PMVT was previously thought to have an incidence of 1.8 persons per 100,000, according to autopsy studies such as Acosta et al’s16. With improvements in diagnostic modalities, the incidence rate has been upgraded to 2.7 persons per 100,000 17. Various etiological factors have now been identified in relation to PMVT. The most common etiology includes malignancy (27%) and cirrhosis (24%) 18. Myeloproliferative disorders (MPD), leukemia/lymphoma, inflammatory bowel disease, pancreatitis, postoperative issues (e.g., post-liver transplant, post-splenectomy), sepsis, connective tissue disorders, and various thrombophilic disorders are also common risk factors for PMVT 5,18. Amongst the thrombophilic states, primary MPD’s are the most common, in 30.5%19. Thrombosis of the larger distal portions of the mesenteric vein is mostly secondary to local factors, such as malignancy, pancreatitis and infection, while thrombosis that originates from the vena recta is most-commonly related to a prothrombotic state3. Infarction of the bowel mostly requires involvement of the venous arcades and vasa recta17,20.
Current guidelines recommend early anticoagulation for at least six months as the standard treatment for acute PMVT5,6. Following early anticoagulation, recanalization occurs in 35–45.4% 21. In the EN-Vie prospective study, wherein 102 patients were enrolled, the 1‐year recanalization rates were 38% and 61% for the portal and superior mesenteric veins, respectively22. However, complete recanalization was less frequent and was only achieved in 20% of patients (19/95) with cavernoma development in 19.9–- 40%21,22. Furthermore, thrombus resolution is rare in patients with higher degrees of PMVT, ascites, and the presence of more than one prothrombotic risk factor 5,22−24. In such an emergency situation, local CDT was done with success in some small-series studies, either through the transjugular route (with or without TIPS creation), a percutaneous transhepatic or transsplenic route, or a transileocolic venous route (either intraoperatively or indirectly via the superior mesenteric artery)7–10, 13,25–28. In a retrospective comparative study of 34 acute PMVT non-cirrhotic patients, Liu et al concluded that indirect thrombolysis via the SMA was safer and more effective than systemic thrombolysis (ST) 28. Another paper reported that the recanalization effect of direct thrombolysis is better than that of indirect treatment (14.3% partial recanalization)10. Hollingshead et al recommended a combined direct and indirect thrombolysis simultaneously for more extensive PMVT patents9. In this study, we started the adjunctive mesenteric arterial thrombolytic infusion in PMVT patients with peripheral mesenteric venules involvement at 3-5 days after the transhepatic treatment with partial recanalization achieved, in order to avoid high concentrations of urokinase retention in the intestinal mucosa, which might carry higher potential risk of intestinal bleeding and also to shorten the femoral arterial indwelling time and patients’ discomfort.
Smalberg et al 15 and Hollingshead et al 9reported major-procedure-related bleeding complications in 50% and 60% respectively of patients treated with local intravascular thrombolysis via the transhepatic approach and/or indirect thrombolysis via the SMA 9. Thereafter, the transhepatic approach was regarded as unsafe, and the transjugular approach (with or without TIPS creation) became the mainstream approach for direct local thrombolysis 9,29. It is worth noting that the dosages of thrombolytic agents used in these two studies (100,000-240,000 IU/hour urokinase concomitant with 1250 IU/hour heparin in Hollingshead’s series 9 and rtPA of 2–4 mg/hour in Smalberg’s series 15) were much higher than those of other series (60.000 IU urokinase or 1 mg rtPA per hour rtPA) 7,10,13 and the present study (10,000-60,000 IU/hour urokinase with 300-400 IU/hour). The different dosages could themselves explain the different bleeding complicating rates, rather than the different approach routes. Even in Rabuffi series 14, they adopted the transhepatic route to treat 3 acute PMVT patients by a 10-Fr atherectomy device and followed by infusion of 80,000-100,000 IU urokinase per hour without bleeding complication encountered. Accordingly, we can conclude that the major bleeding complication of the thrombolytic therapy is more dose-related other than the transhepatic route approach.
The rationale of creating a low pressure system in TIPS is to act as a vacuum for clot fragments and improve the effectiveness of thrombolysis in managing PMVT 30. In theory, TIPS creation in the non-cirrhotic patients is not physiological. Moreover, it is more difficult to create TIPS in the presence of portal vein thrombosis. For the safety of ensuing thrombolytic therapy, techniques with fewer needle puncture passes should be adopted. Surveying previous studies shows that the technical success rate of TIPS in patients with PMVT can be significantly variable, ranging from 35–83%11,25,26,30−34. Qi et al reported that TIPS was successfully placed in 35% (7/20) of their patients with MPV thrombosis, via a transjugular approach alone in 1 successful patient (5%) and a combined transjugular and transhepatic or transsplenic approach in the other 6 successful patients 26. Chen et al proposed a transhepatic balloon-assisted technique to facilitate TIPS creation in the MPV occluded cirrhotic patients and reported 77.8% technical success with exclusion of mesenteric venous occlusion 33. Fanelli et al used a thin (21 G) TIPS-set needle with multiple blind punctures under fluoroscopic guidance with technical success of 83% 25. In Luo et al’s series, TIPS placement was technically successful in 73.3% (11/15) of patients, and all successful cases had either a patent SMV or a large porto-porto collateral vein 11. The conclusions of such studies were that TIPS was not recommended in patients with a total fibrotic cord and/or without a large collateral vein or in those with extensive superior mesenteric vein thrombosis 34. Benmassaoud et al reported two major complications of subcapsular hematoma and hepatic encephalopathy during or after TIPS creation, out of a total of 22 patients 7. In our series, 100% technical success of the transhepatic approach was achieved, without any procedure-related major bleeding complications. Meanwhile, although patients with cirrhosis were excluded from the present study, none were excluded from this study due to thrombus extension, fibrotic cord of MPV or cavernoma formation.
