Abstract
Purpose
Deep vein thrombosis (DVT) of the left and right lower extremities was treated in the same way, but the left and right extremities received different levels of attention. This study aimed to investigate the differences between the right and left lower extremity deep vein thrombosis (LEDVT).
Methods
Clinical characteristics of LEDVT patients from July 2020 to June 2022 were retrospectively analyzed to compare the incidence of LEDVT on different limbs, demographics, predisposing factors, and anatomical characteristics. The exclusion criteria were bilateral LEDVT and recurrent thrombosis. Measured data was analyzed using independent samples t-test or Mann-Whitney test. Count data were analyzed by Chi-square test. A p < 0.05 was considered a statistically significant difference.
Results
There were 478 patients included in this study and the ratio of left to right LEDVT on the left and right limbs was 3.16:1 (363:115). Left LEDVT predominantly affected female, with the major aged > 50 years (50 – 60 years: 16.80%; > 60 years: 57.30%). The primary predisposing factor was iliac vein compression syndrome, with iliofemoral thrombosis being the main type. Male patients with LEDVT on the right limb were predominant and the age of onset was usually ≤ 60 years (52.17%). The main predisposing factor was recent surgery or trauma (< 30 days) and femoropopliteal thrombosis was the main type. In more detail, the left iliac vein was compressed mainly in the proximal segment, and the right iliac vein was compressed mainly in the intermediate and distal segments. Recent surgery or trauma to the locomotor system and genitourinary system often induced LEDVT.
Conclusion
The incidence of LEDVT on the left is significantly higher than that on the right. LEDVT on different sides has different characteristics, which is crucial for prevention and diagnosis in the relevant population so there are also differences in treatment of the affected limbs.
Keywords: Lower extremity deep vein thrombosis, Left and right, Predisposing factor, Characteristics, Difference
1. Introduction
Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), accounts for approximately 1 million new cases each year1 and its incidence is increasing year by year.2 Lower extremity deep vein thrombosis (LEDVT) as a part of VTE can not only induce PE but also have a serious impact on the quality of patients’ lives.
With the increase in patients and the advance of interventional technology, the diagnosis and treatment of LEDVT are becoming more mature. However, the number of LEDVT reports differed due to the different prevalence on the right and left sides of the body. Chen et al.3 reported a right-to-left affected limb ratio of 3.68:1, while Bikdeli et al.,1 observed a left-to-right ratio of 1.30:1. The left-side LEDVT is more prevalent compared to the right-side one, and the right-side LEDVT is often overlooked, of which the comparison for both is even less frequent.
Therefore, this study collected and compared the clinical characteristics of hospitalized patients with acute LEDVT treated in our center and analyzed the difference between the left- and right-side LEDVT to find the better treatment for left and right LEDVT.
2. Methods
From July 2020 to June 2022, patients with acute (< 14 days4) first-episode LEDVT were enrolled in this study, with bilateral LEDVT and recurrent thrombosis being excluded. A total of 478 patients were identified, who were divided into the left-limb group (n = 363) and the right-limb group (n = 115).
2.1. Indicators
All data including age, sex, smoking, drinking, hypertension, diabetes mellitus, coronary artery disease, pregnancy, malignancy, auto-immune disease, thrombophilia, recent surgery or trauma (≤ 30 days), iliac vein compression syndrome (IVCS), iliac vein stenosis (≥ 50%4), and absence of obvious triggers were included. Additionally, the location of thrombosis (ilio-femoral thrombosis, popliteal thrombosis, and below-knee thrombosis) and iliac vein compression segments were collected.
2.2. Definition
The external iliac vein (EIV) and the common iliac vein (CIV) converge at the sacroiliac joint, so we chose the sacroiliac joint as a marker for one segment of the iliac vein and the lumbosacral joint as a marker for the other segment. This is because some of the iliac veins are also compressed by the lumbar vertebrae, as reported by Ou-Yang et al.5 the sources of compression for degenerative IVCS in the lumbar spine including anterior disc bulge or herniation (51%, 17/33), bony redundancy (50%, 16/33), and spondylolisthesis (19%, 8/33). The lumbosacral articular plane was chosen as the boundary of the 5th lumbar vertebra as another segmentation marker. Therefore, we defined the EIV as “distal”, the segment from the proximal end of the CIV to the lumbosacral articular plane as “proximal”, and the segment in between as “intermediate".
