scholarly journals The Effect of Platelets on Thrombin Generation in Cord Blood and Peripheral Neonatal Blood in the Premature Infant; The Event Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3188-3188
Author(s):  
Claire Anne Murphy ◽  
Elaine Neary ◽  
Barry Kevane ◽  
Daniel O'Reilly ◽  
John O'Loughlin ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Umbilical Cord Blood ◽  
Research Funding ◽  
Thrombin Generation ◽  
Phospholipid Content ◽  
Term Infants ◽  
Time To Peak ◽  
Neonatal Blood

Abstract Introduction Infants born very preterm (<32 weeks) are at increased risk of haemorrhage, particularly intraventricular haemorrhage which can result in short and long term morbidity. Routine clinical laboratory tests such as the prothrombin time and activated partial thromboplastin time are frequently abnormal in this patient group but do not appear to correlate with clinical outcomes. Moreover, while reduced levels of circulating coagulation factors and platelet hypo-reactivity have been reported, plasma thrombin generation (TG), has been reported to be similar or even enhanced in very preterm infants when compared to term infants. Extracellular vesicles, comprising of lipid-bound nanoparticles released from cells (including platelets), may potentially play a role in modulating neonatal haemostasis. We aimed to characterize phospholipid (PL)-dependent plasma thrombin generation in platelet-rich (PRP) and platelet-poor plasma (PPP) in premature infants in both umbilical cord blood & peripheral neonatal blood using calibrated automated thrombography (CAT). Methods In this prospective observational study, PRP and PPP was prepared by centrifugation from citrated umbilical cord blood and peripheral neonatal blood collected from premature infants (24 - 31 weeks) and healthy term controls (>37 weeks). No samples were collected from heparinised lines. Parameters of plasma thrombin generation in PRP were assessed using CAT, with thrombin generation stimulated by tissue factor only (TF; final concentration 1pM). CAT was also repeated in PPP using only TF and no exogenous PL (rendering the assay dependent upon the endogenous PL content of plasma). Results In the analysis of umbilical cord blood PRP, plasma thrombin generation was accelerated in the preterm infant group with a significantly shorter time to peak TG observed. The other parameters of TG were similar in both groups (Table 1). In the subset of infants from whom peripheral blood samples were available, there was further evidence of enhanced plasma TG in preterm PRP relative to term infants (Table 2). In this subgroup, the lag time and time to peak thrombin were significantly shorter in the preterm group and peak thrombin was significantly higher. TG was also assessed in both PPP and PRP prepared from umbilical cord blood samples in a subgroup of infants (n=10 term, n=6 preterm) using 1pM TF only, rendering the assay dependent on the phospholipid content of plasma. No difference was observed in any CAT parameters, suggesting that neonatal PPP phospholipid content (potentially from circulating extracellular vesicles) is sufficient to support thrombin generation in the absence of exogenous phospholipid. Conclusion These preliminary data suggest that neonatal PRP, measured in both umbilical cord blood and peripheral neonatal blood, has similar thrombin generation or may even be hypercoagulable, compared with healthy term controls. Moreover, neonatal plasma phospholipid appears to support thrombin generation in the absence of exogenous phospholipid. This ongoing prospective study aims to further characterize the platelet-dependency of neonatal thrombin generation and evaluate the potential role of extracellular vesicles in neonatal haemostasis. Figure 1 Figure 1. Disclosures Maguire: Actelion: Research Funding; Bayer Pharma: Research Funding. Ni Ainle: Leo Pharma: Research Funding; Actelion: Research Funding; Daiichi-Sankyo: Research Funding; Bayer Pharma: Research Funding.

