Portal Vein Thrombosis and Other Venous Anomalies

CHAPTER 62

Portal Vein Thrombosis and Other Venous Anomalies Gabriel T. Schnickel  •  Ronald W. Busuttil

CHAPTER OUTLINE PREVALENCE

OUTCOMES

PATHOPHYSIOLOGY

POSTTRANSPLANT PORTAL VEIN THROMBOSIS

DIAGNOSIS

PORTOSYSTEMIC SHUNTS

OPERATIVE STRATEGY

SUMMARY

Portal vein thrombosis (PVT) is defined as a partial or complete occlusion of the blood flow within the portal vein by an intraluminal thrombus.1 Balfour and Stewart first described this process in the literature in 1868 in a patient who presented with splenomegaly, ascites and variceal dilation.2 Since that initial report it has been thought to be a rare condition, though its reported prevalence varies widely. PVT can be described and classified in numerous categories, including acute or chronic, extrahepatic or intrahepatic, and occlusive or nonocclusive. Despite advancements in knowledge, understanding, and treatment, PVT continues to be a difficult problem, particularly in the transplant population.

PREVALENCE PVT is thought to be a rare event in the general population, resulting from a variety of causes.3-5 A populationbased study of more than 23,000 consecutive autopsies has demonstrated PVT to be more common than previously thought, with a population prevalence of 1.1%. This study also found that 28% of these patients had cirrhosis, one third of whom also had a primary hepatic malignancy. Cirrhosis was present in 5% of the population, 6% of which had PVT at the time of autopsy. Most interesting was the finding of malignancy in 63% of individuals with PVT, implicating the importance of neoplasms in its development.6 The prevalence of PVT among transplant candidates would presumably be close to that of cirrhotic patients in the general population. According to data from the Scientific Registry of Transplant Recipients (SRTR), the rate of PVT among patients wait-listed for liver transplant is 2.1%.7 This is lower than the rates previously discussed and also lower than other data suggest. However,

the prevalence among transplanted patients is nearly double the rate of listed patients at 4.0%.8 This would suggest that perhaps there are missed diagnoses based on imaging or there is a high rate of de novo PVT among patients on the waiting list. The relatively low rate may indicate that some patients are excluded from transplant secondary to PVT or the rate of PVT at transplant is underreported. When considering the incidence of PVT, how it is defined must be taken into account. PVT, as defined earlier, may be partially occlusive and may exist only in an intrahepatic branch or it may be completely occlusive and extend past the confluence into the splenic and mesenteric veins. Yerdel et al9 classified PVT from grade 1 (<50% thrombosis of the portal vein) to grade 4 (complete portal vein [PV] thrombosis and complete superior mesenteric vein [SMV] thrombosis). Starzl’s group defined grade 1 as partial thrombosis of the intrahepatic portal vein branches. Grade 4 in the Starzl classification equaled a near-complete or complete obliteration of the portal vein trunk, but with a patent SMV.3 These systems may seem to differ on only minor points, but this may account in part for the wide variability in the prevalence of PVT reported in the literature.4,5,10 PVT may have its greatest implication when it becomes clinically relevant. PVT was initially considered a contraindication for liver transplant, and patients were excluded from listing based on its presence.11 As experience grew and early success was documented, the rate of PVT transplants increased significantly.5 Lerut et al12 reported on the largest experience to date in 1987, with 393 consecutive orthotopic liver transplants, a 16.3% rate of PV anomalies, 7% of which were thrombosis. The same group in 1992 reported a rate of PVT in 13.8% of transplants. However, only 9% of these were surgically significant, meaning they alter the course of the operation.13 785

786

PART VII  Unusual Operative Problems

As experience was gained, more patients with PVT were listed and underwent transplant, but only a portion of these were surgically significant thrombosis. The average time from listing to transplant may vary widely throughout the world. Some transplant centers have average waiting times greater than 1 year, whereas others may transplant within 6 months of listing the patient. This may be of considerable importance with regard to the incidence and prevalence of PVT and its variability in the listed and transplanted patient population. Francoz et al14 found a 7.4% incidence of de novo thrombosis in patients awaiting transplant, with a mean waiting-list time of 12 months. This rate is in addition to an incidence of 8.4% PVT at the time of listing. Many of these patients were discovered to have PVT on routine surveillance imaging; however, more than half were discovered at the time of transplant and were previously though to have patent portal veins. This study found that the risk for de novo thrombosis was significantly and independently associated with the length of time from listing to transplant.14 The prevalence of PVT varies depending on how it is defined and when it is discovered. It is influenced by severity of liver disease and increases with duration of disease.15 The next question is what factors are behind its development.

