Abstract
We evaluated the clinical features and the risks of 14 patients with 14 limbs affected by saphenous vein thrombophlebitis from April 2007 to May 2013 and compared the results with patients undergoing operative repair of varicose veins (127 patients, 193 limbs) during the study period. The frequency of patients with a body mass index over 25 (78.6% vs. 35.3%, p = 0.0018), varicose change in the saphenous vein (78.6% vs. 6.2%, p <0.0001), and concurrent thrombosis in another vein (50.0% vs. 7.1%, p <0.0001) were all significantly higher than those of the patients under operative repair for varicose veins. These patients with clinical features above may be at an elevated risk of thrombophlebitis of the saphenous trunk. (This article is a translation of J Jpn Coll Angiol 2014; 54: 151–157).
Keywords: saphenous vein, thrombophlebitis, varicose vein, body mass index, deep vein thrombosis
Introduction
Superficial vein thrombosis is a common occurrence and is usually regarded as a benign condition. However, when a thrombus forms in the saphenous trunk, careful management is necessary due to its potential to extend into the deep venous system and cause a pulmonary embolism. This study investigated the clinical features and risks of patients admitted to our hospital with saphenous vein thrombosis.
Materials and Methods
From April 2007 to May 2013, 465 new patients visited our hospital with primary varicose veins in 705 limbs. Within this cohort, a saphenous vein thrombosis was detected in 14 limbs of 14 patients (2.0% and 3.0%, respectively). For each patient, the location and extension of the thrombus, distance from the saphenofemoral junction (SFJ) or saphenopopliteal junction (SPJ) to the thrombus, and the presence of a floating proximal end of the thrombus were evaluated using color Doppler echocardiography. Each patient was interviewed to determine their historical thrombotic risk, and the level of anti-cardiolipin beta-2-glycoprotein-1 antibody, protein C activity, and protein S activity was measured for all patients. Enhanced computed tomography (CT) scan of the lung was performed for each patient to check for pulmonary embolism. Through this study, some clinical features appeared to be found frequently in the patients with saphenous vein thrombosis. Therefore, we also determined patient body mass index (BMI), the presence of varicose changes in the saphenous trunk, and the concurrent presence of thrombosis in other veins for 127 patients (193 limbs) who underwent varicose vein surgery at our hospital during the study period. Of the 154 consecutive patients (220 limbs), we excluded 14 patients (14 limbs) who underwent additional surgery for the same occurrence and 13 patients (13 limbs) with a saphenous thrombosis. The former group was compared with the 14 patients with a saphenous vein thrombosis. Varicose changes were identified as localized dilatation or protrusion of the saphenous wall and severe flexing and meandering of the saphenous trunk for cases where the vein wall was in contact through bending.
Statistical analyses included Student’s t-test, χ2 test, and Fisher’s exact test. P-value <0.05 was considered statistically significant.
Results
The site of each thrombotic saphenous trunk, the clinical classification using Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification of each patient, and the presence of varicose veins in each patient’s contralateral limb are presented in Table 1. The location and extension of the thrombus, the distance from the SFJ or SPJ to the thrombus, the presence of floating proximal end of the thrombus, and pulmonary embolism are shown in Table 2. The seven males and seven females in the study cohort had a mean age of 66.4 ± 13.9. In 8 cases, the thrombus formed in the great saphenous vein (GSV), and in six cases, it formed in the small saphenous vein (SSV).
Table 1.