Alternative Donors (Umbilical Cord Blood and Haploidentical Donors) for Allogeneic Stem Cell Transplantation in Relapsed / Refractory Hodgkin Lymphoma: A Retrospective Analysis of the EBMT Lymphoma Working Party and the Spanish Group of Stem Cell Transplantation (GETH)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4399-4399 ◽  
Author(s):  
Carmen Martinez ◽  
Jorge Gayoso ◽  
Carmen Canals ◽  
Herve Finel ◽  
Andrea Bacigalupo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Research Funding ◽  
Hematopoietic Stem ◽  
Number Of Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently considered the standard of care for those patients with HL that relapse after autologous HSCT. Several studies have shown that fit patients with chemosensitive disease can benefit from alloHSCT using and identical sibling (SIB) or matched-unrelated (MUD) donors. Recently, encouraging results have been obtained using haploidentical donors (HAPLO) and post-transplantation cyclophosphamide (ptCY) as graft-versus-host disease prophylaxis (GVHD). Because information regarding the results of alloHSCT using alternative donors is still scarce, we aimed to compare outcome of umbilical cord blood (UCB) and HAPLO transplants with conventional SIB and MUD for HL. Patients and methods: Information of patients older than 17y with HL who received an alloHSCT from a SIB, MUD (8/8 antigen matched), UCB or a ptCY-based HAPLO between 2010-2013 was downloaded from the EBMT and GETH databases. Results: 773 patients with HL were identified meeting the inclusion criteria. 339 received a transplant from a SIB donor, 276 from a MUD, 101 from HAPLO, and 47 from UCB. A significant higher number of patients treated with alloHSCT from UCB and HAPLO donors received reduced intensity (RIC) regimens in comparison to SIB and MUD (76% and 88% vs. 69% and 69%, respectively, p=0.001). Bone marrow was more frequently used as source of stem cells in the HAPLO group in relation to SIB and MUD (61% vs 10% and 11%, respectively, p=0.001), Other variables such as sex, age, performance status, chemorefractory disease, and previous autologous SCT were balanced. Median follow-up after alloHSCT for all patients was 12 months (1-60). The 1-year probabilities of overall survival (OS) and progression-free survival (PFS) were 80% and 49% after SIB transplant, 69% and 54% after MUD, 65% and 40% after UCB, and 73% and 56% after HAPLO, respectively. The 1-year probabilities of non-relapse mortality (NRM) and relapse rate (RR) were 12% and 38% after SIB, 21% and 25% after MUD, 20% and 40% after UCB, and 18% and 27% after HAPLO. Multivariate analysis showed that, in comparison with standard SIB alloHSCT, UCB was associated with a trend to a higher NRM (p=0.08) and RR (p=0.06), leading to a significant lower OS and PFS (p=0.009, HR 2.1, 95% CI 1.2-3.6; p=0.02, HR 1.6, 95% CI 1.1-2.3; respectively). NRM was also significantly higher after MUD (p=0.004, HR 1.8, 95% CI 1.2-2.6), but in contrast, RR was lower (p=0.003 HR 0.6, 95%CI 0.5-0.9) with a lower OS (p=0.002, HR 1.6, 95% CI 1.2-2.1) and no significant differences in PFS. No significant differences were observed between HAPLO and SIB in NRM, RR, PFS and OS. Conclusions: This registry study suggests that in adults with advanced HL, the outcome of pt-CY-based HAPLO HSCT may be comparable to that of conventional SIB alloHSCT and MUD across multiple centers and conditioning regimens. These findings need to be corroborated by longer follow-up. Figure 1. Figure 1. Disclosures Peggs: Autolus: Consultancy, Equity Ownership; Cellectis: Research Funding. Milpied:Celgene: Honoraria, Research Funding. Afanasiev:CELLTRION, Inc.: Research Funding. Russell:Therakos: Other: shares. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.

scholarly journals Immunomodulatory properties of umbilical cord blood-derived small extracellular vesicles and their therapeutic potential for inflammatory skin disorders

2021 ◽  
Author(s):  
Silvia C Rodrigues ◽  
Renato M S Cardoso ◽  
Patricia C Freire ◽  
Claudia F Gomes ◽  
Filipe V Duarte ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Umbilical Cord Blood ◽  
Skin Diseases ◽  
Therapeutic Potential ◽  
Psoriatic Skin ◽  
Inflammatory Skin Diseases ◽  
Inflammatory Skin ◽  
Anti Inflammatory