2.3. Statistical analysis
Data were analyzed with SPSS 27.0 software. Measured data was expressed as mean ± standard deviation (SD), and comparisons between the 2 groups were analyzed by independent samples t-test or Mann-Whitney test. Comparisons of count data were analyzed by the Chi-square test. A p < 0.05 was considered a statistically significant difference.
3. Results
There were 142 males (39.12%) in the left group, while 66 males (57.39%) in the right group (p < 0.001). A statistical difference was found between the left and right groups in the distribution of age (p = 0.005), which was divided into 4 segments according to the majority age, female retirement age, and male retirement age in China (≤ 18, 18 – 50, 50 – 60, and > 60 years). Among the predisposing factors, recent surgery or trauma, IVCS, and unprovoked factors were statistically different between the 2 groups: 59 patients (51.30%) within the left group experienced surgery or trauma within 30 days, 203 IVCS (55.92%) in the left group, and 22 IVCS (19.13%) in the right group. There were 75 patients (20.66%) with LEDVT with unprovoked factor, while 38 patients (33.04%) were in the right group (Table 1).
Table 1.
Comparison of baseline characteristics in the right and left groups.
| Variables | Left group, n (%) | Right group, n (%) | p value |
|---|---|---|---|
| Total | 363 (75.94) | 115 (24.06) | – |
| Demographic characteristics | |||
| Age (year) | 0.005 | ||
| ≤ 18 | 0 (0) | 2 (1.73) | |
| 19 – 50 | 94 (25.90) | 26 (22.61) | |
| 51 – 60 | 61 (16.80) | 32 (27.83) | |
| > 60 | 208 (57.30) | 55 (47.83) | |
| Male | 142 (39.12) | 66 (57.39) | < 0.001 |
| Causes of DVT | |||
| Pregnancy | 3 (0.83) | 0 (0) | 1.000 |
| Malignancy | 35 (9.64) | 10 (8.70) | 0.762 |
| Auto-immune disease | 15 (4.13) | 8 (6.96) | 0.217 |
| Thrombophilia | 26 (7.16) | 9 (7.83) | 0.812 |
| Recent surgery or trauma | 144 (39.67) | 59 (51.30) | 0.028 |
| IVCS | 203 (55.92) | 22 (19.13) | < 0.001 |
| Unprovoked | 75 (20.66) | 38 (33.04) | 0.006 |
DVT: deep vein thrombosis; IVCS: iliac vein compression syndrome.
p < 0.05 was statistically significantly different.
There was a statistical difference between patients with recent surgery and trauma within the left and right groups (p = 0.049). Forty-three patients aged 50 – 60 years and 104 patients aged > 60 years were found in the left IVCS group, while 7 patients aged 50 – 60 years and 7 patients aged > 60 years were in the right IVCS group (p < 0.05) (Table 2). In addition, among patients with recent surgery or trauma, there was a lower percentage of males in the left group (65 cases, 45.14%) and a higher percentage of males in the right IVCS group (40 cases, 67.80%) (p = 0.003), as well as in the IVCS group (89 cases vs. 15 cases, p = 0.030).
Table 2.
Age distribution of people with different factors (sex, recent surgery or trauma, IVCS) in the left and right groups.
| Variables | Left group, n (%) | Right group, n (%) | p value |
|---|---|---|---|
| Male patients' age, (year) | 0.054 | ||
| ≤18 | 0 (0) | 1 (1.52) | |
| 19 – 50 | 36 (25.35) | 15 (22.73) | |
| 51 – 60 | 28 (19.71) | 22 (33.33) | |
| > 60 | 78 (54.93) | 28 (42.42) | |
| Recent surgery or trauma, (year) | 0.049 | ||
| ≤ 18 | 0 (0) | 0 (0) | |
| 19 - 50 | 45 (31.25) | 18 (30.51) | |
| 51 - 60 | 27 (18.75) | 20 (33.90) | |
| > 60 | 72 (50.00) | 21 (35.59) | |
| IVCS, (year) | 0.045 | ||
| ≤ 18 | 0 (0) | 1 (4.54) | |
| 19 - 50 | 56 (27.59) | 7 (31.82) | |
| 51 - 60 | 43 (21.18) | 7 (31.82) | |
| > 60 | 104 (51.23) | 7 (31.82) |
IVCS: iliac vein compression syndrome.