Patients backgrounds (1)
| Case no. | Age | Sex | Vein | Side | CEAP classification | Varicose veins of contralateral limb |
|---|---|---|---|---|---|---|
| 1 | 67 | M | GSV | rt | C4b | none |
| 2 | 82 | M | SSV | rt | C3 | none |
| 3 | 58 | F | SSV | rt | C3 | none |
| 4 | 73 | F | GSV | lt | C3 | none |
| 5 | 68 | F | GSV | lt | C2 | none |
| 6 | 56 | M | GSV | lt | C4a | C2 |
| 7 | 28 | M | SSV | rt | C4a | C4a |
| 8 | 82 | F | SSV | lt | C4a | none |
| 9 | 62 | F | GSV | rt | C2 | none |
| 10 | 79 | M | GSV | lt | C3 | C3 |
| 11 | 60 | M | GSV | lt | C4a | C4a |
| 12 | 71 | M | SSV | rt | C3 | C2 |
| 13 | 75 | F | SSV | lt | C4a | C3 |
| 14 | 69 | F | GSV | rt | C2 | C2 |
CEAP: clinical-etiology-anatomy-pathophysiology; M: male; F: female; GSV: greater saphenous vein; SSV: smaller saphenous vein
Table 2.
Distribution and extent of thrombus
| Case no. | Age | Sex | Vein | Extent of thrombus | Distance to SFJ | Floating of thrombus | Pulmonary embolism |
|---|---|---|---|---|---|---|---|
| 1 | 67 | M | GSV | SFJ 2.6 cm ~ BKGSV | 2.6 cm | ||
| 2 | 82 | M | SSV | SPJ ~ all SSV | 0 cm | ||
| 3 | 58 | F | SSV | SPJ 0.5 cm ~ 4.5 cm | 0.5 cm | ||
| 4 | 73 | F | GSV | BKGSV | >10 cm | ||
| 5 | 68 | F | GSV | Thigh1/2 ~ BKGSV | >10 cm | ||
| 6 | 56 | M | GSV | SFJ 1.5 cm ~ BK | 1.5 cm | ||
| 7 | 28 | M | SSV | BKGSV | >10 cm | ||
| 8 | 82 | F | SSV | SPJ 5 cm ~ 8 cm | 5 cm | ||
| 9 | 62 | F | GSV | SFJ 1 cm ~ 21 cm | 1 cm | + | |
| 10 | 79 | M | GSV | SFJ 20 cm ~ BK10 cm | >10 cm | ||
| 11 | 60 | M | GSV | AKGSV ~ 5 cm | >10 cm | ||
| 12 | 71 | M | SSV | SPJ 0.9 cm ~ all SSV | 0.9 cm | ||
| 13 | 75 | F | SSV | SPJ 15 cm ~ all SSV | 15 cm | + | |
| 14 | 69 | F | GSV | Thigh1/2 ~ BKGSV | >10 cm | ||
SFJ: sapheno-femoral junction; M: male; F: female; GSV: greater saphenous vein; SSV: smaller saphenous vein; SPJ: sapheno-popliteal junction; AK: above knee; BK: below knee
The thrombus length measured in each patient ranged widely from a short, 3-cm distance to almost the entire length of the saphenous vein. Six cases were diagnosed as ascending thrombophlebitis because of a thrombus extension to the SFJ or SPJ (within 3 cm). Although the thrombus of five of these patients had already extended to near the SFJ or SPJ at their initial visit, only one patient, case number 1, displayed a thrombotic extension to the SFJ after their first visit to our hospital. One patient had a floating thrombus (case 9), and one was found to have an asymptomatic pulmonary embolism (case 13).
Patients with GSV thrombosis underwent partial stripping of the GSV under spinal anesthesia within 2 days of their diagnosis of saphenous thrombosis. The patient with a floating thrombus (case 9) required a femoral vein clamp before manipulation of the GSV. A side clamp of the femoral vein proximal to the SFJ was required for two patients with ascending thrombophlebitis (cases 1 and 7). Stripping using routine surgical procedures was performed on the other five patients.
Three patients with an SSV thrombus distant from the SPJ received high ligation of the SSV without touching the thrombus under local anesthesia in a prone position within 2 days of their hospital visit. Anticoagulation therapy using warfarin was administered for 6 months to two patients (cases 2 and 3) with a thrombus that extended to near the SPJ that would likely require direct operative manipulation of the thrombosed vein. High ligation was performed after regression of the thrombus for these two patients. No surgery was performed in case 12 due to the presence of left lung cancer (squamous cell carcinoma, stage IV) that was identified by CT scan. The patient was transferred to another hospital for treatment.
