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Keywords:

  • deep venous thrombosis;
  • post-thrombotic syndrome;
  • risk factors

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References

Summary. Background: Post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). Objectives: To determine the risk of PTS after DVT and to assess risk factors for PTS. Methods: Patients were recruited from the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Consecutive patients who suffered a first DVT of the leg were included in a follow-up study. All patients completed a questionnaire and DNA was obtained. PTS was ascertained in a structured interview using a clinical classification score. Results: The 1-year cumulative incidence of PTS was 25% and 7% for severe PTS. Elastic compression stockings were prescribed in 1412 (85%) patients. The majority used their stockings every day. Women were at an increased risk compared with men [risk ratio (RR) 1.5, 95% confidence interval (CI) 1.3–1.8]. Similarly, obese patients had a 1.5-fold increased risk of PTS compared with normal weight patients (RR 1.5, 95% CI 1.2–1.9), with a 1-year cumulative incidence of 34% compared with 22%. Patients who already had varicose veins had an increased risk (RR 1.5, 95% CI 1.2–1.8) of PTS. DVT in the femoral and iliac vein was associated with a 1.3-fold increased risk of PTS compared with popliteal vein thrombosis (RR 1.3, 95% CI 1.1–1.6). Patients over 60 years were less likely to develop PTS than patients below the age of 30 (RR 0.6, 95% CI 0.4–0.9). Malignancy, surgery, minor injury, plaster cast, pregnancy or hormone use did not influence the risk of PTS neither did factor (F)V Leiden nor the prothrombin 20210A mutation. Conclusions: PTS is a frequent complication of DVT, despite the widespread use of elastic compression stockings. Women, obese patients, patients with proximal DVT and those with varicose veins have an increased risk of PTS, whereas the elderly appeared to have a decreased risk.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References

Post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). Venous hypertension caused by venous valvular incompetence and persistent obstruction are likely to be the pathogenic mechanism underlying PTS [1–4]. PTS is characterized by symptoms such as a feeling of heaviness and pain and by signs such as edema, hyperpigmentation and new venous ectasia. Severe PTS can lead to leg ulcers. Several studies assessed the incidence of PTS which varied from 15 to 50% between studies [3–10]. This wide range is as a result of differences in the definition of PTS, patient selection and study design. There is no gold standard test for the diagnosis of PTS and the diagnosis is primarily based on clinical features. Elastic compression stockings assist the calf muscle pump and reduce venous hypertension and reflux, thereby reducing edema and improving tissue microcirculation [1]. Randomized controlled trials have shown that daily use of elastic compression stockings after DVT reduces the risk of PTS by approximately 50% [6,8,11].

In contrast to the many identified risk factors for DVT [12], the only identified risk factors for PTS so far are recurrent, ipsilateral DVT and an increased body mass index (BMI) [7,8,13–18]. Age, gender and duration of anticoagulant therapy did not appear to be associated with the risk of developing PTS, but results are conflicting, and most studies are characterized by small numbers of patients [8,14–18].

Hypercoagulable states have been reported to be associated with venous leg ulcers [19–21]. However, factor (F)V Leiden or the prothrombin 20210A mutation were not associated with an increased risk of developing PTS [8,14,18,21]. One study even showed a reduced risk of PTS with the presence of FV Leiden or the prothrombin 20210 mutation [17]. Other venous thrombotic risk factors such as surgery and hormone use have not yet been investigated as potential risk factors for PTS. The objectives of the present large study were to assess the cumulative incidence of PTS after a first DVT and to assess the contribution of risk factors in the development of PTS.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References

Study design

This study was performed in the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis, a large population-based case–control study. Between March 1999 and June 2002, consecutive patients aged between 18 and 70 years with a first episode of DVT of the leg were included from six participating anticoagulation clinics in the Netherlands. Discharge letters and radiology reports of the venous thrombotic event were obtained. Diagnosis of clinically suspected DVT of the leg was objectively confirmed by compression ultrasonography (71%), color-flow Doppler ultrasound (27%) or by other diagnostic methods [contrast venography, impedance plethysmography or computed tomography of the abdomen (2%)] [22].