PATHOPHYSIOLOGY Although Rudolf Virchow helped to elucidate the mechanisms behind the development of pulmonary embolism, his name has famously become associated with the factors that contribute to the development of thrombosis: Virchow’s triad. These factors are hypercoagulability, hemodynamic changes, and endothelial injury. These same factors have proven important in the development of PVT. Alterations in portal venous flow and distortions of normal coagulation, in particular, have been shown to be critical in the formation of PVT.14,16-19 The liver synthesizes coagulation factors, inhibitors, and fibrinolytic proteins. All of these unique factors exist naturally in balance to avoid the generation of excess thrombin.20,21 Protein C, protein S, and antithrombin levels are lower in the serum of patients with liver disease. In fact, patients with higher Model for End-Stage Liver Disease (MELD) scores have been shown to have significantly lower levels of protein C and antithrombin when compared to cirrhotic patients with lower MELD scores. This corollary continues to hold true, because the rate of PVT is associated with higher MELD scores.16 Inherited defects in protein C and S, as well as other defects such as factor V Leiden, have been associated with the development of PVT, yielding further evidence as to the importance of balance between procoagulation factors and inhibitors of coagulation.17,22 Cirrhosis is associated with impairment of hepatic synthesis and a reduction of procoagulants and anticoagulants to an equal degree.18 This balance can be easily upset, as seen in the operating room with surgical bleeding in a cirrhotic patient or the development of an infection in the hospitalized patient with cirrhosis. But that

balance can be disturbed in the opposite direction, resulting in thrombosis. The international normalized ratio (INR), which is used in the transplant population as part of the MELD score, may not accurately assess the bleeding or thrombotic potential of cirrhotic patients.23 INR was developed to measure the effect of vitamin K antagonists in patients with normal liver function and has been shown to be less reliable in the setting of cirrhosis.24 Several studies have demonstrated a higher rate of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, in patients with severe liver disease when compared to controls.25-28 Portal venous flow is abnormal in patients with cirrhosis, and increasing perturbation is associated with a rising MELD score. Stasis in the portal vein is caused in part by splanchnic vasodilation found in cirrhosis. This is further exacerbated by the increased resistance in the hepatic vascular bed caused by the architectural derangements of the scarred, cirrhotic liver. Reduced portal venous blood flow velocity has been shown to be independently associated with the development of PVT. This further illustrates the relationship between rising MELD score and increased incidence of PVT.16

DIAGNOSIS Determining the presence of PVT is critical for transplant evaluation, pretransplant management, and operative planning. Historically the gold standard for diagnosis of PVT has been portal venography or mesenteric arteriography.29 This technique is invasive and carries the risks associated with percutaneous angiography as well as those associated with intravenous contrast use. Ultrasonography and ultrasonography with Doppler have become the diagnostic tests of choice with a sensitivity and specificity ranging from 60% to 100%.30-33 With improvements in resolution, Doppler imaging can detect the presence of solid material within a distended portal vein, the presence of collateral vessels, or cavernous transformation.31 The test is relatively easy to use, carries none of the risks associated with contrast use or radiation, and is safe in the presence of renal failure. Computed tomography (CT) and magnetic resonance imaging (MRI) have the advantage of determining the extent of thrombosis, a critical factor in preoperative assessment. Contrast-enhanced cross-sectional imaging also has the advantage of diagnosing hepatic malignancies that may be present in the setting of PVT and indeed may contribute to its development.33 Tumor thrombus is considered a contraindication for transplantation, and its diagnosis is most reliably made by contrast-enhanced CT or MRI. The prevalence of renal dysfunction and even renal failure in patients with advanced cirrhosis has been well proven, limiting the utility of contrast-enhanced CT or MRI. Spontaneous recanalization has been documented to occur in up to 80% of acute PVTs in noncirrhotic patients.34 The same cannot be said for cirrhotic patients because one of the inciting factors, namely the cirrhotic liver and altered portal flow, is not addressed until transplantation. The current recommendations from the American Association for the Study of Liver Diseases

