Chapter 24: Management of Mesenteric and Portal Vein Thrombosis in Nontransplanted Patients

The development of mesenteric venous thrombosis (MVT) or portal vein thrombosis (PVT) heralds potentially devastating consequences in patients with liver cirrhosis. Not only are such individuals at risk for intestinal ischemia and portal hypertensive complications,1 but liver transplant status and surgical outcome may be adversely affected as well²; timely and effective management of MVT and PVT is thus of paramount importance. Although standard medical and surgical therapies have constituted the traditional management approaches to MVT and PVT, newer, minimally invasive interventional radiologic (IR) treatment strategies have successfully addressed this condition while affording a targeted approach associated with acceptable safety and efficacy. The purpose of this chapter is to review the current status of IR therapies for MVT and PVT, with a focus on patient selection, procedure technique, and interventional outcomes.

Mesenteric and Portal Vein Thrombosis

Epidemiology and Classification

Partial or complete PVT complicates approximately 5% to 25% of liver cirrhosis cases³ and is primarily related to stagnant portal venous blood flow in the setting of portal hypertension⁴ as well as hemostatic derangement. Although malignancy; inflammatory conditions such as diverticulitis, appendicitis, or pancreatitis; vessel injury from surgery; and hypercoagulable states may also underlie PVT,¹ hepatic cirrhosis is a dominant predisposing condition, present in approximately 30% of PVT cases.⁵ Moreover, the incidence of PVT increases with liver disease severity; PVT is uncommon in compensated liver cirrhosis but is more prevalent among decompensated cases requiring transplantation.^6,7

Portal vein thrombosis may also be a consequence of steal phenomenon caused by end-stage portosystemic shunt syndrome in which there is portal hypertension and a portosystemic collateral “stealing” blood from the portal vein and essentially taking over as the splanchnic venous outflow as PVT sets in.⁸

Acute PVT is new or sudden onset of thrombus and is characterized by a lack of collateral vessel formation. Chronic PVT is defined by venous occlusion with development of mature collateral pathways. In differentiating acute and chronic PVT, specific time frames are not compulsory for classification of disease, although acute thrombus typically refers to a clot 14 or less days old, and chronic thrombus refers to a clot 28 or more days old as per the deep venous thrombosis literature⁹; these time frames are not necessarily directly translatable to PVT, however, because cavernous transformation of the portal vein may occur as early as 6 to 20 days after thrombus development.¹⁰

Mesenteric venous thrombosis may develop exclusive of or contemporaneously with PVT; whereas primary MVT represents idiopathic thrombus formation, secondary MVT is related to underlying pathology, such as cirrhosis-related slow flow, inflammatory conditions, or prothrombotic states.¹¹ Interestingly, MVT caused by hypercoagulability typically begins in small peripheral vessels and progresses to involve larger central vessels, but other causes of MVT propagate central to peripheral.¹¹

Both MVT and PVT may be defined by anatomic location. One proposed classification scheme designates six thrombosis patterns outlined as follows: type 1, thrombus within intrahepatic portal vein only; type 2, thrombus within main portal vein only; type 3, thrombus within intrahepatic portal vein and main portal vein; type 4, thrombus within superior mesenteric vein; type 5, thrombus within superior mesenteric vein and main portal vein; and type 6, thrombus within superior mesenteric vein, main portal vein, and intrahepatic portal vein.² Associated varices (if any) are classified according to the thrombosis or occlusion of the mesenteric or portal venous system and the degree of portal systemic or portoportal collateralization ( Fig. 24.1; Table 24.1).⁸

Clinical Presentation, Diagnosis, and Sequelae

The presentation of acute MVT or PVT may be clinically silent, with a diagnosis made incidentally or upon surveillance imaging (which is commonly performed for hepatocellular carcinoma [HCC] detection in patients with cirrhosis) or may involve symptoms such as vague abdominal pain and diarrhea or fever and chills in the setting of septic thrombus.^1,11 Specific laboratory abnormalities are not routinely present because liver function is preserved by increased hepatic arterial flow; it is known that a decrease in portal venous blood flow results in an increase in hepatic arterial flow in a mechanism termed the hepatic arterial buffer response.¹³ Nonetheless, elevation nonspecific liver function test results may be present.¹ Chronic PVT is generally asymptomatic unless complications of portal hypertension or biliary obstruction by enlarged gastric antral, duodenal, or biliary veins—so-called portal cholangiopathy—are present.¹⁴ Preservation of liver function by collateral vessel perfusion averts laboratory abnormalities in chronic PVT.

