Recombinant human thrombopoietin improves platelet counts and reduces platelet transfusion possibility among patients with severe sepsis and thrombocytopenia: A prospective study

Wu, Qin; Ren, Jianan; Wu, Xiuwen; Wang, Gefei; Gu, Guosheng; Liu, Song; Wu, Yin; Hu, Dong; Zhao, Yunzhao; Li, Jieshou

doi:10.1016/j.jcrc.2013.11.023

Cited by 31 publications

(30 citation statements)

References 23 publications

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“…Thrombocytopenia is one characteristic of sepsis that increases the risk of death [17]. Research proves that thrombocytopenia is associated with sepsis, prolonged hospital stays, and increased mortality [18]. The present study found statistically significant differences between patients with septic shock and those with non-septic shock on day 3 and day 5, yet there were no significant differences between these patients on the day of injury.…”

Section: Discussionmentioning

confidence: 39%

The significance of changes in platelet concentration during the early phase after severe burn injury in a Chinese mass casualty

Shou

et al. 2017

Burns &Amp; Trauma

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BackgroundChanges in platelet concentration are common in severe burn patients. Platelets play a key role in the course of disease. This study aims to explore the significance of platelet concentration during the course of the disease in victims of a mass burn casualty.MethodsA total of 180 patients were involved in the “8.2” Kunshan explosion accident in China. The examined data included age, gender, total burn area (% TBSA), third-degree burn area (% TBSA), and platelet concentration within the first 5 days after the burn injury. The patients were divided into two groups according to four indicators (resuscitation, acute respiratory distress syndrome, acute kidney injury, septic shock). We collected several types of data for the patients and divided the patients into a complication group and non-complication group according to the diagnostic criteria. We analyzed the platelet concentration of the two groups using t tests to determine whether significant differences were present. P values < 0.05 were considered statistically significant.ResultsThe group with successful resuscitation had higher platelet concentration than the failure group on day 3 and day 5. The patients who suffered from acute kidney injury (AKI) and septic shock had a lower platelet concentration than non-sufferers on day 3 and day 5.ConclusionsThe platelet concentration of burn patients can dynamically reflect the pathophysiological changes of the body. It can be used as an early objective indicator of prognosis in mass burn casualty cases.

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Section: Discussionmentioning

confidence: 39%

The significance of changes in platelet concentration during the early phase after severe burn injury in a Chinese mass casualty

Shou

et al. 2017

Burns &Amp; Trauma

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“…[38][39][40] The mechanism of MMP-9 downregulation by TPO might be related with the activation of EGR- Recombinant human TPO has been used in the clinics in China for more than 10 years. 15,16 In recent years, the new generation of TPO receptor agonists, such as romiplostim and eltrombopag, have been proved to have clinical efficacy in increasing platelet counts in thrombocytopenia via modulating the TPO receptor. 41,42 Given that recombinant human TPO has been widely used in the hospital in China, we further conduct clinical trials to observe the role of TPO in improving engraftment of transplanted HSPCs in patients with SAA or hematologic malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…14 Given that homing of HSPCs to the BM is the first and critical step for subsequent HSPC engraftment, we are wondering whether TPO regulates the homing of HSPCs to the BM niche, a process that occurs within hours after transplantation. Considering the clinical use of recombinant human TPO in the treatment of thrombopenia, 15,16 further research on its role in affecting HSPC homing to the BM will represent a valuable and rapid pathway for identifying drugs that improve HSPC engraftment efficiency.…”

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confidence: 99%

Thrombopoietin enhances hematopoietic stem and progenitor cell homing by impeding matrix metalloproteinase 9 expression