62  Portal Vein Thrombosis and Other Venous Anomalies

advocate treatment with anticoagulation in noncirrhotic patients.35 No guidelines currently exist for PVT in cirrhosis, for which data are more limited and use of anticoagulation may carry a greater risk. To determine if anticoagulation is appropriate, first the chronicity of the thrombosis must be assessed. The presence of a cavernoma or diminutive cordlike appearance of the portal vein on imaging is consistent with a chronic PVT, and the effect of anticoagulation will be nil. Evaluation of bleeding risk is crucial before initiation of anticoagulation, which should include surveillance esophagogastroduodenoscopy and possible banding of esophageal varices to minimize bleeding potential. Previous variceal bleeds have been shown to be associated with, and a risk factor for, the development of PVT.14 The liver is responsible for the synthesis of procoagulant factors, and advanced liver disease is associated with alterations in the prothrombin time and INR.36 The frequent elevation of INR in the setting of cirrhosis despite new clot formation (PVT) is of unclear significance. This adds a level of complexity to anticoagulation with oral anticoagulants. In addition, the MELD score used to allocate livers is dependant on the INR to assess severity of disease, and treatment with vitamin K antagonists falsely elevates the MELD score.37 Despite these drawbacks to treatment with oral anticoagulants, they have been shown to be effective in treatment of PVT in patients awaiting liver transplant.38 Among patients with PVT treated with vitamin K antagonists to achieve an INR of 2.0 to 3.0, 42% were found to have complete recanalization, whereas those who did not receive anticoagulation had no recannalization.14 Alternatively, lowmolecular-weight heparin (LMWH) has also been demonstrated to be effective in treatment of PVT in cirrhotic patients. There are benefits to the use of LMWH in this population. First, it does not alter the INR, and therefore MELD scores remain unchanged. Second, dosing is weight based and following levels is not necessary. Although data suggest excellent results with 50% to 75% recanalization rates with low incidence of bleeding complications, LMWH does require a prolonged treatment period of more than 6 months.39 Although the half-life is reasonably short, there is no way to reverse its effects if an organ becomes available while the patient is on the waiting list, leading to a potential bleeding risk. Renal dysfunction is also well documented in cirrhotic patients, and this has been demonstrated to alter the effect of LMWH, which is eliminated by the kidney, leading to a prolonged half-life and difficulty with dosing. All of these may lead to an increased bleeding potential.

OPERATIVE STRATEGY Early reports of transplantation with PVT described the experience of 32 adult transplants at a single center resulting in three intraoperative deaths, all related to issues with the portal vein. As a result PVT came to be considered a contraindication for liver transplant.11 The first successful experience of liver transplant with PVT was reported in 1985 by Shaw et al5 and described their experience in six patients with portal vein anomalies. Two of these were

787

adults with PVT, and four were children with diminutive, sclerosed portal veins. This report described the technique of extensive dissection to the confluence of the splenic and mesenteric veins with the use of vessel grafts.5 This experience yielded encouraging results with excellent survival and portal vein patency. These results lead to an increasing willingness to transplant those patients with difficult portal vein problems. Advanced knowledge of the vascular anatomy is extremely helpful when preparing for the operation. Awareness of the presence and extent of PVT will help not only with the technical aspects but can also be critical in planning before the operation even starts. If there is preoperative imaging demonstrating an extensive PVT thrombectomy, the surgeon may want to discuss with the team the likelihood of increased blood loss and longer operative time. This knowledge may also help in donor selection and allow the procurement team to retrieve an adequate length of donor portal vein and vessels for vascular grafts. This point may be critical if there are also pancreas and intestinal transplant teams involved in the same procurement because vessels may become scarce. Preoperative imaging may also demonstrate cavernous transformation and extensive thrombosis that may eliminate any opportunity for thrombectomy so precious time is not wasted in pursuit of an operative strategy that has little chance of working. However, as discussed earlier, PVT is discovered at the time of operation with reasonable frequency, and one must always be prepared for any contingency. Assessment of the portal vein starts with dissection of the porta hepatis, where large collateral vessels may be encountered. Once the thrombosis is identified, the proximal extent must be determined by careful dissection, following the portal vein to the confluence of the splenic vein and SMV behind the head of the pancreas. The thrombosed portion will be firm on palpation, but dissection may lead to a soft patent vessel at the confluence. Most cases of PVT can be managed with thromboendovenectomy alone. This can be accomplished by first establishing control of the distal end of the thrombosed vein either with stay sutures or vascular-tipped clamps. If the thrombus is acute and soft, it may be amenable to the use of a Fogarty catheter. This is passed carefully into the proximal vein, the balloon is inflated, and the clot is swept out. Great care must be taken not to lacerate the proximal vein behind the pancreas with the catheter because this will be difficult to repair. If the thrombus is more chronic and well established, it may be approached using a spatula to tease out the thrombus, much like performing an endarterectomy (Fig. 62-1). The vein is carefully everted to reveal more proximal portions and extend the endovenectomy until the clot can be removed. This may be extensive and require the placement of tonsil clamps on the thrombus sequentially to apply constant distal traction. Alternatively, rather than using a spatula, the thrombus may be grasped with a tonsil clamp, and with gentle pressure and rotation the thrombus is pushed into the lumen with countertraction on the vein. Then the thrombus is pulled out and free of the vessel. Again, great care must be taken not to injure the posterior wall of the vein, because it may be quite fragile. Once the thrombus is