Fig. 24.1 Classification of ectopic varices. Baseline labeled anatomy images to help interpret the images of the classification system. (They are the templates for the remainder of the figures.) The image demonstrates a representative portal or mesenteric vein branch (Port Circ) on the right and a representative systemic vein branch (Syst Circ) on the left of a cross-section through a bowel loop that is a representative of the gastrointestinal tract (GIT). Typical portal venous (splanchnic veins) branches would include the portal vein proper, mesenteric vein (and tributaries), and splenic vein. Typical systemic veins (but not confined to the examples given) include the inferior vena cava, gonadal veins, renal veins, and retroperitoneal and paravertebral veins. Varices (ectopic varices) are seen in the wall of the bowel. (a) The “ectopic varices” in this depicted instance is supplied and drained by portal collaterals (hollow white arrows) and is also drained (efferent collateral) by a portosystemic collateral (black arrow). (b) The “ectopic varices” in this depicted instance is supplied and drained by portal collaterals (hollow white arrows) and is not drained by a portosystemic collateral. The efferent collateral drainage is portal and not systemic. In both parts (a) and (b), there is no portal venous occlusion. (c) Overview of the classification system. Please see Table 24.1 for clarification. In short, type a is nonocclusive and is pressure driven (oncotic). Type a usually has some element of portosystemic collaterals (types a2 and a3) to decompress the higher portal pressure. Type b is the occlusive type and can have no portosystemic collaterals; the varices can simply be part of a portal to portal “bypass” of a focal occlusion (type b1); however, portosystemic collaterals can exist (types b2 and b3). (d) Illustration demonstrating type 1 ectopic varices without portal venous branch occlusion (type 1a) and with portal venous branch occlusion (type 1b). The portal venous branch can be any vein (location or size) in the portal circulation. This includes mesenteric vein and tributaries and portal vein tributaries as well as the main portal, mesenteric, and splenic veins. Obviously, balloon-occluded retrograde transvenous obliteration (BRTO) of these ectopic varices (type 1) is not feasible because, by definition, BRTO is via the portosystemic collaterals from the systemic venous side, and in type 1, there are no portosystemic collaterals. Any balloon obliteration would be from the portal venous side. In essence, type 1b can be applied to gastric varices (GV) in the presence of splenic vein thrombosis (segmental or sentinel portal hypertension) and absence of a gastrorenal shunt (GRS). BATO: balloon-occluded antegrade transvenous obliteration; HTN: hypertension.

Fig. 24.1 (e) Illustration demonstrating type 2 ectopic varices without portal venous branch occlusion (type 2a) and with portal venous branch occlusion (type 2b). The portal venous branch can be any vein (location or size) in the portal circulation. BRTO of these ectopic varices (type 2) is feasible because, by definition, BRTO is via the portosystemic collaterals from the systemic venous side, and in type 2, there are rudimentary portosystemic collaterals. Rudimentary means that it is not the main efferent outflow of the ectopic varices. The main efferent outflow of the ectopic varices in type 2 is portal and not portosystemic. Flow in the existing portosystemic collaterals may be minimal and may even fluctuate. (f) Illustration demonstrating type 3 ectopic varices without portal venous branch occlusion (type 3a) and with portal venous branch occlusion (type 3b). The portal venous branch can be any vein (location or size) in the portal circulation. BRTO of these ectopic varices (type 2) is feasible because, by definition, BRTO is via the portosystemic collaterals from the systemic venous side, and in type 3, there are predominant portosystemic collaterals. Predominant means that it is the main efferent outflow of the ectopic varices. The main efferent outflow of the ectopic varices in type 3 is portosystemic and not portoportal. Used with permission from Saad WE, Lippert A, Saad NE, Caldwell S. Ectopic varices: anatomical classification, hemodynamic classification, and hemodynamic-based management. Tech Vasc Interv Radiol 2013;16:158–175.

