Inflammatory bowel diseases are associated with an increased risk of vascular complications. The most important are arterial and venous thromboembolisms, which are considered as specific extraintestinal manifestations of inflammatory bowel diseases. Among venous thromboembolism events, portal vein thrombosis has been described in inflammatory bowel diseases. We report three cases of portal vein thrombosis occurring in patients with active inflammatory bowel disease. In two of them, hepatic abscess was present. Furthermore, we performed a systematic review based on the clinical literature published on this topic.
In inflammatory bowel diseases (IBD) there is a high incidence of thromboembolic complications, as a consequence of hypercoagulability status. Thrombosis of the splenic-mesenteric-portal system is a rare event; however, due to advances in diagnostic tools, many cases of mesenteric or portal vein thrombosis have recently been described in IBD patients; its incidence seems to be higher than among the general population [
An in-depth search in PubMed was based on four search terms: “inflammatory bowel diseases” OR “Crohn’s disease” OR “ulcerative colitis” AND “portal vein thrombosis” (MeSH terms). Review articles and case reports not regarding this topic were excluded. The remaining articles were categorised by topic and summarised.
Table
Characteristics of the reports of the literature regarding the portal vein thrombosis in inflammatory bowel disease.
Author | No. of patients |
Biochemical risk factors for PVT | Therapy | Outcome |
---|---|---|---|---|
Maconi | 8 (6 CD; 2 UC) | (i) Lupus anticoagulant (1) |
Anticoagulant (4) | Recanalization |
Lefevre | 1 (UC) | Ht for prothrombin-G20210A mutation | Oral anticoagulant | Recanalization |
Jackson | 3 (1 UC; 2 CD) | Lupus anticoagulant + Ht for factor V Leiden mutation (1 pt) | Oral anticoagulant | NA |
Ibele | 1 (UC) | None | Oral anticoagulant | Recanalization |
Di Fabio | 1 (CD) | None | Thrombobectomy + oral anticoagulant | Recanalization |
Aguas | 1 (CD) | None | Heparin | Recanalization |
Palkovist | 1 (UD) | None | LMWH | Portal cavernoma |
Latzman | 1 (CD) | Ht for prothrombin-G20210A mutaion | Thrombobectomy + oral anticoagulant | Recanalization |
Hatoum | 3 (CD) | Factor V Leiden mutation (1) | LMWH + oral anticoagulant (1 pt) | Recanalization |
Shaked | 1 (CD) | None | Heparin + oral anticoagulant | Recanalization |
Guglielmi | 1 (CD) | None | Thrombolysis + LMWH | Recanalization |
Verna | 1 (UC) | Elevated FVII | No therapy | Atrophy of left hepatic lobe |
Mijnhout | 1 (CD) | 1 (CD) | Heparin + oral anticoagulant | Recanalization |
Fichera | 4 (1 CD, 3 UC) | Ht for prothrombin-G20210A mutation | Oral anticoagulant | Recanalization |
Remzi | 41 (26 UC, 15 IC) | NA | Anticoagulation (8 pts) | Recanalization (5/13 pts) |
Hagimoto | 1 (UC) | NA | Thrombolysis + oral anticoagulant | Recanalization |
Schafer | 1 (CD) | None | Thrombolysis | Recanalization |
Farkas | 1 (UC) | None | Oral anticoagulant | Recanalization |
Tsujikawa | 1 (CD) | None | Thrombolysis + heparin + oral anticoagulant | Recanalization |
Tung | 1 (CD) | None | LMWH | Recanalization |
Miyazaki | 1 (UC) | None | Thrombolysis + oral anticoagulant | Recanalization |
Irving | 4 (CD) | None | LMWH + oral anticoagulant | Recanalization |
Mathieu | 1 (CD) | Acquired protein C deficiency | LMWH | Recanalization |
Crowe | 1 (CD) | None | Oral anticoagulant | Recanalization |
Brinberg | 1 (CD) | None | Heparin | Recanalization |
Ht: heterozygosis, LMWH: low molecular weight heparin, IC: indeterminate colitis, UC: ulcerative colitis, CD: Crohn’s disease, and MTHFR: methyl-tetrahydrofolate reductase.
A 66-year-old woman, with a 10-year diagnosis of inflammatory ileal Crohn’s disease (CD), on treatment with budesonide for active disease, was admitted to our unit for fever with chills. There was no history of previous thromboembolic events. Physical examination revealed tachycardia, without any abdominal tenderness or masses; blood tests showed leucocytosis (13000 white blood cells (WBC)/mm3), thrombocytosis (360000 platelets/mm3), and increased ESR (25 mm/Ih) and PCR (18 mg%); 3 blood cultures isolated
Abdominal US showing a portal vein thrombosis extended to intrahepatic branches.
Residual portal cavernoma showed at CT scan.
A 41-year-old woman with a family history of IBD was admitted to our unit because of the onset of bloody diarrhoea. There was no history of previous tromboembolic events. Clinical examination showed fever (38.5°C), hypotension (80/50 mmHg), tachycardia (115 beats/minute), tachypnea, and abdominal distension without bowel movements; blood tests showed leucocytosis (18000 white blood cells (WBC)/mm3) and increased ESR (30 mm/Ih) and PCR (25 mg%). An abdominal plain X-ray showed a dilation of the transverse colon (diameter 6 cm), while an abdominal US Doppler and CT scan showed ascites, complete thrombosis of portal, mesenteric and splenic veins, and wall thickening of the large bowel. The patient received steroids, ciprofloxacin, and metronidazole. Coagulation study showed heterozygosis for MTHFR gene mutation; antithrombin, protein C and S activity, plasma homocysteine level, PT, and aPTT were normal; anticardiolipin and anti-phospholipid antibodies were negative; no mutation of the JAK-2 gene was found. During hospitalization the patient complained of acute dyspnoea, with oxygen desaturation. A chest CT scan showed pulmonary embolism. Treatment with LMWH (1 mg/kg/twice daily) was started, with progressive disappearance of respiratory complaints. Colonoscopy with biopsy, performed after resolution of the colon dilation, diagnosed an ulcerative pancolitis. The patient continued treatment with steroids at tapering doses and started azathioprine. A US Doppler after 1 month showed complete recanalization of portal three. LMWH was discontinued after 3 months. A US Doppler control after 6 months showed patent portal tree.