788

PART VII  Unusual Operative Problems

Donor portal vein

Recipient portal vein (clotted) Recipient splenic vein

FIGURE 62-1 n The majority of cases of portal vein thrombosis can be treated with eversion thromboendovenectomy.

removed by either technique, the flow must be assessed. Inadequate flow will yield poor graft function and potential rethrombosis. If the flow is deemed inadequate, a Fogarty catheter may again be used and passed into both the splenic and superior mesenteric veins. If bypass is being used, a cannula may be safely placed in the portal vein at this time and bypass used with reliable flows and no risk for clot propagating into the systemic circulation. If the vein appears thin and fragile, the patient may be maintained on systemic bypass alone, because he or she likely has extensive collaterals, or the inferior mesenteric vein may be used with adequate flow in most cases. If the transplant is being performed in a caval-sparing technique, the thrombectomized portal vein can be used for a temporary portacaval shunt to maintain stability. In those cases in which the thrombus extends beyond the confluence of the superior mesenteric vein and thromboendovenectomy is not possible, a vein graft may be necessary. This is accomplished with a jump graft to the proximal SMV. The SMV is exposed below the transverse mesocolon at the root of the small bowel mesentery. Next, the proximal anastomosis is completed in an end-to-side fashion. The vein graft is tunneled through the mesentery of the transverse colon and anterior to the pancreas to prevent overdissection of the pancreas and its associated risks (Fig. 62-2). The vein graft should not be used for bypass cannula placement. In the event that the entire portomesenteric venous system is thrombosed without a proximal SMV target for vein graft, alternative inflow can be used. The coronary vein may be used either by a direct anastomosis to the portal vein or with a jump graft. Alternatively, a large unnamed collateral vessel can also successfully be used with adequate inflow. Great care must be taken in these situations because the collateral vessels are extremely delicate and will tear easily and may not hold suture. Splanchnic blood flow to the liver has long been thought to be critical to successful liver transplantation. This was clear in early animal studies, which demonstrated the need for portal inflow, and in the experience of Starzl’s group, which reported 100% mortality when

Graft Recipient superior mesenteric vein FIGURE 62-2 n Portal flow may be established with an interposition graft from the superior mesenteric vein to the donor portal vein.

portal venous inflow from the splanchnic bed was not provided to the allograft.5 Inflow to the graft using the inferior vena cava was reported by Tzakis et al40 in 1998 with the results of nine patients from four centers using the hemitransposition technique. Portal inflow was accomplished with either an end-to-side or end-to-end anastomosis of the infrahepatic vena cava to the portal vein so that the entirety of caval flow is directed to the portal vein (Fig. 62-3). Short-term results were encouraging, considering the gravity of the problem, with five of nine patients alive at 6 to 11 months.40 Long-term outcomes of this cohort, and in the majority of literature regarding caval inflow, are limited. More recently Bhangui et al41 reported a 12-year experience providing caval inflow by cavoportal anastomosis or renoportal anastomosis. During this time a total of 20 patients underwent liver transplantation with caval inflow (3 cavoportal anastomosis and 17 renoportal anastomosis). These operations were carried out in patients that had complete thrombosis of the portomesenteric system with no collateral targets. Long-term results at 1, 3, and 5 years were 83%, 75%, and 60% for all patients, with 2 of the 3 cavoportal anastomosis patients alive at 2 and 10 years at last follow-up.41

OUTCOMES The initial published account of liver transplant in patients with PVT reported universally poor outcomes, leading to listing denials for patients with PVT.11 The same group in Pittsburgh, 3 years later, reported on successful transplantation in two adults with PVT using vein grafts.5 The University of Pittsburgh Medical Center experience continued to increase the transplantation rate

62  Portal Vein Thrombosis and Other Venous Anomalies

789

A

IVC

Portal vein

Caval clip

IVC

B

IVC Portal vein

Renal vein

C FIGURE 62-3 n Portal inflow to the graft may be restored with end-to-end or end-to-side portacaval anastomosis. IVC, Inferior vena cava.