Patients who were unable to fill in a questionnaire (see below) because of language or severe psychiatric problems were excluded. Among the 2730 eligible patients, 132 died before they could participate, 31 patients were in the end stage of a disease, 227 patients could not be located and 424 refused to participate, resulting into 1916 participating patients in the MEGA case–control study. In April 2000, three questions regarding PTS were added to the interview (see below) and 157 patients, who were interviewed before this date, and 13 patients with missing items regarding PTS in the interview, were excluded. No information on the left or right side of DVT was available for 78 patients which led to 1668 patients being included in the present analysis. These 1668 patients filled in a questionnaire and participated in an interview. All patients filled in a detailed questionnaire on acquired risk factors for venous thrombosis such as malignancy, surgery, minor injury, plaster cast, bedridden, pregnancy and use of female hormones. The questionnaire was sent within a few weeks after the event and covered the period of 1 year prior to the date of the thrombotic event. When the patient was unable to fill in the questionnaire, questions were asked by phone, using a standardized mini-questionnaire. Patients were divided into groups with idiopathic deep venous thrombosis and provoked venous thrombosis associated with one or more of the following risk factors; malignancy, surgery, plaster cast, minor injury, bedridden at home or in the hospital, pregnancy and the use of female hormones. Surgery, plaster cast, minor injury and bedridden at home or in the hospital were considered as a risk factor when present in the 3 months prior to the thrombosis. Pregnancy was a risk factor when a woman was pregnant at the time of thrombosis or when she gave birth within 3 months prior to the thrombotic event. Female hormones used at the time of the thrombosis were considered as risk factors.

BMI was calculated from self-reported weight and height (weight/height2). BMI was categorized according to the criteria of the World Health Organization (2000) (World Health Organisation. Obesity: Preventing and Managing the Global Epidemic. WHO Obesity Technical Report 2000; Series 894. World Health Organisation, Geneva, Switzerland), defining BMI in adults under 18.5 kg m−2 as underweight, a BMI between 18.5 and 25 kg m−2 as normal, a BMI of 25–30 kg m−2 as overweight and a BMI ≥ 30 kg m−2 as obesity.

Three months after the patients had discontinued their oral anticoagulant therapy, they were invited to the anticoagulation clinic. An independent research assistant, who was not involved in their treatment, interviewed the patients and took a blood sample. In those patients who continued to take oral anticoagulant therapy for more than 1 year after the event, blood samples were drawn during therapy and an interview took place at the same time. If patients were unable to come to the anticoagulation clinic, an interview was conducted by telephone and buccal swabs were sent by mail to replace the blood sample [229 out of 1668 patients (13.7%)].

During the in-person or telephone interview, details on frequency and duration of the use of elastic compression stockings were asked. PTS was assessed by asking for five symptoms and four signs (Table 1). These items were based on the Villalta scale and modified in order to be used in the interview [7]. Each item scored one point if present. The nine items were summed into a post-thrombotic score. PTS was considered absent with a post-thrombotic score between 0 and 3 points. PTS was considered moderate in patients with a score between 4 and 6 points and severe with a score equal to or greater than seven or the presence of a venous ulcer. Only the symptoms and signs of the leg in which the DVT occurred, were used to assess the presence and severity of PTS. The post-thrombotic score showed an excellent relation to the Villalta scale with a kappa of 0.88 (95% Confidence interval 0.79–0.96). The study protocol was approved by the Ethics Committee of the Leiden University Medical Center, Leiden, The Netherlands. Written informed consent was obtained from all participants [22].

Table 1.   Post-thrombotic symptoms and signs in 1668 patients
Symptomsn (%)Signsn (%)
Spontaneous pain in calf433 (26)Newly formed varicose veins218 (13)
Spontaneous pain on walking243 (15)Swelling of foot or calf576 (35)
Spontaneous pain on standing293 (18)Skin changes, pigmentation, discoloration418 (25)
Pain worsening during the day393 (24)Skin changes with venous ulcer48 (3)
Heaviness of leg620 (37)  

Laboratory measurements

Blood was collected from the antecubital vein into vacuum tubes containing 0.106 mol L−1 trisodium citrate. High molecular weight DNA was isolated from leukocytes using a standard salting-out procedure and stored at −20 °C until amplification. When a blood sample was unavailable, three large cotton (buccal) swabs in a total of 6 ml SDS-proteinase K solution were obtained. DNA was extracted from these buccal swabs and frozen at −20 °C until further analysis [22]. FV Leiden (G1691A) and the prothrombin (G20210A) mutation were simultaneously detected by duplex polymerase chain reaction (PCR) [23,24].

