Pharmacomechanical thrombolysis with a rotator thrombolysis device in iliofemoral deep venous thrombosis

Introduction

Deep venous thrombosis (DVT) is a challenging disease that can cause serious morbidity and mortality, such as pulmonary embolism (PE), if left untreated. It affects future quality of life of patients and increases hospital cost due to extended hospital stay when it develops among hospitalized patients.^1,2 The management of DVT has two main steps: prophylaxis and treatment. Prophylaxis consists of extremity exercise, compression stocking, and appropriate anticoagulation, and it is the preferential and targeted goal to avoid adverse outcomes.^3,4 Treatment mainly aims to avoid complications and to reduce complaints. Although the complaints of patients may continue for weeks or even months, previous treatment regimens are composed of anticoagulant usage and compression stocking alone. ⁴ Moreover, post thrombotic syndrome (PTS) may occur in patients receiving a standard anticoagulation regimen. Even under long-term anticoagulation therapy, PTS incidence was reported to reach 28% and 36% at 5 and 12 years, respectively. ⁴

Lysis of thrombi can be an optional remedy to provide venous patency for selected patients with DVT. Thrombolysis techniques with catheter-directed and pharmacomechanical procedures have gained importance and reliability due to the positive results of previous scientific reports. ⁵ These techniques reduce post-thrombotic morbidity and the complaints of patients in the early periods, protect venous valve competence, and provide early thrombus removal. ¹ Nevertheless, some important points are purported to have used these techniques more effectively, particularly, proximal DVT (iliac and femoral vein involvement) with acute thrombosis formation and low bleeding risk (patients without concomitant bleeding disorder such as bleeding diathesis).^1,5 Catheter-directed thrombolysis or pharmacomechanical thrombolysis may be preferred as a first-stage therapy in DVT patients with these properties according to the Catheter-directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis randomized study. ⁵

In this study, we aimed to evaluate the demographic variables, outcomes (relief duration of complaints), patency success rates, recurrence rates, venous insufficiency rates, and treatment regimens of DVT patients who underwent catheter-directed thrombolysis during the postoperative six-month follow-up period.

Method

Procedure

The selected patients (iliofemoral DVT with acute thrombosis formation and low bleeding risk as previously described by Enden et al. ⁵ ) were referred to the angiography laboratory. Prilocaine (citanest ®, 20 mL flacon, AstraZeneca, Istanbul, Turkey) was applied as local anesthesia to the puncture sites (contralateral groin and ipsilateral popliteal fossa). Thereafter, the contralateral femoral vein was punctured using the Seldinger technique, and a 7 F sheath was placed into the femoral vein. After the renal vein was visualized with contrast, a temporary vena cava filter (Figure 1a) (Angel®, BiO2 Medical Inc. San Antonio, TX, USA) was replaced in the infrarenal segment through the contralateral femoral vein to prevent PE during the procedure (Figure 1(a) and (b)). According to previous literature that reported on case series using this technique, the insertion of the vena cava filter aims to trap fragmented clots.^6,7 The design of filter is similar with a central venous catheter that allows to remove filter by same sheath and prevents hematoma formation or bleeding due to removal of sheath during procedure (Figure 1a). Thereafter, the patients were rotated to inverse position to easily apply the popliteal vein. The popliteal vein was punctured using the Seldinger technique, and a 7 F sheath was placed into it. The deep venous system was visualized with a small amount of contrast injected through the popliteal sheath (Figure 2c). The rotator thrombolysis device was applied to the occluded segment of the iliac and femoral veins with a subsequent thrombolytic agent injection. A Cleaner® (Rex Medical, Fort Worth, TX, USA) rotator thrombolytic device (Figure 1b) was chosen for the mechanical thrombolysis, and it began operating in the popliteal sheath. Reteplase (Rapilysin® 10 U, Roche Diagnostics GmbH, Mannheim, Germany), which was diluted in 0.9% NaCl solution to produce a concentration of 0.001562 U/mL, ⁸ was infused slowly into the thrombosed vein through the infusion lumen of the Cleaner® (Figure 2d). The rotator thrombolytic device was activated for 5–10 min in each vein segment. The deep venous system was re-visualized after reaching the distal vena cava. The device was activated again in the segments that were visualized with partial thrombosis. The remaining residual stenosis of less than 10% was considered as complete recanalization (Figure 1e). After a total venous patency was provided, the popliteal sheath was removed, the puncture site was compressed for 10 min, and the leg was bandaged. The vena cava filter was removed on the third day after implantation. Compression therapy was applied to the both two legs until the filter was removed. The patients were mobilized immediately after the procedure in the intensive care unit. OPEN IN VIEWER

Figure 1.

(a) Retrievable vena cava filter (Angel®, BiO2 Medical Inc. San Antonio, TX, USA), Arrow shows filter cap of device; (b) Rotator thrombolytic device (Cleaner®, Rex Medical, Fort Worth, TX, USA) Arrow shows rotator cap of device.

OPEN IN VIEWER

Figure 2.

(a). Visualization to the position of renal vein and vena cava inferior (arrow indicates left renal vein); (b) Infrarenal placement of vena cava filter (black arrow); (c) Visualization of the thrombosed popliteal vein (arrow indicates occluded segment of popliteal vein); (d) Application of rotator device from distal site of thrombosed vein (arrow indicates rotator tip of device); (e) Complete recanalization after application.

