Immature platelet fraction measured on the Sysmex XN hemocytometer predicts thrombopoietic recovery after autologous stem cell transplantation

The average platelet count in humans ranges between 150 and 350 × 109/L 1. Thrombocytopenia, that is, the state of decreased platelet concentration in peripheral blood, may be due to several causes, roughly divided into three main mechanisms: (i) aberrant distribution of platelets due to dilution, bleeding, or splenomegaly, (ii) increased platelet destruction or consumption, and (iii) a decreased platelet production. To correctly diagnose the cause of thrombocytopenia, it is crucial to distinguish between these three mechanisms 2. The assessment of thrombopoietic activity may be useful in differentiating between these three. Immature platelets, newly released from megakaryocytes in the bone marrow, are supposedly a marker of thrombopoietic activity: High immature platelet fraction (IPF) suggests increased thrombopoiesis, where-as low IPF suggests decreased thrombopoiesis 3,4. Immature platelets decrease in size and RNA content as they age, analogous to reticulocytes 5,6. Their characteristics allow us to differentiate immature from mature platelets, not only by flow cytometry, but also on the newest generation hemocytometers 3,7–9. In 1969, Ingram and Coopersmith were the first to show an increase in immature platelets in mature beagles subjected to severe blood loss, reflecting increased thrombopoietic activity 5. Several more recent publications confirmed this observation 2,10–12. This might also be of interest in patients undergoing stem cell transplantation (SCT) for hematological malignancies 7,13–19. In the post-transplant period, patients have a significantly lower concentration of platelets due to a decrease in thrombopoiesis. As platelets play an essential role in primary hemostasis, severe thrombocytopenia is associated with an increased risk of bleeding 20. Studies in thrombocytopenic patients have shown concordance between the onset of bleeding and platelet count. A minimum platelet count of 5 × 109/L is thought to be sufficient to maintain vascular integrity and prevent severe bleeding 21,22. Prophylactic platelet transfusions are administered to prevent severe and life-threatening bleeding in thrombocytopenic patients 23. According to current consensus, prophylactic platelet transfusions are ordered when platelet count falls below a threshold of 10 × 109/L 23–25. Disadvantages of prophylactic transfusions may be major and minor adverse effects for patients, varying from mild transfusion reaction to anaphylaxis or severe infection. Also, high costs and the future shortage of donors should be kept in mind 23. Furthermore, it is debatable whether this prophylactic strategy is actually necessary. Some studies suggest that a therapeutic transfusion strategy is safe in a selected group of stable patients without sepsis, infections or an increased bleeding risk 23,26. A previous study even suggested that platelet transfusions may inhibit thrombopoiesis by binding thrombopoietin 27. A strategy to reduce platelet transfusions in thrombocytopenic patients after SCT may be based on a better prediction of the thrombopoietic recovery. If a reliable prediction of the natural recovery of the platelet number within a few days is feasible, a valid decision whether or not to give a prophylactic platelet transfusion would be facilitated. The number of immature platelets could be used as such a predictor, as various studies have described a rise in the number of immature platelets shortly preceding platelet recovery 13–17,28. Some studies also proposed a cutoff value for immature platelets predicting platelet recovery 18,29. Different definitions of platelet recovery were used in combination with a less standardized, more time-consuming method of measurement of immature platelets. A fundamental step toward the implementation of immature platelets in transfusion management after SCT is defining a reliable cutoff value based on a standardized technique. The aim of this study was to define a cutoff value for immature platelets predicting thrombopoietic recovery using the novel Sysmex XN analyzer (Sysmex corporation, Kobe, Japan).