Statistical analyses

The follow-up started at diagnosis of DVT in the leg and ended at the time of the interview. Cumulative incidence was estimated using the Kaplan–Meier life table technique. The reported risk ratios are based on the method of Zhang [25]. In short, crude odds ratios were used to estimate the relative risk of PTS. Logistic regression was used to adjust for age and gender only, and for age and gender combined with BMI, duration of symptoms, varicose veins, localization of DVT, malignancy and elastic compression stockings. Ninety-five percent confidence intervals (CI) were calculated using the standard error obtained from the logistic regression model. As PTS is common (over 10% incidence), the odds ratio (OR) overestimates the true relative risk (RR). Therefore, the odds ratio and 95% CI were converted to the risk ratio by taking into account the prevalence of the risk factor in non-exposed individuals [25].

As patients had various durations of follow-up and anticoagulation use, all analyses were stratified by follow-up and period of anticoagulation use. The Mantel–Haenszel common OR was used to estimate the relative risk of PTS, taking these various durations into account. As these stratified ORs did not differ from the crude analyses, the risk ratios presented are adjusted for age and gender and other risk factors as indicated above. All computations were performed with the use of spss software, version 14.0 (SPSS Inc., Chicago, IL, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References

Patient characteristics of the 1668 patients are summarized in Table 2. There were 880 (53%) women, mean age at diagnosis of DVT was 48 years and patients had a mean BMI of 27 kg m−2. Median duration of symptoms before diagnosis of DVT was 4 days (5th–95th percentile 0–69). Thrombosis was unilateral on the left side in 972 (58%) patients, on the right side in 683 (41%) and bilateral in 13 (1%) patients. DVT was idiopathic in 24% of all patients. Median duration of anticoagulation use was 6 months (5th–95th percentile 2–14). Median duration of follow-up was 10 months (5th–95th percentile 6–18).

Table 2.   Characteristics of 1668 patients with a first deep venous thrombosis of the leg
Characteristic 
  1. SD, standard deviation; BMI, body mass index; DVT, deep venous thrombosis.*Unknown in ≤74 patients. Unknown in 213 patients. Unknown in 465 patients.

Women no (%)880 (53)
Age (years), mean (SD)48 (13)
 5th–95th percentile 26–67
BMI (kg m−2), mean (SD)*27 (5)
 5th–95th percentile 21–36
Duration of symptoms before diagnosis (days), median*4
 5th–95th percentile  0–69
Varicose veins at diagnosis470 (28%)
Side of DVT (%)
 Left972 (58)
 Right683 (41)
 Bilateral13 (1)
Localization of DVT (%)
 Calf vein 203 (17)
 Popliteal vein498 (41)
 Femoral and iliac vein502 (42)
Malignancy*137 (8%)
Surgery within 3 months*357 (21%)
Minor Injury within 3 months*405 (24%)
Plaster cast within 3 months105 (6%)
Pregnancy among women <50 years*73 (13%)
Oral anticonceptive use among women <50 years417 (74%)
Hormonal replacement therapy among women ≥50 years*39 (13%)
Idiopathic DVT*389 (24%)
Factor V Leiden mutation*315 (19%)
Prothrombin 20210A mutation*92 (6%)

Cumulative incidence and severity of post-thrombotic syndrome

The 1-year cumulative incidence of PTS was 25%, with a cumulative incidence of 7% for severe PTS. Table 1 shows the frequency of the nine post-thrombotic symptoms and signs. The most frequent symptom reported by 620 (37%) patients was a feeling of heaviness of the leg. Swelling of the foot or calf was present in 576 (35%) of the patients. An ulcer was present in 48 out of 1668 (3%) patients. All patients categorized as having severe post-thrombotic syndrome had heaviness and pain of the leg. These symptoms were combined with swelling and skin changes most of the time (93%) and with newly formed varicose veins or venous ulcers in 41% of the patients. Only 466 out of 1668 patients (28%) had a post-thrombotic score of zero points.

