Comprehensive Management of Thrombosed Lower Extremity Venous Aneurysms: A Single-Center Retrospective Analysis and Insights Into Clinical Strategies

Abstract

Objective

Venous aneurysms are rare vascular abnormalities associated with venous thromboembolism. In this study, we presented our experience in managing thrombosed lower extremity venous aneurysms and evaluate the impact of vitamin D deficiency and genetic thrombophilic risk factors on patient management and outcomes.

Methods

A single-center retrospective observational analysis was conducted on ten patients with thrombosed lower limb venous aneurysms who underwent surgical procedures at our hospital from July 2014 to February 2023. Collected data included venous duplex ultrasonographic imaging and laboratory tests including genetic thrombophilic risk factors and assessments of vitamin D levels.

Results

There were 5 males and 5 females. The mean age was 46.6 ± 12.1 years. The aneurysms were located in the popliteal vein in three patients, the great saphenous vein in six, and the small saphenous vein in one. Venous duplex imaging revealed saccular aneurysms in eight patients and fusiform aneurysms in two, with a mean diameter of 37.2 ± 10.6 mm, ranging from 23 to 52 mm. Laboratory tests indicated vitamin D deficiency in all of the patients, and genetic thrombophilic risk factors were identified in two cases. Surgical interventions consisted of tangential excision with lateral venorrhaphy in three patients and total excision and ligation in seven patients. The postoperative period was favorable for all patients.

Conclusions

Surgical treatment of thrombosed venous aneurysms in the lower extremities is essential to prevent complications such as thromboembolism. A comprehensive approach, including knowledge of genetic risk factors and vitamin D levels, may improve patient outcomes.

Keywords

aneurysm venous thromboembolism lower extremity vitamin D deficiency

Introduction

Venous aneurysms are rare vascular abnormalities that predispose to venous thromboembolism due to flow disturbances.¹ They can occur at any age and exhibit an equal sex distribution.² They have been described throughout various parts of the venous system, including the head, neck, thorax, intra-abdominal, and extremity veins.³ A venous aneurysm is defined as a focal solitary venous dilatation that communicates with the normal venous segment via a single channel and is not located within a varicose vein.^4,5 Although the literature does not define standard size criteria to define a venous dilatation as an aneurysm, it is usually accepted as an aneurysm if the diameter of the venous dilatation is two or three times the normal vein diameter.^6,7

The natural history and clinical characteristics of venous aneurysmal dilatations are related to their location and diameter.⁸ They may be asymptomatic for a long time, but if thrombosis occurs, the first clinical manifestations may be symptoms of pulmonary embolism (PE), venous return obstruction, or compression of adjacent structures.⁹

While upper-extremity venous aneurysms are usually asymptomatic and are treated mostly for cosmetic reasons, those located in the lower extremities are associated with thromboembolism.¹⁰ Even with effective anticoagulant therapy, aneurysmal dilatation presents a favorable environment for sustained clot formation and dissemination.⁵ Therefore, lower limb thrombosed venous aneurysmal dilatations require surgical therapy as anticoagulant therapy alone is inadequate to relieve compression symptoms or avoid the risk of further thromboembolic events.

While a venous aneurysm’s size, location, and morphology play a crucial role in the development of thrombosis in the aneurysm sac, recent studies have identified additional factors affecting venous thromboembolism, suggesting an association between vitamin D deficiency and an increased risk of venous thromboembolism.^11–13 Individuals with vitamin D deficiency exhibit endothelial dysfunction which can contribute to thrombus formation.¹³ Hereditary thrombophilia risk factors have been demonstrated to affect the development of venous thromboembolism.¹⁴ Therefore, investigating these factors may provide valuable insights into the individual risk profile of patients with these vascular anomalies. Identifying underlying thrombophilic conditions may influence treatment strategies and potentially guide individualized approaches to prevent future thromboembolic events. Previous studies have reported that these risk factors are detectable in only about 50% of patients with confirmed deep venous thrombosis, highlighting the need for further research to understand their role in thrombosed venous aneurysms.¹⁵

Because of the low incidence of venous aneurysms, there are limited studies regarding the appropriate management of these patients. The purpose of this study is to present our experience in the surgical treatment and perioperative management of thrombosed lower extremity venous aneurysms while addressing the impact of vitamin D deficiency and genetic thrombophilic risk factors on patient management and outcomes.