Depending on the site of surgery or trauma, the highest percentage of LEDVT occurred in the locomotor system (64.58% in the left group and 61.52% in the right group), followed by the genitourinary system (14.58% in the left group) and the respiratory and circulatory system (11.86% in the right group), respectively. Among patients with recent surgery or trauma, iliofemoral thrombosis (62.50%) was the main mechanism in the left group, while femoropopliteal thrombosis (52.54%) was the main mechanism in the right group (Table 3).
Table 3.
Thrombosis location of patients with recent surgery or trauma on different systems in the left and right groups.
| Variables | Left group, n (%) | Right group, n (%) | p value |
|---|---|---|---|
| Thrombosis location | 0.015 | ||
| Iliofemoral | 90 (62.50) | 24 (40.68) | |
| Femoropopliteal | 47 (32.64) | 31 (52.54) | |
| Iinfrapopliteal | 7 (4.86) | 4 (6.78) | |
| Thrombosis location | |||
| Nervous | 0.369 | ||
| Iliofemoral | 4 (57.14) | 1 (20.00) | |
| Femoropopliteal | 3 (42.86) | 3 (60.00) | |
| Iinfrapopliteal | 0 (0) | 1 (20.00) | |
| Respire-circulatory | 0.070 | ||
| Iliofemoral | 11 (78.57) | 2 (28.57) | |
| Femoropopliteal | 3 (21.43) | 4 (57.14) | |
| Iinfrapopliteal | 0 (0) | 1 (14.29) | |
| Digestive | 1.000 | ||
| Iliofemoral | 5 (55.56) | 4 (66.67) | |
| Femoropopliteal | 3 (33.33) | 2 (33.33) | |
| Iinfrapopliteal | 1 (11.11) | 0 (0) | |
| Genitourinary | 0.184 | ||
| Iliofemoral | 14 (66.67) | 2 (40.00) | |
| Femoropopliteal | 4 (19.05) | 3 (60.00) | |
| Iinfrapopliteal | 3 (14.28) | 0 (0) | |
| Locomoto | 0.132 | ||
| Iliofemoral | 56 (60.22) | 15 (41.67) | |
| Femoropopliteal | 34 (36.56) | 19 (52.78) | |
| Infrapopliteal | 3 (3.22) | 2 (5.55) |
IVCS: iliac vein compression syndrome.
For patients with IVCS, the left group was predominantly subjected to proximal compression (48.77%), and the percentage of compression types including proximal (proximal, proximal + intermediate, proximal + distal, and total) was even more than 88.18%, while the right group was predominantly subjected to distal compression (40.91%), with the type of non-proximal compression accounting for 81.82% (p < 0.05). Iliofemoral thrombosis was the main mechanism in IVCS patients of both groups. (Table 4).
Table 4.
Iliac vein compression sites and thrombosis location of patients with IVCS in the left and right groups.
| Variables | Left group, n (%) | Right group, n (%) | p value |
|---|---|---|---|
| Compression sites | < 0.001 | ||
| Proximal | 99 (48.77) | 2 (9.09) | |
| Intermediate | 7 (3.45) | 7 (31.82) | |
| Distal | 12 (5.91) | 9 (40.91) | |
| Proximal + intermediate | 44 (21.67) | 0 (0) | |
| Proximal + distal | 19 (9.36) | 0 (0) | |
| Intermediate + distal | 5 (2.46) | 2 (9.09) | |
| Total | 17 (8.38) | 2 (9.09) | |
| Thrombosis location | 0.274 | ||
| Iliofemoral | 174 (85.71) | 16 (72.73) | |
| Femoropopliteal | 27 (13.30) | 6 (27.27) | |
| Infrapopliteal | 2 (0.99) | 0 (0) |
IVCS: iliac vein compression syndrome.
