partial or complete portal vein thrombosis ( pvt ) complicates 5 - 26% of liver cirrhosis cases , and is primarily related to stagnant portal venous blood flow in the setting of portal hypertension .
the presence of pvt negatively impacts liver transplant patients ; not only are auxiliary ( intraoperative thrombectomy or jump graft creation ) or advanced ( renoportal anastomosis , cavoportal hemitransposition , and multivisceral transplantation ) maneuvers required at the time of surgery depending on the extent of clot formation , but posttransplant mortality risk is also increased .
preoperative management of pvt and prevention of clot propagation is thus of paramount importance in liver transplant candidates . while systemic anticoagulation may result in portal recanalization in 40 - 70% of cases
, it does not improve portal hemodynamics ; thus contributing to thrombus progression in a small percentage of cases , and its use may be precluded in cirrhotic individuals with gastroesophageal variceal bleeding risk . by establishing a low pressure outflow pathway for splanchnic blood volume , transjugular intrahepatic portosystemic shunt ( tips )
creation can increase portal venous flow , and therefore represents an emerging approach for the dissolution of pvt in cirrhotic patients .
herein , we present a series of cases highlighting the utility of tips in producing and preserving portal venous patency in liver transplant candidates .
institutional review board approval is not required for small retrospective case studies at the authors hospital .
four patients with liver cirrhosis and partial pvt underwent tips creation for preservation of portal venous patency for potential liver transplantation between june 2010 and january 2012 .
three of four patients were formally listed with the united network for organ sharing ( unos ) ; one patient underwent tips in anticipation of future listing .
the indications for proactive early liver transplantation listing consisted of clinical signs of liver decompensation , namely occurrence of ascites and/or anasarca , in registered patients .
the study cohort consisted of one man and three women of mean age 58  11 ( range : 45 - 69 ) years .
causes of underlying liver disease included nonalcoholic steatohepatitis ( nash ) ( n = 2 ) , nonalcoholic fatty liver disease ( n = 1 ) , autoimmune hepatitis ( n = 1 ) .
child - pugh class included a ( n = 2 ) , b ( n = 1 ) , and c ( n = 1 ) ; and mean model for end - stage liver disease ( meld ) score was 14  4 .
pvt was associated with nonocclusive superior mesenteric vein ( smv ) thrombus in one case and partial splenic vein clot in one case .
none of the patients were on systemic anticoagulation due to grade 2 esophageal varices diagnosed endoscopically in all cases .
all patients were referred to interventional radiology ( ir ) for tips for the specific indication to preserve portal venous patency .
next , a rsch - uchida transjugular liver access set ( cook medical co. , bloomington in ) was used to access the right portal vein .
after portal vein catheterization and direct portal vein pressure measurement , balloon dilation of the hepatic parenchymal tract was performed .
subsequently , an 8 ( n = 1 ) or 10 mm ( n = 3 ) viatorr covered stent grafts ( w.l . gore and associates , flagstaff , az ) were deployed across the liver tract .
balloon angioplasty was performed using a 6 - 8 mm balloon . after measurement of final portal and right atrial pressures ,
clot dissolution techniques , including catheter - directed thrombolysis and mechanical thrombectomy , were not employed .
mean initial portosystemic pressure gradient ( psg ) was 18  7 ( range : 9 - 26 ) mmhg , and mean final psg was 8  1 ( range : 7 - 9 ) mmhg .
mean psg reduction was 10  8 ( range : 0 - 19 ) mmhg .
one patient developed mild hepatic encephalopathy ( west haven classification system grade 1 ) after tips .
following tips creation , patients underwent cross - sectional imaging at approximately 1-month post - procedure and then at 3 - 4 month interval to assess clot clearance and venous patency .
after tips , doppler ultrasound imaging performed at median 27  79 ( mean : 63 ) days post - procedure showed mean portal venous velocity increase from 13.5  6.7 ( range : 5.521.8 ) cm / s to 84.9  22.2 ( range : 68.0 - 116.8 ) cm / s , or an increase of 71.5  28.5 ( range : 46.2 - 111.3 ) cm / s .
pvt and concomitant smv or splenic vein thrombus spontaneously fully cleared in all cases within mean 79  47 ( range : 16 - 124 ) days post - tips [ figures 1 and 2 ] .
although no patient has yet undergone liver transplantation to date , as only 19% of liver transplantations occur in patients with meld scores < 15 in the geographic region of our transplant center , no recurrence of pvt has been identified after mean 460  199 ( range : 185 - 609 ) days of imaging follow - up . one patient died 620 days after tips due to sepsis .
the other three patients remain alive at mean 489  123 ( range : 358 - 602 ) days after tips .
( a and b ) contrast - enhanced axial magnetic resonance images reveal left intrahepatic portal vein thrombosis ( arrowhead ) and nonocclusive superior mesenteric vein clot ( arrowhead ) .
( c ) digital subtraction venogram performed after 10 mm transjugular intrahepatic portosystemic shunt creation demonstrates widely patent shunt .