in patients with PVT, gaining valuable operative experience and improving outcomes. They next reported a rate of PVT at transplant of 6% (22 of 393 transplants). At that time they advocated avoiding PV bypass and the use of extensive PV dissection using long donor portal vein or interposition vein grafts from donor iliac vein, pulmonary artery, or inferior vena cava. The posttransplant thrombosis rate in this population was 2.2%.12 A group at University of California, Los Angeles (UCLA) first published their experience with PVT in 1991, at which time they found a PVT rate at transplant of 4%. They strongly advocated thrombectomy, which was successful in 14 of 23 patients. Portal venous bypass was used successfully following thrombectomy with no incidence of clot propagation. These early results found a significantly higher rate of primary nonfunction (35%

versus 8%) and higher 3-month mortality (35% versus 12%) in the PVT group.10 The same group at UCLA demonstrated that with greater experience, transplantation with PVT can significantly improve over time. Five years after their initial report they published their experience in over 1423 transplants, with a PVT rate at transplant of 4.9%. The utilization of thromboendovenectomy increased over time, with a success rate of 87% requiring interposition grafting in only 9% of patients. The 1-year actuarial survival rate improved from 66% in the first 35 transplants to 82% in the more recent 35 patients. As a total group the PVT patients had a higher rate of transfusion requirements and retransplantation and a lower 1-year survival (84% versus 74%) when compared to controls. However, they were able to demonstrate that the modern group of

790

PART VII  Unusual Operative Problems

PVT patients was found to have statistically no difference in 1-year survival when compared to the control group (82% versus 84%). This again demonstrated the improved survival with greater experience.4 The Barcelona group reported an experience with 42 patients with PVT over 5 years (12.5% of all transplants). The PVT was described based on the classification system described by Yerdal with grades 1 to 4. There were longer operative times, higher transfusion rates, and longer hospital stays in the PVT group, but there was no significant difference in 3-year survival (75% versus 77% in the control group). Despite these survival rates the incidence of posttransplant PVT was much higher in the PVT group (15% versus 2.4%). This encompassed all four grades of PVT, but when describing the results of the grade 3 to 4 patients, experience was limited and outcomes were more sobering.42 More recent experiences out of Spain found a PVT rate of 7.8% at transplant. The importance of this study was the comparison of partial versus complete thrombosis of the portal vein. Forty-one percent of the portal vein thromboses were described as complete compared to the remainder, which were described as partial. When these two groups were compared individually to the control group, which had no PVT, survival was significantly worse only if the patient had complete PVT (55% versus 83% at 1 year), but not if the clot was only partially occlusive (82% 1-year survival). This emphasizes the importance of the extent of thrombosis and not just its presence.43 An extensive look at the incidence and outcomes of PVT in the modern era uses the SRTR database. The prevalence of PVT among wait-listed candidates was 2.1%, whereas the incidence at transplant was 4%. The presence of PVT was associated with a significantly higher posttransplant mortality only during the first year (hazard ratio, 1.50). When statistical modeling was used, the threshold for transplant benefit among patients with PVT was shifted from MELD 11 to MELD 13. Liver transplant benefit was reduced for lower MELD patients, with a posttransplant mortality greater than four times the waiting list mortality. This study was entirely dependant on the accuracy of reporting from transplant centers across the country and does not delineate based on the extent of thrombosis. They also report a lower incidence of PVT than any of the modern experiences described earlier.44

POSTTRANSPLANT PORTAL VEIN THROMBOSIS PVT following transplant has been reported to occur in 2% to 7% of all orthotopic liver transplants and can result in serious morbidity and mortality. Risk factors for the development of PVT include preexisting PVT, use of venous conduits, prior shunt surgery, and small portal vein size. The consequences of PVT include portal hypertension with variceal bleeding, ascites, thrombocytopenia, and acute graft failure. The largest reported experience to date out of UCLA describes the vascular complications of more than 4200 transplants. The rate of

PVT was 2.0% of all transplants, but higher in the cadaveric split, living donor, and pediatric transplants (5.4%, 8.7%, and 5.7%). Most patients presented with elevated transaminase levels, but 24% presented with ascites and 12% with gastrointestinal bleeding. Most were early PVT (65%), and most developed graft failure (75%). Treatment included anticoagulation, surgical revision, retransplantation, catheter-based therapy, and portosystemic shunting. Surgical intervention yielded dismal results, with a salvage rate of 36%, whereas anticoagulation salvaged 48% of grafts. Posttransplant PVT was associated with significantly worse patient and graft survival.45