Results

The mean age of the patients was 42.55 ± 21.13 years. Among the patients, 28 (41.8%) were females and 39 (58.2%) were males. The predisposing factors are as follows: trauma (also includes trauma-related immobilization) for 29 (43.3%) patients, pregnancy for 14 patients (20.9%), major surgical operation (includes major hip, knee, and abdominal surgery) for seven (10.5%) patients, immobilization (includes stroke, intensive care unit stay, etc.) for five (7.5%) patients, malignancy for four (5.9%) patients, and unknown etiology for eight patients (11.9%).

The mean operation time was 52.24 ± 33.61 min (placement of the filter and thrombolysis with the rotator device). Total immediate recanalization was provided to all patients. Pain relief was observed in the early hours after operation (1 h to 12 h; mean 5.52 ± 3.25). Swelling of the limb recovered later than pain (6 h to 18 h; mean 9.88 ± 4.12 h vs. 3 h to 9 h; mean 5.52 ± 3.25 h). During the procedure, no notable decrease in oxygen saturation was observed. Early postoperative complications (e.g. hematoma, bleeding, and early re-occlusion) or any recurrence or further thrombosis (e.g. symptomatic PE and contralateral vein thrombosis) were not observed in any of the patients.

Low molecular weight heparin (tinzaparin sodium 175 IU/kg daily) was prescribed to the women who continued breastfeeding after pregnancy. Rivaroxaban was prescribed to patients with malignancy because of the important drug interactions of warfarin. Warfarin was prescribed to other patients who were not at risk for a drug interaction or had lower confidence interval for oral administration to maintain the international normalization ratio between 2.0 and 3.0 level.

Re-occlusion or deep venous insufficiency was not observed from the Doppler ultrasound at the sixth month, and complete deep venous patency was detected in all patients. However, low-grade saphenofemoral reflux (grades I-II: as described previously ⁹ ) was detected in eight (12%) patients.

Discussion

The pharmacomechanical thrombolysis was successfully performed without any complication, and postoperative complete recanalization was achieved in all patients with an acute event. The symptoms regressed in a short period of time (swelling and pain). Re-occlusion or more than a mild deep venous insufficiency was not detected in the six-month follow-up period.

Conventional therapy for iliofemoral DVT is systemic heparinization, followed by oral anticoagulants and compression stockings, which can be performed in almost all medical clinics. Although these methods may provide sufficient recovery, the duration of treatment and the regression of symptoms can be prolonged. Moreover, residual thrombosis can remain in the deep venous system of the limb, and the disorder can progress to a chronic form. Previous studies reported that PE would develop in half of the proximal DVT cases if left untreated, and PE could occur in 4% of patients with anticoagulant treated proximal DVT.^4,10 Moreover, PTS can occur in 50% of patients with proximal DVT after two years despite adequate anticoagulation. ¹¹ This situation can be explained by the observation that the anticoagulation of DVT blocks thrombus propagation and prevents new thrombus formation without precipitating thrombolysis. Therefore, early thrombolysis can be beneficial to preserve venous valvular functions in addition to anticoagulation.^11,12 However, systemic thrombolytic utilizations have severe adverse effects such as serious bleeding complications. Recently, catheter-directed thrombolysis or pharmacomechanical thrombolysis techniques have been developed for local thrombolytic applications to thrombotic segments and for avoiding systemic complications.^11,13,14 The success rate of these techniques was reported to be 80–90% in selected patients and associated with a reduced length of hospital stay. ¹² We applied pharmacomechanical thrombolysis only in patients with acute proximal deep venous thrombosis. We achieved success in all patients, and deep venous insufficiency was not detected at the six-month follow-up.

The most reported complication of these techniques is the local or systemic hemorrhage in 5–11% of cases. Nevertheless, lower bleeding rates compared with systemic thrombolysis were reported because of a reduced dose of the thrombolytic agent.^12,15 Pulmonary emboli are another described complication of thrombolysis at a rate of 1–4.55%, ¹² and they can be prevented by vena cava filters. However, vena cava filters also have self-thrombotic potential that leads to recurrent thrombotic events. Retrievable vena cava filters may reduce this potential with early removal after pharmacomechanical thrombolysis. However, a definitive consensus has not yet been achieved regarding this issue.^12,16 Major bleeding complications were not observed in our series. However, we neglected puncture bleeding that stopped with compression. Newly occurred pulmonary emboli were not observed during and after pharmacomechanical thrombolysis in our series. To avoid this complication, the retrievable vena cava filter was placed before starting the thrombolysis procedure in every patient.

No consensus has yet been achieved regarding the continuation of anticoagulant treatment after catheter-directed thrombolysis or pharmacomechanical thrombolysis of DVT. The duration of the anticoagulation treatment can be elucidated according to recommendations from the American College of Chest Physicians as follows: at least three months for the first event with a reversible or time-limited risk factor for venous thromboembolic disease (e.g. trauma, surgery), at least 6 months for the first episode of idiopathic venous thromboembolic disease, and at least 12 months for recurrent idiopathic venous thromboembolic disease or continuing risk factor (e.g. thrombophilia). ¹⁷ For instance, Chang et al. suggested that oral anticoagulation should not be stopped until the patient’s final evaluation at the end of six months after thrombolytic treatment for acute proximal DVT. ¹⁸ In our study, pharmacomechanical thrombolysis was performed on the patients with acute DVT with no previous history of venous thrombosis. Thus, anticoagulation was continued for three to six months (according to predisposing factors) after pharmacomechanical thrombolysis.

To sum up, pharmacomechanical thrombolysis is an effective treatment for patients with acute proximal DVT. Early intervention using this technique protects the venous valve structures against the harmful effects of PTS at the six-month follow-up. However, we consider that the most important determinant of success is patient selection. The success rates may be reduced in cases with disrupted venous valve functions and recurrent chronic venous thrombosis.