Endovascular Thrombus Removal for Treating Post-Partum Iliofemoral Deep Vein Thrombosis: A Single-Centre Retrospective Cohort Study

Abstract

Objective

To evaluate the safety and efficacy of percutaneous thrombectomy for treating postpartum iliofemoral vein thrombosis.

Methods

A retrospective analysis was performed on patients with continuous postpartum acute symptomatic iliofemoral deep vein thrombosis who were treated in our center, including all patients who underwent pharmacomechanical thrombolysis (PMT) or only catheter-directed thrombolysis (CDT) (study group), and patients that received simple anticoagulation treatment (control group). We evaluated the incidence of lower extremity postthrombotic syndrome, recanalization rate of lower extremity veins, and complications in the study and control groups.

Results

Overall, 72 postpartum women were included in this study, including the PMT combined with CDT group (14 cases, 15 limbs), CDT alone group (26 cases, 27 limbs), and anticoagulant therapy alone group (32 cases, 34 limbs). The thrombectomy group completed the treatment with a technical success rate of 100%, and no serious bleeding complications occurred. The patency rate of lower limb veins in the thrombectomy group was 85.09 ± 16.51% after treatment and 82.60 ± 21.45% after 1 year. At the 1-year follow-up, the Villalta score in the study group was lower (1.90 ± 2.45 vs 8.50 ± 5.33, P < .001), and the incidence of postthrombotic syndrome was significantly different between the groups (17.50% in the study group vs 68.75% in the anticoagulant group, P < .001).

Conclusions

Lower extremity venous thrombectomy is a safe and effective treatment for postpartum iliofemoral venous thrombosis. It can improve the patency rate of lower extremity veins and reduce the incidence of postthrombotic syndrome compared with anticoagulation alone.

Article Highlights

Type of Research: Single-center retrospective cohort study.

Key Findings: Endovascular thrombus removal for treating 40 postpartum patients with iliofemoral vein thrombosis was compared with 32 cases treated with anticoagulant therapy alone: the Villalta score was lower (1.90 ± 2.45 vs 8.50 ± 5.33), the incidence of postthrombotic syndrome (PTS) was reduced (17.50% vs 68.75%), and no serious bleeding complications occurred.

Take Home Message: Lower extremity venous thrombectomy (pharmacomechanical and catheter-directed thrombolysis [CDT]) is a safe and effective treatment for postpartum iliofemoral venous thrombosis that can improve the patency rate of lower extremity veins and reduce the incidence of PTS compared with anticoagulation alone.

Table of Contents Summary: In this retrospective study of 72 postpartum patients with iliofemoral vein thrombosis who received treatment, the incidence of PTS was reduced by the treatment with percutaneous thrombectomy. Percutaneous thrombectomy is a safe and effective treatment for postpartum iliofemoral vein thrombosis.

Introduction

Postpartum patients are prone to symptomatic iliofemoral vein thrombosis because of their special physiological states, such as slow blood flow and hypercoagulability in lower limbs. Iliofemoral vein thrombosis has been treated using standardized anticoagulation therapy; however, PTS incidence is still as high as 20‒50%, ¹ and the prevalence of PTS after pregnancy-related lower extremity deep vein thrombosis (DVT) is estimated to be 42% after anticoagulation. ² However, maternal age is generally young, requiring the maintenance of a high quality of life in the future, and PTS seriously affects the quality of life of such patients. ³

Lower extremity venous thrombectomy (pharmacomechanical thrombolysis [PMT] and CDT) is the main method for treating iliofemoral venous thrombosis; it removes thrombus, restores lumen patency, and reduces the incidence of PTS.^4,5 Thrombolytic therapy was previously considered a relative taboo for postpartum patients, because of the potential bleeding risk. ⁶ The CaVent study excluded patients with iliofemoral venous thrombosis within 7 days after delivery and 14 days after surgery, ⁷ and there was no subgroup analysis of postpartum patients in the ATTRACT study. ⁸

However, the safety of lower extremity venous thrombosis clearance in postpartum symptomatic DVT and the reduction of PTS incidence require further studying. This study aimed to compare the early results of lower extremity venous thrombosis clearance and simple anticoagulation in treating postpartum acute iliofemoral venous thrombosis.

