Pancreas Transplant Venous Thrombosis: Role of Endovascular Interventions for Graft Salvage
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- Stockland, A.H., Willingham, D.L., Paz-Fumagalli, R. et al. Cardiovasc Intervent Radiol (2009) 32: 279. doi:10.1007/s00270-009-9507-9
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Venous thrombosis of pancreas transplant allografts often leads to graft loss. We evaluated the efficacy of emergent endovascular techniques to salvage thrombosed pancreatic allografts in a series of six patients. Of the 76 pancreas transplants performed between 2002 and 2006, six patients were diagnosed with venous thrombosis on MRI between 2 and 28 days posttransplant (mean, 9 days). Five patients were systemic-enteric (donor portal vein anastomosis to recipient iliac vein) and one patient was portal-enteric (donor portal vein anastomosis to recipient superior mesenteric vein). Conventional venography confirmed the diagnosis of venous thrombosis in all patients. One patient was treated with catheter-directed venous thrombolysis and balloon thrombectomy. Another patient was treated with rheolytic thrombectomy alone. The remaining four patients were treated with a combination of these mechanical and thrombolytic techniques. Completion venography revealed >50% clot reduction and resumption of venous drainage in all patients. One patient required additional intervention 16 days later for recurrent thrombosis. Two patients required metal stent placement for anastomotic stenoses or kinks. One patient required pancreatectomy 36 h after attempted salvage secondary to a major hemorrhage and graft necrosis. Two patients recovered pancreatic function initially but lost graft function at 8 and 14 months, respectively, from severe chronic rejection. Patient survival was 100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft loss from rejection was 33%. In conclusion, early recognition and treatment of venous thrombosis after pancreas transplantation has acceptable morbidity and no mortality using short-term endovascular pharmacomechanical therapy.
KeywordsPancreas transplantVenous thrombolysisVenous stents
The rate of pancreas transplant graft failure is significantly higher than that for liver or renal transplants . One of the major reasons for early graft failure is allograft venous thrombosis . With the advent of better immunosuppressive therapy and donor selection, immunologic loss of pancreas grafts has diminished over the years, making venous thrombosis the most prevalent threat to modern pancreas transplant surgery. While advances in surgical techniques have lowered the incidence of venous thrombosis in pancreas transplantation (from 20% to 10%), this complication still remains the most common cause of early technical failure (70%) [3, 4]. Treatment options include pancreatectomy, partial pancreatectomy, early retransplantation, or surgical thrombectomy and vascular revision . In our experience, a less invasive alternative is early endovascular intervention directed at venous thrombus removal. We evaluated this treatment option in a series of six patients.
Patients and Methods
The remaining five patients required “power-pulse” rheolytic thrombectomy  using 5–10 mg of tissue plasminogen activator (tPA; Alteplase, Genentech, San Francisco, CA) mixed with 10–20 ml of normal saline. This solution was used as the reservoir for the Angiojet device, which delivered the thrombolytic solution forcefully within the thrombus. After these rheolytic treatments, the venous segments were further cleared with two or three “sweeps” with a 5-Fr compliant balloon catheter to remove residual thrombus from both venous limbs. After this clot fragmentation and removal, venous flow was restored in all but one patient, who then had a short (2-h) course of thrombolytic infusion (5 mg tPA in 50 ml saline) to clear resistant clot within the mid donor splenic vein. No patients received overnight thrombolytic infusions, however. Three of five (60% of) eligible patients (one patient was ineligible for inferior vena cava filtration, as he had enteric venous drainage) had retrievable vena cava filters placed, although, interestingly, none of the six patients experienced clinical pulmonary embolism.
Upon completion of percutaneous thrombus removal, venography showed a >50% reduction of venous clot burden and resumption of venous drainage in all patients. Imaging (CT or MRI) performed within 1 week confirmed continued venous patency and improved graft enhancement in all patients. One patient suffered a life-threatening intra-abdominal hemorrhage 36 h following intervention while on heparin. This patient required surgical hematoma evacuation and removal of the ischemic allograft. The venous and arterial anastomoses were intact at surgery and no active bleeding was encountered. The graft was ischemic due to compression by surrounding hematoma with kinking of the vascular pedicle. Two patients recovered pancreatic function initially but eventually lost graft function, at 8 and 14 months, respectively, due to severe chronic rejection. The remaining three patients had little or no insulin requirement and have maintained normal C-peptide levels (2.0–2.7 ng/ml) for a mean follow-up period of 373 days (range, 112–628 days). Patient survival was 100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft loss from rejection was 33%.