PORTOSYSTEMIC SHUNTS Patients with central portosystemic shunts were long considered to represent a higher surgical risk.10,12 The presence of a central shunt has been extensively associated with an increased rate of PVT. Portosystemic shunts may also result in sclerosis of the portal vein, and in some cases it may be completely absent. These findings are frequently determined by preoperative imaging, making operative planning easier. The shunt may be left in place during portions of the hepatectomy, if patent, to continue to decompress the portal system. The portacaval shunt is dismantled before the completion of the recipient hepatectomy; care must be taken to maintain as much length of vein as possible, and the portal vein may be used for bypass at this point. Shunts located away from the hilum, mesocaval, or splenorenal cause fewer problems during the operation but may need to be taken down, if causing portal vein steal, to improve portal flow-by.10,46,47 Surgical shunts have largely been replaced by percutaneous methods of portal decompression. Transjugular intrahepatic portosystemic shunt (TIPS) has revolutionized the treatment of refractory portal hypertension. There has been a dramatic shift away from open surgical shunts to the use of TIPS, particularly as a bridge to liver transplant. TIPS is especially useful in those patients awaiting transplant because it does not distort the extrahepatic vascular anatomy or violate the tissue planes in the way that a surgical shunt does.48,49 A case-matched study found that TIPS does not significantly affect the course of a transplant operation; there is no difference in operative time, transfusion requirement, or short-term survival.50 In a more recent study of 818 transplants, 61 of which had a TIPS placed before transplantation, there was no difference in 1-, 3-, or 5-year survival between the TIPS group and controls. The use of venovenous bypass was higher in the TIPS group, though used in only 31% of cases (versus 18% in controls). The number of posttransplant vascular complications was similar between the groups, with one case of PVT in each cohort.51 From a technical standpoint, common problems associated with TIPS placements are the migration of the stent either proximally, in the portal vein, into the SMV, or distally into the suprahepatic cava or right atrium.52 These situations may add to the complexity of the transplant operation and require creative solutions. When a

62  Portal Vein Thrombosis and Other Venous Anomalies

791

long-term success. Recognition of these complicating factors can usually be accomplished with preoperative imaging. Appropriate planning is essential. An understanding of the nature of the problem can help with pretransplant medical management, limit intraoperative emergencies, and lower morbidity. There are many strategies and techniques that can be employed, and understanding these options improves preparedness and therefore results.

Blood flow

Staples

FIGURE 62-4 n A spontaneous splenorenal shunt can be addressed by ligation of the left renal vein when there is resultant diminutive portal flow.

stent has migrated proximally, it is important to gain control of the vessel beyond because stent removal may damage the vein. In the case of imbedded stents that cannot physically be removed from the vein, anastomosis directly to the stent has been described, as has the use of vein grafts to the SMV using the same techniques previously discussed.51 Because the portal flow has been altered by TIPS placement, these patients may not tolerate clamping of the portal vein as well as those with extensive collaterals and no shunt. A more liberal use of venovenous bypass in the setting of TIPS may be warranted. The exact mechanisms involved in portal hypertension and the development of collateral vessels remain to be fully elucidated. These collaterals, which include splenorenal shunts, develop spontaneously and siphon blood from the splanchnic circulation into the systemic circulation. This may lead to decreased portal venous flow after allograft reperfusion, with resultant graft dysfunction. Splenorenal shunts are present in nearly 14% to 21% of cirrhotic patients and so can be a frequent occurrence in the transplant population. They may be diagnosed on preoperative imaging. If portal venous flow is diminutive and ligation of collaterals does not improve flow, ligation of the left renal vein can augment portal flow by eliminating the steal from the splenorenal shunt. This is easily accomplished because the vena cava has already been dissected. The dissection is extended caudally, exposing the renal vein, which is encircled and temporarily occluded (Fig. 62-4). If portal flow is enhanced, then the renal vein is ligated.53 Renal function is preserved, and portal flow is enhanced. Experience is limited largely to case reports in the literature.

SUMMARY PVT and venous anomalies add a measure of complexity to liver transplantation and if not carefully and thoughtfully addressed can negatively affect both short- and

Pearls and Pitfalls • In most cases of portal vein thrombosis (PVT), thromboendovenectomy can effectively obtain excellent inflow and does not preclude the use of venovenous bypass. • Portal vein thrombosis is associated with increased morbidity and mortality in liver transplantation. If detected early, PVT may be effectively treated with complete recanalization before transplant. • PVT is more common than previously thought and can be detected easily by cross-sectional imaging or duplex ultrasonography. • Because PVT can add significant complexity to the transplant operation, cross-sectional imaging is crucial for advanced planning and can help identify alternative inflow if necessary. • Communication among the transplant team is critical to allow adequate donor portal vein length and donor vessels if a conduit is deemed necessary. Appropriate timing of both donor and recipient operations should also be discussed because the dissection and identification of adequate inflow may take additional time. It is also important to alert the anesthesia team to the potential for greater blood loss and prolonged operative time. • An understanding of all possible reconstruction and inflow alternatives is critical because PVT or other venous anomalies may be encountered unexpectedly during the recipient operation, and establishing timely vascular in   flow is crucial.