Risk factors for post-thrombotic syndrome

The 1-year cumulative incidence of PTS in women was 31% compared with 17% in men. Women had a 1.5-fold higher risk of developing PTS than men (RR 1.5, 95% CI 1.3–1.8), also after adjustment for other risk factors (RRadjusted 1.5, 95% CI 1.1–1.9) (Table 3). In patients over 60 years, the 1-year cumulative incidence was 16%, which was much lower than the 26% cumulative incidence in patients below the age of 30 years (RR 0.6, 95% CI 0.4–0.9). In obese patients, the 1-year cumulative incidence was 34%, compared with 22% in normal weight patients, leading to a 1.5-fold increased risk of PTS (RR 1.5, 95% CI 1.2–1.9). Height of patients did not affect the risk of PTS. Patients with more than 2 weeks of symptoms before the DVT had a 1.4-fold increased risk compared with patient with symptoms for less than 2 weeks (RR 1.4, 95% CI 1.2–1.7). After adjustment for other risk factors for PTS this effect was no longer present (RRadjusted 1.2, 95% CI 0.9–1.6). Varicose veins were present in 470 out of 1455 (28%) patients prior to the DVT, in whom the 1-year cumulative incidence of PTS was 30%. These patients had a 1.5-fold increased risk of PTS compared with patients without varicose veins (RR 1.5, 95% CI 1.2–1.8). Newly formed varicose veins is one of the items of the post-thrombotic score. When this specific item was excluded from the post-thrombotic score, the risk ratio for varicose veins was only slightly lower (RR 1.4, 95% CI 1.1–1.7). Proximal localization of thrombosis in the femoral and iliac vein was associated with a 1.3-fold increased risk of PTS compared with popliteal vein thrombosis (RR 1.3, 95% CI 1.1–1.6). Calf vein thrombosis conferred a similar risk for PTS as popliteal vein thrombosis. Patients with malignancy were less likely to develop PTS than patients without a malignancy (RR 0.7, 95% CI 0.4–1.0), which was less pronounced after adjustment for other risk factors (RRadjusted 0.8, 95% CI 0.4–1.4).

Table 3.   Risk factors associated with post-thrombotic syndrome
 nPTS, nOne-year cumulative incidence (%) Risk ratio* Risk ratioadjusted
  1. BMI, body mass index; DVT, deep venous thrombosis. *Adjusted for age and gender if applicable. Adjusted for age, gender and other risk factors for PTS if applicable (BMI, duration of symptoms, varicose veins, localization, malignancy, recurrent deep venous thrombosis, elastic compression stocking). Unknown in ≤74 patients. §Unknown in 213 patients. Unknown in 465 patients.

Gender
 Women880235311.5 (1.3–1.8)1.5 (1.1–1.9)
 Men7881291711
Age (years)
 18–29200512511
 30–3931175261.0 (0.7–1.4)0.8 (0.5–1.2)
 40–49391111301.2 (0.9–1.6)1.1 (0.8–1.6)
 50–5945687240.9 (0.6–1.2)0.7 (0.4–1.1)
 60–6931040160.6 (0.4–0.9)0.4 (0.2–0.7)
BMI
 Underweight154361.3 (0.5–2.7)1.4 (0.4–3.6)
 Normal5491092211
 Overweight702132221.1 (0.8–1.3)1.2 (0.9–1.6)
 Obese343102341.5 (1.2–1.9)1.9 (1.4–2.4)
Duration symptoms before diagnosis, weeks
 ≥2368105291.4 (1.2–1.7)1.2 (0.9–1.6)
 <212402452411
Varicose veins at diagnosis§
 Yes470130301.5 (1.2–1.8)1.5 (1.2–1.9)
 No9851802011
Localization of DVT
 Calf vein20337250.9 (0.6–1.3)0.9 (0.6–1.3)
 Popliteal vein4981002311
 Femoral and iliac vein502128261.3 (1.1–1.6)1.4 (1.1–1.8)
Malignancy
 Yes13719150.7 (0.4–1.0)0.8 (0.4–1.4)
 No15303442511

Surgery, minor injury or plaster cast were not associated with the development of PTS, nor were pregnancy or the use of female hormones. Patients with an idiopathic DVT conferred a similar risk for PTS compared with patients with a provoked DVT (RR 0.9, 95% CI 0.7–1.2). The presence of FV Leiden or the prothrombin 20210A mutation was not associated with the development of PTS (Table 4).

Table 4.   Risk factors not associated with post-thrombotic syndrome
Risk factornPTS, nOne-year cumulative incidence (%)Risk ratio*
  1. HRT, hormonal replacement therapy; DVT, deep venous thrombosis. *Adjusted for age and gender. Unknown in ≤74 patients.

