Patient characteristics
Forty patients with reVTE that were alive and whose contact data were available were identified from the cohort database of DVT patients treated at the outpatient clinic of the Maastricht University Medical Centre [
14]. Twenty-nine patients responded to our invitation to participate in this exploratory case-control study and signed the informed consent form. These 29 patients were then age and sex matched to 29 controls who had not experienced reVTE according to the data available in the database. Therefore, in total 58 patients signed informed consent and were included in the study. Information obtained during data ascertainment of the patients’ medical records and at the study visit showed that in two out of the 29 patients the recurrent event concerned an upper extremity thrombosis. Furthermore, five of the 29 matched controls for whom no reVTE was recorded in the database actually had experienced a reVTE. Hence the final study sample includes 56 patients of which 32 patients with reVTE (26 reDVT and 6 PE) and 24 patients who had not experienced a recurrent event (Table
1). Patients had a median age of 67.0 (Inter Quartile Range 57.0–71.0) years and were predominantly male (82.1%). An unprovoked cause of the first DVT was significantly more common in patients with reVTE: 23 out of 32 patients (71.9%) versus ten out of 24 patients (41.7%), (
P = 0.03). In seven patients (six (18.8%) versus one (4.2%);
p = 0.219) thrombophilia was known; the prevalence of elevated factor VIII (defined as > 213% [
14]) was significantly higher in patients with reVTE (six (18.8%) versus none (0.0%);
p = 0.035).
Table 1
Baseline characteristics
Age, years | 68.0 (61.3–72.0) | 65.0 (45.3–70.8) | 0.223 |
Sex | | | 0.298 |
- Male | 28 (87.5) | 18 (75.0) | 0.298 |
- Female | 4 (12.5) | 6 (25.0) | 0.298 |
Unprovoked DVT | 23 (71.9) | 10 (41.7) | 0.030 |
Affected side initial event | | | 0.697 |
- Left | 13 (40.6) | 11 (45.8) | 0.697 |
- Right | 19 (59.4) | 13 (54.2) | 0.697 |
Affected side recurrent event |
- Ipsilateral (± pulmonary embolism) | 17 (53.1) | n/a | – |
- Contralateral (± pulmonary embolism) | 9 (28.1) | n/a | – |
- Pulmonary embolism | 6 (18.8) | n/a | – |
History of pulmonary embolism | 8 (25.0)a | 4 (16.7)b | 0.525 |
Family history of DVT | 10 (31.3) | 3 (12.5) | 0.122 |
Antithrombotic therapy | 32 (100.0) | 17 (70.8) | 0.001 |
Antithrombotic therapy, type | | | 0.071 |
- VKA | 26 (81.3%) | 16 (66.7) | 0.212 |
- DOACc | 6 (18.8%) | 0 (0.0) | 0.035 |
Elastic compression stockings, use | 19 (59.4) | 3 (12.5) | < 0.001 |
The current use of anticoagulant therapy and compression therapy was significantly higher in the reVTE-group: 100% (32 out of 32) versus 70.8% (17 out of 24), p = 0.001, and 59.4% (19 out of 32) versus 12.5% (three out of 24), p < 0.001, respectively. Most commonly used were the VKA: 26 out of 32 (81.3%) in patients with reVTE versus 16 (66.7%) out of 24 controls. A significant difference in the use of direct oral anticoagulants was seen, being restricted to patients with reVTE: six out of 32 (18.8%) versus none of the controls (0.0%), p = 0.035). Indication for indefinite treatment duration was more frequent in patients with reVTE: 30 out of 32 (93.8%) versus six out of 24 (25.0%), p < 0.001.