REFERENCES 1. Bayraktar Y, Harmanci O. Etiology and consequences of thrombosis in abdominal vessels. World J Gastroenterol. 2006 Feb 28;12(8): 1165-1174. 2. Wang JT, Zhao HY, Liu YL. Portal vein thrombosis. Hepatobiliary Pancreat Dis Int. 2005 Nov;4(4):515-518. 3. Stieber AC, Zetti G, Todo S, et al. The spectrum of portal vein thrombosis in liver transplantation. Ann Surg. 1991;213:199-206. 4. Seu P, Shackleton CR, Shaked A, et al. Improved results of liver transplantation in patients with portal vein thrombosis. Arch Surg. 1996;131:840-845. 5. Shaw BW, Iwatsuki S, Bron K, Starzl TE. Portal vein grafts in hepatic transplantation. Surg Gynecol Obstet. 1985;161:66-68. 6. Ogren M, Bergqvist D, Bjorck M, et al. Portal vein thrombosis: prevalence, patient characteristics and lifetime risk: a population study based on 23,796 consecutive autopsies. World J Gastroenterol. 2006;12:2115-2119. 7. Englesbe MJ, Schaubel DE, Cai S, et al. Portal vein thrombosis and liver transplant survival benefit. Liver Transpl. 2010 Aug;16(8): 999-1005. 8. Tripathi D, Therapondos G, Redhead DN, et al. Transjugular intrahepatic portosystemic stent-shunt and its effects on orthotopic liver transplantation. Eur J Gastroenterol Hepatol. 2002;14: 827-832.

792

PART VII  Unusual Operative Problems

9. Yerdel MA, Gunson B, Mirza D, et al. Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome. Transplantation. 2000;69:1873-1881. 10. Shaked A, Busuttil RW. Liver transplantation in patients with portal vein thrombosis and central portacaval shunts. Ann Surg. 1991;214:696-702. 11. Van Thiel DH, Schade RR, Starzl TE, et al. Liver transplantation in adults. Hepatology. 1982;2:637-640. 12. Lerut J, Tzakis AG, Bron K, et al. Complications of venous reconstruction in human orthotopic liver transplantation. Ann Surg. 1987;205:404-414. 13. Nonami T, Yokoyama I, Iwatsuki S, Starzl TE. The incidence of portal vein thrombosis at liver transplantation. Hepatology. 1992 Nov;16(5):1195-1198. 14. Francoz C, Belghiti J, Vilgrain V, et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut. 2005;54:691-697. 15. Doenecke A, Tsui TY, Zuelke C, et al. Pre-existent portal vein thrombosis in liver transplantation: influence of pre-operative disease severity. Clin Transplant. 2010 Jan-Feb;24(1):48-55. 16. Zocco MA, Di SE, De CR, et al. Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development. J Hepatol. 2009;51:682-689. 17. Amitrano L, Brancaccio V, Guardascione MA, et al. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology. 2000;31:345-348. 18. Tripodi A, Primignani M, Chantarangkul V, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009 Dec;137(6):2105-2111. 19. Martinelli I, Primignani M, Aghemo A, et al. High levels of factor VIII and risk of extra-hepatic portal vein obstruction. J Hepatol. 2009;50:916-922. 20. Tripodi A, Salerno F, Chantarangkul V, et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology. 2005;41:553-558. 21. Tripodi A, Primignani M, Chantarangkul V, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006;44:440-445. 22. Romero GM, Suarez GE, Lopez LD, et al. Antiphospholipid antibodies are related to portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol. 2000;31:237-240. 23. Arjal R, Trotter JF. International normalized ratio of prothrombin time in the model for end-stage liver disease score: an unreliable measure. Clin Liver Dis. 2009;13:67-71. 24. Trotter JF, Olson J, Lefkowitz J, et al. Changes in international normalized ratio (INR) and model for endstage liver disease (MELD) based on selection of clinical laboratory. Am J Transplant. 2007;7:1624-1628. 25. Gulley D, Teal E, Suvannasankha A, et al. Deep vein thrombosis and pulmonary embolism in cirrhosis patients. Dig Dis Sci. 2008; 53:3012-3017. 26. Northup PG, McMahon MM, Ruhl AP, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol. 2006;101: 1524-1528. 27. Sogaard KK, Horvath-Puho E, Gronbaek H, et al. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol. 2009;104:96-101. 28. Martinelli I, Primignani M, Aghemo A, et al. High levels of factor VIII and risk of extra-hepatic portal vein obstruction. J Hepatol. 2009;50:916-922. 29. Bach AM, Hann LE, Brown KT, et al. Portal vein evaluation with US: comparison to angiography combined with CT arterial portography. Radiology. 1996;201:149-154. 30. Subramanyam BR, Balthazar EJ, Lefleur RS, et al. Portal venous thrombosis: correlative analysis of sonography, CT and angiography. Am J Gastroenterol. 1984;79:773-776. 31. Ueno N, Sasaki A, Tomiyama T, et al. Color Doppler ultrasonography in the diagnosis of cavernous transformation of the portal vein. J Clin Ultrasound. 1997;25:227-233.