Surgery within 3 months
 Yes35782221.1 (0.9–1.3)
 No1308281251
Minor injury within 3 months
 Yes40587251.0 (0.8–1.2)
 No1251274251
Plaster cast within 3 months
 Yes10524281.1 (0.7–1.5)
 No1563340241
Pregnant among women <50 years
 Yes7323351.1 (0.8–1.6)
 No489141321
Oral anti-conceptive use among women <50
 Yes417120301.0 (0.7–1.3)
 No14644371
HRT among women ≥50 years
 Yes399391.0 (0.5–1.8)
 No26558271
Idiopathic DVT
 Yes38964180.9 (0.7–1.2)
 No1205284271
Factor V Leiden mutation
 Yes31574301.1 (0.9–1.4)
 No1311284241
Prothrombin 20210A mutation
 Yes9225241.2 (0.9–1.7)
 No1535333251

Elastic compression stockings

Elastic compression stockings were prescribed in 1412 (85%) patients. The majority (77%) of these patients reported wearing their stockings every day, 300 (21%) patients did not wear them daily and only 30 (2%) never used their elastic compression stockings. Most patients (81%) started to wear elastic compression stockings within 2 months after the DVT.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References

Twenty-five percent of all patients with a first DVT in the leg developed PTS within a year, even although a large majority of the patients reported wearing elastic stockings. Women, obese patients, patients with proximal DVT and those with varicose veins had an increased risk of PTS, whereas elderly patients appeared to have a decreased risk. FV Leiden and prothrombin 20210A mutation were not associated with the risk of PTS.

In our study, the 25% 1-year cumulative incidence of PTS is comparable with the 27% incidence of PTS after 1 year reported in patients who used elastic compression stockings [6].

This is the first large follow-up study that assesses acquired and genetic risk factors for the development of PTS in 1668 patients with a first DVT. Women were at a higher risk of PTS than men, with a cumulative incidence of 31% vs. 17%. The influence of gender on the development of PTS showed contradictory results in previous studies. Only one follow-up study in 244 patients showed an increased risk for women [16], whereas another study showed an increased risk for men [18]. However, most studies did not find an association [8,15,17]. These contradictory results may be explained by small study populations [15,17] and the inclusion of patients with recurrent thrombosis [8,16–18]. Recurrent DVT is a risk factor for PTS and might have concealed the impact of gender.

Our finding that obesity was associated with PTS has been reported before [14–18]. Excess body weight might increase venous pressure and promote reflux in already compromised veins. Moreover, a high BMI might be related to a lack of physical exercise and therefore a poor function of the muscle pump. Obesity is highly prevalent in the general population, with a prevalence of 21% in our study population, and showed an increased risk of PTS, with a cumulative incidence of 34% after 1 year. It is of interest that a high BMI is a risk factor for PTS, as obesity is a potentially modifiable risk factor and thus weight reduction may play a role in the prevention of PTS.

This study identified the presence of varicose veins before the development of DVT as a risk factor for PTS. Patients with varicose veins might have a diminished calf muscle pump function as a result of pre-existing reflux, leading to higher walking venous pressure and the development of chronic venous insufficiency [1]. Our study found that proximal DVT is a risk factor for PTS [18,26]. This association between localization of the initial thrombus and PTS was not observed in all previous studies [7,18]. It is an important finding that calf vein thrombosis conferred a similar risk for PTS as popliteal vein thrombosis. This finding stresses the importance of treatment for symptomatic calf vein thrombosis.

Other studies have reported recurrent venous thrombosis as a risk factor of PTS [7,8,14,16,18]. Unfortunately, we were unable to investigate recurrent thrombosis as a risk factor for PTS.

The reduced PTS risk in older patients is an interesting finding and in contradiction to the increased risk in elderly patients reported in some [8,16,18], but not all other studies [15,17]. We included patients below 70 years, where older patients were included in other studies, which makes it difficult to compare the results [8,15–17]. The reduced PTS risk may reflect differences in thrombus propagation in elderly patients. Recanalization of the thrombus is a relatively fast process, and most vein segments are recanalized within 3 months. In older patients, thrombus evolution is an unstable process with continuing propagation for 2 years [27] and therefore older people might develop PTS later than younger people.

