Sepsis-associated Thrombocytopenia and Platelet Transfusion （STAPT）

Sepsis is the most common cause of thrombocytopenia in intensive care unit (ICU) patients, with an incidence rate as high as 35%-59%. Severe thrombocytopenia (≤50×10⁹/L) accounts for 30% of cases, and the degree of thrombocytopenia is positively correlated with mortality risk \[1-3\]. Studies have shown that patients with sepsis-associated thrombocytopenia (SAT) not only experience prolonged ICU stays and mechanical ventilation duration but also have significantly increased rates of major bleeding events and renal replacement therapy. Meanwhile, the 28-day mortality rate rises with the severity of thrombocytopenia \[4, 5\]. Platelets play a dual role in sepsis: on one hand, they act as "innocent bystanders" reflecting disease severity; on the other hand, they participate in the pathological process through immune regulation and microvascular protection. For example, platelets contribute to host defense by facilitating neutrophil extracellular traps (NETs) formation mediated by Toll-like receptor 4 (TLR4), but a reduction in platelet count can lead to impaired endothelial barrier function, exacerbating organ edema and bleeding risk \[6, 7\]. Furthermore, dynamic changes in platelet morphological parameters, such as mean platelet volume (MPV) and platelet distribution width (PDW), are independently associated with inflammatory response and mortality, highlighting the importance of platelet function monitoring \[8\].

In clinical practice, the primary goal of exogenous platelet transfusion in SAT patients is to rapidly increase circulating platelet counts in cases of inadequate platelet production or excessive consumption, thereby reducing bleeding risk. Due to the complex mechanisms of thrombocytopenia in sepsis-including bone marrow suppression, peripheral consumption (e.g., disseminated intravascular coagulation (DIC), immune-mediated destruction), and splenic sequestration-endogenous platelet recovery is often delayed. Exogenous transfusion provides immediate platelet supplementation, particularly for patients with severe thrombocytopenia (≤50×10⁹/L) accompanied by bleeding tendencies or those requiring invasive procedures (e.g., surgery, central venous catheterization) \[9\]. Compared to endogenous platelet production (which typically takes 5-7 days), exogenous transfusion helps to rapidly correct hemostatic function, reduce the risk of spontaneous bleeding (such as gastrointestinal or intracranial bleeding); improve endothelial barrier function, decrease microvascular leakage, thereby alleviating organ edema and hypoxic injury; and provide platelets with immunomodulatory activity, potentially regulating excessive inflammatory responses through the release of anti-inflammatory factors (e.g., TGF-β, IL-10) \[10, 11\].

However, current treatment strategies for SAT remain controversial. Some studies indicate that platelet transfusion may increase in-hospital mortality, particularly in patients with severe thrombocytopenia (≤50×10⁹/L), where transfusion is associated with higher 28-day and 90-day mortality rates, along with risks such as transfusion reactions and alloimmunization \[12, 13\]. Potential mechanisms include: the inflammatory microenvironment in septic patients may cause rapid activation or destruction of transfused platelets, reducing transfusion efficacy; allogeneic platelets may carry pro-inflammatory mediators (e.g., mitochondrial DNA, high mobility group box 1 (HMGB1)), further exacerbating systemic inflammatory response; and transfusion-related complications, such as transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and alloimmune reactions, may contribute to adverse clinical outcomes \[14, 15\]. Additionally, recent studies have found that platelet function may be impaired in septic patients (e.g., increased glycoprotein Ibα (GPIbα) shedding), leading to reduced adhesion and aggregation capacity of transfused platelets and potentially worsening endothelial dysfunction \[16\].

Previous studies on platelet transfusion and outcomes in SAT patients were all based on database analyses. The results showed that platelet transfusion in septic patients with thrombocytopenia was associated with increased mortality \[17, 18\]. Currently, there are no multicenter studies on platelet transfusion specifically for SAT patients, and the benefits and risks of platelet transfusion still require further validation based on large-sample data.

In summary, investigating the correlation between platelet transfusion during ICU stay and 28-day mortality in SAT patients, as well as evaluating the impact of platelet transfusion on bleeding and thrombotic events and inflammation control, is of great significance for optimizing SAT management strategies. This study aims to analyze the effect of platelet transfusion on the prognosis of SAT patients, thereby providing an evidence-based foundation for clinical decision-making.

• Bleeding events [Time frame: Within 28 days from ICU admission or at the time of ICU transfer/discharge.]
• Thrombotic events [Time frame: Within 28 days from ICU admission or at the time of ICU transfer/discharge.]
• ICU length of stay within 28 days [Time frame: within 28 days after ICU admission]
• Platelet transfusion therapy-related endpoints [Time frame: Post-transfusion day 1, 3, 5, and 7]
• Laboratory indicator-related endpoints [Time frame: Post-transfusion day 1, 3, 5, and 7]