32. Bach AM, Hann LE, Brown KT, et al. Portal vein evaluation with US: comparison to angiography combined with CT arterial portography. Radiology. 1996;201:149-154. 33. Kreft B, Strunk H, Flacke S, et al. Detection of thrombosis in the portal venous system: comparison of contrast-enhanced MR angiography with intraarterial digital subtraction angiography. Radiology. 2000;216:86-92. 34. Condat B, Pessione F, Hillaire S, et al. Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy. Gastroenterology. 2001;120:490-497. 35. Sarin SK, Sollano JD, Chawla YK, et al. Consensus on extrahepatic portal vein obstruction. Liver Int. 2006;26:512-519. 36. Kovacs MJ, Wong A, MacKinnon K, et al. Assessment of the validity of the INR system for patients with liver impairment. Thromb Haemost. 1994;71:727-730. 37. Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91-96. 38. Senzolo M, Ferronato C, Burra P, Sartori MT. Anticoagulation for portal vein thrombosis in cirrhotic patients should be always considered. Intern Emerg Med. 2009;4:161-162. 39. Amitrano L, Guardascione MA, Menchise A, et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol. 2010 Jul;44(6):448-451. 40. Tzakis AG, Kirkegaard P, Pinna AD, et al. Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal vein thrombosis. Transplantation. 1998;65:619-624. 41. Bhangui P, Lim C, Salloum C, et al. Caval inflow to the graft for liver transplantation in patients with diffuse portal vein thrombosis: a 12-year experience. Ann Surg. 2011 Dec;254(6):1008-1016. 42. Lladó L, Fabregat J, Castellote J, et al. Management of portal vein thrombosis in liver transplantation: influence on morbidity and mortality. Clin Transplant. 2007 Nov-Dec;21(6):716-721. 43. Suarez Artacho G, Barrera Pulido L, Alamo Martinez JM, et al. Outcomes of liver transplantation in candidates with portal vein thrombosis. Transplant Proc. 2010 Oct;42(8):3156-3158. 44. Englesbe MJ, Schaubel DE, Cai S, et al. Portal vein thrombosis and liver transplant survival benefit. Liver Transpl. 2010 Aug;16(8): 999-1005. 45. Duffy JP, Hong JC, Farmer DG, et al. Vascular complications of orthotopic liver transplantation: experience in more than 4,200 patients. J Am Coll Surg. 2009 May;208(5):896-903. discussion 903–5. 46. Brems JJ, Hiat JR, Klien AS, et al. Effect of a prior portasystemic shunt on subsequent liver transplantation. Ann Surg. 1989;209: 51-56. 47. Mazzaferro V, Todo S, Tzakis AG, et al. Liver transplantation in patients with previous portasystemic shunt. Am J Surg. 1990;160: 111-116. 48. Freeman Jr RB, FitzMaurice SE, Greenfield AE, et al. Is the transjugular intrahepatic portocaval shunt procedure beneficial for liver transplant recipients? Transplantation. 1994;58:297-300. 49. Tripathi D, Therapondos G, Redhead DN, et al. Transjugular intrahepatic portosystemic stent-shunt and its effects on orthotopic liver transplantation. Eur J Gastroenterol Hepatol. 2002;14: 827-832. 50. Somberg KA, Lombardero MS, Lawlor SM, et al. A controlled analysis of the transjugular intrahepatic portosystemic shunt in liver transplant recipients. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database. Transplantation. 1997 Apr 27;63(8):1074-1079. 51. Guerrini GP, Pleguezuelo M, Maimone S, et al. Impact of tips preliver transplantation for the outcome posttransplantation. Am J Transplant. 2009 Jan;9(1):192-200. Epub 2008 Nov 27. 52. Clavien PA, Selzner M, Tuttle-Newhall JE, et al. Liver transplantation complicated by misplaced TIPS in the portal vein. Ann Surg. 1998;227:440-445. 53. Slater RR, Jabbour N, Abbass AA, et al. Left renal vein ligation: a technique to mitigate low portal flow from splenic vein siphon during liver transplantation. Am J Transplant. 2011 Aug;11(8): 1743-1747.