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Long-term anticoagulation (AC) in patients with portal vein thrombosis is recommended by international guidelines to improve recanalization rates.
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In this study, long-term AC was associated with a trend towards higher portal vein thrombosis (PVT) regression rates, which attained statistical significance in patients with decompensated cirrhosis.
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Furthermore, long-term AC was associated with significant improvements in hepatic synthesis function (albumin).
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In patients with liver cirrhosis AC appears to be safe, as no AC-associated bleeding events occurred in patients with conventional AC and only one bleeding event in DOAC patients.
Introduction
Patients and methods
Study design and inclusion of subjects
Clinical and radiological parameters
Laboratory parameters
Definitions, time points and groups
Statistics
Results
Patients’ characteristics
Patients: n = 51 (100%) | |||
---|---|---|---|
Age (years)
| 52.9 ± 12.5 |
NSBB
| 22 (43.1%) |
Gender (M/F, %M)
| 32/19 (62.7%) |
PPI
| 45 (88.2%) |
Etiology of liver disease
|
Ascites
| 34 (66.7%) | |
Alcohol | 24 (47.1%) |
Overt HE
| 7 (13.7%) |
Viral | 6 (11.8%) |
Bilirubin (mg/dl)
| 1.78 (1.88) |
Other | 21 (41.1%) |
Albumin (g/dl)
| 33.3 ± 7.5 |
Child-Pugh A
| 14 (27.5%) |
INR
| 1.45 ± 0.32 |
Child-Pugh B
| 19 (37.3%) |
CRP (mg/dl)
| 1.26 (2.99) |
Child-Pugh C
| 18 (35.2%) |
Platelets (G/l)
| 113 (175) |
Child-Pugh score
| 8.6 ± 2.7 |
Severity of PVT
| |
MELD
| 13.6 ± 6.5 | Partial PVT | 27 (52.9%) |
Diabetes
| 5 (9.8%) | Complete PVT | 24 (47.1%) |
Arterial hypertension
| 6 (11.8%) |
Follow-up (months)
| 44.1 (14.0–79.1) |
Varices
| 39 (76.5%) | Duration of anticoagulation (months) in n = 16 patients | 12.0 (8.7–29.0) |
Previous variceal bleeding
| 21 (41.2%) |
Clinical presentation at PVT diagnosis
Early anticoagulation and regression rates of PVT
Long-term anticoagulation and outcome of PVT
Long-term anticoagulation and outcome of PVT in patients with decompensated cirrhosis
No long-term anticoagulation (n = 29) | Long-term anticoagulation (n = 10) | p-value | |
---|---|---|---|
Regression/resolution of PVT | 7 (24.1) | 7 (70.0) | p = 0.031 |
Stabilization of PVT | 11 (37.9) | 1 (10.0) | |
Progression of PVT | 11 (37.9) | 2 (20.0) |
Effects of anticoagulation on serum transaminases
Impact of anticoagulation on ascites control and liver synthetic function
Safety of anticoagulation in patients with non-malignant PVT
Anticoagulation (n = 16) | No anticoagulation (n = 35) | p-value | |
---|---|---|---|
Bleeding episodes
| 0 | 16 | – |
Patients experiencing bleeding
| 0 (−) | 8 (22.9%) | 0.045 |
Bleeding sites
| |||
Gastric varices | 3 (19%) | – | |
Esophageal varices | 6 (38%) | ||
Gastric angiodysplasia | 1 (6%) | ||
Esophageal ulcus post EBL | 2 (13%) | ||
Portal hypertensive gastropathy | 2 (12%) | ||
Duodenal ulcus | 2 (12%) |
DOAC treatment for splanchnic vein thrombosis
Patients: n = 10 (100%) | |||
---|---|---|---|
Age (years)
| 50 ± 18 |
Previous variceal bleeding
| 2 (20%) |
Gender (M/F, %M)
| 2/8 (20%) |
Bilirubin (mg/dl)
| 0.49 (0.31) |
Liver cirrhosis
| 3 (30%) |
Albumin (g/dl)
| 39.1 ± 5.0 |
Occlusion (partial/complete, % complete)
| 4/6 (60%) |
INR
| 1.21 ± 0.30 |
Extension
|
DOAC used
| ||
V. portae