Methods

This observational study was conducted in accordance with the STROBE Statement and Checklist for observational studies.¹⁶

Study Design and Population

This study is a single-center retrospective observational analysis of data collected at Bozok University Hospital in Turkey. The study included ten patients who were treated surgically for a thrombosed venous aneurysm in the lower extremity from July 2014 to February 2023. Venous aneurysms secondary to vascular access, aneurysms with varicose veins, venous malformations, arterialized vein graft aneurysms, and primary venous aneurysms without thrombosis were excluded.

Data Collection

Preoperative venous duplex ultrasonographic imaging examined the anatomy and function of the superficial and deep veins of both lower extremities in detail. The venous reflux examination was performed with the patient standing, focusing on the leg not bearing weight. Using an ultrasound system equipped with a 10 MHz transducer, both longitudinal and transverse scans of the venous systems in the lower limbs were conducted. Forward flow augmentation was achieved through manual muscle compression, and reflux was identified upon release, with reflux durations greater than 0.5 seconds noted as positive. Additionally, a Valsalva maneuver was employed to assess reflux in proximal veins. Both grayscale and power Doppler color imaging were utilized during the procedure. For any detected aneurysms, transverse and longitudinal measurements were taken, including anterior-posterior and latero-lateral diameters at the point of maximum venous dilation in the transverse scan. Consistent with prior reports, a venous aneurysm was defined as a dilation of 1.5-2 times the normal vein diameter.^17,18 The diameter, length, morphology of the aneurysm, and the extent of thrombosis were identified. In addition to routine radiological examination and laboratory testing, serum 25-hydroxyvitamin D [25(OH)D] levels were measured to detect vitamin D deficiency. Predisposing genetic thrombophilic risk factors such as factor V Leiden mutation (FVL), prothrombin G20210 A gene mutation, antithrombin III, protein C, protein S, and methylenetetrahydrofolate reductase (MTHFR) C677 T gene mutation were also investigated. These assessments were performed irrespective of anticoagulant therapy status.

Postoperative Course and Follow-up

All patients received low molecular weight heparin for 2-3 days, followed by vitamin K antagonist as anticoagulant prophylaxis for 3-6 months. Lifelong vitamin K antagonist was recommended for patients with documented predisposing genetic factors. Vitamin D supplementation was administered to the patients prior to the surgical intervention and was continued after the procedure until achievement of optimal serum levels. We encouraged our patients to continue wearing compression stockings of 20-30 mmHg for at least one month. During the follow-up, duplex ultrasound was performed on all surgically treated individuals at 3 and 6 months and then annually. The primary outcomes were the evaluation of the venous thromboembolic events and aneurysm recurrence after the surgical procedure.

Statistical Analysis

A descriptive analysis was performed. The data of continuous variables were presented as median and range or mean and standard deviation according to their distribution. SPSS version 25.0. (Armonk, NY: IBM Corp.) was used for the analysis.

Results

There were 5 males and 5 females with a mean age at the time of diagnosis of 46.6 ± 12.1 years (range 33-71 years). They had no surgical intervention or vascular access procedure, inflammation, or any systemic disease. Three patients had a history of smoking and hypertension. All patients had a non-pulsatile mass in the lower extremity. Due to thrombosis, direct compression of the masses did not reduce their size. The main presentations of the patients were swelling and pain. In addition, one patient had bleeding from the aneurysmatic saphenous vein due to skin ulcer formation. One patient had a history of distal deep venous thrombosis. Table 1 shows patient details.

Table 1.

Demographics and Clinical Characteristics of Patients With Thrombosed Lower Limb Venous Aneurysm.

Patient	Age	Gender	Clinical presentation	D vitamin level ng/mL	Genetic mutation
1	52	Female	Swelling, pain	11.94	N/I
2	71	Male	Swelling, pain, tingling	5.12	N/I
3	41	Female	Swelling, pain	7.55	FVL heterozygote
4	59	Female	Swelling, pain	15.30	N/I
5	33	Female	Swelling, pain	5.72	N/I
6	49	Female	Swelling, pain, history of DVT	8.81	MTHFR (C677 T) homozygote
7	50	Male	Swelling, pain, leg edema	8.65	N/I
8	34	Male	Pain	5.93	N/I
9	41	Male	Swelling, pain, bleeding	7.21	N/I
10	36	Male	Swelling, pain	17.34	N/I

MTHFR: Methylenetetrahydrofolate Reductase, FVL: Factor V Leiden Mutation, DVT: Deep Venous Thrombosis, N/I: Not Identified.

