairment and high socioeconomic costs (Vedantham et al, 2006). Estimates of the 2-year cumulative incidence of PTS vary enormously, ranging between 23% and 60% (Ashrani and Heit, 2009). In most cases, PTS develops within 1 to 2 years after DVT and severe PTS occurs in 5% to 10% of patients after DVT (Kahn and Ginsberg, 2004). Patients with iliofemoral DVT are at particularly high risk for PTS and late disability (Vedantham et al, 2006). The primary goals in the treatment of acute DVT of the lower extremity are elimination of the embolic potential of existing thrombus, restoration of unobstructed flow, prevention of further thrombosis, and preservation of venous valve function.

The standard treatment recommended for acute DVT of the leg according to the latest ACCP guidelines is initial treatment with low-molecular-weight heparin (LMWH), unfractioned heparin (UFH), or fondaparinux for at least 5 days and until the INR is > 2.0 for 24 h, along with concurrent initiation of vitamin K antagonist (VKA) on the first treatment day. However, anticoagulation does not have significant fibrinolytic activity and patients with severe, extensive, proximal DVTs remain at high risk of developing post thrombotic morbidity, with up to 75% having chronic painful edema and 40% having venous claudication when treated with anticoagulant therapy alone (Kearon et al, 2008).

A study in Germany found that systemic thrombolytic treatment for acute DVT achieved significantly better short-term and 12 month follow-up clinical outcomes than

conventional heparin/anticoagulation therapy, but at the expense of a serious increase in major bleeding (6%) and pulmonary embolism (4.5%), compared with no occurrences in those receiving conventional regimens. Thrombus reduction >50% or complete recanalization was observed in 6%, 36% and 54% of patients on heparin therapy, patients on local treatment and systemic lysis, respectively (Schweizer et al, 2000). Recently, Comerota analyzed twelve studies published between 1968 and 1990 that randomized patients with acute DVT to anticoagulation alone versus systemic thrombolytic therapy. On comparison of the patients managed with anticoagulation alone versus those treated with systemic thrombolysis, summary analysis of the lytic outcomes in the 12 trials demonstrated that 5 % vs. 45% had significant or complete lysis, 14% vs. 18% had partial lysis and 81% vs. 37%

had either no objective phlebographic clearing or had extension of their thrombus. Major bleeding complications in the anticoagulation group were between 27% compared to 2-33% in the thrombolysis group, whereas minor bleeding complications in the anticoagulation group were between 0.4-12% and 5-25% in the thrombolysis group (Comerota, 2010). At present the ACCP recommends systemic thrombolytic therapy if CDT is not available only in selected patients with extensive proximal DVT (e.g., symptoms for < 14 days, good functional status, life expectancy of > 1 year) who have a low risk of bleeding (Kearon et al, 2008).

Delivering the thrombolytic agent directly into the thrombus by means of catheter-directed thrombolysis (CDT) techniques offers significant advantages over systemic therapy, such as better efficacy, lower drug dosages and infusion time, less complications and it is more cost effective. A single-center, retrospective study of 32 patients treated either with systemic thrombolysis (16) or catheter-directed local thrombolysis (16) for massive iliofemoral thrombosis was undertaken to assess preservation of venous valve function 2-3

years after treatment. Initial technical success rates were not available for comparison. Major bleeding complications were encountered in 13% of CDT patients versus 6% in systemic-treated patients, whereas minor bleeding events were 25% (CDT) versus 38% (systemic thrombolysis). The mid-term results suggest that CDT achieves better lysis (50% vs. 31%) and preservation of valve function (44% vs 13%) than systemic thrombolysis (Laiho et al, 2004). So far, the largest published experience with catheter-directed thrombolysis (CDT) approach in lower-extremity DVT has been from the National Venous Thrombolysis Registry, which reported a collective multicenter experience with 287 patients (303 limbs) in whom one-year follow-up was available (Mewissen et al, 1999). Of the 287 patients treated, 66% had acute DVT and the location of DVT was in the iliofemoral segment in 71% of patients with involvement of the inferior vena cava (ICV) in 21%. Complete thrombolysis was achieved in 31% of cases, whereas partial (>50%) thrombolysis with restoration of forward flow was achieved in 52% of patients. One third of patients received adjunctive stenting for residual narrowing. Overall, thrombosis-free survival was observed in 60% of patients at 1 year. Seventy-eight percent of patients with complete lysis had patent veins at 1 year, compared to only 37% who had insignificant lysis (<50%). For a patient with acute IFDVT and no history of previous DVT, when CDT was performed via the popliteal vein accessed with ultrasound guidance, complete lysis occurred in 65% and the 1-year patency was 96%. Complications included an 11% incidence of major bleeding that required transfusion of blood products and a 16% incidence of minor bleeding. The risks of intracranial hemorrhage and death were 0.2 and 0.4% respectively (Mewissen et al, 1999).