Liu¹,

Ding

Zhang

et al. 2020

Stem Cells Translational Medicine

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We reported a novel function of recombinant human thrombopoietin (TPO) in increasing hematopoietic stem and progenitor cell (HSPC) homing to the bone marrow (BM). Single doses of TPO treatment to the recipients immediately after BM transplantation showed significantly improved homing of HSPCs to the BM, which subsequently resulted in enhanced short-and long-term engraftment of HSPCs in mice. We found that TPO could downregulate the expression and secretion of matrix metalloproteinase 9 in BM cells. As a result, SDF-1α level was increased in the BM niche. Blocking the interaction of SDF-1α and CXCR4 on HSPCs by using AMD3100 could significantly reverse the TPO-enhanced HSPC homing effect. More importantly, a single dose of TPO remarkably promoted human HSPC homing and subsequent engraftment to the BM of nonobese diabetic/severe combined immunodeficiency mice. We then performed a clinical trial to evaluate the effect of TPO treatment in patients receiving haploidentical BM and mobilized peripheral blood transplantation. Surprisingly, single doses of TPO treatment to patients followed by hematopoietic stem cell transplantation significantly improved platelet engraftment in the cohort of patients with severe aplastic anemia (SAA). The mean volume of platelet and red blood cell transfusion was remarkably reduced in the cohort of patients with SAA or hematological malignancies receiving TPO treatment. Thus, our data provide a simple, feasible, and efficient approach to improve clinical outcomes in patients with allogenic hematopoietic stem cell transplantation. The clinical trial was Yiming Liu and Li Ding contributed equally to this work.

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“…For sepsis, a retrospective study in elderly sepsis patients with thrombocytopenia reported that rhTPO increased PCs, reduced bleeding events, recovered organ function [39]. And rhTPO could rapidly restore PCs in 76.32% of patients with thrombocytopenia within 5 days, reduce the number of platelet transfusion and 28-day mortality in perioperative patients with abdominal infection [40]. However, there are the limitations in these two trials: 1) sepsis patients both were diagnosed by sepsis-1.0 standard; 2) PCs of whom was less than 100 × 10 9 /L;…”

Section: Discussionmentioning

confidence: 99%

The effect of recombinant human thrombopoietin (rhTPO) on sepsis patients with acute severe thrombocytopenia: a study protocol for a multicentre randomised controlled trial (RESCUE trial)

et al. 2019

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Background: Sepsis is still a common critical disease with high morbidity and mortality in intensive care unit. Despite published guidelines for sepsis, development of antibiotic therapy and advanced organ support technologies, the mortality of sepsis patients is still 25% or more. It is necessary to distinguish the subtypes of sepsis, and the targeted therapy for the patients need to be explored. Platelets have various biological functions in hemostasis and thrombosis, host defense, inflammatory/immune responses and tissue repair/regeneration. Moreover, severe thrombocytopenia or sustained thrombocytopenia was closely associated with multiply organ dysfunction and higher mortality in sepsis patients. The clinical therapies for thrombocytopenia are platelet transfusion and platelet-elevating drugs. However, platelet transfusion has many defects in clinical practice in sepsis patients, and the impact of platelet-elevating drugs for sepsis patients is still unclear. RESCUE trial is aim to explore the effect of a platelet-elevating drug, recombinant human thrombopoietin (rhTPO), as an effective rescue therapy on sepsis patients with acute severe thrombocytopenia. Methods: It is a randomized, open-label, multi-center, controlled trial in 5 tertiary academic hospitals including medical, surgical or general ICUs. In this study, a total of 200 sepsis patients with severe thrombocytopenia will be randomly assigned in a 1:1 ratio to the control and rhTPO group. The patients will be followed up to 28 days after randomization. All patients in two groups receive the same treatment based on the guideline of Surviving Sepsis Campaign. Primary outcome is 28-day mortality. Secondary outcomes are the changes of PCs, blood transfusion, biomarkers of infection and organ function, days free from advanced organ support, drug-related adverse events, the length of ICU and hospital stay. Discussion: RESCUE trial is the first randomized controlled trial to explore the impact of rhTPO for severe thrombocytopenia in sepsis patients diagnosed by sepsis-3.0 standard. Furthermore, RESCUE trial results will be of significant clinical value on the targeted therapy and add clinical evidence that rhTPO is an effective rescue therapy for these sepsis patients.

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Recombinant human thrombopoietin improves platelet counts and reduces platelet transfusion possibility among patients with severe sepsis and thrombocytopenia: A prospective study

Cited by 31 publications

References 23 publications

The significance of changes in platelet concentration during the early phase after severe burn injury in a Chinese mass casualty

The significance of changes in platelet concentration during the early phase after severe burn injury in a Chinese mass casualty

Thrombopoietin enhances hematopoietic stem and progenitor cell homing by impeding matrix metalloproteinase 9 expression

The effect of recombinant human thrombopoietin (rhTPO) on sepsis patients with acute severe thrombocytopenia: a study protocol for a multicentre randomised controlled trial (RESCUE trial)

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