Advancing surgical techniques, better patient selection, and immunosuppressive drugs have improved long-term outcomes after pancreas transplantation. Nevertheless, complications leading to early graft loss remain a significant problem, with thrombosis responsible for the majority of failures. According to the International Pancreas Transplant Registry at the University of Minnesota (IPTR) 2004 Annual Report, vascular thrombosis resulted in 2.7–8.0% of graft loss, with a higher incidence in the PTA group compared to the PAK and SPK groups . Although early thrombosis may be associated with acute or hyperacute rejection, the majority (60%) of grafts lost to thrombosis are histopathologically normal . While some investigators suggest that altered coagulation may play a role in posttransplant venous thrombosis , suboptimal surgical technique, prolonged cold ischemic time, and postoperative inflammation and edema are the most commonly implicated factors [10, 11]. The risk of thrombosis is even further increased due to the low venous flow within a pancreas graft deprived of its splenic inflow. Various groups have correlated graft thrombosis rates with surgical technique and found evidence of higher rates of thrombosis in portoiliac as opposed to portocaval venous drainage  and higher thrombosis rates in enteric exocrine drainage versus bladder drainage in both the SPK and the PAK population . Given that pancreas grafts are predisposed to thrombosis, some propose routine postoperative anticoagulation [11, 13], although meticulous surgical technique and rigorous avoidance of pretransplant organ damage are probably more effective methods to decrease the incidence of early thrombosis [14, 15]. Other innovative options to increase pancreatic venous flow and avert thrombotic complications include creation of arteriovenous fistula between the splenic artery and vein, inclusion of the donor spleen during pancreas transplant, and composite transplantation of the kidney and pancreas, whereby the renal vein joins and augments splenic vein outflow [16–20]. Treatment options for graft thrombosis have historically included surgical venous thrombectomy, pancreatectomy, early pancreas retransplantation, and partial pancreatectomy [21, 22].
Endovascular management of venous thrombosis has been widely used successfully for dialysis grafts and extremity thrombosis for years. Use of similar techniques in the salvage of a pancreas transplant due to venous thrombosis seems reasonable given the higher morbidity of surgical alternatives. A few small series illustrate the use of thrombolysis in the setting of venous thrombosis. However, the patients described (one to five patients in each study) had largely asymptomatic and partial venous thrombosis. Urokinase bolus therapy normalized flow in the majority of the patients so treated [21, 23, 24]. Another group described the use of chemical or pharmacomechanical thrombolysis in patients with leg swelling due to iliac venous thrombosis on the side of recent pancreatic transplantation . However, these patients had intact pancreas graft venous drainage and this series involved treatment of clot upstream from a patent pancreatic venous anastomosis. Our patients were all symptomatic on the basis of local pain over the transplanted pancreas and significant spikes in blood glucose postoperatively. One weakness of our study is that we did not search for or include those patients with subclinical and partial graft venous thrombosis, and therefore, we cannot report a true incidence of thrombotic complications in pancreas transplants. However, it is debatable whether asymptomatic thrombus requires such aggressive clot removal or any treatment other than anticoagulation and watchful waiting. Since the majority of the patients (four of six) responded to short-term thrombolytic administration and rheolytic thrombectomy alone, it is likely that most pancreatic graft thromboses are the result of the low-flow environment inherent in pancreatic transplantation. For this same reason, we consider anticoagulation mandatory in these patients postthrombectomy. Two patients required venous stent placement for anastomotic problems, probably related to extrinsic venous compression or kinking. While one of these patients eventually lost graft function, the other patient with venous stents maintains excellent pancreatic function 1 year after treatment. As this study describes a small patient cohort in a retrospective fashion, we cannot comment on the long-term complete or partial patency of the treated donor venous segments since the imaging follow-up was quite limited. However, it is the clinical success of this technique in salvaging half of the pancreas transplants for the long term which is the notable finding in our small series. Since retransplantation is rarely an option in the setting of acute graft venous thrombosis due to organ availability issues, the ability to salvage at least some of these grafts with minimally invasive techniques is even more important.
Early percutaneous endovascular interventions for pancreas transplant venous thrombosis allows graft salvage in half of cases, with bleeding being the most significant complication, occurring in one of six treated patients. Intervention was successful in patients as early as 2 days postoperatively. Prompt pharmacomechanical therapy, thus, may obviate the need for pancreatectomy or early retransplantation.