Methods

Clinical Data

From February 2013 to October 2021, 72 consecutive postpartum patients (76 limbs) with acute symptomatic iliofemoral DVT were analyzed retrospectively. The inclusion criteria were as follows: (1) onset time within 2 weeks, puerperium (within 42 days after placenta delivery), and 18‒45 years of age; (2) the first iliofemoral vein thrombosis was confirmed using color Doppler ultrasound or deep venography of lower limbs; (3) the patients had no contraindications to anticoagulation and thrombolysis; (4) the expected survival time was more than 1 year, and the patient could tolerate the surgery without serious organ dysfunction. The clinical manifestations of the study and control groups were swelling, pain, and increased tissue tension in the affected limb. This study was approved by the clinical research and applied ethics committee in the Union Medical College Hospital affiliated with Fujian Medical University. In addition, all patients signed written informed consent forms.

Treatment Methods

Before treatment, all patients in the two groups were examined using gynecological color Doppler ultrasound to rule out the possibility of placental residue. They were administered anticoagulant therapy by subcutaneous injection of low molecular weight heparin (LMWH, Fragmin, Vetter Pharma-Fertigung GmbH & Co. KG).

The research group initially punctured the small saphenous vein or the popliteal vein under B-ultrasound and inserted the 7F vascular sheath. We then confirmed the position of venous thrombosis in the lower limbs by segmental angiography of the sheath. All patients were implanted with a retrievable filter of the inferior vena cava (IVCF, Optease, Cordis Company of America or Aegisy, Shenzhen Xianjian) to prevent pulmonary embolism, and the filter was removed as soon as possible after treatment. Patients that developed iliofemoral DVT within 10 days after delivery were implanted with IVCF for anticoagulation treatment, and thrombectomy was performed 10 days after delivery. Furthermore, after the guide wire (TERUMO, Japan) reached the inferior vena cava through the diseased segment, the Amplatz Super Stiff guidewire (Boston Scientific Corporation, USA) was used to establish the approach, which was sent into a 6f AngioJet Solent Omni (Boston Scientific) catheter and PMT was started in spraying and suction mode. In the spray mode, 300 000 units of urokinase were dissolved in 150 ml of normal saline for the entire process of injection perfusion in the thrombus. After waiting for 30 min, we switched the thrombectomy mode and changed the perfusion solution to heparin saline (2500 U heparin + 500 ml saline). The thrombus aspiration catheter was used to aspirate the thrombus from the distal to the proximal end along the guide wire at a speed of 1‒2 mm/s, and the place with a heavy thrombus load was repeatedly aspirated. The conditions for stopping thrombectomy were: (1) thrombosis of the iliofemoral vein was completely cleared; (2) after repeated aspiration, the residual thrombus could not be aspirated; (3) the patient could not tolerate thrombectomy during surgery; and (4) the total suction time was not more than 480 s for cases with complete occlusion and 240 s for cases with partial occlusion and partial blood flow.

If the patient showed that the residual thrombus was still obvious after repeated aspiration, as in the simple CDT treatment group, a suitable length of unifuse perfusion thrombolytic catheter (AngioDynamics, USA) with a side hole was selected and embedded in the entire thrombus process; then, urokinase 30 000 to 40 000 units/h was continuously pumped through the thrombolytic catheter. On the first, third, and fifth days of thrombolytic treatment, lower extremity venography was performed to understand the residual thrombus dissolution, in order to adjust the position of the thrombolytic catheter and determine whether to terminate the thrombolytic treatment. Hemoglobin levels, coagulation, and liver and kidney functions were monitored every 12 h after surgery. In addition, fluid replacement, diuresis, alkaline urine treatment, vaginal bleeding, and hematuria were closely observed. The conditions for CDT termination were: (1) reexamination showed that the thrombus was completely dissolved; (2) the thrombolytic effect showed no progress before and after angiography; (3) Fibrinogen (FIB) was <1.2 g/L; and (4) massive bleeding or serious complications.

For patients whose thrombus clearance rate was >90% (Grade III thrombus clearance), ⁹ and only the left iliac vein was severely narrowed or occluded (degree ≥50%), balloon catheter dilation or stenting of the iliac vein was encouraged according to patients’ wishes (Bard BD Company, Cordis Angio Dynamics Company, USA). After treatment, all patients in both groups were administered warfarin or rivaroxaban for at least 6 months. Patients were also given compression stockings for a long time and were followed up regularly at 1, 3, 6, and 12 months.