The catheter-directed venous thrombolysis in acute iliofemoral vein thrombosis trial (the CaVenT Study), is an ongoing open, multicenter, randomized, controlled trial with 103 patients comparing catheter-directed thrombolysis versus anticoagulation therapy alone.

Fifty patients were allocated adjunctive CDT along with anticoagulation and 53 patients underwent standard anticoagulation therapy alone. After CDT, grade III (complete) lysis was achieved in 48% and grade II (50%–90%) lysis in 40% patients. One patient suffered major bleeding and two had clinically relevant bleeding related to the CDT procedure. After 6 months, iliofemoral patency was found in 32 (64.0%) in the CDT group vs. 19 (35.8%) controls. The long-term results of the CaVenT study are awaited (Enden et al, 2009). The current ACCP guidelines suggest that CDT may be used to reduce acute symptoms and postthrombotic morbidity if appropriate expertise and resources are available in selected patients with extensive acute proximal DVT (e.g., iliofemoral DVT, symptoms for < 14 days, good functional status, life expectancy > 1 year) who have a low risk of bleeding. They further recommend correction of underlying venous lesions using balloon angioplasty and stents after successful CDT in patients with acute DVT and the same intensity and duration of anticoagulant therapy as for comparable patients who do not undergo CDT (Kearon et al, 2008). The Society of Interventional Radiology (SIR) considers the use of CDT as an adjunct to anticoagulant therapy as an acceptable initial treatment strategy for acute iliofemoral DVT in carefully selected ambulatory patients with long life expectancy who are considered to be at low risk for bleeding (Vedantham et al, 2006)

Pharmacomechanical thrombolysis (PMT) devices such as the Arrow Trerotola, AngioJet, and Trellis system may attenuate the morbidity of CDT by permitting a dose

compared to the use of PMT alone (62.4% + 24.9 vs. 26% + 24.1). The different devices all appeared to be safe, with no reported procedure-related deaths or strokes and <1% incidence of symptomatic PE. Bleeding complications were reported in 6/16 studies, in which 4-14%

of patients required transfusion (global incidence 11/146 patients, 7.5%). Seventy five percent to 98% of patients demonstrated significant mid-term improvement in symptoms with similar radiological findings (Karthikesalingam et al, 2011). The ACCP suggests pharmacomechanical thrombolysis (e.g., with inclusion of thrombus fragmentation and/or aspiration) in preference to CDT alone in patients with acute DVT to shorten treatment time if appropriate expertise and resources are available and does not recommend treatment with percutaneous mechanical thrombectomy alone (Kearon et al, 2008).

A previous study on the treatment of acute lower extremity DVT with combined aspiration thrombectomy and CDT reported an initial technical success rate of 91%, and 50% patients underwent stenting and balloon angioplasy in the left common iliac vein. There was a 1% incidence of major bleeding, 4% incidence of minor bleeding and 61% patients were detected to have PE pre-operatively. On follow-up multi-detector computerized tomography (MDCT) venography at 5.7 ± 5.6 months, 72% showed no thrombus, 22%

