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Authors: Patrick Starlinger, Christine Brostjan, Thomas Gruenberger
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. We want to thank Alkozai et al. for their interest in our work and the concomitant illustration of their observations. In our recently published investigation, we reported intraplatelet (IP) 5‐hydroxytryptamine (5‐HT) levels to significantly decrease on the first postoperative day (POD) after liver resection. This effect was observed for the total IP 5‐HT pool as well as after adjustment for circulating platelet counts. Importantly, we were able to document that perioperative IP 5‐HT levels were associated with postoperative liver dysfunction and morbidity in patients undergoing liver resection. Alkozai et al. here report on their results in a similar setting, in which the investigators chose platelet‐rich plasma to determine perioperative IP 5‐HT levels per platelet in 16 patients undergoing a right hemihepatectomy. However, in contrast to our results, they were unable to detect a reduction in IP 5‐HT levels immediately (on POD 1) after liver resection. During the past years, we have gained expertise in highly standardized platelet‐poor plasma preparation to avoid artificial platelet activation during blood processing, which might substantially affect the measurement of factors stored in platelet granules.1 We applied this technique to determine IP 5‐HT by subtracting plasma from serum 5‐HT values reflecting the total IP pool. While we also analyzed platelet extracts, we specifically chose to use IP 5‐HT levels obtained by this highly standardized methodology to avoid potential fluctuations introduced by platelet isolation and protein extraction. However, 5‐HT determined in platelet extracts was also significantly decreased after liver resection. Thus, to adequately assess IP 5‐HT content, it is important to exclude already released, circulating plasma 5‐HT. This might either be achieved by subtracting circulating plasma 5‐HT from serum levels or by preparation of platelet extracts. In contrast, the analysis of platelet‐rich plasma lacks the ability to distinguish between circulating and IP 5‐HT, which may account for the divergent results by Alkozai et al. Furthermore, the number of investigated patients (N = 16) may limit the statistical power, as compared to our investigation (35 patients in the exploration set and 25 in the validation set). Additionally, Alkozai et al. measured IP 5‐HT in the portal, as well as the hepatic, vein after parenchymal transection (at the onset of liver regeneration). Similarly, in a currently ongoing trial (ClinicalTrials.gov identifier: NCT02113059) we apply our standardized serum‐plasma subtraction method and platelet extract preparation to evaluate the IP 5‐HT loss during liver passage. Whereas our preliminary evaluation (15 patients) suggests a reduction of IP 5‐HT in the hepatic vein, final results of this study will ultimately have to determine whether 5‐HT is specifically released in the initial period after liver resection. Taken together, measurement of IP 5‐HT requires a highly standardized method excluding plasma levels.3 We propose that the choice of blood specimen (platelet‐rich plasma) and limited number of patients may account for the seemingly contradictory results of Alkozai et al.