No anticoagulation therapy was administered after surgery, except for case number 13 who had an asymptomatic pulmonary embolism and was prescribed warfarin for 6 months. Compression therapy using an elastic stocking was generally prescribed for at least 3 weeks after surgery, and seven patients with superficial thrombophlebitis of a varicose vein were continued on compression therapy until their symptoms improved.
The thrombotic risks of patients with saphenous thrombosis are presented in Table 3. One patient had Protein C deficiency (37% measured activity; 64%–146% of the standard level), and another patient was undergoing hormone therapy using estriol. Lung cancer was identified in one patient and the other one, being a truck driver, used to sit for extended periods of time.
Table 3.
Risks of thrombosis
| Case no. | Age | Sex | Vein | BMI | Varicose change of saphenous trunk | Thrombophlebitis of saphenous branch | DVT | Thrombophilia | Malignancy | Hormone therapy | Long time driving |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 67 | M | GSV | 25.7 | + | + | |||||
| 2 | 82 | M | SSV | 27.5 | + | ||||||
| 3 | 58 | F | SSV | 28.5 | + | ||||||
| 4 | 73 | F | GSV | 26.2 | + | + | |||||
| 5 | 68 | F | GSV | 28.0 | + | ||||||
| 6 | 56 | M | GSV | 30.9 | + | + | |||||
| 7 | 28 | M | SSV | 23.0 | + | + | |||||
| 8 | 82 | F | SSV | 24.9 | + | ||||||
| 9 | 62 | F | GSV | 20.3 | + | + | |||||
| 10 | 79 | M | GSV | 25.2 | + | + | |||||
| 11 | 60 | M | GSV | 27.6 | + | + | |||||
| 12 | 71 | M | SSV | 27.4 | + | + (*1) | + (*2) | ||||
| 13 | 75 | F | SSV | 27.8 | + | ||||||
| 14 | 69 | F | GSV | 29.3 | + | + | |||||
*1: protein C deficiency. *2: lung cancer. M: male; F: female; BMI: body mass index; DVT: deep venous thrombosis; GSV: greater saphenous vein; SSV: smaller saphenous vein
Other than the formerly well-established risks, some clinical features appeared to be found frequently in the patients with saphenous vein thrombosis through this study. The frequency of patients with a high BMI (more than 25) was 78.6% (11 of 14 cases). The frequency of patients with varicose changes of the saphenous trunk was also 78.6% (11 of 14 cases). Furthermore, of seven patients with thrombotic varices, we excluded two patients as their thrombi continued to the saphenous thrombi; the remaining five patients had thrombophlebitis of varicose vein isolated from the saphenous thrombus. Gathering two patients with deep venous thrombosis discontinued to the saphenous thrombus, 7 of 14 patients (50.0%) had more than one independent, simultaneous thrombosis.
To evaluate how these risks may possibly influence saphenous thrombosis, the rates for patients with predictable risks above those who underwent an operation for varicose veins (127 patients, 193 limbs; Group S) were evaluated and compared with those of patients with a saphenous thrombosis (Group T) during the same period.
The background characteristics of patients in each group are presented in Table 4. There were no significant differences between the two groups in age, gender, number of incompetent veins, and CEAP classification. The number of patients presenting with each risk is reported in Table 5.
Table 4.
Patients backgrounds (2)
| Patients with saphenous thrombophlebitis | All patients with varicose veins under operation | p value | |
|---|---|---|---|
| Number of patients | 14 | 127 | |
| Number of limbs | 14 | 193 | |
| Age | 66.4 ± 13.9 | 63.1 ± 13.1 | 0.383 |
| Sex | |||
| Male | 7 | 52 | 0.98 |
| Female | 7 | 75 | |
| Vein | |||
| GSV | 7 | 157* | 0.187 |
| SSV | 7 | 42* | |
| CEAP classification | |||
| C2 | 3 | 80 | 0.29 |
| C3 | 5 | 61 | |
| C4a | 5 | 42 | |
| C4b | 1 | 3 | |
| C5 | 0 | 2 | |
| C6 | 0 | 5 | |
*Including 6 limbs with both GSV/SSV insufficiency. GSV: Greater saphenous vein; SSV: Smaller saphenous vein
Table 5.