Observation Indicators

Lower limb vein patency rate after treatment and during follow-up

The efficacy of venous patency was evaluated according to the criteria proposed by Porter, ¹⁰ and the results of venography or color Doppler ultrasound of the affected limbs of the two patient groups after treatment were evaluated. The venous segments included the inferior vena cava, common iliac vein, external iliac vein, common femoral vein, upper segment of the femoral vein, lower segment of the femoral vein, and popliteal vein. The total occlusion of the whole segment of the lumen was three points, the occlusion that did not involve the whole segment of the lumen was two points, the partial patency of the lumen was one point, and the complete patency was 0 point. Venous lumen patency rate = (patency score before treatment − patency score after treatment)/patency score before treatment × 100%.

Complication

The safety results included major bleeding (abdominal bleeding, cerebral hemorrhage, and vaginal bleeding) and minor bleeding (gingival, nasal, and skin). In addition, blood, urine, hemoglobin changes, bacteremia, and renal function changes were monitored.

Incidence of PTS (main result)

The diagnosis of lower limb PTS was based on Villalta score, ¹¹ with a total score of 33 points: 0‒4 points were no PTS; 5‒9 points were mild PTS; 10‒14 points were moderate PTS; 15‒33 points were severe PTS; ulcer was 15 points.

Statistical Methods

The SPSS 18.0 statistical software was used for statistical analyses. The measurement data were expressed as x ± s, and a paired t-test was used to express the application rate or constituent ratio of the counting data. We used the Mann–Whitney U test to compare continuous nonparametric data. The chi-square test or Fisher's exact test was used to classify the data. P < .05 indicated that the difference was statistically significant.

Results

Baseline Patient Data

Overall, 72 postpartum women were included in this study, including the PMT group (14 cases, 15 limbs), CDT group (26 cases, 27 limbs), and anticoagulant treatment group (32 cases, 34 limbs). In the study group, the average age of puerpera was 30.85 ± 5.97 (20-43) years, and the average age of the anticoagulation group was 31.81 ± 5.31 (22-44) years. In the two groups, cesarean section was performed more than spontaneous delivery, and the general data of the two groups were comparable (Table 1).

Table 1.

General Data Statistics of Two Groups of Patients.

Variables	Study group (n = 40)	Control group (n = 32)	P value
Age (years)	30.85 ± 5.97 (20∼43)	31.81 ± 5.31 (22∼44)	.478
Affected limb
Left	37 (92.50%)	27 (84.38%)	.534 a
Right	1 (2.50%)	3 (9.37%)
Bilateral	2 (5.00%)	2 (6.25%)
Course of disease (d)	5.03 ± 3.67 (1∼14)	6.43 ± 3.50 (1∼14)	.102
Mode of delivery
Cesarean section	36	27	.498 a
Vaginal delivery	4	5
Postpartum time (days)	19.23 ± 9.23 (5∼42)	20.28 ± 8.87 (7∼42)	.625
Parity
1	33	28	.744 a
2	7	4
Thrombosed segments
Iliofemoral vein	34(85.00%)	30 (93.75%)	.287 a
Iliofemoral vein Involving IVC	6(15.00%)	2 (6.25%)
Symptomatic PE	3 (7.50%)	1 (3.12%)	.624 a
Circumference difference of lower limbs (cm)
Thigh	3.71 ± 2.11	3.56 ± 1.36	.729
Calf	2.70 ± 1.36	2.58 ± 0.98	.671
Lower limb vein score	16.53 ± 2.49 (8∼20)	15.59 ± 3.14 (8∼20)	.179 b
Risk factors
Take hormones	3(7.50%)	2(6.25%)	1.000 a
May–Thurner syndrome	37(92.50%)	/	/
Tumour	0	0	/

^a Fisher exact test.

^b Mann–Whitney U test.

Surgical Process and Therapeutic Effect

The study group successfully completed thrombectomy with a technical success rate of 100% (Figure 1). All patients’ lower limb symptoms were effectively relieved. After the thrombus was cleared, the inferior vena cava filter was removed. In the study group, the lower limb vein score before and after treatment was statistically significant (16.59 ± 2.45 vs 2.50 ± 2.84, P < .001), and the lower limb vein recanalization rate was 85.09 ± 16.5% (Table 2). We also observed that PMT combined with CDT reduced the amount of urokinase used in the study group compared with CDT alone (5.26 ± 1.58 vs 2.81 ± 1.23 million units, P < .001), and shortened the number of thrombolytic days (6.08 ± 1.72 vs 3.07 ± 1.21 d, P < .001).

Figure 1.