Both MVT and PVT may be diagnosed with a high sensitivity and specificity using cross-sectional imaging such as contrast enhanced computed tomography (CT) or magnetic resonance (MR) imaging15; these studies generally reveal a filling defect in the portal venous system accompanied by atypical or heterogeneous hepatic parenchymal enhancement in acute PVT and show a diminutive or absent portal vein replaced by serpiginous collateral vessels in chronic PVT. Color Doppler ultrasonography may also be used¹⁶ and demonstrates hyperechoic thrombus within the portal venous system as well as lack of blood flow in acute PVT; chronic PVT findings of hepatic hilar collateral veins are similar to those with CT or MRI. In select instances, mesenteric arteriography can assist in diagnosing small peripheral vein thrombosis that is beyond the imaging resolution of cross-sectional modalities.¹⁷ It is important to distinguish bland MVT or PVT from tumor invasion, which may occur in the setting of HCC; distinguishing features of tumor invasion include vessel distension, casting, filling defect, arterial enhancement or internal color Doppler flow, and contiguity with the intrahepatic tumor.¹⁸ Detection and diagnosis of HCC obviously affect clinical management.

Both MVT and PVT may be associated with several clinically significant consequences, including intestinal ischemia, portal hypertension with variceal hemorrhage, and portal cholangiopathy. Bowel infarction is a particularly devastating occurrence and is suggested by abdominal pain of insidious onset and severity disproportionate to examination findings; overt or occult gastrointestinal (GI) bleeding may also be present.11 Portal hypertension from chronic PVT may spur variceal hemorrhage, a life-threatening complication associated with immediate mortality rate ranging from 5% to 8% when uncontrolled and up to a 20% overall mortality rate within 6 weeks.¹⁹ Associated varices (if any) are classified according to the thrombosis or occlusion of the mesenteric or portal venous system and the degree of portal systemic or portoportal collateralization ( Fig. 24.1; Table 24.1).⁸ Portal cholangiopathy may result in obstructive jaundice or cholangitis requiring biliary drainage.¹⁴ In the long term, PVT also negatively impacts liver transplant patients; not only are auxiliary maneuvers (e.g., intraoperative thrombectomy or jump graft creation) or advanced techniques (e.g., renoportal anastomosis, cavoportal hemitransposition, multivisceral transplantation) required at the time of orthotopic liver transplant (OLT) surgery depending on the extent of clot formation, but posttransplant mortality risk is also increased.²⁰

Conventional Medical and Surgical Therapies

Systemic anticoagulation represents the standard first-line therapy for acute MVT and PVT; correction of underlying causal factors should also be pursued. Current treatment recommendations advise for a 3- to 6-month anticoagulation course or long-term anticoagulation in individuals with persistent predisposing risk factors.¹ However, although systemic anticoagulation may result in portal vein recanalization in 40% to 70% of cases,^7,21,22 it does not improve portal hemodynamics, thus contributing to thrombus progression in a small percentage of cases.⁴ Moreover, its use may be precluded in individuals with cirrhosis and gastroesophageal variceal bleeding risk. In the setting of chronic PVT, systemic anticoagulation may be used to prevent recurrent thrombosis but should not be initiated before preventive, prophylactic treatment of varices using beta-blockers or endoscopic therapy.¹ Of note, septic MVT or PVT mandates intravenous (IV) antibiotic therapy.

