The Development of Marked Collateral Circulation due to Inferior Vena Cava Filter Occlusion in a Patient with Chronic Thromboembolic Pulmonary Hypertension Complicated with Anti-phospholipid Syndrome.

A 30-year-old Japanese man was diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) with lupus anticoagulants (LAs) in 2003. He underwent pulmonary endarterectomy after the placement of an inferior vena cava filter (IVCF) in 2004, and treatment with warfarin was continued. In 2014, IVCF occlusion and marked collateral circulation were noted during an examination for transient dyspnea; however, his warfarin level was within the therapeutic range for 88.9% of the time from 2003 to 2014. We herein report a rare case of CTEPH and LAs with IVCF occlusion; in such cases, intense treatment may be required.

Introduction

In the clinical setting, inferior vena cava filters (IVCFs) are used to prevent pulmonary thromboembolism (PTE) from deep vein thrombosis (DVT) in the lower limbs and pelvis. However, the long-term use of IVCFs has been reported to induce various complications, such as perforation of the inferior vena cava (IVC) and the development of thrombi in the IVCF (1, 2). Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension that is caused by non-resolving thrombi in the pulmonary arteries and pulmonary vascular remodeling (3). In patients with CTEPH, an IVCF is placed prior to the performance of pulmonary endarterectomy (PEA), in order to prevent the recurrence of PTE from DVT during the perioperative period (4, 5). We herein present the case of a patient with CTEPH that was complicated by anti-phospholipid syndrome (APS), who developed IVCF occlusion accompanied by significant hyperplasia of the collateral vessels.

Case Report

A 30-year-old Japanese man was diagnosed with CTEPH and primary APS in December 2002 after continuously testing positive for lupus anticoagulants (LAs). He underwent PEA after the placement of a permanent monoconical IVCF (Greenfield™ Vena Cava Filter; Boston Scientific, Natick, MA, USA) in May 2003. His pulmonary hemodynamics and symptoms improved after PEA and anticoagulation therapy with warfarin was continued. He visited our hospital for blood tests, which included the evaluation of his prothrombin time (PT)-international normalized ratio (INR) and D-dimer level, every month. From 2003 to 2013, he was stable and had no symptoms indicating the deterioration of his respiratory status or the recurrence of PTE and DVT. Moreover, from 2003 to 2013, warfarin remained within the therapeutic range (PT-INR, 1.5-3.0) for 88.9% of the time; his D-dimer level remained at <1.0 ng/mL, and his platelet count was normal.

In October 2013, he experienced shortness of breath on exertion (modified Medical Research Council dyspnea scale grade 1). Contrast computed tomography (CT) did not reveal a recurrence of PTE; however, the IVCF appeared to have been displaced outside the blood vessel (Fig. 1). He was admitted to our department in January 2014 to evaluate the cause of his shortness of breath on exertion and to assess the complications of the indwelling IVCF. At the time of admission, the patient's shortness of breath on exertion had already disappeared. His body weight was 69 kg and his height was 168 cm. His vital signs were as follows: blood pressure, 122/77 mmHg; pulse rate, 70 beats/min; SpO2 level while breathing room air, 95%; and body temperature, 37.0°C. He had no cardiac murmur and no abnormal respiratory sounds. He had no swelling or pain in his lower limbs.

Figure 1.

Contrast CT obtained in December 2013 showing an IVCF (arrow) that appeared to have been displaced outside the blood vessel. CT: computed tomography, IVCF: inferior vena cava filter. Arrow, IVCF; 1, inferior vena cava

Chest radiography, electrocardiography, and transthoracic echocardiography revealed no abnormalities. The patient's pulmonary function test results, including his DLCO level, proved to be normal as well. His D-dimer value was negative, and his PT-INR with the oral administration of warfarin (3.5 mg/day) was 1.79. His renal and liver function test results were normal. Repeat contrast CT (Aquilion One; Toshiba Medical, Tochigi, Japan) with a slice thickness of 2 mm, 0.35 s/rotation, and three-dimensional (3D) image reconstruction revealed the complete obstruction of the IVC at the site of the IVCF placement. The IVC showed aneurysm-like changes; blood flow below the occluded site of the IVC returned from the azygos vein to the superior vena cava via the collateral circulation (Fig. 2). There was no recurrence of CTEPH or obvious lung lesions. A retrospective review of follow-up contrast CT in 2006 revealed thrombi in the IVCF, but no DVT or collateral circulation were detected (Fig. 3).

Figure 2.

