Data collection
This retrospective study was approved by the Institutional Review Board and was performed in the Department of Cardiovascular Surgery, 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 ultrasound. Clinical data including demographics, co-morbidities, risk factors, ultrasound report, venography reports, operative note and complications were tabulated.
Diagnosis
DVT was diagnosed according to the clinical manifestation, the level of D-dimer, ultrasound. Only those patients with iliac or femoral vein thrombus were included. DVT Patients with duration time (calculating from onset of symptoms) ranging from 14 days to 1 month were classified as subacute DVT.
Definition of variables
Efficacy outcome included thrombolysis degree, clinical improvement, mid-thigh and mid-crus circumferences after CDT. Complete thrombolysis was defined as > 90% thrombus removal, and nearly no clot was found after the procedure. And the case with 50-90% thrombosis removal was scored as partial thrombolysis. 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 upper margin of the patella, while mid-crus circumferences were 10 cm below lower margin of the tibial tuberosity.
Safety outcomes comprised CDT‑related complications during hospital stay, including major and minor bleeding, symptomatic PE and death. Major bleeding and minor bleeding was defined as described.9 Systematic PE and intracranial hemorrhage were diagnosed with computer tomography, which was given for patients with sign of PE (anhelation, hyoxemia and so on) or intracranial hemorrhage (such as unconsciousness, powerless).
Groups
CDT was mainly performed by 2 surgical teams, and they provided anticoagulation treatment with different regimen of LMWH. According to the dose of LMWH, patients were divided into TPDA group and sub-TPDA group.
Anticoagulation therapy
All patients accepted a weight-based (1 mg/kg) twice-a-day regimen of LMWH (Lovenox; Sanofi, Paris, France) before and after CDT. During CDT, for sub-TPDA group, LMWH were given at a fixed-dose of 40 mg every 12 h, while TPDA group were administrated with the same weight-based (1 mg/kg) twice-a-day regimen.
Catheter-directed thrombolysis
A recyclable inferior vena cava filter (OptEase (Cordis, USA) or Celect (Cook, USA)) 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 infusion catheter was advanced. The tip of infusion catheter was placed within thrombus, and its position changed according to ultrasound or venography. The length of the lateral‑hole segment for placing into the thrombus was selected based on thrombus distribution. Urokinase (Livzon Pharmaceutical Group, Inc., China) was delivered at a speed of 0.83~5 x 104 U/h based on primarily the surgeon's preference, experience and risks of bleeding.
Coagulation function was tested daily. Infusion rate of urokinase dosage was adjusted according to Fibrinogen (FIB) concentration: infusion rate was slowed down by 50% if plasma FIB concentration decreased to <1.5 g/L; CDT was suspended and was restarted with a rate slowed down by 50%, if plasma FIB concentration dropped to <1.0 g/L.
For cases experienced complete thrombolysis, CDT was discontinued. If partial thrombolysis was confirmed on venography or ultrasound, whether CDT was continued depends on surgeons’preference or experience. If CDT was continued, the catheter position might be adjusted. Adjunctive balloon, stent was used for those cases with iliac vein compression or residua stenosis after CDT. During CDT, patients were requested to rest in bed. The affected limb was elevated and extract of horse chestnut seeds tablets (Aescuven forte, CesraArzneimittelGmbll&CoKG, Germany) were used to alleviate swelling.
Management of bleeding
If patients manifested with major bleeding, CDT was discontinued. FIB, prothrombin complex or fresh frozen plasma was given. Proton-pump inhibitors were administrated for those patients experienced gastrointestinal bleeding. If patients had minor bleeding, CDT was suspended and resumed at a reduced dosage if minor bleeding could be well 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 were analyzed with analysis of variance, paired t tests or Mann-Whitney testing, and categoric variables with Chi-square test or Fisher’s exact probabilities.