Reshma Rana Magar, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This systematic review and meta-analysis investigated the role of heparin thromboprophylaxis in simultaneous pancreas-kidney (SPK) transplantation, pancreas after kidney (PAK) transplantation and pancreas transplant alone (PTA). Study selection and data extraction were performed in duplicate. Only 11 studies, all of which were retrospective, were included. However, all the included studies were considered high quality (MINORS score > 60%). The authors found that heparin thromboprophylaxis reduced early pancreas thrombosis and pancreas loss by over two-folds for SPK, PAK and PTA, without resulting in an increase in the incidence of bleeding or acute return to the operating room. Heterogeneity was high for some of the outcomes but was not explored. No adjustments for confounders were made in the analyses.
Expert Review
Reviewer:
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Clinical Impact Rating
2
Review:
Graft thrombosis is a recognised and feared complication of pancreas transplantation, resulting from a thromboinflammatory response and relatively low flow through the graft (1). It is more frequently seen in circulatory death (DCD) grafts and following pancreas transplant alone (PTA) compared to simultaneous pancreas kidney transplant (SPK) (1,2). Most centres employ some form of anticoagulation protocol in the peri-operative period to reduce the risk of thrombosis, although exact protocols vary considerably, and the evidence-base is limited. Use of anticoagulation is often monitored and adjusted using measures such as the activated partial thromboplastin clotting time (APTT) or thromboelastogram (TEG), with limited evidence that TEG monitoring may be beneficial (3,4). In their recent systematic review, Ai Li et al. attempt to summarise the literature regarding heparin thromboprophylaxis following pancreas transplantation (5). They identified 11 studies investigating heparin use in SPK and PTA recipients, of which just 4 were comparative and none were prospective. They conclude that heparinization significantly decreases the risk of early pancreatic thrombosis and graft loss due to thrombosis, with no evidence of increased bleeding or reoperation risk. Whilst the limited amount of observational data published in the literature does appear to support this conclusion overall, there are significant limitations to this study. There is no randomised controlled trial evidence available, and very limited comparative data meaning that the authors resort to comparing single-arm observational data to the control cohorts of other studies. Given the differences in protocols and surgical techniques between centres, the validity of this is uncertain. Even in the four comparative studies, there is significant heterogeneity in treatment protocols and monitoring strategies, meaning that the optimum regimen is unclear. The authors employ fixed effects methods in some of their meta-analysis. Given the heterogeneous and observational nature of the data, the assumptions of a fixed effects analysis are probably not met. Indeed, re-analysis using a random effects model increases uncertainty and loses the significant treatment effects seen in fixed effects analysis. It is unlikely that there is enough equipoise to undertake a large RCT of heparin versus no heparin following pancreas transplantation as most centres now use some form of anticoagulation. However, there is scope for future studies to investigate the optimal protocol and monitoring strategy for anticoagulation, including the use of TEG monitoring.
Aims:
This study aimed to assess the effect of heparin thromboprophylaxis in simultaneous pancreas-kidney (SPK) transplantation, pancreas after kidney (PAK) transplantation and pancreas transplant alone (PTA).
Interventions:
A literature search was performed on PubMed, EMBASE, BIOSIS, MEDLINE, Cochrane Library and Web of Science. Two reviewers independently selected studies for inclusion and extracted the data. Risk of bias was assessed using the Methodological Index for Non-Randomized Studies (MINORS).
Participants:
11 studies were included in the review.
Outcomes:
Outcomes of interest were pancreas thrombosis during early post-transplant period, incidence of postoperative bleeding, pancreas graft loss due to thrombosis, acute return to the operating room, and units of packed red blood cells (pRBC) used.
Follow Up:
N/A
Thrombosis is a leading causes of pancreas graft loss after simultaneous pancreas kidney (SPK), pancreas after kidney (PAK), and pancreas transplant alone (PTA). There remains no standardized thromboprophylaxis protocol. The aim of this systematic review and meta-analysis is to evaluate the impact of heparin thromboprophylaxis on the incidence of pancreas thrombosis, pancreas graft loss, bleeding, and secondary outcomes in SPK, PAK, and PTA. Following PRISMA guidelines, we systematically searched BIOSIS®, PubMed®, Cochrane Library®, EMBASE®, MEDLINE®, and Web of Science® on April 21, 2021. Primary peer-reviewed studies that met inclusion criteria were included. Two methods of quantitative synthesis were performed to account for comparative and non-comparative studies. We included 11 studies, comprising of 1,122 patients in the heparin group and 236 patients in the no-heparin group. When compared to the no-heparin control, prophylactic heparinization significantly decreased the risk of early pancreas thrombosis and pancreas loss for SPK, PAK and PTA without increasing the incidence of bleeding or acute return to the operating room. Heparin thromboprophylaxis yields an approximate two-fold reduction in both pancreas thrombosis and pancreas loss for SPK, PAK and PTA. We report the dosage, frequency, and duration of heparin administration to consolidate the available evidence.
CET Conclusion