Umbilical cord blood (UCB) has long been seen as a rich source of naive cells with strong regenerative potential, likely mediated by small extracellular vesicles (sEV). More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell sEV (herein referred as Exo-101), and explore their therapeutic potential for inflammatory skin diseases. Exo-101 was shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with Exo-101 resulted in an reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, Exo-101 reduced the expression of inflammatory and psoriatic markers IL-6, IL-8, CXCL10, COX-2, S100A7 and DEFB4. In vivo, Exo-101 significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of Exo-101, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.

scholarly journals A Comparison of the Percentage of Fetal Hemoglobin in Human Umbilical Cord Blood as Determined by Chromatography and by Alkali Denaturation

Blood ◽  
1963 ◽  
Vol 22 (5) ◽  
pp. 554-565 ◽  
Author(s):  
DAVID H. ARMSTRONG ◽  
W. A. SCHROEDER ◽  
WILLIAM D. FENNINGER
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Fetal Hemoglobin ◽  
Full Term ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Careful Study ◽  
Term Infants ◽  
Accuracy And Precision

Abstract A comparison has been made of the determination of fetal hemoglobin in human umbilical cord blood by column chromatography and alkali denaturation. A careful study has also been made of the variables that control the accuracy and precision of the methods. Minor modification has led to much improved control of the 1-minute alkali denaturation procedure. The percentage of fetal hemoglobin in the umiblical cord blood of full term infants has been found to cover a far narrower range than is commonly reported. By chromatography, the average is 85.5 per cent with a range from 79 to 91 per cent that includes more than 95 per cent of normal full term infants. By alkali denaturation, the average is 74.0 per cent with a range from 63 to 87 per cent. Possible correlations with several clinical parameters have been examined. The highest correlation by both methods of determination occurred in the group of 12 samples from infants with a duration of gestation less than 37 weeks. In this group the linear correlation with weight was greater than 0.6. The precision and accuracy of the chromatographic method recommend it in the study of such subjects as prematurity, twinning, dysmaturity, intrauterine growth retardation, and infants of diabetic mothers.

The Feature of SALL4 and BMI-1 Expression in Placenta and Umbilical Cord Blood

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4800-4800
Author(s):  
Shaohua Chen ◽  
Qi Shen ◽  
Lijian Yang ◽  
Bo Li ◽  
Yupo Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Research Funding ◽  
Mononuclear Cells ◽  
Expression Level ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem ◽  
Expression Levels

Abstract Abstract 4800 The SALL4 is a newly discovered pluripotency stem cell factor involved in the self-renewing, hematopoietic stem cells (HSCs) and leukemic stem cells. Its important role in normal HSCs and leukemic stem cells is supported by its interactions with several key players, like BMI-1, a putative oncogene of the Polycomb group family, controlling specific target genes involved in development, cell differentiation, proliferation, and senescence. Little is known the expression feature of SALL4 and BMI-1 mRNA in placenta and umbilical cord blood (UCB). In this study, the mRNA expression level of SALL4 and BMI-1 in 10 cases placenta tissues and the mononuclear cells from the corresponding UCB (CBMCs) were measured by real-time PCR with SYBR Green I technique, β2-microglobulin gene (β2M) was used as an endogenous reference, mononuclear cells from 10 healthy adults peripheral blood (PBMCs) and 2 cases of adult thymic cells served as control. The result showed that the expression level of both SALL4 and BMI-1 in placenta (Median: 34.36 and 17.55 respectively) were significantly higher than those from CBMCs (Median: 11.3 and 2.07 respectively) (p=0.007, p=0.001) and PBMCs (Median: 0.64 and 0.03 respectively) (P<0.001, P<0.001). Moreover, both SALL4 and BMI-1 expression levels in CBMCs were significant higher than those from PBMCs (P=0.002, P=0.001). And the expression of SALL4 could be detected in thymic cells. Correlation analysis was performed among the relative expression levels of SALL4 and BMI-1. The results showed that significant positive correlation between the expression levels of SALL4 and BMI-1 was observed in placenta tissues and CBMCs, as well as in PBMCs (rs=0.648, P=0.043, rs=0.721, P=0.019, rs=-0.697, P=0.025). In conclusions, the expression level of SALL4 and BMI-1 might be related to the numbers of hematopoietic stem cells, placenta tissues may be as an appropriate model for investigating gene regulation of SALL4 and BMI-1, while the significance of expression both genes in PBMCs and thymic cells is needed further investigation. Disclosures: Chen: National Natural Science Foundation of China(no. 30871091): Research Funding; the Fundamental Research Funds for the Central Universities (No. 21610603): Research Funding.

