May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department?

Segre, Elisabetta; Pigozzi, Luca; Lison, Davide; Pivetta, Emanuele; Bosco, Ornella; Vizio, Barbara; Suppo, Umberto; Turvani, Fabrizio; Morello, Fulvio; Battista, Stefania; Moiraghi, Corrado; Montrucchio, Giuseppe; Lupia, Enrico

doi:10.1515/cclm-2014-0219

Cited by 19 publications

(20 citation statements)

References 12 publications

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“…21 In strong contrast, we directly demonstrate that supra-steady-state enhanced Mpl stimulation drives dormant HSCs into division and expansion, a situation that might occur, for example, in sepsis-mediated inflammation. 22,23 Indeed, prior studies demonstrated that Tpo and Mpl signaling is essential for HSC homeostasis 24,25 and their expansion after transplantation, 25 whereas, seemingly contradictorily, other studies demonstrated that Tpo and Mpl signaling is critical for keeping HSCs in a quiescent state. 12,24 We suggest that this discrepancy might result from Mpl signaling strength: although data on HSC quiescence stem from loss-of-function studies, 12,24 we examined here the effect of supra-steady-state Mpl signaling, more comparable to studies on higher doses of thrombopoietin administration 12 or on genetic deficiency of lymphocyte adaptor protein, a negative regulator of Tpo-induced signaling.…”

Section: Resultsmentioning

confidence: 99%

Enhanced thrombopoietin but not G-CSF receptor stimulation induces self-renewing hematopoietic stem cell divisions in vivo

Kovtonyuk

Manz

Takizawa

2016

Blood

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Key Points• Mpl agonist, but not granulocyte colonystimulating factor, induces self-renewing HSC divisions and expansions.In steady-state adult hematopoiesis, most hematopoietic stem cells (HSCs) are in the resting phase of the cell cycle. Upon enhanced hematopoietic demand, HSCs can be induced to divide and self-renew or differentiate. However, the cell-extrinsic signals inducing HSC cycling remain to be elucidated. Using in vivo high-resolution single HSC divisional tracking, we directly demonstrate that clinically applied thrombopoietin receptor but not granulocyte colony-stimulating factor (G-CSF) receptor agonists drive HSCs into self-renewing divisions leading to quantitative expansion of functional HSC as defined by their in vivo serial multilineage and long-term repopulating potential. These results suggest that thrombopoietin mimetics might be applicable to expand HSCs in vivo and to sensitize thrombopoietin receptor-expressing HSCs to cell cycle-dependent cytotoxic agents. (Blood. 2016;127(25):3175-3179)

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Section: Resultsmentioning

confidence: 99%

Enhanced thrombopoietin but not G-CSF receptor stimulation induces self-renewing hematopoietic stem cell divisions in vivo

Kovtonyuk

Manz

Takizawa

2016

Blood

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“…This resulted in reduced thrombus formation without change in bleeding time, or hemostatic function, and suggests a potentially safer target for pharmacotherapy for stroke and heart attack [34]. A recent study highlights the potential for TPO to be used as a biomarker in the diagnosis and assessment of sepsis severity, in patients presenting to the emergency department with systemic inflammatory response syndrome [35]. A complete evaluation of the cardiovascular effects of TPO in vivo may provide an additional clue for the development of new therapeutic interventions in the setting of cardiovascular disease [16].…”

Section: Discussionmentioning

confidence: 99%

Association between Circulating Thrombopoietin Levels and Cardiovascular Risk Prediction Scores in Renal Transplant Recipients

Mansell

Elmoselhi²,

Shoker³

2015

Am J Nephrol

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Background/Aims: The 7-year Major Adverse Cardiovascular Events Calculator (CRCRTR-MACE) predicts cardiovascular events (CVE) in renal transplant recipients (RTR), and thrombopoietin (TPO) is a humoral inflammatory factor implicated in cardiovascular disease (CVD). The aim of the study was to determine if circulating TPO levels in stable RTR are positively associated with variable(s) in the CRCRTR-MACE score. Methods: CRCRTR-MACE scores were calculated in 95 stable RTR. TPO levels were measured by multiplexed fluorescent bead-based immunoassay in all patients and 48 controls. Multivariate analysis (MVA) was performed between TPO and CV risk variables and patient demographics. Stepwise regression with backward elimination of insignificant variables estimated the impact of risk variables on TPO levels. Significance was defined at p < 0.05. Normalized data were presented as mean ± SD and non-normalized data as median (maximum to minimum). Results: The risk of a CVE within 7 years as predicted by the median was 9.97% (range 1.93-84.2). The percentage of patients who were above 20% risk for a CVE was 28.4%. Control TPO level of 170.41 (4.4-995.9) pg/ml was significantly lower than that of 237.90 (32.77-1,386.79) pg/ml in RTR (p = 0.010). TPO level correlated significantly with the total CRCRTR-MACE score (R = 0.310, p = 0.004), smoking (p = 0.009) and eGFR (R = -0.275, p = 0.012) but not with age, diabetes, LDL level or history of CVE. Only the total CRCRTR-MACE score (p = 0.013) and smoking (p = 0.009) remained significant in the MVA. Stepwise regression estimated that smoking increased TPO levels by 206.28 pg/ml and each 10% increase in CRCRTR-MACE score increased TPO levels by an additional 44.4 pg/ml. Conclusion: TPO levels are increased in RTR with high CRCRTR-MACE, particularly in smokers with diminished eGFR. Circulating TPO may serve as a biomarker and treatment target for CVD in RTR.

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“…The levels of TPO are increased in inflammatory states as a result of IL-6 stimulation [14]. In the ED the plasma TPO concentration was significantly higher in patients with SIRS secondary to infection compared to those with non-septic SIRS [15]. In the ED the plasma TPO concentration was significantly higher in patients with SIRS secondary to infection compared to those with non-septic SIRS [15].…”

Section: Thrombopoietin (Tpo)mentioning

confidence: 99%

Understanding platelet dysfunction in sepsis

et al. 2015

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May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department?

Abstract: Our preliminary results suggest that TPO may have the potential to be considered a promising early biomarker for both the diagnosis of sepsis and the assessment of sepsis severity in patients with SIRS entering the ED.

Cited by 19 publications

References 12 publications

Enhanced thrombopoietin but not G-CSF receptor stimulation induces self-renewing hematopoietic stem cell divisions in vivo

Enhanced thrombopoietin but not G-CSF receptor stimulation induces self-renewing hematopoietic stem cell divisions in vivo

Association between Circulating Thrombopoietin Levels and Cardiovascular Risk Prediction Scores in Renal Transplant Recipients

Understanding platelet dysfunction in sepsis

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