( d and e ) contrast - enhanced magnetic resonance images taken 4-months later displays complete recanalization of left portal vein and superior mesenteric vein ( white arrowheads ) .
( a ) contrast -enhanced axial computed tomography image reveals nonocclusive thrombus at portal confluence ( white arrowhead ) and within splenic vein ( black arrowhead ) .
( b ) digital subtraction venogram performed after 10 mm transjugular intrahepatic portosystemic shunt creation demonstrates patent shunt , and shows presence of filling defect at portal confluence ( arrowhead ) .
( c ) contrast enhanced magnetic resonance images taken 6-months later displays complete recanalization of portal vein ( white arrowhead ) and splenic vein ( black arrowhead ) .
four patients with liver cirrhosis and partial pvt underwent tips creation for preservation of portal venous patency for potential liver transplantation between june 2010 and january 2012 .
three of four patients were formally listed with the united network for organ sharing ( unos ) ; one patient underwent tips in anticipation of future listing .
the indications for proactive early liver transplantation listing consisted of clinical signs of liver decompensation , namely occurrence of ascites and/or anasarca , in registered patients .
the study cohort consisted of one man and three women of mean age 58  11 ( range : 45 - 69 ) years .
causes of underlying liver disease included nonalcoholic steatohepatitis ( nash ) ( n = 2 ) , nonalcoholic fatty liver disease ( n = 1 ) , autoimmune hepatitis ( n = 1 ) .
child - pugh class included a ( n = 2 ) , b ( n = 1 ) , and c ( n = 1 ) ; and mean model for end - stage liver disease ( meld ) score was 14  4 .
pvt was associated with nonocclusive superior mesenteric vein ( smv ) thrombus in one case and partial splenic vein clot in one case .
none of the patients were on systemic anticoagulation due to grade 2 esophageal varices diagnosed endoscopically in all cases .
all patients were referred to interventional radiology ( ir ) for tips for the specific indication to preserve portal venous patency .
next , a rsch - uchida transjugular liver access set ( cook medical co. , bloomington in ) was used to access the right portal vein .
after portal vein catheterization and direct portal vein pressure measurement , balloon dilation of the hepatic parenchymal tract was performed .
subsequently , an 8 ( n = 1 ) or 10 mm ( n = 3 ) viatorr covered stent grafts ( w.l . gore and associates , flagstaff , az ) were deployed across the liver tract .
after measurement of final portal and right atrial pressures , completion shunt venography was performed .
clot dissolution techniques , including catheter - directed thrombolysis and mechanical thrombectomy , were not employed .
mean initial portosystemic pressure gradient ( psg ) was 18  7 ( range : 9 - 26 ) mmhg , and mean final psg was 8  1 ( range : 7 - 9 ) mmhg .
mean psg reduction was 10  8 ( range : 0 - 19 ) mmhg .
one patient developed mild hepatic encephalopathy ( west haven classification system grade 1 ) after tips .
following tips creation , patients underwent cross - sectional imaging at approximately 1-month post - procedure and then at 3 - 4 month interval to assess clot clearance and venous patency .
after tips , doppler ultrasound imaging performed at median 27  79 ( mean : 63 ) days post - procedure showed mean portal venous velocity increase from 13.5  6.7 ( range : 5.521.8 ) cm / s to 84.9  22.2 ( range : 68.0 - 116.8 ) cm / s , or an increase of 71.5  28.5 ( range : 46.2 - 111.3 ) cm / s .
pvt and concomitant smv or splenic vein thrombus spontaneously fully cleared in all cases within mean 79  47 ( range : 16 - 124 ) days post - tips [ figures 1 and 2 ] . although no patient has yet undergone liver transplantation to date , as only 19% of liver transplantations occur in patients with meld scores < 15 in the geographic region of our transplant center , no recurrence of pvt has been identified after mean 460  199 ( range : 185 - 609 ) days of imaging follow - up .
the other three patients remain alive at mean 489  123 ( range : 358 - 602 ) days after tips .
( a and b ) contrast - enhanced axial magnetic resonance images reveal left intrahepatic portal vein thrombosis ( arrowhead ) and nonocclusive superior mesenteric vein clot ( arrowhead ) .
( c ) digital subtraction venogram performed after 10 mm transjugular intrahepatic portosystemic shunt creation demonstrates widely patent shunt .
( d and e ) contrast - enhanced magnetic resonance images taken 4-months later displays complete recanalization of left portal vein and superior mesenteric vein ( white arrowheads ) .
( a ) contrast -enhanced axial computed tomography image reveals nonocclusive thrombus at portal confluence ( white arrowhead ) and within splenic vein ( black arrowhead ) .
( b ) digital subtraction venogram performed after 10 mm transjugular intrahepatic portosystemic shunt creation demonstrates patent shunt , and shows presence of filling defect at portal confluence ( arrowhead ) .