Surgical management of MVT or PVT is not routinely pursued in the absence of profound mesenteric ischemia evidenced by transmural bowel infarction or peritonitis.²³ When clinical signs and imaging features of intestinal necrosis are present, emergent laparotomy and segmental resection are pursued for removal of nonviable bowel segments.²⁴ As a means of conserving viable intestinal segments, 24-hour delayed follow-up “second look” laparotomy has been proposed to avoid primary resection of bowel that may be viable.²⁵ Open thrombectomy may also be pursued at the time of surgery,^26,27 although it may be technically difficult to remove all of the thrombus, particularly from small branches of the mesenteric and portal veins. Despite advances in medical and surgical therapy, MVT and PVT remain potentially lethal, particularly in the setting of bowel infarction, with mortality rates up to 30%.^1,28

Interventional Radiologic Management Approaches and Rationale

Interventional radiologic treatment approaches to MVT and PVT may aim to clear thrombus by several means, including flow-enhanced dispersal, thrombolytic agent–assisted dissolution, direct mechanical disruption, maceration, aspiration, or stent muralization or recanalization. Different interventional approaches allow for these various management strategies and may be used in isolation or combination to optimize therapy.

Transjugular Intrahepatic Portosystemic Shunt Creation

The success of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertensive complications²⁹ has prompted translation of this procedure from traditional indications, such as medically refractory gastroesophageal variceal hemorrhage³⁰ and intractable ascites³¹ or hepatic hydrothorax,³² to newer indications, such as early use in variceal bleeding patients³³ as well as application of TIPS for the treatment of PVT. This developing indication for TIPS may enhance the care of patients with cirrhosis and liver transplant candidates by averting PVT complications and ensuring conventional operative approaches to transplantation, which may be significantly complicated or even precluded in the setting of partial or complete PVT,⁴ as well as optimizing posttransplant survival, which is negatively impacted by PVT.²⁰ TIPS functions to clear clot by providing portal venous access for thrombolytic agent–assisted dissolution, direct mechanical disruption, maceration, or aspiration and by establishing a low-pressure outflow conduit for splanchnic blood volume and concomitantly increasing portal venous flow, which favorably assists the dissolution of PVT in patients with cirrhosis.

When applied for the purpose of direct pharmacomechanical PVT clearance, the TIPS approach into the portal vein confers advantages of theoretically less bleeding risk because of a lower risk of liver capsular transgression, applicability to patients with ascites, larger caliber and more longitudinal access of entry to the portal vein, and a large-bore outflow pathway for clot clearance (e.g., Pullback Fogarty Embolectomy) in cases of PVT compared with transhepatic portal venous access.³⁴ The main disadvantages of the TIPS approach are poor access to peripheral intrahepatic portal vein branches³⁴ and potentially greater technical difficulty in obtaining portal venous access compared with ultrasound-guided transhepatic puncture if intrahepatic branches are thrombosed. Another disadvantage of TIPS during pharmacolysis of PVT is that after flow is established, the TIPS may be the predominant outflow and prevent chemical agents from bathing the “end artery” portal vein branches.

Increased portal venous flow velocity after TIPS favorably affects thrombus dissolution. Although the biochemical mechanism of fibrinolysis is well described, the role of hemodynamic factors in this process is often neglected. Originally described by Virchow, flow stasis contributes to vascular thrombosis by reducing laminar clearance of local thrombin and fibrin monomer.³⁵ Experimental and mathematical models have demonstrated that the shear forces exerted by circulating blood promote mechanical dissolution of nonocclusive thrombi.^36–38 Higher velocity blood flow results in increased rates of mechanical degradation, as well as increased deposition of physiologic fibrinolytic agents.³⁹ The improved portal venous flow after TIPS creation helps dissolve existing thrombus through flow-enhanced dissolution and may obviate the need for concomitant use of anticoagulation^7,22,40 or mechanical or thrombolytic techniques.⁴¹

