Data collection
This retrospective study was approved by the Institutional Review Board and was performed in the Department of Cardiovascular Surgery at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University. Patients who underwent CDT at our institution during the period from January 2014 to December 2019 were included. Informed consent was obtained from involved patients. Patients were diagnosed with DVT according to clinical features and ultrasounds. Clinical data including demographics, co-morbidities, risk factors, ultrasound reports, venography reports, operative notes, and complications were tabulated.
Diagnosis
DVT was diagnosed according to clinical manifestation, the level of D-dimer, and ultrasound. Only patients with iliac or femoral vein thrombus were included. DVT patients with duration time (calculated from onset of symptoms) ranging from 14 days to one month were classified as subacute DVT.
Definition of variables
Efficacy outcomes included thrombolysis degree, clinical improvement, and mid-thigh and mid-crus circumferences after CDT. Thrombolytic efficacy of CDT was confirmed by color doppler ultrasound or venography. A scoring system mentioned by Mewissen et al7 was used for evaluating thrombolytic outcome in this study. Complete thrombolysis was defined as > 90% thrombus removal, and few clots were found after the procedure. Partial thrombosis was defined as 50-90% thrombosis removal. Clinical improvement was defined as a significant decrease in pain and/or swelling of the affected extremity during hospitalization. Mid-thigh circumferences were measured 15 cm above the upper margin of the patella, while mid-crus circumferences were 10 cm below the lower margin of the tibial tuberosity.
Safety outcomes comprised CDT‑related complications during hospital stays, including major and minor bleeding, symptomatic PE, and death. Major and minor bleeding was defined as described.10 Systematic PE and intracranial hemorrhage were diagnosed with computer tomography, which was given for patients with signs of PE (anhelation, hyoxemia, etc.) or intracranial hemorrhage (unconsciousness, powerlessness).
Groups
CDT was performed by two surgical teams, and they provided anticoagulation treatment with different regimens of LMWH. Patients were divided into TPDA and sub-TPDA groups according to LMWH dosage.
Anticoagulation therapy
All patients accepted a weight-based (one mg/kg) twice-a-day regimen of LMWH (Lovenox; Sanofi, Paris, France) before and after CDT. During CDT, for the sub-TPDA group, LMWH were given at a fixed-dose of 40 mg every 12 h, while the TPDA group was administered the same weight-based (one mg/kg) twice-a-day regimen.
Catheter-directed thrombolysis
A recyclable inferior vena cava filter (OptEase (Cordis, USA) or Celect (Cook, USA)) was generally recommended for patients with high risk of PE: (1). previous PE; (2) planning to accept pneumatic compression treatment. The filter was implanted via the healthy femoral or jugular vein before CDT, and it was removed when the CDT ended.
Retrograde catheterization of the femoral vein in the healthy lower extremity or antegrade catheterization of the popliteal vein in the affected lower extremity was performed. A 4F or 5F multi-sidehole infusion catheter (UniFuse, (Angiodynamics, USA)) was advanced. The tip of the infusion catheter was placed within the thrombus, and its position changed according to ultrasound or venography. The length of the lateral‑hole segment for placement into the thrombus was selected based on thrombus distribution. Dose of urokinase (Livzon Pharmaceutical Group, Inc., China) was calculated according to weights of patients. Urokinase was first injected at a bolus dose of 2~3 x 105 U. Then urokinase was continuously infused with a dose of 1~1.5 x 104 U/kg/d. In other words, the urokinase was given with a dose of 4~12 x 105 U per day (the weight ranged 40~80kg).11 In rare cases with high risks of bleeding, the estimated dose might be reduced by half.12
Coagulation function was tested daily. Infusion rate of urokinase dosage was adjusted according to Fibrinogen (FIB) concentration: infusion rate slowed by 50% if plasma FIB concentration decreased to <1.5 g/L; CDT was suspended and restarted with a rate slowed down by 50% if plasma FIB concentration dropped to <1.0 g/L.
For patients who experienced complete thrombolysis, CDT was discontinued. For patients who experienced partial thrombolysis, CDT was discontinued if patients met at least one criterion: (1). serum level of D-dimer exhibited no significant change; (2). complications with bleeding; (3). ultrasound or venography indicated no improvement. During, the catheter position might be adjusted according to thrombolytic outcome. Generally, thrombolytic duration time should be less than seven days.
Adjunctive balloons and stents were used for cases with iliac vein compression or residua stenosis after CDT. During CDT, patients were put on bedrest. The affected limb was elevated and extracts of horse chestnut seeds’ tablets (Aescuven forte, CesraArzneimittelGmbll&CoKG, Germany) were used to alleviate swelling. Pneumatic compression treatment was conserved for patients who accepted ICF implantation during CDT. Elastic compression stockings were given for patients after CDT.
Management of bleeding
If patients manifested major bleeding, CDT was discontinued. FIB, prothrombin complex, or fresh frozen plasma was given. Proton-pump inhibitors were administrated for patients who experienced gastrointestinal bleeding. If patients had minor bleeding, CDT was suspended and resumed at a reduced dosage if minor bleeding could be controlled. If the minor bleeding continued, CDT was discontinued permanently.
Statistical analysis
The continuous variables were expressed as the mean (standard deviation) or median (range), whereas the categorical variables were recorded as the number and percentage. A P value < 0.05 indicated a significant difference. Continuous data was analyzed with analysis of variance, paired t tests or Mann-Whitney testing, and categoric variables with Chi-square test or Fisher’s exact probabilities.