Risks of saphenous thrombophlebitis
| Patients with saphenous thrombophlebitis (*1) | Patients with varicose veins under operation (*2) | p value | |
|---|---|---|---|
| Body Mass Index | |||
| <25 | 3 | 77 | 0.0018 |
| ≥25 | 11 | 42 | |
| Varicose change of saphenous trunk | |||
| (–) | 3 | 181 | <0.0001 |
| (+) | 11 | 12 | |
| Thrombosis of other veins | |||
| (–) | 7 | 9 | <0.0001 |
| (+) | 7 | 118 | |
*1 14 patients, 14 limbs. *2 Body Mass Index: 119 patients. Varicose change of saphenous trunk: 193 limbs. Thrombosis of other veins: 127 patients
The frequency of patients having a high BMI was 11 in 14 patients (78.6%) in Group T; this was significantly higher than that in Group S (35.3%; 42 of 119 patients, excluding 8 from the original 127 patients because their records did not list their body weight or height; p = 0.0018). The mean BMI value in Group T was also significantly higher than that in Group S (26.6 ± 2.68 vs. 24.4 ± 3.88; p = 0.039). Furthermore, the rate of patients with varicose change in Group T (78.6%; 11 of 14 limbs) was significantly higher than that in Group S (6.2%; 12 of 193 limbs; p <0.0001).
Despite 7 of 14 patients in Group T (50.0%) having a concurrent venous thrombosis that discontinued to the saphenous thrombus, only 9 of 127 Group S patients (7.1%) had an independent, simultaneous venous thrombus (p <0.0001).
Discussion
Among the 465 patients and 705 limbs evaluated, saphenous thrombosis was found in 14 limbs from 14 patients (2.0% and 3.0%, respectively) who visited our hospital for the first time with primary varicose veins during the investigation period. According to Leon and colleagues, the incidence of superficial thrombophlebitis is approximately 3%–11% in the general population.1) Hirooka and colleagues also reported 11 patients with saphenous vein thrombosis (2.0%) among 529 patients undergoing GSV stripping surgery.2) These results are generally consistent with the frequency of saphenous vein thrombosis observed in the present study. While there are few reports of saphenous vein thrombosis in Japan,2–6) the incidence of this disease may be higher than anticipated as indicated by our results presented above.
Extension of the thrombus toward the deep vein and potential complications of pulmonary embolism should be monitored as part of the management of patients with saphenous vein thrombosis.
The incidence of contiguous propagation into deep vein of the saphenous thrombus is reportedly 7%–25%.7) The most common involvement is the GSV thrombus into the femoral vein through the SFJ, while an SSV thrombus into the popliteal vein through the SPJ is relatively less frequent. Extension through a perforating vein may also occur.1,7) Careful management is necessary for patients with ascending thrombophlebitis, a contiguous involvement of a saphenous vein thrombus into a deep vein, which could potentially cause a pulmonary embolism.8)
Moreover, the presence of a thrombus in the saphenous vein may increase the risk of pulmonary embolism. Although the incidence of pulmonary embolism complicated with superficial thrombophlebitis is reportedly 0.9%–7.8%,1,8) the incidence among patients with saphenous thrombosis is reported to be up to 33%.9)
In this study, 6 of 14 patients identified with saphenous thrombosis (42.9%) had thrombus extending to the SFJ or SPJ (within 3 cm). An asymptomatic pulmonary embolism was found in one patient (7.1%) in whom the distance between thrombus and junction to a deep vein was relatively long and had not been diagnosed with ascending thrombophlebitis. Therefore, the risk of pulmonary embolism for patients with saphenous thrombosis may not be low.
