Procedure notes - Aspiration Thrombectomy as the Sole Treatment for Acute and Sub-acute Deep Ve

B. METHODS

1. Procedure notes

1.a. Initial heparinization, IVC filter placement and initial intravenous venography procedure

Heparinization was started when DVT was diagnosed. Heparinization was started 1 to 193 hours (mean, 34.1 hours) before the procedure via a peripheral intravenous line with dose of Heparin between 750 to 165,000 units (mean, 25,459 units). The average rate of Heparin infusion was 746.5 units per hour. Heparin was administered at a therapeutic-level to attain an International Normalized Ratio (INR) in the range of 2.0-3.0.

As a prophylactic measure against the formation of pulmonary embolism retrievable IVC filters were inserted in 100/108 patients (92.6%) prior to aspiration thrombectomy, due to the invasive nature of the procedure, as per the Society of Interventional Radiology (SIR) guidelines (Vedantham et al, 2006). The types of filters deployed were Günther Tulip Filter (GTF; William Cook Europe, Bjaeverskov, Denmark) and Cordis OptEase IVC filter (Cordis Endovascular, Warren, NJ). Three of the patients had previously inserted IVC filters and five of the patients underwent aspiration thrombectomy without the insertion of an IVC filter.

After the procedure, the IVC filters were removed in an average of 10 days, range (3-29 days), in 50/100 cases (50%). Filter retrieval was attempted only in patients with absent or minimal thrombus trapped in the filter as visualized on direct venography. Günther Tulip filters were retrieved via internal jugular vein access, whereas OptEase filters (Cordis) were retrieved by a common femoral vein access as demonstrated in figure 1 and figure 2 below.

Fifty of the retrievable IVC filters were left in place due to various reasons, as well as the 3 permanent filters that were already present before the procedure.

The patient was placed in prone position and the ipsilateral popliteal vein was accessed under ultrasonographic guidance with 12 to 14F sheath after local anesthesia. An initial ascending venography was performed to assess the extent of venous thrombosis.

Fig. 1. Removal of the Günther Tulip filter. Vena cavogram performed before filter removal shows normal IVC and the filter is removed via the internal jugular vein access.

Fig. 2. Removal of the Cordis OptEase filter. Vena cavogram performed before filter removal shows normal IVC and the filter is removed via the common femoral vein approach.

1.b. Aspiration thrombectomy procedure

Manual aspiration thrombectomy was done using a 9-10 F introducer sheath. The connecting hub of the 9 F braided introducer sheath was removed and connected to a 50cc

syringe for suction. The aspiration thrombectomy was performed by repeated pumping movement of the syringe plunger while maintaining a negative pressure within the barrel of the syringe and slowly withdrawing the introducer sheath along with the syringe. During the pumping action care was taken to maintain a negative pressure within the barrel by not allowing the plunger to retract to the end of the syringe barrel. The proper aspiration thrombectomy method is somewhat strenuous but manages to produce a high yield of thrombus extraction in each session.

The aspirate was filtered with 4 by 4 gauze pieces and the blood separated from the clot.

The amount of aspirated blood separated from the clot was measured. Conversion to thrombolysis was done when the aspirated blood was over 400 cc or when the aspiration thrombectomy was incomplete. On completion of the procedure venography was performed to evaluate the success of the aspiration thrombectomy and to plan further treatment if required.

In case of significant residual venous stenosis post procedure we performed stent insertion and percutaneous transluminal angioplasty (PTA). Venous stenoses were noted in 79/108 patients (73.1%) located at the left common iliac vein (n=57), left external iliac vein (n=2), left common iliac vein and left external iliac vein (n=10), right common iliac vein (n=8), right external iliac (n=1), and right common femoral vein (n=1). The residual stenotic lesions were treated with stent placement and balloon angioplasty. The stents deployed were Smart nitinol bare stent (SMART; Cordis, Miami, FL), or ComVi stent (Taewoong Medical Inc., Seoul, Korea). The stent sizes most commonly used were 14mm x8cm and 12mm x8cm and they were mostly dilated with the help of a 10 mm balloon followed by a 12 mm balloon and up to 14 mm balloons in some cases. Nine of the patients required two overlapping stents in the left common iliac and left external iliac veins, so a total of 88 stents were placed.

Seventy eight stents were placed on the left side and 10 stents were placed on the right side.

The most common location of the stents was in the left common iliac vein. The locations of the stents were as tabulated in Table 4.

Table 4: Location of the stents (n=88).

Stent location Number (% of total)

Left common iliac vein 58 (65.9 %)

Left external iliac vein 2 (2.3 %)

Left common iliac vein + left external iliac vein 18 (20.5%)

Right common iliac vein 8 (9.1%)

Right external iliac vein 1 (1.1%)

Right common femoral vein 1 (1.1%)

Symptomatic relief was achieved in all patients. The characteristics of the stented patient group were as shown in Table 5. More female patients (65%) underwent stenting than male patients (35%). The majority of stents were placed in the left side and presence of MTS was seen in 72% of patients.

Table 5: Stented patient group characteristics (n=79)

Mean age (range) 59 (22-87) years

Sex (M/F) 28/51

Side of DVT (Right/Left/Bilateral) 9/69/1 DVT extent (Iliofemoral/ Femoropopliteal) 78/1

15 location of DVT in the remaining stented patients are shown in Table 6.

Table 6: location of DVT in the stented patients (n=79).

DVT location (n = 78) left

16 2. Definitions and Statistical analysis

The guidelines provided by Vedantham et al. in the “Reporting Standards for Endovascular Treatment of Lower Extremity DVT” were adhered to in the definitions and reporting of the findings of this study. Anatomical success was defined as a successful restoration of antegrade in-line flow in the treated vein with elimination of any underlying obstructive lesion as assessed on the procedural venogram. According to post-procedural venography, we defined technical success as over ninety five percent of thrombus extraction. The results were quantified as follows: 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). Follow-up time after the procedure was graded as short-term (up to 1 y), mid-term (1–3 y), or long-term (>3 y) study (Vendantham et al, 2006).

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

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