partial thrombus, and 6% showed obstruction. On short term follow-up (<1 y), 38%

developed PTS and 8% were admitted due to DVT recurrence. A telephone interview of 81% patients at 22.8 ± 10.7 months postoperatively revealed that 46% were asymptomatic, 46% had moderate improvement, and 6% were mildly improved (Jeon et al, 2010). In another study that employed aspiration thrombectomy treatment for acute lower extremity DVT without CDT, the initial technical success was 88.9% and 81.4% underwent stenting in the common iliac vein or external iliac vein due to residual stenosis. The clinical and imaging follow-up periods were 3-40 months (mean 15 months). On follow-up sonography

or CT, the patency of all lower deep veins was well preserved, including the stents, except in two patients who showed a recurrent DVT after 2 weeks and 2 months respectively (Kwon et al, 2009). The initial technical success result of 85% and 73% rate of post procedural stenting in the current study using the aspiration thrombectomy as the sole approach to the treatment of acute lower extremity proximal DVT compares favorably with the previous studies. Unfortunately, mid-term and long-term follow-up results were not available in these studies to compare their findings with the present study.

Mid-term and long-term prospective data on the treatment of acute DVT of the lower extremity is scant in literature. Four ongoing studies were identified, which have not published their results to date: the PEARL registry (NCT00778336), the ATTRACT trial (NCT00790335), the CAVA trial (NCT00970619) and the SONIC I Safety and Efficacy study (NCT00640731). One study comparing the 1, 3 and 5 years results after conventional anticoagulation versus lysis/stenting showed that the primary iliofemoral venous patency rates at 1, 3, and 5 years were 24%, 18%, and 18% in the anticoagulation group versus 83%, 69%, and 69% in the lysis/stenting group (AbuRahma et al, 2001). The results of the present aspiration thrombectomy study of 85%, 64% and 59.6% primary venous patency rates at immediate post procedure, mid-term follow-up and long-term follow-up respectively are comparable to the patency rates reported for the lysis/stenting group. In comparing the long-term symptom resolution between the two groups, 30% of patients reported resolution of symptoms in the anticoagulation group in contrast to 78% in the lysis/stenting group (AbuRahma et al, 2001). The patients treated with aspiration thrombectomy in the current study had 73.3% and 71.1% resolution of symptoms at mid-term and long-term follow-up, similar to the results of the lysis/stenting group in the study by AbuRahma et al.

In both the mid-term and long-term follow-ups of the present study the most common risk factors identified in DVT recurrence were the presence of MTS, IVC filter and post-operative status. There was also a relatively higher incidence of DVT recurrence in the patients who had originally presented with sub-acute DVT in comparison to acute DVT on both mid-term and long-term follow-up, 5 versus 7 and 5 versus 5, especially considering the low percentage of initial patients in the sub-acute group (13.9%) versus the acute group (86/1%). These results suggest that this treatment module should exclude those patients with sub-acute DVT of the lower extremity, due to the hard organized nature of the thrombi.

Out of the 55.5% of patients with May Thurner syndrome (MTS) who underwent aspiration thrombectomy in this study, 70% were female. Ninety five percent (57/60) of the patients with MTS required stent placement post aspiration thrombectomy. Forty six patients with MTS remained during mid-term follow up, and 6 patients had recurrence of DVT in the same side as the treated venous segment, whereas 86.96% had no evidence of DVT recurrence. Thirty two MTS patients remained during long-term follow up, and 5 patients had recurrence of DVT, whereas 84.37% were asymptomatic.

The limitations of this study are that the limb circumference of the patients were not measured pre and post procedure, valvular reflex was not assessed at the onset of the study and late valvular dysfunction status could not be clinically evaluated using duplex ultrasonographic data.

V. CONCLUSION

Aspiration thrombectomy is a safe and effective treatment for acute proximal DVT.

Clinical mid and long-term results are encouraging. In the background of recent internal bleeding, recent surgery, patients with bleeding disorders, severe hypertension, or recent cardiovascular accident, thrombolysis of suprapopliteal DVT is contraindicated and aspiration thrombectomy could be the alternative treatment choice. The advocacy of aspiration thrombectomy as the sole treatment for acute DVT could also be justified on the basis of cost effectiveness and less potential for vein wall damage.

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