To prevent the extension of a thrombus and the occurrence of pulmonary embolism, early treatment, such as that by anticoagulation or surgical operation for reduction of thrombotic elongation and isolation of the embolic source from the deep vein, is necessary for patients with saphenous thrombosis.1,8–12)
With one exception (case 12 with lung cancer), all patients in this study underwent surgery to prevent extension of the saphenous thrombus to a deep vein. Four cases underwent surgery after anticoagulation therapy. Careful observation and early surgery, if possible, is needed for patients under anticoagulation therapy because progression of the thrombus into a deep vein has been reported despite patients being prescribed an anticoagulant.10) We found no patients with extension of a thrombus while they were receiving anticoagulation therapy.
Driving or sitting for long periods of time, pregnancy, hormone therapy, prolonged immobilization in bed, recent surgery, and trauma are well known to increase the risks of thrombophlebitis.1) Malignancy was also reported to have a weak association with superficial thrombophlebitis.1) Patients with superficial thrombophlebitis should be screened for hypercoagulability because of their high prevalence of hypercoagulable states caused by a deficiency in antithrombin III or abnormalities in protein C and S.1,13) Male gender, history of thromboembolism, severe venous insufficiency, and shorter interval between symptom onset and diagnosis (less than 7 days) are also reported to be risk factors associated with complications after superficial vein thrombosis.12)
In this study, Protein C deficiency, hormone therapy, malignancy, and driving as an occupation were found to increase the risk of thrombosis. Preventing venous thrombosis occurrence is needed for all patients with risk factors, including those listed above as a matter of course.
Moreover, it was remarkable that in patients having saphenous vein thrombosis, the frequency of high BMI, varicose changes in the saphenous trunk, and concurrent independent thrombosis in other veins were significantly higher than in patients who underwent operation for varicose veins without saphenous vein thrombosis. The basis for these differences and their relationship, if any, with saphenous vein thrombosis is unclear.
Metabolic syndrome is reportedly an independent risk factor of deep venous thrombosis14–16) due to thrombogenicity caused by deceleration of endothelial function, reduction in adiponectin concentration, and increased PAI-1.16–18) Obesity may cause greater thrombogenicity and increase the risk of thrombosis in patients with a high BMI.
Varicose changes of the saphenous trunk were also frequently found in patients with saphenous thrombosis. Decreasing speed or stasis of blood flow in the saphenous trunk following varicose changes, degeneration of endothelial cells, and the reduced antithrombotic function of the varicose vein wall may all cause thrombogenicity leading to the saphenous thrombus.19)
Patients in this study frequently presented with a concurrent thrombosis. They had no associated thrombotic risks, except for one patient with protein C deficiency, and their thrombi were isolated from the saphenous thrombus, except for two cases excluded from the comparison. According to these findings, the existence of thrombus may cause local hypercoagulability and consequently result in the formation of a saphenous thrombus.20)
The symptoms listed above as well as a high BMI, varicose changes in the saphenous trunk, and concurrent venous thrombosis, which is commonly found in patients with varicose veins, may be at high risk of saphenous thrombosis and thus require careful observation and treatment for saphenous veins.
Conclusion
We evaluated the clinical features and risks of 14 patients with 14 limbs affected by saphenous vein thrombophlebitis and compared the results with similar patients undergoing operative repair of varicose veins (127 patients, 193 limbs) during the study period. The frequency of saphenous thrombosis in this study demonstrates that the condition is not rare among patients with varicose veins. Patients with a higher body mass index (>25), varicose changes in the saphenous vein, and a concurrent thrombosis in another vein may be at an elevated risk for thrombophlebitis of the saphenous trunk.
Disclosure Statement
The author has no conflict of interest to disclose.
Acknowledgment
I am deeply grateful to Dr. Hitoshi Goto (Tohoku University) for his advices and comments.
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