Study outcomes
There was no significant difference in the prevalence of VO between groups: six (18.8%) in patients who had experienced a recurrent event versus five (20.8%) in patients who did not; OR 0.88 (95%CI 0.23–3.30),
p = 1.000 (Table
2). The presence of abnormalities on duplex findings such as extraluminal compression (four (12.5%) versus three (12.5%), OR 1.00 (95%CI 0.20–4.96),
p = 1.000), intraluminal post-thrombotic sequelae (28 (87.5%) versus 18 (75.0%), OR 2.33 (95%CI 0.58–9.43),
p = 0.298), or venous insufficiency (19 (59.4%) versus 10 (41.7%), OR 2.05 (95%CI 0.70–6.00),
p = 0.189) did not differ either (Table
3).
Table 2
Details in patients with central venous obstructions and anatomic anomalies
Anatomic anomalies |
#1 | Duplication of the VP, fibrosis of the VF | #1 | Aneurysm VP | |
#2 | Duplication of the VF | #2 | Duplication and fibrosis of the VF | |
Central venous obstructions |
#3 | Extraluminal compression: CIV and EIV | #3 | Extraluminal compression: ICVir and CIV | |
#4 | Extraluminal compression: CIVa | #4 | Extraluminal compression: ICVir and CIV | |
#5 | Extraluminal compression: ICVir and CIVb | #5 | Extraluminal compression: CIVc | |
#6 | Extraluminal compression: CIVc | | | |
Table 3
Results duplex assessmenta
Extraluminal compression | 4 (12.5) | 3 (12.5) | 7 (12.5) | 1.00 (0.20–4.96) |
Extraluminal compression, per vein segment |
ICVir | 1 (3.1) | 2 (8.3) | 3 (5.6) | 0.36 (0.03–1.16) |
CIV | 4 (12.5) | 3 (12.5) | 7 (12.5) | 1.00 (0.20–4.96) |
EIV | 1 (3.1) | 0 (0.0) | 1 (1.8) | 2.33 (0.09–59.8) |
Post-thrombotic sequalaeb | 28 (87.5) | 18 (75.0) | 46 (82.1) | 2.33 (0.58–9.43) |
Trabeculations, per vein segment |
ICVsr | 1 (3.1) | 0 (0.0) | 1 (1.8) | 2.33 (0.09–59.8) |
ICVir | 1 (3.1) | 1 (4.2) | 2 (3.6) | 0.74 (0.04–12.5) |
CIV | 2 (6.3) | 3 (12.5) | 5 (8.9) | 0.47 (0.07–3.04) |
EIV | 3 (9.4) | 3 (12.5) | 6 (10.7) | 0.72 (0.13–3.95) |
CFV | 3 (9.4) | 4 (16.7) | 7 (12.5) | 0.52 (0.10–2.57) |
FV | 18 (56.3) | 9 (37.5) | 27 (48.2) | 2.14 (0.73–6.32) |
DFV | 1 (3.1) | 1 (4.2) | 2 (3.6) | 0.74 (0.04–12.5) |
PV | 27 (79.4) | 16 (66.7) | 43 (76.8) | 2.70 (0.75–9.68) |
Venous insufficiencyc | 19 (59.4) | 10 (41.7) | 29 (51.8) | 2.05 (0.70–6.00) |
Venous insufficiency, per vein segment |
CFV | 3 (9.4) | 0 (0.0) | 3 (5.6) | 5.81 (0.29–118.1) |
PV | 19 (59.4) | 10 (41.7) | 29 (51.8) | 2.05 (0.70–6.00) |
Compression was seen solely in the caval and iliac tract: the ICVir (one (3.1%) versus two (8.3%) respectively, p = 1.000), the CIV (four (12.5%) versus three (12.5%), p = 1.000), and EIV (one (3.1%) versus none (0.0%), p = 0.126). Trabeculations were most commonly seen in the popliteal (27 (79.4%) versus 16 (66.7%), p = 0.200) and femoral vein (18 (56.3%) versus 9 (37.5%), p = 0.165). In only two (6.3%) versus five (20.8%) patients all vein segments were free of anomalies (p = 0.642). There was no difference for any of the results whether the right or left leg was affected.
