Two key factors led us in deciding to offer LT to JW patients. The first was our large experience in the procedure. In fact, we transplanted our first JW patient in 2007, 11 years and 930 procedures from the start of our LT program in 1996. The second was the rate of bloodless LT characterizing our activity in the years prior to that decision6. In our experience, a careful selection of recipients was a key-player as we decided to admit JW patients to the pre-LT screening only if they did not show indicators of severe portal hypertension since bleeding in LT is predominantly linked to portal hypertension rather than primary coagulopathy9-13. Thus, early referral and careful timing for listing is highly desirable in these patients. Predicting cases requiring peri-operative transfusions is very desirable, particularly in JW patients, but it remains a very difficult task in LT9, 12-13. In fact, despite several investigations have attempted to identify preoperative predictors of blood transfusion, their value remain inconsistent and weak3, 9-15. In recent years, models to predict blood utilization with preoperative variables have been proposed12, 15-16. However, their limitations and differences in the results highlight significant concerns about their generalizability and recognize that it may be very difficult to develop a single, reliable, and universally applicable model to predict transfusion requirements for patients undergoing LT. In our series, the use of techniques that minimize blood loss played a major role. The adoption of a fluid restriction policy and low CVP is important as it results helpful in decreasing blood transfusion requirements during LT9, 17. In fact, liberal volume loading in cirrhotic patients tends to pool in the splanchnic circulation with minimal improvement in cardiac preload or output but increased risk of surgical bleeding because of congestion of the portal circulation10-11, 16. Moreover, dilution of clotting factors and clot disturbance can result, particularly if colloids are used 3, 14. Further, lowering the pressure in the central veins can help in minimizing blood loss also because it may augment venous drainage from the liver, encouraging flow of blood away from the surgical field10-12-13. Other intra-operative blood conservation strategies can be important to achieve transfusion-free surgery. In our JW patients we performed ANH but only in selected patients in order not to excessively dilute clotting factors, including PLT. Finally, in the view of a multimodal strategy aimed at reducing blood loss10, we used in all cases the veno-venous bypass to minimize the impact of mesenteric congestion and abdominal bleeding during portal and caval cross-clamping18. In case of peri-operative coagulopathy, since JW will not accept fresh frozen plasma or platelets, the use of coagulation factor concentrates and/or tranexamic acid guided by rotational thromboelastometry (ROTEM®) or thrombelastography (TEG™)9-12 should be considered. Therefore, the use of fibrinogen concentrate (which can support fibrin clotting without transfusion of PLT), clotting factors concentrates and tranexamic acid should be explained and proposed to these patients in the consideration that acceptance of blood fractions by JW depends on patient’s free will, apart from church doctrine1, 5, 14. Regarding the use of recombinant erythropoietin to optimize red cell mass, it has a number of potential benefits. The most obvious is that patients will start LT with a higher blood Hb level that, besides enabling use of ANH10-11 , correlates with peri-operative low or no use of red blood cells transfusion3, 19. Since erythropoietin’s use was associated to a possible risk of thromboembolism19 , we performed regular clinical and laboratory monitoring of LT candidates on erythropoietin treatment also in consideration that the waiting time for a suitable deceased donor is unpredictable. The use of ICS in patients with hepatocellular carcinoma could be discussed because of the potential risk of infusing malignant cells into patients. To date, 4 studies have evaluated the oncological safety of using ICS in LT. One concluded that the device is effective in removing malignant cells from the aspirate, except in cases of tumor rupture whereas the other 3, evaluating clinical outcomes such as mortality and recurrence, did not demonstrate negative effects associated with the use of ICS20. On the contrary, the use of cell salvage during LT for hepatocellular
carcinoma has been found to reduce the exposure to allogeneic blood and to be cost-effective21. In summary, also according to the most recent guidelines22, despite theoretical risks and benefits, there is no conclusive evidence that ICS can induce metastases or affect cancer prognosis. The theoretical risk of inducing metastatic spread (unproven) is offset by reduced allogeneic transfusion and immunomodulation, which is proven22.
Few other cases of LT in JW have been reported so far and, since the first one ever in 199423, our series is, to the best of our knowledge, the second most numerous overall and the largest from deceased donors. In fact, Jabbour and colleagues from University of Southern California reported in 2005 the results of 27 consecutive LT in JW patients, 19 from living and only 8 from deceased donors whereas Detry and colleagues reported 6 cases from Liege in Belgium24,7. Other smaller case series are available from different countries25-27.
It is undeniable that a rather diffused concern exists about offering LT to JW patients. In fact, the acceptance of solid organ transplantation and contemporary refusal of transfusion are hardly understandable for non-JW. However, it is important to remember that, as far as organ transplants are concerned, each Witness is called on to decide personally whether to accept them or not, with the proviso that no part of the transplantation process may include the use of blood or its main fractions1, 5,14. Therefore, each JW patient should be interviewed individually excluding external pressure and the use of every available peri-operative option aimed at a blood sparing management, including the use of factors and fibrinogen concentrates, should be carefully discussed and clarified. Since our patients have been transplanted over a period of 10 years, it could be argued that peri-operative management policies could have changed during this period with a possible effect of time on results. However, no substantial changes in clinical care of recipients were made during the considered period and there was also consistency in anesthesiology and perioperative treatments.
In summary, we herein presented the results of the largest LT program from deceased donors in JW patients that has been reported so far. Our experience shows that the risk-to-benefits ratio of LT can be maintained in selected adult JW patients provided that it is carried out at a very experienced centre and according to a multidisciplinary approach. We reported our experience in the aim to offer a template for a broader concept of transfusion-free surgery principles rather than as a focus on a technical achievement in such a complicated clinical setting. Anesthesiologists, as users of blood products, are called to lead a continuous re-evaluation process aimed at defining the most proficient approach to bloodless surgery and at contributing to the debate about benchmarking in difficult clinical scenarios.