Imaging data of a postpartum patient with iliofemoral vein thrombosis. A 33-year-old patient had left lower limb swelling for 5 days, 20 days after cesarean section. Imaging data: 1-4: anterograde angiography confirmed iliofemoral vein thrombosis and left common iliac vein occlusion; 5-6: catheter directed thrombolysis; 7-9: after 5 days of thrombolytic therapy, angiography showed that most of the thrombus dissolved, and severe left common iliac vein stenosis remained; 10: balloon catheter dilation of left common iliac vein lesions; 11: angiography after stent opening left iliac vein lesion showed that the blood flow was completely unobstructed; 12-14: three years after operation, the reexamination showed that the iliofemoral vein and stent were completely unobstructed.

Table 2.

Comparison of Results Within the Study Group.

Statistical items	Before treatment	After treatment	P value
Haemoglobin	118.70 ± 14.80	110.37 ± 14.19	<.001
Circumference difference of lower limbs (cm)
Thigh	3.71 ± 2.11	0.35 ± 0.57	<.001
Calf	2.70 ± 1.36	0.39 ± 0.60	<.001
Lower limb vein score	16.60 ± 2.45 (8∼20)	2.50 ± 2.84 (0-9)	<.001

Complications

There were no major bleeding events, pulmonary embolisms, and death in the study group. All 14 patients who underwent PMT had hemoglobinuria after surgery, which improved within 24 h without renal function damage. In the study group, there was one case of bleeding at the popliteal vein puncture, and one case of bleeding at the inguinal puncture. Two patients had a slight increase in vaginal bleeding, which decreased after receiving a reduced dose of urokinase thrombolysis treatment. During thrombolysis, one patient developed hypofibrinogenemia, which decreased to 1.23 g/L, and returned to normal after treatment with fresh frozen plasma and cryoprecipitate. Another patient developed heparin-induced thrombocytopenia, with platelet count dropping to 53 × 10⁹/L; in that case, the LMWH treatment was stopped, rivaroxaban was given to replace anticoagulation during thrombolysis, and the treatment was completed successfully. There was a statistically significant difference in hemoglobin levels before and after treatment in the study group, with a decrease of 8.33 g/L in hemoglobin levels, and no blood transfusion was performed.

Primary and Secondary Follow-up Results

Both patient groups completed at least 1 year of follow-up, during which no patient died, and no bleeding complications occurred. The follow-up time of the study group was 12 to 62 months, with an average of 24.5 ± 10.5 months. The follow-up time of the anticoagulant group was 12 to 37 months, with an average of 23.92 ± 7.30 months. In the study group, one patient experienced thrombosis recurrence 6 months after treatment, and the symptoms improved after anticoagulation treatment. In the anticoagulation group, there were two patients with a recurrence of thrombus, and anticoagulation treatment was continued. At 1 year follow-up, the venous patency rate in the study group was 82.60 ± 21.45%. The difference in the incidence of PTS in the two groups was statistically significant (P < .001); there were seven patients with mild-to-moderate PTS in the study group and 22 patients with a significantly higher incidence of PTS in the control group (Table 3).

Table 3.

Comparison of Results Between Study and Control Group.

Statistical items	Study group	Control group	P value
Recannalization percentage of venous lumen after treatment (%)	85.09 ± 16.51	/	/
Iliac vein stent implantation (case)	12	/	/
Complication
Massive bleeding	0	0	/
Small bleeding	4	1	1.000 a
Renal damage	0	0	/
Villalta score after 1 year	1.90 ± 2.45	8.50 ± 5.33	<.001
PTS incidence after 1 year
No PTS	33	10	<.001 b
Mild PTS	6	3
Moderate PTS	1	5
Severe PTS	0	14

Abbreviation: PTS, postthrombotic syndrome.

^a Fisher exact test.

^b Fisher's exact test for no PTS versus mild to severe PTS.

Discussion

In this study, most patients responded well to the treatment of postpartum iliofemoral vein thrombosis with thrombectomy, without increasing major bleeding events or other serious complications. After 1 year, the incidence of PTS in the thrombectomy group was only 17.5%, as opposed to 68.75% in the anticoagulant group. Thus, thrombectomy seems to be a safe and effective treatment for postpartum iliofemoral vein thrombosis.

