The present study demonstrates that platelet transfusion in sepsis patients with severe thrombocytopenia is not associated with 28-day mortality or LOS-ICU. This result was robust in the PSM analysis after adjustment for covariates including platelet counts and SOFA scores. According to our findings, it seems that platelet transfusion is not a reasonable choice to correct sepsis-induced thrombocytopenia, aiming at improving the prognosis of sepsis patients with severe thrombocytopenia.
A low platelet count, thrombocytopenia, commonly occurs in sepsis patients. According to previous research, nearly 35–59% of patients with sepsis develop thrombocytopenia(18, 19), which has been recognized as an independent risk factor for mortality and a marker for disease severity(20). Moreover, it is also an important index to evaluate the prognosis of patients(21). Sepsis patients with a low platelet count or dynamic thrombocytopenia show a poor prognosis and increased mortality (22). There are several main mechanism of developing thrombocytopenia in sepsis patients: 1) bacteria and their products directly inhibit bone marrow hematopoietic function and destroy megakaryocytes, which results in decreased platelet production; 2) platelet aggregation and destruction are increased due to the host's own immunity and other factors, such as nonspecific platelet-associated antibodies and cytokine-driven hemophagocytosis of platelets (23); 3) activated platelet mediate the reaction between leukocytes and endothelial cells by secreting cytokines, which amplifies the host inflammatory response and further reduces the number of platelet in the circulation via positive feedback; 4) fluid resuscitation and surgical operation may have an influence on platelet count.
Sepsis patients with platelet counts less than 50 x 109/L are considered to have sepsis-induced thrombocytopenia (24), which has a high mortality and poor prognosis. It was reported that non-resolution of thrombocytopenia was associated with increased 28-day mortality, instead of thrombocytopenia itself (9). Currently, there is no effective treatment for this condition. Infection control, organ support therapy and immune response regulation remain the mainstream treatments. In recent years, recombinant human thrombopoietin (rhTPO) was reported improving platelet count and reducing platelet transfusion possibility among patients with severe sepsis and thrombocytopenia in a prospective study (11). In another research, it suggested that rescue therapy with rhTPO could rapidly lead to a recovery of the platelet count, increase survival days and reduce the 28-day mortality in sepsis patients with severe thrombocytopenia (25). Nevertheless, Yu Liu et al. found that rhTPO is efficacious in increasing the patients' platelet counts, resulting in a shorter ICU stay time (9.20 ± 5.38 vs 10.88 ± 6.82, p = 0.047) for patients with severe thrombocytopenia or patients with severe sepsis, while there was no significant difference in 28-days mortality ( rhTPO group: 25.0% vs. control group: 34.1%, p = 0.158) between the two groups (26). Therefore, whether patients with sepsis-induced thrombocytopenia can benefit from rhTPO therapy still remains a question according to the controversial results.
Platelet transfusion is a regular clinical practice in thrombocytopenic patients for preventing or treating hemorrhages. Approximately 1,937,000 platelet component transfusions are given in the United States in 2017(27). There are some evidences suggesting that platelet transfusion is associated with adverse effects including infection (28). Some experts believe that conventional platelet transfusion therapy may worsens patient's procoagulant and anticoagulant disorders. However, the other study noted that platelet transfusion was not associated with increased mortality or infective complications following first cardiac surgery (29). A recent publication by Ning S and colleagues reported that platelet transfusions were not associated with increased risk of death in critically ill patients neither in ICU (HR, 0.78; 95%CI, 0.60–1.02; p = 0.41) nor in hospital (HR, 0.89; 95%CI, 0.68–1.09; p = 0.41)(16). In our study, we found nearly the same result among sepsis patients with thrombocytopenia, that platelet transfusion was not associated with increased risk of 28-day mortality or LOS-ICU. Regarding to our negative finding, platelet transfusion cannot benefit patients with sepsis-induced thrombocytopenia, which may also put patients into a potential risk of infection, it is reasonable to avoid unnecessary transfusions.
In present study, there are still several limitations. Firstly, as a retrospective design, the adjustment of relevant but missing data was not allowed. Although we did perform propensity score matching to reduce the imbalance, estimation of the propensity score could only be based on the acquirable data. Secondly, bacteria species and sources that were not recorded in our data could not be included in the analysis. Thirdly, patients who have been administrated with β-lactam or sulfa antibiotics, which may result in antibiotic-induced thrombocytopenia, did not excluded in this study. Lastly, well-organized prospective randomized clinical trials are required to analyze the role of platelet transfusion in sepsis-induced thrombocytopenia and identify patients most likely to benefit from platelet transfusion.