The venous aneurysm was diagnosed by physical examination in six patients. One patient had initially been misdiagnosed with an inguinal hernia. Venous duplex imaging showed an aneurysmal sac and endoluminal echoic material suggestive of thrombus in all patients. A saccular aneurysm was identified in eight patients, while two patients had fusiform aneurysms. The locations of the thrombosed aneurysms were the popliteal vein in three patients, the great saphenous vein (GSV) in six, and the small saphenous vein (SSV) in one. The mean diameter of the aneurysms was 37.2 ± 10.6 mm (range, 23-52 mm) (Table 2).

Table 2.

Operative Details of the Patients’ Cohort.

Patient	Anatomical location	Diameter (mm)	Morphology	Intervention	Follow-up (months)
1	Right great saphenous vein	31	Saccular	Excision with ligation	13
2	Left great saphenous vein	34	Fusiform	Excision with ligation	9
3	Left popliteal vein	52	Saccular	Tangential excision with lateral venous repair	36
4	Left small saphenous vein	29	Saccular	Excision with ligation	24
5	Left great saphenous vein	23	Saccular	Excision with ligation	13
6	Left great saphenous vein	25	Saccular	Excision with ligation	33
7	Left popliteal vein	41	Saccular	Tangential excision with lateral venous repair	22
8	Left popliteal vein	51	Saccular	Tangential excision with lateral venous repair	33
9	Right great saphenous vein	38	Saccular	Excision with ligation	7
10	Left great saphenous vein	48	Fusiform	Excision with ligation	16

The routine hematology and biochemistry test results were within normal limits in all patients. The mean serum [25(OH)D] level was 9.35 ± 4.2 ng/mL, ranging from 5.93 ng/mL to 17.34 ng/mL, (normal range: 20-40 ng/mL). Vitamin D deficiency was severe (<10 ng/mL) in seven patients. Predisposed genetic mutation for thrombophilia was detected in two patients, one patient had a heterozygous FVL mutation, and the other had a homozygote mutation in MTHFR gene (C677 T). No inherited thrombophilic mutations were identified in the remaining patients. (See Table 1.)

Treatment and Operative Techniques

Treatments and operative techniques are listed in Table 2. Surgery was performed under spinal anesthesia in seven patients with superficial venous aneurysms (SVA). General anesthesia was preferred for the remaining three patients with popliteal vein aneurysms (PVA), because of the length of the surgical procedure and need for a vascular graft. In patients with PVAs, the aneurysm was resected after tangential placement of the vascular clamp, and lateral venous repair was performed. No interposition grafts were required in the patients with PVA. Since the venous aneurysm was close to the saphenofemoral junction (SFJ) in two patients with GSV aneurysm, aneurysm resection was performed after SFJ ligation to prevent thromboembolism. Similarly, in the patient with the SSV aneurysm close to the saphenopopliteal junction (SPJ), the aneurysmal sac was resected after ligation of SPJ. In the remaining patients with a proximal GSV aneurysm, the aneurysmal sac was dissected from the surrounding adhesions and excised (Figure 1).

Postoperative Course and Follow-up

The postoperative period was favorable for all patients. The mean time of follow-up was 20.6 ± 10.6 months, ranging from 7 to 36 months. During the follow-up period, no postoperative complications such as venous insufficiency and venous thromboembolism were encountered. There was no aneurysm recurrence in any patient. Furthermore, all popliteal venous repairs were found to be patent.

Histopathological examination showed that the wall of the aneurysmal sac was thinner than the adjacent normal vein wall in all patients. Figure 2 shows the signs associated with thrombosis and inflammation.

Discussion

Venous aneurysms are uncommon forms of vascular malformations.¹⁹ The most prevalent locations of venous aneurysms are the popliteal vein, portal vein, and superior mesenteric vein.²⁰ PVAs constitute 45% of the total cases, followed by portal vein aneurysms at 30%.²¹ The most frequently documented types of aneurysms include those of the extrahepatic portal vein, popliteal vein, and internal or external jugular vein.²² This study reports our experience in the perioperative management of thrombosed lower limb venous aneurysms.

Unlike secondary venous aneurysms, the cause of primary venous aneurysms is still unknown. However, various hypotheses have been suggested, such as endophlebohypertrophy which is a dilatation of the vessel wall followed by early hypertrophy and congenital weakness or degenerative changes due to connective tissue disorder or local inflammatory process.²³ In addition, recent human and experimental studies suggest that the expression of matrix metalloproteinases (MMP-2, MMP-9, and MMP-14) by smooth vascular cells and endothelial cells may affect the relaxation/contraction properties of the venous wall and contribute to the development of venous aneurysms.⁸ Pascarella et al.²⁴ suggested that SVA of the lower limb may develop as a result of blood flow pulsatility and turbulence caused by reflux from incompetent valves. This hypothesis links the formation of SVAs to underlying venous insufficiency. However, we found no evidence of chronic venous disease or varicose veins in the patients from our series who had SVA in both the GSV and the SSV. This suggests that not all SVAs are secondary to varicose veins. Therefore, while venous aneurysms in patients with varicose veins can be considered secondary, primary venous aneurysms may occur independently of chronic venous disease.