4. Discussion
LEDVT occurs due to slow or stagnant blood flow, vascular endothelial damage, and hypercoagulability, which disrupt the balance between anticoagulation and fibrinolysis, thereby promoting clot formation.6 However, the risk factors for LEDVT vary depending on the affected limb. As previously noted, the incidence of left-side LEDVT was significantly higher than that of right-side LEDVT, which was associated with differences in the risk factors for injury occurring on both sides.
May and Thurner7 found that bone spurs in the lumen of the iliac veins were more common on the left side at autopsy. The subsequent study indicated that the left iliac vein was more likely to form intraluminal spurs compared to the right iliac vein due to additional compression on the iliac arteries by lumbar vertebrae and appendicular structures.8 The incidence of compression varies, with the most frequent occurrences being: proximal left CIV, distal left CIV, proximal right CIV, left EIV, and distal inferior vena cava (IVC). Right common iliac artery compression usually occurs at the IVC bifurcation.9,10 Consistent with our study, these findings suggested that proximal CIV was most common in left-side IVCS, while EIV compression was most common in right-side IVCS. The left CIV was compressed by the right common iliac artery, meanwhile, the companion vein was predominantly compressed by the eponymous artery (Fig. 1). Additionally, many patients exhibited “double compression” (Fig. 2), characterized by either a more tortuous common iliac artery leading to prolonged segments of iliac vein compression or 2 points of compression.10 The left CIV was compressed by the right common iliac artery. In addition to vascular compression, iliac vein compression can also result from tumors, hematomas, foreign bodies, and anatomical structures such as the colon or uterus. For example, the sigmoid colon might compress the left iliac vein,11 and changes in pelvic anatomy during pregnancy can compress the iliac vascular system.12 Furthermore, the right common iliac artery converges into the IVC at a greater angle compared to the left side, which may restrict blood flow. A study has suggested that the mean shear rate in the left CIV was higher than in the right CIV, which might contribute to the increased thrombosis risk in patients with IVCS.13
Fig. 1.
(A) Compression on proximal right iliac vein (common iliac vein)-compressed area at the black arrow, lumbosacral joint at the white arrow. (B) Compression on middle right iliac vein (common iliac vein)-compressed area at the black arrow, the sacroiliac joint at the white arrow. (C) Compression on distal right iliac vein (external iliac vein)-compressed area at the black arrow, femoral head at the white arrow. (D) It showed the most common iliac vein compression syndrome; the black arrow pointed to the left common iliac vein compressed by the right common iliac artery, and the white arrow pointed to the inferior vena cava bifurcation.
Fig. 2.
(A) Proximal + intermediate right iliac vein compression: the black arrows pointed to the compressions on the common iliac vein, and the white arrow pointed to the lumbosacral joint. (B) The black arrows pointed to the compressions on the common iliac vein, the normal vein was between 2 areas.
DVT is often caused by unprovoked factors.14 Systemic conditions such as hypertension, diabetes mellitus, autoimmune disease, thrombophilia, and other comorbidities contribute to DVT development; however, these factors did not differ significantly between the 2 study groups. In addition to venous compression, which impairs blood flow, malignant tumors can also lead to hypercoagulability. Nevertheless, no significant difference was observed between the left and right groups. Sex and age were identified as independent risk factors in this study. The findings indicated that the risk of thrombosis increases with age, which aligned with Heit's perspective.15 However, the age distribution differed between the groups, with the left group predominantly comprising patients over 50 years and the right group mainly comprising patients under 60 years. Furthermore, female predominance was observed in the left IVCS group, whereas male predominance was observed in the right IVCS group. This disparity may be attributed to several factors: (1) females were more likely to develop left IVCS, while males were more likely to develop right IVCS;4,16 (2) individuals age, heavier workloads, and delayed retirement might increase the risk of surgery or trauma, thereby elevating the risk of thrombosis.
