Reply to: Is platelet transfusion necessary in cirrhotic patients with splenomegaly?

To the Editor: We read with interest the Letter by Yates and Sarode (1) concerning our paper on global hemostasis tests in patients with cirrhosis before and after prophylactic platelet transfusion published recently in Liver International (2) and we would like to comment on the following aspects. We wish to point out that our paper (2) was mainly concerned to describe the behavior of two ex-vivo tests (i.e., thrombin generation in plateletrich plasma and thromboelastometry in whole blood) that although not specifically designed to explore the function of platelets in vivo are those that mimic much more closely than any other conventional test the contribution of platelets to thrombin generation and clot formation. Incidentally, we wish to remind that this approach was never tested in patients with cirrhosis undergoing platelet transfusion. We showed that one adult platelet unit is unable to increase substantially the platelet count in these patients and that the two tests were scarcely affected by the infusion. At variance with Yates and Sarode (1) we maintain that the practice of infusing one single adult platelet unit, regardless of the baseline platelet count is common among clinicians. In addition, it should be noted that the recent recommendations for liver biopsy issued by the American Association for the Study of the Liver (3) suggest to consider prophylactic transfusion when platelet counts are less than 50 9 10/L. Finally, a recent study was undertaken to investigate the value of drug-induced platelets increase in patients with cirrhosis undergoing invasive procedures and was interrupted prematurely because of an increased number of thrombotic events in the active arm of the study (4). All the above considerations lead to the conclusion that platelet count restoration in patients with cirrhosis prior to invasive procedure is considered a relevant issue by the medical community and should therefore be investigated with appropriate clinical trials to establish the threshold platelet count that is clinically effective and the laboratory tools to judge on efficacy. In this respect, we believe that our study can be considered as a contribution to reach this goal. The argument of Yates and Sarode (1) that we should have used in our experiments platelet-rich plasma from healthy subjects (2) does not appear to be appropriate as we investigated under the same experimental conditions both preand post-infusion platelet-rich plasmas. Hence, we were in the optimal experimental situation to see any meaningful difference in thrombin generation or thromboelastometry after platelet transfusion. We agree with Yates and Sarode (1) that red blood cells may contribute to thrombin generation. However, it should be noted that while thrombin generation in platelet-rich plasma does not account for this effect, thromboelastometry (that uses whole blood) should do. We agree with Yates and Sarode (1) that sequestration of platelets owing to splenomegaly may have occurred in our patients and could therefore be the likely explanation for the poor increase of peripheral platelet counts and consequently thrombin generation/thromboelastometry after transfusion. However, it could be argued that sequestered platelets are unlikely to support thrombin generation within the systemic circulation and therefore the conditions of our experiments are likely to mimic what presumably occurs in vivo. Finally, we wish to point out that we did not suggest (or recommend) in any part of this (2) nor in other manuscripts (5) the use of platelet transfusion in patients with cirrhosis. We are fully aware and mentioned specifically in the manuscript that in cirrhosis not only coagulation is rebalanced (6), but also primary hemostasis (i.e. platelet-vessel wall interaction) is somewhat restored because of the increasing levels of von Willebrand factor that may compensate for the defect of platelet numbers and function (7). Because of this, caution should be exerted in making decision for transfusion of platelet or plasma (or other procoagulant factors) in these frail patients (5, 6). This has been stated clearly in the last part of the discussion (2).