Most venous aneurysms, particularly the SVAs, are palpable and easily compressible and usually can be diagnosed by inspection and palpation. However, thrombosed aneurysms are not compressible and may be misinterpreted as lower extremity soft tissue masses or femoral or inguinal hernias.²⁵ Preoperative venous duplex ultrasound imaging can establish a definitive diagnosis. Computed tomography, magnetic resonance imaging, venography, and radionuclide venography are also employed in the diagnosis of venous aneurysms. Venography is no longer required for the diagnosis of venous aneurysms, and in rare cases, it may not detect thrombosed saccular venous aneurysms. Previous studies have recommended use of venography or computed tomography to accurately determine the venous anatomy before surgical repair, particularly in individuals with a history of deep vein thrombosis.^6,10 In many clinical situations, venous duplex imaging is reliable in determining the true size of the aneurysm as well as the presence and extent of thrombus within the aneurysmal sac and can provide a comprehensive functional evaluation of the venous system.⁶

Venous aneurysms can cause serious complications such as deep vein thrombosis, thrombophlebitis, venous insufficiency, and PE. Saccular venous aneurysms pose unique issues and considerations, including thrombosis and rupture, which are influenced by hemodynamic factors. Blood flow within these aneurysms can become turbulent and slow and the saccular shape creates a large recirculation zone with low flow velocities, promoting blood stasis. These stagnant flow areas with low shear stress, and vortices can occur within the aneurysm sac, causing thrombus formation. In contrast, Fusiform aneurysms typically do not exhibit any disturbance in blood flow within the aneurysmal sac. The absence of flow disturbances in fusiform aneurysms indicates a lower risk of thromboembolic complications compared to saccular aneurysms.²⁶

PE is assumed to be less common in the superficial veins of the lower extremities than in the deep veins, possibly due to forceful drainage of the deep veins. It has been suggested that this rapid emptying process may contribute to dislodging thrombi accumulated in the aneurysms of the deep veins.¹⁷ According to Gabrielli et al.,¹⁰ both small deep vein aneurysms and large SVAs pose a risk of developing PE. The possibility of an underlying PVA should also be considered in the differential diagnosis of PE patients without deep venous thrombosis.²⁷ Therefore, lower extremity venous duplex imaging is recommended for all PE patients to avoid overlooking the diagnosis of an underlying venous aneurysm.²⁸ Hereditary thrombophilic risk factors may contribute to thrombus formation in the aneurysmal sac,²⁹ as observed in two of our patients with heterozygous FVL and homozygote mutation in MTHFR gene (C677 T). It is important to note that while heterozygous FVL increases the risk of an initial VTE event, it does not significantly raise the risk for recurrent VTE events.³⁰ This distinction is crucial in understanding the varying impacts of different thrombophilic risk factors.

Management of venous aneurysms remains a subject of ongoing debate. Previous studies suggest surgical intervention for deep venous aneurysms, particularly for asymptomatic patients with saccular aneurysms, regardless of size, or for those with fusiform morphology over 20 mm, due to the risk of unanticipated thromboembolic events.^6,31,32 However, a previous review recommended treating only symptomatic cases or those with mural thrombus regardless of size or morphology.³ In a recently published multicenter study, popliteal aneurysms presenting with venous thromboembolism were found to have a mean size of 38 mm and a minimum diameter of 27 mm. Therefore, for PVAs, 25 mm has been suggested as a size threshold at which repair should be recommended in surgically suitable patients to reduce the risk of venous thromboembolism.³³ It has been reported that even with anticoagulation therapy, there is a high risk of thromboembolic complications in patients with deep venous aneurysms.¹⁸ Nasr et al.³⁴ reported a 43% failure of medical treatment of patients who had PVA and received anticoagulation treatment alone, with one death out of 23 patients due to PE. PE developed in 40% of patients without an intraluminal thrombus and in 44% of patients with an intraluminal thrombus. Aldridge et al.²⁸ also reported inadequacy of anticoagulation alone as treatment for PVAs, as 35% of the patients with PVA reviewed by their group who received only anticoagulation experienced recurrent PE. None of the patients who had surgical resection experienced PE. Other studies reported similar outcomes.^35–37 Based on these findings in the literature, we believe that anticoagulation therapy may be ineffective in preventing thromboembolic complications, and that surgical treatment should be preferred in all patients with symptomatic or asymptomatic deep vein aneurysms. Surgery is not indicated for SVAs, except for a disfiguring lesion or symptomatic cases.³⁸ The importance of thrombus in SVA is still unknown. Therefore, it may not be an indication for surgery in the absence of deep venous thrombosis or PE symptoms. Regular observation with Doppler USG is recommended for small SVA.³⁹ However, we recommend surgical intervention for superficial thrombosed venous aneurysms if they are near the SFJ or SPJ.