Venous thrombosis is prone to occur because of the special physiological conditions of pregnant women. Compared with nonpregnant women, the incidence rate of venous thromboembolism in pregnancy and puerperium is increased 4 to 5 times, especially in puerperal women. ¹² In addition, because of the traditional Chinese custom of “zuo yue zi,” most postpartum patients stay in bed for a long time and have little lower limb activity within 1 month, plus a high-protein and high-fat diet. Hence their blood is usually in a hypercoagulable state, which is prone to lower limb venous thrombosis. Moreover, postpartum patients are generally young and have high requirements for quality of life; such patients have high enthusiasm for thrombectomy. The incidence of PTS in the study group was low. During the 1-year follow-up, the incidence of PTS in postnatal patients in the study group was 17.5%; furthermore, it was only mild and moderate, without severe PTS cases.

There are several studies on using thrombectomy in perinatal patients, including pregnant patients with postpartum thrombosis.^13–15 These studies have reported promising results. However, owing to ethical constraints, we do not use thrombectomy for patients with thrombosis during pregnancy, unless the patient agrees to forfeit the pregnancy; hence, such patients were excluded from our study. There are also studies^14,15 on postpartum thrombectomy alone, but these have not been compared with patients treated with simple anticoagulation therapy. Therefore, our study has made some progress compared with others; however, it is still limited to the enrolled patients. Therefore, there are deviations in the data, and further studies are needed to support our findings.

In the CaVent study, ⁶ CDT can rapidly clear the venous thrombosis of lower limbs, reducing the incidence of PTS at the cost of a minor additional risk of bleeding. The PEARL study ¹⁶ showed that PMT could reduce the use of CDT and the potential bleeding risk. However, the ATTRACT study ⁷ reported otherwise, showing that thrombectomy does not reduce the incidence of PTS and may increase the risk of massive hemorrhage. Compared with the ATTRACT study, patients in this study had no major bleeding complications, and minor bleeding was within the predictable range, including bleeding at the puncture site and minimal vaginal bleeding. Moreover, patients who underwent PMT in the study group developed hemoglobinuria, which passed the AngioJet operation process and were treated with hydration and alkalization. The patients had no renal function damage. In addition, the patients’ hemoglobin level after removing lower limb venous thrombosis decreased to a certain extent compared with that before thrombolytic therapy. The hemoglobin level decreased by 8.33 g/L, the patients were treated with appropriate iron supplementation, and all patients were not treated with blood transfusion.

Compared with other studies the risk of bleeding in this study was relatively low, and these are the main reasons that potentially explain this. First, we used low-dose urokinase for thrombolytic therapy. The dosage of urokinase is 750 000‒1 million units/day, while closely monitoring the blood coagulation function. Based on our experience, the thrombolytic effect of low-dose urokinase is milder than that of thrombolytic drugs such as alteplase, which can reduce the risk of bleeding. We have used alteplase for PMT treatment in other patients with iliofemoral veins in the nonpuerperium period, and one patient had gingival bleeding after spraying the drug. For postnatal patients, we suggest that low-dose urokinase thrombolytic therapy should be used.

Second, among patients in the study group, five had iliofemoral venous thrombosis within 10 days after cesarean section. If a thrombectomy was performed immediately, thrombolytic drugs might potentially increase the risk of massive bleeding in the uterus and abdominal cavity. During treatment, we first performed temporary inferior vena cava filter insertion before thrombectomy 10 days after the delivery of the patient, and no major bleeding events occurred. Therefore, for postpartum patients, we recommend thrombectomy 10 days later.

Twelve patients with residual iliac vein stenosis (≥50%) or occlusion after thrombectomy in the study group underwent iliac vein balloon dilation and stent placement. Adequate thrombectomy and stent placement prevent reocclusion because the power of reintervention is low. ¹⁵ However, there are still controversies about whether to place iliac vein stents in patients with fertility requirements. It is believed that pregnancy will not negatively impact iliac vein stents, and iliac vein stents are not taboo for women of reproductive age ¹⁷ ; however, this observation still needs to be observed in many clinical cases. In this study, patients with fertility requirements were not treated with iliac vein stents after communicating with their families.

Our study has some limitations that should be acknowledged. First, this is not a prospective randomized study. Second, the number of cases enrolled was small, and the follow-up time was limited. Hence, further studies are needed to validate our findings.

Conclusion

Percutaneous thrombectomy (including PMT and CDT) reduces the incidence of PTS and improves the clinical prognosis of deep iliofemoral vein thrombosis compared with routine treatment using anticoagulants, only at the cost of minor additional bleeding risk.