Efficacy and Safety of Recombinant Human Thrombopoietin on Sepsis Patients With Thrombocytopenia: A Systematic Review and Meta-Analysis

Abstract

Background: The efficacy and safety of the administration of recombinant human thrombopoietin (rhTPO) in sepsis patients with thrombocytopenia were still inconclusive. Objectives: To investigate whether rhTPO is a benefit for sepsis patients with thrombocytopenia. Methods: PubMed, Cochrane library, Embase, China National Knowledge Infrastructure, and Wanfang Database were electronically searched to the randomized controlled trials (RCTs) from inception to March 4, 2020. The primary outcome was the level of platelet (PLT) on the 7 th day of treatment, and secondary outcomes were 28-d mortality, the level of coagulation indicators, hepatic and renal function indicators, blood transfusion, and length of intensive care unit (ICU) stay. Results: Ten RCTs involving 681 patients were included. For compared with conventional antibiotic therapy, rhTPO could significantly increase platelet counts (PCs) [standardized mean difference (SMD), 2.61; 95% confidence interval (CI), 1.28-3.94; P < 0.001], decreased 28-d mortality [relative risk (RR), 0.66; 95%CI, 0.46-0.97; P=0.03], transfusion volume of blood products and length of ICU stay. Additionally, for compared with conventional antibiotic therapy combined with intravenous immunoglobulin, the pooled results shown that rhTPO also associated with an improvement of PCs on 7 th of treatment (SMD, 0.86; 95%CI, 0.54-1.17; P < 0.001), and a reduced transfusion volume of blood products. However, there were no differences in 28-d mortality and the length of ICU stay. Conclusions: Current evidence shown that rhTPO could increase PCs on 7 th day of treatment and reduce the transfusion volume of blood products in sepsis-related

A Network Meta-Analysis of Two Doses of Recombinant Human Thrombopoietin for Treating Sepsis-Related Thrombocytopenia

“…Evidence suggests that patients with sepsis-related thrombocytopenia have longer ICU stays [4] and a worse prognosis [8,10]. As a novel rescue therapy, rhTPO has been shown to be efective in increasing peripheral PLT levels [19], as confrmed by a recent pairwise meta-analysis [15]. Unfortunately, which doses of rhTPO might be optimal for septic patients with thrombocytopenia remains unclear as a direct comparison is absent.…”

“…However, rhTPO 15000 U/ kg/day may be the best option for shortening the ICU stay and increasing peripheral PLT levels on the 7th day posttreatment. Notably, a pairwise meta-analysis [15] determined whether rhTPO is a benefcial strategy in septic patients with thrombocytopenia. Based on pooled results from 10 eligible RCTs, rhTPO was associated with increased PLT levels on the 7 th day posttreatment and decreased blood product transfusions during hospitalization.…”

“…A series of treatments, such as anti-infective therapy, transfusion of PLT, intravenous injection of recombinant human interleukin (rhIL) including rhIL-6 and rhIL-11, intravenous immunoglobulin (IVIG), and administration of platelet-elevating drugs, are currently available for sepsisassociated thrombocytopenia [13][14][15]. Because of the scarcity of resources, transfusion-related complications, and PLT antibody production, the clinical application of PLT transfusion is strictly limited to patients with sepsis [16,17].…”

“…Therefore, rhTPO may be a rescue therapy for septic patients with thrombocytopenia. In addition, a recent meta-analysis demonstrated that in patients with sepsis-associated thrombocytopenia, PLT levels were significantly elevated on the 7 th day after administration of rhTPO, and blood product transfusion volumes were reduced [ 15 ]. Notably, two different dosing regimens of rhTPO, including rhTPO 300 U/kg/day and rhTPO 15000 U/day, were available for treating septic patients with thrombocytopenia, but which dosing regimen might be better remains unclear [ 22 ].…”

Research Advances in the Subtype of Sepsis-Associated Thrombocytopenia

“…A recent systematic review involving 10 randomized controlled trials (RCTs) also agreed that although rhTPO appeared to benefit those patients with SAT, conclusions need to be verified exhaustively by performing additional multicenter RCTs. 64 Heretofore, 2 large-scale RCTs of SAT patients are ongoing, which will provide higher-quality evidence to confirm the efficacy and safety of rhTPO. 65,66 The presence of immune mechanisms in increased platelet destruction subtype provides the potential for immunoglobulins, glucocorticoids, immunosuppressants and plasma exchange.…”