Our study revealed that the proportion of DVT induced by recent surgery or trauma varied between the left and right groups across different systems. In the left group, the musculoskeletal and reproductive systems were more prone to thrombosis, whereas in the right group, the locomotor and vascular systems predominated. Anesthesia conditions and surgery or trauma sites also influenced the occurrence of LEDVT. For example, the incidence of thrombosis following closed lower extremity fractures was 4.86%,17 15.1% after lumbar fractures,18 and 11.55% after gynecologic laparoscopic surgery,19 which might be associated with sex and age distribution. Iliofemoral thrombosis was the main cause in both groups, which might be associated with the injury sites on the lower extremities and right IVCS.
Iliofemoral thrombosis was more common in the left group and femoropopliteal thrombosis was in the right group, which was different from the most common patterns of below-knee thrombosis usually observed.18,20, 21, 22 Aside from this distinction, our findings generally align with previous reports. This discrepancy might be attributed to the fact that our data were primarily collected from inpatients rather than outpatients or those seen in consultations. However, some literature has reported that among patients with isolated acute DVT for the first time,23,24 distal DVT was more common in females, whereas males had a higher incidence of proximal DVT. This was inconsistent with our findings, of which the explanations were as follows: (1) Due to different definitions, previous studies often grouped all 3 iliofemoral-popliteal segments under the proximal category, while our study distinguished between iliofemoral and femoropopliteal regions and analyzed them separately. (2) Patients undergoing left-sided surgery or trauma patients with underlying iliac vein compression were more susceptible to iliofemoral vein thrombosis. It has been established that the rate of iliac vein thrombosis is significantly higher in patients with left-side DVT compared to right-side DVT. The presence of left-side iliac vein compression might promote the progression of infrapopliteal DVT into iliac vein thrombosis, making it more common in patients with left-side DVT.16 (3) Thrombosis was influenced not only by pelvic vein anatomy and endothelial injury, but also by age, tumor, and other VTE risk factors.25 (4) Although the overall percentage of lower extremity surgery or trauma was similar between the right and left sides, subtle differences in injury sites might contribute to the variation in thrombus formation. For example, endothelial injuries in different vascular regions can affect the location of thrombotic episodes.
Although iliofemoral thrombosis was predominant in the left group, the incidence of PE was lower compared to the right group, likely due to the protective effect of IVCS. On the right side, despite a higher occurrence of femoropopliteal thrombosis, the lower incidence of IVCS and the smaller angle between the right iliac vein and IVC contributed to the reduced risk of PE. However, iliofemoral thrombosis on the left side resulted in more severe swelling and an increased risk of post-thrombotic syndrome. Therefore, catheter-directed thrombolysis and iliac vein stent implantation should be more aggressively pursued for left-side thrombosis, while filter implantation should be more aggressively considered for right-side thrombosis.
This study has certain limitations. First, as a retrospective, single-center study with a small sample size, there is a potential for bias in the findings. Second, while the study analyzed factors associated with thrombosis, it did not extensively explore the interactions between these factors. Finally, due to the limited research on different treatments for thrombosis on both sides, we are conducting studies to better tailor treatment strategies to the side on which thrombosis occurs.
In conclusion, the incidence of left-sided LEDVT is significantly higher than that of the right, yet both warrant equal attention. The distinct characteristics of LEDVT on each side are crucial for prevention and diagnosis in the relevant population, necessitating tailored treatment approaches based on the side of the affected limbs.
CRediT authorship contribution statement
Chong-Li Ren: Conceptualization, Formal analysis, Project administration, Software, Writing – original draft, Writing – review & editing. Jian-Ming Sun: Conceptualization, Methodology, Project administration, Supervision, Writing – review & editing. Hai-Yang Wang: Funding acquisition, Project administration, Supervision, Writing – review & editing. Jian Fu: Investigation, Methodology, Supervision, Validation. Ye-Liang Xu: Data curation, Software. Jin Wang: Data curation. Meng-Lin Nie: Conceptualization, Formal analysis, Methodology, Project administration, Software, Supervision, Writing – original draft, Writing – review & editing.
Ethical statement
The study was approved by the Ethics Committee, which waived the requirement of signing an informed consent form due to the retrospective nature of the study.
Funding
This work was supported by Natural Science Foundation of Chongqing, China (grant No. CSTB2023NSCQ-MSX0723).
Declaration of conflicting interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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