In our study, neither FV Leiden nor the prothrombin 20210A mutation were associated with the onset of PTS, which is in contrast to what has been suggested by other investigators [19–21]. This is an important observation as the role of inherited thrombophilia with regard to the risk of PTS is not well established [8,14,17–21]. It was recently shown that FV Leiden and the prothrombin 20210A mutation do not increase the risk of a recurrent thrombotic event [28]. These results suggest that inherited thrombophilic work-up is not likely to confer clinical benefit to the patient regarding the prediction of the development of PTS.

This study describes the widespread use of elastic compression stockings. Wearing elastic compression stockings is a hassle in daily life for patients. It can be difficult to put them on and take them off, and they can be uncomfortable. The appearance of elastic compression stockings is also considered a reason for non-regular use. Despite these disadvantages the majority of these patients reported to be compliant and use their stockings every day. This is in accordance with a survey that showed that patients with DVT are willing to comply with elastic compression stocking therapy [29].

The 25% 1-year cumulative incidence of PTS is based on symptoms and signs reported by patients, this may be considered as a drawback of this study. However, there is no gold standard test for the diagnosis of PTS. This diagnosis can be based on clinical signs and symptoms or on objective assessment of venous valvular insufficiency and venous hypertension. We used a standardized clinical scale, with signs and symptoms to define presence and severity PTS, which was derived from the Villalta scale. Sustained venous hypertension, the underlying pathogenic mechanism of PTS, can be reliably measured by invasive ambulatory venous pressure tests. This technique requires special equipment, is invasive, time-consuming and cumbersome. It has been shown that PTS diagnosed with the Villalta scale is associated with an increased mean invasive venous ambulatory pressure of over 40 mmHg [30], suggesting that the use of this scale seems justified. However, until uniform diagnostic criteria for PTS diagnosis are defined, this will remain a limitation of all clinical studies.

Furthermore, it is difficult to assess whether the symptoms and signs were directly as a result of venous valvular incompetence or venous outflow obstruction related to the DVT, or to other causes of leg venous hypertension. However, information obtained about signs and symptoms in the leg without DVT shows a much lower frequency of between 0.4 and 2% (data not shown) than in the leg with deep venous thrombosis. This supports the hypothesis that these signs and symptoms are indeed post-thrombotic and not as a result of other causes of venous hypertension of the leg.

We assessed the presence and severity of PTS at a median of 10 months after diagnosis of DVT and at only one point in time. It usually takes 3–6 months after an acute DVT for the initial pain and swelling to resolve and the diagnosis of PTS should be deferred until later [9,10,27]. In most cases, PTS will become apparent within 1 year after the acute DVT, with little increase in incidence thereafter [9]. Thus, the 25% 1-year cumulative incidence we found may have been an underestimation.

We conclude that PTS remains a frequent complication in patients with DVT despite the frequent use of elastic compression stockings. Female gender, older age, obesity and varicose veins were all associated with the development of PTS, whereas genetic risk factors were not.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References

The authors wish to thank the (former) directors of the Anticoagulation Clinics of Amersfoort, Amsterdam (M. Remkes), Leiden (F.J.M. van der Meer), The Hague (E. van Meegen), Rotterdam (A.A.H. Kasbergen) and Utrecht (J. de Vries-Goldschmeding) who made the recruitment of patients possible. The interviewers J.C.M. van den Berg, B. Berbee, J.E. Kroon, S. van der Leden, M. Roosen and E.C. Willems of Brilman performed the blood draws. I. de Jonge, R. Roelofsen, M. Streevelaar, L.M.J. Timmers and J.J. Schreijer are thanked for their secretarial and administrative support and data management. The fellows I.D. Bezemer, J.W. Blom, A. van Hylckama Vlieg, E.R. Pomp and K.J. van Stralen took part in every step of the data collection. C.J.M. van Dijk, R. van Eck, J. van der Meijden, P.J. Noordijk and Th. Visser performed the laboratory measurements. H.L. Vos supervised the technical aspects of DNA analysis. We express our gratitude to all individuals who participated in the MEGA study. This research was supported by the Netherlands Heart Foundation (NHS 98.113), the Dutch Cancer Foundation (RUL 99/1992) and the Netherlands Organization for Scientific Research (912-03-033|2003). The funding organizations did not play a role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Disclosure of Conflict of Interests

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References

The authors state that they have no conflict of interest.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
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