The mean Villalta score was 5.55 ± 3.02 in patients with reVTE compared to 5.26 ± 2.63 in patients without reVTE (
p = 0.909), composed of objective (4.03 ± 3.07 versus 3.08 ± 1.74,
p = 0.519) and subjective (1.63 ± 1.43 versus 2.22 ± 2.30,
p = 0.512) components. No significant trends were seen in the mean total (
p = 0.909), objective (
p = 0.519), or subjective (
p = 0.512) Villalta-score. PTS and PTS severity was similar between groups. There were no differences in the reported QoL according to the SF36v2, overall score (
p = 0.493) as well as the scores per individual category (all
P > 0.156), and the VEINES-QOL/Sym (
p = 0.518 for the total score and
p = 0.966 for the intrinsic score) (Table
4).
Table 4
Long-term treatment outcomes
| 5.55 ± 3.02 | 5.26 ± 2.63 | 5.43 ± 2.84 | – |
- Subjective score | 1.63 ± 1.43 | 2.22 ± 2.30 | 1.87 ± 1.85 | – |
- Objective score | 4.03 ± 3.07 | 3.08 ± 1.74 | 3.62 ± 2.60 | – |
Post-Thrombotic syndromea [ 15, 17] | 20 (62.5) | 14 (58.3) | 34 (60.7) | 1.19 (0.40–3.51) |
- None (0–4) | 11 (34.4) | 9 (37.5) | 20 (35.7) | 0.87 (0.29–2.63) |
- Mild (5–9) | 17 (53.1) | 11 (45.8) | 28 (50.0) | 1.34 (0.46–3.87) |
- Moderate (10–14) | 3 (9.4) | 3 (12.5) | 6 (10.7) | 0.72 (0.13–3.95) |
- Severe (≥15 or venous ulceration) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0.75 (0.01–39.3) |
- Missing | 1 (3.1) | 1 (4.2) | 2 (3.6) | 0.74 (0.04–12.5) |
SF-36b − Reported health transition | 51.7 ± 18.5 | 52.1 ± 14.6 | 51.9 ± 16.7 | – |
VEINES QOL/Symc | 49.5 ± 11.1 | 51.5 ± 8.2 | 50.4 ± 9.9 | – |
VEINES QOL/Sym, intrinsic scored | 71.3 ± 14.8 | 72.4 ± 12.2 | 71.8 ± 13.6 | – |
Furthermore, analyses regarding outcomes of the DUS assessment and the clinical assessments for the Villalta-score, PTS, PTS severity, and QoL were also performed for two subgroups: patients with or without an unprovoked cause for the primary DVT and patients with and without VO.
These analyses showed that patients with an unprovoked cause of the primary DVT (n = 33, 58.9%) did not differ from patients with a provoked primary event nor were there differences in outcomes.
VO was found in 11 (19.6%) of the 56 patients of which seven (12.5%) included extraluminal caval or iliac compression. Patients with VO were significantly younger than patients without VO (61.0 (IQR 32.0–69.0) versus 68.0 (IQR 59.5–72.0), p = 0.046). Apart from age there were no other differences between these groups. Based on the definition used, compression was seen only in the patients with VO: seven (63.6%) versus none (0.0%), OR 0.01 (95%CI 0.00–0.14), p < 0.001. No differences were seen regarding intraluminal post-thrombotic trabeculations (nine (81.8%) versus 37 (82.2%), OR 1.03 (95%CI 0.19–5.70), p = 1.000) or venous insufficiency (six (54.5%) versus 23 (51.1%), OR 0.87 (95%CI 0.23–3.27), p = 1.000). The Villalta scores did not differ between groups (Total Villalta: 5.11 ± 2.80 versus 5.49 ± 2.87, p = 0.639; objective Villalta: 4.00 ± 3.02 versus 3.53 ± 2.53, p = 0.748; and subjective Villalta score: 1.50 ± 1.51 versus 1.96 ± 1.92, p = 0.546. Results regarding PTS, PTS severity, and QoL were also comparable between patients with and without VO.