(A) A CT angiogram on admission showing a dilated and obstructed IVC (1) at the site of the indwelling IVCF (arrow). Blood flow below the site of IVC occlusion returned from the azygos vein to the superior vena cava via the collateral circulation (2, 3). In addition, both sides of the iliac vein (4) were markedly expanded. (B) A 3-dimensional image constructed from the contrast CT images showing the occlusion of the IVC and a detailed view of the collateral circulation. CT: computed tomography, IVC: inferior vena cava, IVCF: inferior vena cava filter. Arrow, IVCF; 1, IVC; 1’, the remaining IVC from the renal vein of the head side; 2, the ascending lumbar vein; 3, the lumbar vein; 4, the iliac vein

Figure 3.

A retrospective review of follow-up contrast CT in 2006 showing thrombi (triangle) in the IVCF. CT: computed tomography, IVCF: inferior vena cava filter. Arrow, IVCF; 1, inferior vena cava

Right heart catheterization revealed a normal mean pulmonary artery pressure of 18 mmHg, a pulmonary arterial wedge pressure of 7 mmHg, a pulmonary vascular resistance of 1.9 Wood units, and a cardiac index of 3.3 L/min/m2. Angiography of the IVC and the left iliac vein confirmed IVC occlusion at the site of the IVCF and the presence of significant collateral circulation, similar to that which was found by contrast CT (Fig. 4, 5). In addition, DVT was observed in the lower limb, and collateral circulation could not be detected. Pulmonary angiography revealed no evidence of acute or chronic PTE. Because he was asymptomatic at that time, we only offered close observation with strict anticoagulation therapy, with a target PT-INR of 2-3. For 3 years after discharge, until 2016, there were no signs indicating a recurrence of DVT or PTE.

Figure 4.

An angiogram of the IVC and left iliac vein confirming IVC occlusion at the site of the IVCF and the presence of marked collateral circulation, similar to the contrast CT findings. IVC: inferior vena cava, IVCF: inferior vena cava filter, CT: computed tomography (Arrow, IVCF; 1, IVC; 2, ascending lumbar vein; 3, iliolumbar vein; 4, iliac vein; 5, azygos vein; 6, hemi azygos vein)

Figure 5.

A schematic illustration of the 3-dimensional image constructed from the contrast CT images and angiography of the IVC. CT: computed tomography, IVC: inferior vena cava, IVCF: inferior vena cava filter

Discussion

We presented a case with CTEPH that was complicated by APS in a patient who developed IVCF occlusion with significant hyperplasia of the collateral vessels. Thus far, there have been no reports about complications associated with indwelling IVCF in patients with CTEPH. Furthermore, we obtained detailed and interesting images of significant collateral circulation with the 3D reconstruction of contrast CT images.

The adaptation of an IVCF in PTE patients is controversial. Generally, an IVCF is inserted to prevent PTE in the perioperative period of PEA. All but one of the CTEPH patients who underwent IVCF placement at the time of PEA. The IVCF placement rate in the Japanese national registry of CTEPH patients was reported to be 26.9%, while that in the international registry was 12.4% (6). Japanese patients were more likely to receive an IVCF, even in medically treated cases (6). Although IVCFs have been shown to reduce the recurrence of PTE, they do not have a significant effect on immediate or long-term mortality; moreover, they significantly increase the incidence of DVT (7, 8). It was recently reported that among hospitalized patients with severe acute PTE, the use of retrievable IVCFs plus anticoagulation therapy did not reduce the risk of symptomatic recurrent PTE in comparison to the administration of anticoagulation therapy alone (9). There are no reports concerning on the efficacy of IVCF in CTEPH patients; but the placement of an IVCF during the perioperative period, while anticoagulation therapy is stopped, has been performed at our institution because the University of California, San Diego, which is the largest center for the treatment of CTPEH, routinely inserts IVCFs in the preoperative period.

Permanent IVCFs have been used in the past; however, retrievable IVCFs have been used because they can be removed once anticoagulant therapy is resumed after PEA. In fact, retrievable IVCFs should be removed when the initial indications no longer exist or when the contraindications to anticoagulation have resolved (10-12). Although the removal of retrievable IVCFs is recommended within 2 weeks after implantation (13), it is often not possible due to bleeding or prolonged intubation after PEA. In the present case, a permanent IVCF was inserted prior to PEA because longer postoperative intubation and immobilization were usual at that time. Meanwhile, the mean retrieval rate of retrievable IVCFs was 34%, according to a recent systemic review of 37 studies (14) on PTE. Retrievable IVCFs are associated with significantly higher complication rates than permanent IVCFs (15, 16). The complications of retrievable IVCFs have been associated with their long-term use, and thus their early removal has been emphasized (14).