A 52-year-old male with a 20-year history of small bowel CD resected twice, after recent detection of stenotic recurrence, was admitted to our unit because of the onset of fever and diarrhoea. No history of previous thromboembolic events was present. Clinical examination showed fever (39°C) and painful abdominal distension; blood tests showed leucocytosis (16000 white blood cells (WBC)/mm3) and increased ESR (22 mm/Ih) and PCR (24 mg%). A CT scan showed gas in the portal vein and a liver abscess (Figure
CT scan showing gas in portal vein and a liver abscess.
These three cases of portal thrombosis in IBD show that this complication, despite its rarity, needs to be searched for in case of clinical suspicion, and that treatment with LMWH leads to complete resolution of this complication.
Portal/mesenteric vein thrombosis, particularly in the nonsurgical setting, is a rare complication in IBD patients [
Portal/mesenteric vein thrombosis in IBD, seen in a study performed by the Mayo Clinic, was reported in 1.3% of cases, with a mortality rate of 50% [
Maconi et al. [
Portal thrombosis occurs more frequently in the setting of abdominal surgery [
PVT has been seen in UC patients following restorative proctocolectomy [
Portal/mesenteric vein thrombosis, and more generally VTE, has been considered a manifestation which seems to be related to intestinal inflammatory activity. Indeed, in a different chronic inflammatory disease like Rheumatoid Arthritis, in which there is no intestinal inflammation, there is no increased incidence of PVT compared to the general population [
The causes of portal/mesenteric thrombosis in IBD are manifold; in most patients, recognized acquired prothrombotic factors can be identified, such as inflammation, immobilization, extent of colon disease, surgery, central catheters, corticosteroids, and smoking [
On the other hand, thromboembolic complications in IBD, such as PVT, may be associated with coagulation abnormalities, which are induced by chronic bowel inflammation [
Several kinds of presentation of portal/mesenteric vein thrombosis have been reported: IBD flares and sepsis (especially perioperative) have been more frequently described; however, other rare modalities reported are variceal bleeding (VB) and hepatic portal venous gas (HVPG) [
Thromboembolic complications of IBD are by no means benign: the mortality rate has been reported to be as high as 22%–25% [
The most widely recognized pathophysiological factor of PVT is the presence of ulceration and the loss of integrity of the normal mucosa barrier in the bowel, which may result in microbial invasion or translocation of the portal vein system, with seeding in the parenchyma giving rise to portal pylephlebitis—defined as septic thrombophlebitis of the portal vein or of its tributaries—and PVT.
However, the presence of portal venous gas (PVG) associated with PVT could be a rare but serious, even catastrophic condition in IBD patients [
PVG in IBD patients can be caused by mucosal damage alone, or it can occur in combination with bowel distension, sepsis, and invasion by gas-producing bacteria, or after colonoscopy, upper gastrointestinal barium examination, barium enema, or blunt abdominal trauma. PVG is not always a surgical condition, and its treatment should be based on the underlying disease and the patient’s current clinical condition [
Regarding diagnosis of PVT in IBD patients, abdominal US with colour Doppler proves crucial. However, CT scan is more sensitive than US (which is more operator dependent and gives results that are less reproducible than those of CT) for detecting a thrombus within the splenic and mesenteric veins, and therefore it should be the preferred imaging technique for detecting both thrombi and pericolonic abscesses, especially in a setting of pylephlebitis [
Anticoagulants, such as LMWH and warfarin, are mainstays of primary therapy, even in the setting of gastrointestinal bleeding [
Other therapeutic approaches for acute portal/mesenteric vein thrombosis are, in extreme cases, surgical interventions, thrombolysis, and intravascular thrombectomy devices [
Minimizing modifiable risk factors is also a mainstay of therapy. Smoking, oral contraceptives, and hormone replacement therapy should be discontinued, and prolonged immobility should be avoided as far as possible [
Summing up, whether or not to anticoagulate patients with IBD and PVT remains controversial: certainly, anticoagulation in the setting of active IBD may result in increased haemorrhage risk. Those patients whose portal/mesenteric vein thrombosis developed in the setting of significant systemic inflammation should be treated on an individual basis [
In conclusion, portal/mesenteric vein thrombosis proves to be more frequent in IBD patients than in healthy controls, and among IBD patients this complication occurs more frequently in the setting of abdominal surgery. Several factors, inherited or acquired, related or not to IBD, seem to be involved in its pathogenesis. Abdominal US is the first-line technique to detect portal/mesenteric vein thrombosis, though, to date, CT scan remains the gold standard technique. To date, there is no proved effective treatment for pylephlebitis and for portal/mesenteric vein thrombosis in IBD, as the natural history of these conditions is not well defined. However, in IBD patients, especially ones with bloody diarrhoea, there is still a controversy as to whether anticoagulation should be maintained lifelong, just as there is insufficient information about the timing and duration of treatment with anticoagulation in the subset of IBD patients without known coagulation disorders.
The authors declare that they have no conflict of interests.