Various surgical techniques to repair venous aneurysms have been defined, including tangential aneurysmectomy with lateral venorrhaphy, ligation and aneurysm excision with interposition vein graft, or end-to-end anastomosis. The anatomical location usually dictates the surgical approach. Regardless of the chosen technique, it is crucial to address the principles of preserving vascular continuity and eliminating diseased vein walls.^40,41 Resection of thrombosed vein aneurysms requires care to prevent spreading the thrombosis to the deep venous system.⁴² Therefore, proximal control of the popliteal vein is required to prevent embolization during the approach to the PVAs.⁴³ Similarly, resection of SVAs near the SFJ and SPJ needs caution to avoid embolization from the junctions to the deep venous system. After the excision of deep venous aneurysms in the lower extremities, surgical techniques to restore venous patency should be favored over venous ligation. Deep vein ligation is not recommended, particularly in young patients or those with reflux symptoms at the level of the venous aneurysmal sac.³³ Adequate collateral venous circulation should be demonstrated before ligating any lower extremity vein, as simple ligation of the deep veins (popliteal and iliofemoral veins) predisposes the patient to post-thrombotic leg syndrome.⁴⁴ Nevertheless, venous repair should be preferred to ligation since even short-term patency will contribute to the establishment of venous and lymphatic collateralization.⁴⁵

The long-term patency rate of venous repairs varies between 40% and 93%.² The best patency rates were obtained with tangential excision and lateral venorrhaphy techniques. The patency rate of complex venous repairs using panel or spiral venous grafts ranges from 40% to 50%.⁴⁶ For postoperative management, short-term postoperative anticoagulation has been reported to be advantageous, particularly following tangential aneurysmectomy; this is often followed by a standard recommendation of oral anticoagulation for all patients for 3-6 months.^6,28

As in previous studies that found a relationship between vitamin D levels and venous thrombosis,^13,47 the present study emphasizes the potential role of vitamin D deficiency in thrombosed lower extremity venous aneurysms. Consistent with the existing literature, all patients in our series exhibited vitamin D deficiency as defined by serum [25(OH)D] concentration less than 20 ng/mL.¹² The active metabolite of vitamin D has been demonstrated to have anticoagulant activities by upregulating thrombomodulin and downregulating the coagulation initiator tissue factor.⁴⁸ Vitamin D analogs have been found to affect the production of thrombospondin-1, thrombomodulin, and plasminogen activator inhibitor-1, leading to an overall antithrombotic effect in human aortic smooth muscle cells.⁴⁹ Therefore, the observed vitamin D deficit in our patients is consistent with the present knowledge of its potential role in promoting thrombus development within venous aneurysmal sacs. While our study is limited by a small sample size and cannot currently provide definitive clinical or statistical evidence, our findings highlight the need for further research into the potential benefits of vitamin D supplementation in addition to anticoagulant prophylaxis during the postoperative period, which may improve venous patency by alleviating the underlying inflammatory and prothrombotic conditions associated with vitamin D deficiency.

Limitations and Strengths

Our study represents a single-center experience and includes a small sample size, which may restrict the generalizability of findings. The relatively short follow-up period may not properly capture long-term consequences. However, the study gives a comprehensive clinical characterization of thrombosed lower limb venous aneurysms, including clinical presentations, diagnostics, and surgical treatments. The study’s depth is increased by the multidimensional approach, which includes investigation of vitamin D deficiency and genetic thrombophilic risk factors.

Conclusion

This study sheds light on the treatment of thrombosed venous aneurysms in the lower limbs. Regardless of their size or morphology, thrombosed venous aneurysms of lower extremity deep veins should be managed surgically to avoid potential thromboembolic complications while superficial aneurysms should be treated surgically only if symptomatic. In addition, the presence of genetic thrombophilic risk factors along with vitamin D deficiency may further increase the risk of venous thrombosis and might be considered in the management of venous aneurysms. However, our study needs to be supported by a large sample and long-term observational studies.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Statement

ORCID iD

Sameh Alagha

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