The incidence of IVCF occlusion is reported to be 2-30% (1). However, the incidence of IVCF occlusion in CTEPH patients has not been reported. In the present case, the thrombi in the IVCF on contrast CT were overlooked in 2006. The PT-INR values from 2003 to 2013 were as follows: 1.5 to <2.0, 54.3%; 2.0 to <2.5, 27.2%; and 2.5 to <3.0, 7.4%. In addition, all of the D-dimer values were negative during the same period, with the highest value being 0.7 μg/mL. With regard to coagulation abnormalities, the patient was only positive for LAs. Thus, in the present case, the predisposing condition for IVCF occlusion was presumed to be the thrombi in the patient's IVCF and APS. Xiao et al. (17) reported that the development of a thrombus in an IVCF reduced filter patency and venous return from the lower extremities and that it may progress to complete IVC occlusion. Hypercoagulable/malignant conditions may affect the formation of thrombi and IVCF occlusion (18). In addition, the biconical IVCF design also induces IVCF thrombosis because of the inverted conical design and the resultant flow dynamics (19). Reports have indicated that occlusion and/or the development of thrombi in the IVCF occurred in patients with polycythemia vera, heparin-induced thrombocytopenia, and patients without anticoagulants (20-22). Furthermore, there have been reports that occlusion and/or the development of a thrombus in the IVC occurred in a patient with hereditary protein C deficiency and APS, even without an indwelling IVCF (23-25). Thus, coagulation abnormalities may predispose the IVCF to occlusion. In particular, because LAs are found in 10-20% of patients with CTEPH (26, 27), it is necessary to pay more attention to IVCF occlusion in patients with CTEPH and other coagulation abnormalities.

The effectiveness of the concurrent use of anticoagulation therapy in patients in with an IVCF is controversial. Furthermore, the optimal management of IVC thrombosis has not been established (21). Yazu et al. (28) reported that the incidence of IVC occlusion in Japanese patients with indwelling IVCFs significantly decreased after concurrent therapy. In Japan, anticoagulant therapy with a target PT-INR in the range of 1.5-2.5, has been recommended for venous thromboembolism patients (29). On the other hand, patients with APS should be treated with a target PT-INR of 2.5 (target range, 2.0-3.0) (30). In our case, a PT-INR of >2 was only observed 34.6% of the time and was mostly controlled at a PT-INR of 1.5-2 from 2003 to 2013. For patients with accompanying APS, the use of our target PT-INR based on the Japanese guidelines, may not be sufficient. In contrast, Ahmad et al. (31) reported that there was no difference in the regression of thrombi in the IVCFs of a group of patients who received anticoagulation therapy and a group who did not. Thus, invasive treatments, such as percutaneous mechanical thrombectomy, stenting, and catheter-directed thrombolysis, should be considered after the detection of a thrombus in an IVCF (17, 21, 22, 32).

In the present case, IVCF occlusion was considered to have gradually developed because hyperplasia of the collateral circulation developed without swelling or pain in the lower limbs. Because of collateral vein drainage, some patients with IVCF thrombosis may not manifest lower extremity symptoms (17). Conversely, Gurewich et al. (33) reported that the resultant venous tributaries serve as alternative routes for PTE. The transient shortness of breath on exertion in the present case may have been caused by a recurrence of PTE through collateral circulation. Careful observation is therefore necessary. For example, the performance of contrast CT may even be useful in cases in which there is only a slight increase in the D-dimer and additional soluble fibrin monomer complex (SFMC) levels, which are markers of acute thrombosis. If possible, the IVCF should be removed after PEA, even in patients with CTEPH. In the present case, the thrombi in the IVCF were overlooked on contrast CT in 2006; the doctors may have mistaken the patient's thrombi for artifacts related to the IVCF at that time. In addition, this case demonstrated that 3D contrast CT images may be useful for the early detection of IVCF occlusion and the presence of collateral circulation.

We presented a case of CTEPH that was complicated with APS in a patient who developed IVCF occlusion that was accompanied by significant hyperplasia of the collateral vessels. In such cases, careful prolonged observation and more intense treatment may be required.

Author's disclosure of potential Conflicts of Interest (COI).

Nobuhiro Tanabe: Honoraria, Pfizer; Others, Actelion Pharmaceuticals. Koichiro Tatsumi: Honoraria, GlaxoSmithKline and Pfizer.

Financial Support

Koichiro Tatsumi received a grant from the Respiratory Failure Research Group from the Ministry of Health, Labor, and Welfare, Japan (No 21590962). Nobuhiro Tanabe received a research grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No 22590849), and received a grant from the Japanese Respiratory Society.