Nomogram for the Therapeutic Efficacy of Apheresis Platelet Transfusion in Hematologic Patients

Platelets are widely used to treat or prevent bleeding, especially in patients with hematologic diseases [1]. About 10 million patients receive platelet transfusions every year, and among them, up to 67% have hematologic diseases; furthermore, the number of transfusions increases annually [2, 3]. However, for patients who receive long-term platelet transfusions, there might be cases of platelet transfusion refractoriness(PTR), such as failure to improve clinical symptoms or inadequate increase in platelet count after two or more consecutive transfusions of sufficient amount [4, 5]. PTR has caused unnecessary waste of blood platelets, making the already tight supply of blood platelets even more in short supply [6]. PTR can be caused by non-immune and immune factors. Among them, non-immune factors, such as fever, bleeding, spleen enlargement, disseminated intravascular coagulation (DIC), graft-versus-host disease (GVHD, drugs( such as amphotericin, vancomycin, etc.), longer platelet storage time and poor platelet quality, are the dominant ones, accounting for approximately 80% [7‐9], while the remaining 20% are caused by immune factors, include human leukocyte antigen (HLA) antibodies, platelet alloantibodies, ABO antibodies and drug-dependent autoantibody [10, 11]. Currently, most studies discuss the factors that affect the efficacy of platelet transfusions from the perspectives of patient factors and platelet product quality [9, 12‐14]. However, only a few studies have analyzed if the relevant factors of blood donors affect the effectiveness of platelet transfusion. Therefore, this study incorporates patient, platelet product, and blood donor factors into its analysis to establish a predictive model of efficacy, predict the probability of achieving satisfactory transfusion effects in patients with hematologic diseases, reduce the occurrence of ineffective transfusions, and guide clinical platelet transfusion.

The hematopoietic system in the bone marrow of patients with blood disease is suppressed or even destroyed due to disease reasons, and platelet production and maturation are hindered. These patients usually need to receive repeated platelet transfusions to prevent or treat bleeding [16]. However, not every infusion can achieve satisfactory results. Both immunological and non-immunological factors contribute to the occurrence of PTR [17]. Moreover, individual variations significantly impact the effectiveness of platelet transfusion outcomes. In current study, the immunological factor is platelet antibody, and other factors are all non-immunological factors.

Logistic regression analysis found that the age, body mass index, pre-donation platelet count, and number of platelet donations of blood donors had no significant effect on the effectiveness of patient transfusion. Numerous studies have consistently demonstrated an elevated risk of mortality in patients receiving red blood cells donated by female blood donors. However, in the realm of platelet transfusion, no research has identified gender as a factor that contributes to an increased risk of adverse events [18‐20]. Consistent with these findings, our study likewise did not uncover any significant influence of gender on the effectiveness of platelet transfusion. It may be that we strictly screen blood donors during platelet collection, and the collection process is strictly implemented according to requirements. Each bag of apheresis platelets meets the requirements for clinical infusion. Although the factors of blood donors currently included in the analysis have no significant impact on the infusion effect, it cannot be confirmed whether other factors, such as the lifestyle, pregnancy history and medication history of blood donors, will affect the infusion effect. This remains to be further investigated and analyzed. The extended storage time of platelets will reduce the efficiency of infusion. Studies have shown that the extended storage time will reduce the number and aggregation function of platelets, while increasing the release of inflammatory factors, especially after the third day, resulting in a decrease in the efficiency of platelet infusion [9, 21, 22]. Therefore, we recommend that for patients with poor conditions and requiring long-term multiple platelet transfusions, try to give them more fresh platelets.

The blood indicators before platelet transfusion considerably affect transfusion efficacy. Patients with near-normal WBC counts and Hb before transfusion have a mild condition, and the destruction of bone marrow hematopoiesis is minimal, which increases the effectiveness of transfusion. However, excessive PLTs before transfusion can reduce the efficiency of transfusion, so the threshold for platelet transfusion must be controlled when PLTs are too high to avoid preventive transfusion. An increase in the body mass index and blood volume of patients reduces the increase in PLTs after transfusion [15]. Therefore, patients should control their weight to prevent excessive blood volume from weakening the infusion effect.

In agreement with existing data, our data indicate a high risk of poor PLT increment associated with the presence of platelet antibodies and increased numbers of transfusions [13]. We found that patients who had myelodysplastic syndrome had a higher risk of refractoriness to platelet transfusion compared with patients who had acute leukemia [23, 24]. However, after controlling for confounding factors, the multivariable logistic regression suggested that myelodysplastic syndrome did not considerably affect the efficacy of platelet transfusion. However, when patients are transfused with platelets, the effectiveness of the transfusion will be greatly reduced if they have a fever, GVHD, splenomegaly, and bleeding. The rise in body temperature due to fever stimulates an increase in the release of inflammatory factors and tumor necrosis factors. Additionally, this elevation in temperature facilitates blood circulation, which subsequently accelerates the destruction of platelets by the mononuclear macrophage system [14]. Changes in the spleen cause platelets to be retained, concurrently augmenting the phagocytic activity of macrophages, ultimately leading to an increased destruction of platelets. Therefore, patients should control their body temperature before receiving platelet transfusions, and platelet transfusions should not be performed on patients with a high fever unless the case is an emergency. We recommend splenectomy for patients with spleen enlargement and surgical indications. Platelets after hematopoietic stem cell transplantation and irradiation do not reduce the efficiency of transfusion.

The nomogram is a commonly used tool in medical research. It integrates different factors on the basis of clinical characteristics, making the regression analysis visual and intuitive in revealing the effects of different factors on outcomes [25‐27]. Although all the factors in the nomogram model influence the infusion effect, the nomogram we constructed showes the state of platelet infusion exerts a much greater effect on the infusion than the number of platelet infusions and the storage days of platelet products. Current research on the efficacy of platelet transfusion focuses on analyzing the influencing factors through transfusion efficacy, and models for predicting outcomes are lacking. In this study, we obtained the independent risk factors that affect transfusion efficacy through logistic regression analysis. With the help of R software, we established a predictive nomogram model that combines multiple clinical factors to quantitatively calculate the probability of obtaining effective transfusion for patients, which can help clinicians implement measures in advance.

The AUC of the predictive model constructed by R software in this study was 0.756, and the calibration curve obtained through internal validation was similar to the real one, indicating that the model has good diagnostic value. The limitation of this study is the lack of external validation. In the future, cooperation with other medical centers should be established to prevent model overfitting and obtain an accurate predictive model, thereby further improving the efficiency of platelet transfusion.