scholarly journals Epigenome wide comparison of DNA methylation profile between paired umbilical cord blood and neonatal blood on Guthrie cards

Epigenetics ◽  
2019 ◽  
Vol 15 (5) ◽  
pp. 454-461 ◽  
Author(s):  
Yu Jiang ◽  
Jinfeng Wei ◽  
Hongmei Zhang ◽  
Susan Ewart ◽  
Faisal I. Rezwan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Methylation Profile ◽  
Dna Methylation Profile ◽  
Neonatal Blood ◽  
Guthrie Cards

scholarly journals Osteoblasts secrete miRNA-containing extracellular vesicles that enhance expansion of human umbilical cord blood cells

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jess Morhayim ◽  
Jeroen van de Peppel ◽  
Eric Braakman ◽  
Elwin W. J. C. Rombouts ◽  
Mariette N. D. ter Borg ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Umbilical Cord Blood ◽  
Blood Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Cord Blood Cells ◽  
Umbilical Cord Blood Cells

scholarly journals High correlations in gene expression between paired umbilical cord blood and neonatal blood of healthy newborns on Guthrie cards

2013 ◽  
Vol 26 (18) ◽  
pp. 1765-1767 ◽  
Author(s):  
Jaime Slaughter ◽  
Changshuai Wei ◽  
Steven J. Korzeniewski ◽  
Qing Lu ◽  
John S. Beck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Neonatal Blood ◽  
Guthrie Cards

scholarly journals Remifentanil Degradation in Umbilical Cord Blood of Preterm Infants

2011 ◽  
Vol 114 (3) ◽  
pp. 570-577 ◽  
Author(s):  
Lars Welzing ◽  
Sabine Ebenfeld ◽  
Verena Dlugay ◽  
Martin H. J. Wiesen ◽  
Bernhard Roth ◽  
...  
Keyword(s):  
Cord Blood ◽  
Preterm Infants ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Pharmacokinetic Data ◽  
Serum Samples ◽  
Term Infants ◽  
Very Preterm Infants ◽  
Cord Serum ◽  
Very Preterm

Background No pharmacokinetic data about remifentanil in preterm infants exist, although remifentanil is increasingly used in this especially vulnerable subgroup of pediatric patients. Unfortunately, ethical restrictions in the volume of blood that can be withdrawn for kinetic sampling nearly prohibit pharmacokinetic studies in preterm infants. Methods Because remifentanil is rapidly metabolized by nonspecific blood esterases, we collected umbilical cord serum of preterm and term infants to investigate whether the activity of nonspecific blood esterases depends on gestational age. Umbilical cord serum, buffer solution, ascorbic acid, and remifentanil were mixed in a glass vial placed in a shaking water bath at 37°C. Subsequently, serum samples were subjected to liquid chromatography-mass spectrometry-based analysis of remifentanil and its metabolite GR90291 after 0, 30, 60, 100, and 150 min. Results We analyzed umbilical cord serum samples of 34 preterm infants (24-36 gestational weeks) and six term infants. The degradation rates of remifentanil to its major metabolite GR90291 were comparable in preterm and term infants. The overall median degradation half-life of remifentanil was 143 ± (interquartile range) 47 min (minimum, 76 min; maximum, 221 min) without significant differences between very preterm infants (less than 28 gestational weeks) and term infants. The remifentanil concentration remained stable in control runs without serum. Conclusions Our study demonstrates that very preterm infants exhibit a high nonspecific esterase activity in umbilical cord blood that is comparable with that of term infants. These results support clinical experiences that remifentanil is rapidly metabolized by preterm infants without prolonged side effects.

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