Portal vein thrombosis is classified based on the clinical and imaging presentation (acute or subacute vs chronic; benign vs malignant, and intrahepatic vs extrahepatic extent). These classifications guide therapy and have prognostic implications 29. Although current guidelines recommend early anticoagulation as the standard treatment for acute PMVT 5,6, the definition of acute PMVT is ambiguous. Parikh et al 35 considered acute PMVT as symptoms develop < 60 days before presentation, and there is no clinical, radiological, or endoscopic evidence of portal hypertension or collateral circulation. Singal et al 36 stated that acute MVT is characterized by symptomatic presentation within 24 to 72 hours of thrombus formation with sudden onset of symptoms, whereas subacute MVT presents during days to weeks of nonspecific symptoms. Chronic PMVT usually presents with complications of portal hypertension or may be detected as an incidental finding on computed tomography (CT) imaging (28.1%) 23,36. As the symptoms of chronic PMVT may be acutely exacerbated due to thrombus progression into the peripheral mesenteric veins, it is imperative to reestablish porto-mesenteric blood flow as soon as possible. Benmassaoud et al proposed a stepwise protocol by using systemic anticoagulation or thrombolysis first and then followed by local CDT for treatment-resistant patients 7. In their series, the average duration before initiation of CDT was 4 days, stating that longer intervals would be associated with a decreased chance of recanalization, leaving the patient at risk of progressive intestinal ischemia and long-term sequelae of portal hypertension. As complete recanalization from systemic therapy was only achieved of 13.6% (3/22) of their patients 7, and our protocol of transhepatic CDT under ultrasonographic guidance puncture with tailored thrombolytic regimen carries few risks, it is our recommendation that primary local CDT should be started as soon as possible once the diagnosis of PMVT is made, even under the circumstance that the thrombus might be chronic. Two previous articles, focusing on managing the chronic non-cirrhotic portal venous thrombosis via TIPS and metallic stenting without infusions of thrombolytic agents 11,26, reported the technical success of 35% in one series 26 and 50% in the other series if the mesenteric vein were also involved. To our best knowledge, the present study reports the first experience of managing including the chronic PMVT by local CDT with a tailored dosage (e.g. 240,000 IU urokinase for pulse-spray injection and 60,000-30,000 IU per hour for even up to 30 days’ continuous infusion) without the need of intensive monitoring. The experience of clinical success to dissolve chronic thrombus is similar to some previous reports on chronic arterial occlusive disease 37 and chronic PTFE graft occlusion in hemodialysis patients 38.
Previous studies have shown recanalization rates of CDT for PMVT ranging from 52.3–94.1%, with complete recanalization of 6.3–52.9% 9,13,39−42. Klinger et al reported that the one- and two-year secondary PV patency rates in 17 consecutive acute non-cirrhotic PMVT patients were both 88.2% without significant difference in patients with TIPS-implantation at the end of thrombolysis compared to patients without TIPS-implantation (p=0.2) 13. In our series, the overall successful recanalization rate of the PMVT patients was 100% (15 patients) with complete recanalization in 80.0% (12/15 patients). The 2 patients with partial recanalization even after TIPS creation eventually showed re-occlusion of the PMV. All PMVT patients in the present study with complete recanalization showed good long-term patency. As a result, completely recanalizing the thrombosed PMV should be the goal of this treatment strategy with TIPS creation only for recanalization failure of the intra-hepatic portal flow in these non-cirrhotic PMVT patients. The overall one- and two-year secondary patency rates in our series were both 84.6%.
Firstly, our study was limited due to the retrospective, non-controlled study design and a small study population of the non-cirrhotic PMVT. Unfortunately, this is the reality when studying a rare disease associated with significant morbidity, mortality, and limited therapeutic options. Secondly, thrombectomy devices were not used to accelerate the clearance of acute or subacute thrombi in our study, as they are expensive and a clinically acute presentation may be actually be caused by a chronic thrombus with acute clinical exacerbation. The real clinical benefits of the thrombectomy devices in these patients may be limited. Lastly, the long-term vascular patency, especially of the partially recanalized PMV, cannot be determined from such a small patient group.