Direct Portal and Mesenteric Vein Thrombolysis and Thrombectomy

A direct transhepatic approach to the portal and mesenteric venous system confers definitive access to clot for potential clearance using thrombolysis or thrombectomy (or both). Catheter-directed thrombolysis (CDT) aims to dissolve thrombus in a targeted fashion through direct intraclot fibrinolytic agent infusion. Contemporary CDT primarily uses recombinant tissue plasminogen activator (TPA), a protein that activates the serine protease enzyme plasmin and initiates fibrinolysis by plasmin-induced degradation of crosslinked fibrin mesh within blood clot, which is consequently more susceptible to further enzymatic proteolysis. The glycoprotein enzyme urokinase and the beta-hemolytic streptococcus glycoprotein streptokinase have also been used in thrombolytic therapy but represent more historical agents; newer fibrinolytic agents that have greater fibrin specificity are also commercially available. CDT has been applied in multiple clinical settings and has a firm basis in systemic arterial and venous recanalization42–45 as well as hemodialysis graft clot dissolution,⁴⁶ among other applications. The efficacy of therapy is greater in acute or soft thrombus compared with chronic, organized clot because of reduced platelet composition and fibrin cross-linking,⁴⁷ and thrombolysis may be augmented by concomitant techniques such as ultrasound-accelerated fibrinolytic agent deposition using systems such as the EkoSonic Endovascular System (EKOS Corporation, Bothell, Washington).

Catheter-directed thrombolysis may be supplemented with mechanical thrombectomy, which represents an attractive means to disrupt thrombus caused by more rapid clot clearance compared with enzymatic thrombolysis.⁴⁸ Mechanical thrombectomy typically uses clot disruption, maceration, or aspiration using commercially available guidewires, compliant (e.g., Fogarty) or noncompliant (e.g., angioplasty) balloons, rotating devices such as the Arrow-Trerotola percutaneous thrombectomy device (Arrow International, Asheboro, North Carolina) or Trellis Peripheral Infusion System (Covidien, Dublin, Ireland), or rheolytic devices that disrupt the clot through saline injection and aspiration such as the AngioJet Ultra Thrombectomy System (Bayer Healthcare, Leverkusen, Germany), among others. Disadvantages of mechanical devices include risk of vessel injury and cost.⁴⁸

A transhepatic portal venous approach to portal and mesenteric vein thrombolysis and thrombectomy confers benefits of direct access to the portal vein, technically easier access to the peripheral intrahepatic portal vein branches,³⁴ and more straightforward portal venous access compared with TIPS if intrahepatic branches are thrombosed because direct sonographic guidance may be used instead of solely fluoroscopy. Downsides of transhepatic portal venous access include increased bleeding risk caused by liver capsular traversal, access size limitation, and angulated entry into the main portal vein.³⁴

Indirect Mesenteric and Portal Vein Thrombolysis via the Superior Mesenteric Artery

In addition to direct CDT of MVT and PVT, thrombolysis may be undertaken via an indirect approach using the superior mesenteric artery (SMA) as a conduit to deliver thrombolytic agent to the portal and mesenteric venous clot via transcapillary traversal. Potential benefits of this approach include technical simplicity; theoretically reduced bleeding risk because of avoidance of liver parenchymal puncture; and bathing of small mesenteric capillaries and venules with fibrinolytic agent, allowing restoration of small branch vessel patency.⁴⁹ Drawbacks to this procedure include lack of direct fibrinolytic agent infusion into the thrombus, potentially increasing length of thrombolysis,⁵⁰ as well as the potential for inducing GI bleeding, especially in the setting of borderline intestinal infarction because of venous engorgement.

Portal Vein Recanalization for Chronic Occlusion

Chronic portal vein occlusion, characterized by fibrotic, shrunken, and cordlike transformation of the portal vein, represents a major therapeutic challenge. Despite cavernous transformation or formation of hepatic hilar collateral vessels in many cases, the splanchnic blood volume may not be adequately drained, rendering patients at risk for portal hypertensive complications. IR recanalization techniques may be used to reestablish patency in chronically occluded venous systems; in the setting of chronic PVT or portal vein occlusion, this may be pursued with the intent of relieving portal hypertension and its complications or reinstating liver transplant candidacy.

Patient Selection

Procedure Indications

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