| 4 (40%) | Edoxaban (30 or 60 mg once daily) | 4 (40%) |
V. portae + V. mes. sup | 2 (20%) | Apixaban (5 mg twice daily) | 3 (30%) |
V. portae + V. mes. sup. + V. lienalis | 3 (30%) | Rivaroxaban (10 mg once daily) | 2 (20%) |
V. lienalis
| 1 (10%) | Dabigatran (110 mg twice daily) | 1 (10%) |
Varices at treatment start
| 8 (80%) |
Follow-up on DOAC treatment (months)
| 9.2 (5.4–13.7) |
Outcome
| |||
Regression/resolution of PVT | 2 (20%) | ||
Stable PVT including patients with unchanged cavernous transformation of portal vein | 8 (80%) | ||
Bleeding events during DOAC treatment | 1 (10%) |
Review of the literature on the course of PVT and efficacy of anticoagulation
Study | Study design | Patients with PVT | Child A/B/C | Partial/complete | Anticoagulation given | Follow-Up | Improvement/Recanalization | Bleeding | Conclusion |
---|---|---|---|---|---|---|---|---|---|
Francoz C, Gut 2005 [11] | Prospective cohort study | 29/251 | 4/19/6 | 20 (69.0%)/ 9 (31.0%) | 19 (65.5%) received AC ([LMWH:nadroparin 5700 U/day]/VKA: INR 2–3) 10 (34.5%) did not receive AC | 12.1 m | 8/19 (42.1%) 0/10 (0%) | 1 (bleeding from post-ligation ulcer) | PVT screening on OLT list AC is safe and impacts recanalization |
Luca A, Radiology 2012 [8] | Prospective cohort study | 42/42 | Mean CPS: 8.1 | 42 (100%)/ 0 (−) | 0 (−) received AC / 42 (100%) did not receive AC | 27 m | (−) 19 (45%) | n/r | Partial PVT improved spontaneously in 45% Progression was not associated with outcome |
Nery F, Hepatology 2015 [9] | Prospective cohort study | 118/1243 | 863/380/0 | 101 (85.6%)/ 17 (14.4%) | 6 (5.1%) received AC (n/r which anticoagulation)/ 112 (94.9%) did not receive AC | 47 m | n/r | n/r | PVT development is associated with liver disease severity PVT does not lead to further progression of liver disease |
Senzolo M, Liver Int 2012 [10] | Prospective cohort study | 56/56 | Treated: 11/16/8 Control: 5/9/7 | 24 (68.6%)/ 11 (31.4%) | 33 (58.9%) received AC (LMWH:nadroparin 95 U anti-Xa/kg/day) 21 (37.5%) did not receive AC | 21.6 m | 21/33 (63.6%) 1/21 (4.8%) | 3 (epistaxis, haematuria, ICB) | Anticoagulation (and TIPS) achieves good chance of repermeation and decreases PHT-related complications and progression |
Amitrano, J Clin GE 2010 [12] | Prospective cohort study | 39/39 | B/C: 46.4% | 23 (82.1%)/ 5 (17.9%) | 28 (71.8%) received AC (LMWH: enoxaparin 200 U/kg/day) 11 did not receive AC | 11 m | 21/28 (75%) n/r | 2 (Mild PHG-related anemia) | LMWH is safe and effective for cirrhotic patients with PVT |
Delgado MG, CGH 2012 [13] | Retrospective cohort study | 55/55 | 25/21/9 | 41 (74.5%)/ 14 (25.5%) | 55 (100%) received AC (LMWH/VKA) | 19 m | 33/55 (60%) Rethrombosis in 21 (38.5%) | 11 (variceal bleeding, GI-bleeding, others) | AC is safe with recanalization rates of 60% and should be maintained to prevent Re-PVT |
Werner KT, DigDisSci 2013 [14] | Retrospective cohort study | 69/537 | n/r MELD: 7–29 | n/r | 28 (40.6%) received AC (warfarin: INR: 2–3)/ 41 did not receive AC | 10.1 m | 23/28 (82%) | 1 (vaginal) | AC is safe and effective in patients with ESLD awaiting OLT |
Cui SB, Eur J GH 2015 [19] | Prospective randomized cohort study | 65/65 | CPS: 7.0 | 54 (83.1%)/ 11 (16.9%) | 65 (100%) received AC (LMWH: Enoxaparin) n = 34 1.5 mg/kg (q24h) n = 31 1 mg/kg (q12h) | 6 m | 51/65 (78.5%) | No VB 10 mild bleeding | Enoxaparin is effective/safe, 1 mg/q12h seems better than 1.5 mg/q24h for cirrhotic PVT |