( c ) contrast enhanced magnetic resonance images taken 6-months later displays complete recanalization of portal vein ( white arrowhead ) and splenic vein ( black arrowhead ) .
the success of tips in the management of portal hypertensive complications has prompted translation of this procedure from traditional indications , such as medically refractory gastroesophageal variceal hemorrhage and intractable ascites or hepatic hydrothorax , to newer indications , such as early use in variceal bleeding patients . in this vein ,
the application of tips for the treatment of pvt represents another developing indication for this procedure , and may enhance the care of liver transplant candidates by ensuring conventional operative approaches to transplantation , which may be significantly complicated or even precluded in the setting of partial or complete pvt , as well as optimizing posttransplant survival , which is negatively impacted by pvt . in the current case series , partial pvt
was successfully cleared from the portal venous system as well as the superior mesenteric and splenic veins using tips to enhance portal venous flow .
although the biochemistry 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 .
experimental and mathematical models have demonstrated that the shear forces exerted by circulating blood promote mechanical dissolution of nonocclusive thrombi .
higher velocity blood flow results in increased rates of mechanical degradation , as well as increased deposition of physiologic fibrinolytic agents . in the cases herein
, portal venous flow was increased more than five - fold after tips to a mean of greater than 80 cm / s ; normal portal venous flow velocity approximates 16 - 40 cm / s .
the increased portal venous flow following tips creation may resolve any extant thrombus and obviate the need for concomitant use of anticoagulation and/or mechanical or thrombolytic techniques . as a final note , because complete pvt may damage vascular endothelium and increase probability for recurrent clot formation , early tips intervention should be considered while pvt is partial or nonocclusive to avert this risk .
our experience with flow - enabled pvt dissolution is corroborated by other series describing the effectiveness of tips in promoting portal venous patency .
two studies have addressed the specific application of tips for maintenance of portal venous patency in liver transplant patients . in 2012 ,
davola et al . , reported 100% portal vein patency in 15 patients with main trunk or branch vessel partial pvt who underwent tips followed by orthotopic liver transplantation ( olt ) at median 185 days postprocedure . in that study ,
a control group of eight patients with similar nonocclusive pvt who did not undergo tips showed 50% portal vein patency at olt performed at median 213 days after pvt diagnosis . in 2006 ,
, reported nearly 90% improvement in portal venous patency 2 - 45 months post - tips for treatment of varying degrees of nonocclusive pvt .
the findings of these studies are further supported by report of at least one individual case describing use of tips to keep the portal vein open for liver transplantation .
other large studies have confirmed the utility of tips in treating pvt in cirrhotic patients without specific intent as a bridge to liver transplantation . in 2011 , luca et al .
, described 87% patency improvement ( complete recanalization in 57% ) among 70 patients with nontumoral pvt who underwent tips . in 2011 , han et al .
, reported 100% portal venous patency after tips in 43 patients with varying degrees of pvt .
once a contraindication to tips creation , pvt may now represent an unequivocal procedural indication for tips given the efficacy demonstrated in such investigations .
the benefits of tips for clearance of pvt must be weighed against possible risks . when performed by experienced operators in properly selected candidates
tips complications that particularly affect subsequent transplantation are uncommon , and the presence of tips does not typically impact operative technique or result in detrimental effects on posttransplant patient clinical outcomes . as a matter of caution ,
ir operators should take great care in proper stent length selection as well as device deployment , as shunt extension into the portal vein or hepatic level inferior vena cava ( ivc ) and right atrium , either due to device misplacement or migration , may leave inadequate room for vascular cross - clamping at the time of surgery .
in conclusion , we describe four cases of partial pvt in liver transplant candidates successfully cleared after tips creation . in all cases ,
portosystemic shunting of blood resulted in rapid and effective flow - enabled clearance of clot and intermediate to long - term preservation of vessel patency . while our clinical observations are made on the basis of a small sample size and
should thus not be overstated , the findings herein are corroborated by other studies presenting similar findings , and affirm the utility of tips for maintenance of portal venous patency prior to liver transplant and highlight this application as an emerging indication for tips .
 maintenance of portal venous patency is vital to liver transplant candidates , as the presence of portal vein thrombosis ( pvt ) adversely impacts clinical outcomes by increasing surgical complexity and decreasing postoperative survival . by enhancing portal venous blood flow , transjugular intrahepatic portosystemic shunt ( tips ) 
 creation may enable clearance of pvt and preservation of portal venous patency in cirrhotic patients . herein , we describe four cases in which tips produced and sustained an open portal venous system in liver transplant candidates with partial pvt . 
 all patients demonstrated rapid and effective flow - enabled clearance of clot and intermediate to long - term preservation of portal venous flow . on this basis 
 , we propose that maintenance of portal venous patency in liver transplant candidates with partial pvt represents a developing indication for tips . 
INTRODUCTION
CASE REPORT
Patients and PVT
TIPS creation
Portal venous patency, liver transplantation, and patient survival
DISCUSSION
CONCLUSION