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INTRODUCTION: It is recommended to use two chronometric assays of different principles for the diagnosis of lupus anticoagulant (LA), consisting in diluted Russell Viper Venom Time (dRVVT) and activated Partial Thromboplastin Time (aPTT). Yet, there are only a few integrated aPTT assays; this study aims to evaluate one of them: Cephen LS/Cephen (Hyphen Biomed). METHOD: 249 samples of patients were included in this study. Normal reference ranges were determined with platelet-poor plasma (PPP) from healthy blood donors. Performances were then evaluated by comparing Cephen LS/Cephen test results to the results of the laboratory's reference assay for the diagnosis of LA and to clinical data, both on non-anticoagulated and anticoagulated patients' samples (Unfractioned heparin (UFH), Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA) and apixaban). Interference of UFH, LMWH and VKA were also evaluated thanks to spiking experiment of increasing heparin concentrations or factor deficiency. RESULTS: Cephen LS/Cephen test had 48.6% sensitivity towards LA. Although UFH and VKA seemed to interfere with this assay and were likely to cause false negative, LMWH and apixaban did not. Finally, combination of Cephen LS/ Cephen with dRVVT had 89.0% sensitivity. CONCLUSION: Cephen LS/Cephen seems relevant for LA diagnosis, in combination with dRVVT, and might be used in patients undergoing LMWH or apixaban therapy.
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RUNX1 is essential during human hematopoiesis. Numerous RUNX1 deregulations have been described, including translocations and germline or somatic mutations. Recurrent de novo RUNX1 mutations in acute myeloid leukemias (AML) prompted the creation of a provisional entity of AML with mutated RUNX1 in the 2016 WHO. In addition, recent genomic studies underlined rare AML patients with plasmacytoid dendritic cell (pDC) expansion and high RUNX1 mutations frequency. To better characterized AML with RUNX1 mutations, we retrospectively investigated a cohort of 32 patients diagnosed at Strasbourg University Hospital. Detailed clinical and biological features were aggregated. The presence of a pDC contingent was assessed by cytology and flow cytometry. In our cohort, no common features were identified either in term of cytology, stage of leukemia arrest or mutational features. Based on our observations, mutated RUNX1 AMLs do not appear to be a distinct AML entity. The new 2022 WHO classification includes AML with mutated RUNX1 within AML myelodysplasia-related category. We also identified within our cohort a patient whose AML fulfilled AML-pDC criteria, a rare and newly included entity in the last WHO classification.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal , Hospitales Universitarios , Leucemia Mieloide Aguda , Mutación , Humanos , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Masculino , Femenino , Estudios Retrospectivos , Hospitales Universitarios/organización & administración , Persona de Mediana Edad , Anciano , Adulto , Francia/epidemiología , Adulto Joven , Anciano de 80 o más Años , Estudios de CohortesRESUMEN
INTRODUCTION: Toll-like receptors play crucial roles in the sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4. METHODS: In this study, we conducted a comprehensive analysis of TLRs 1-10 expressions in white blood cells from 71 patients with bacterial and viral infections. Patients were divided into 4 groups based on disease type and severity (sepsis, septic shock, moderate, and severe COVID-19) and compared to 7 healthy volunteers. RESULTS: We observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in septic shock neutrophils compared to the control group (p < 0.001). Severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to controls (p < 0.05). Septic shock patients also showed a similar increase in TLR7 in neutrophils along with elevated intermediate monocytes (CD14+CD16+) compared to the control group (p < 0.005 and p < 0.001, respectively). However, TLR expression remained unchanged in lymphocytes. CONCLUSION: This study provides further insights into the mechanisms of TLR activation in various infectious conditions. Additional analysis is needed to assess their correlation with patient outcome and to evaluate the impact of TLR-pathway modulation during septic shock and severe COVID-19.
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COVID-19 , SARS-CoV-2 , Receptor Toll-Like 10 , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Bacterianas/inmunología , COVID-19/inmunología , COVID-19/sangre , Leucocitos/inmunología , Leucocitos/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Neutrófilos/inmunología , SARS-CoV-2/inmunología , Sepsis/inmunología , Choque Séptico/inmunología , Choque Séptico/sangre , Receptor Toll-Like 1/metabolismo , Receptor Toll-Like 1/genética , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 7/genética , Receptores Toll-Like/metabolismo , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy associated with thrombosis that requires a quick diagnosis. Therefore, laboratory assays must provide an accurate and swift answer. This work aims to evaluate the performances of an ELISA assay, especially when combined with 4T risk score, and a functional assay. METHODS: Data were collected for 894 patients treated by heparin who underwent anticoagulant switch because of HIT suspicion and were examined by a multidisciplinary expert team who confirmed or ruled out HIT diagnosis. All patients were tested for anti-PF4 IgG with Asserachrom HPIA IgG (ELISA), and 307 were tested with a platelet aggregation test done on platelet-rich plasma (PRP-PAT). The 4T risk score was available for 607 of them. RESULTS: HIT was diagnosed in 232 patients. 4T risk score had a 94.2% negative predictive value (NPV) for risk scores ≤3 and 77.3% for risk scores ≤5. The sensitivity of ELISA was 90.9%, its specificity 79.0%, and its NPV 96.1%. When combined with 4T risk score, its NPV reached 100% and 97% for risk scores ≤3 and ≤5, respectively. PRP-PAT sensitivity was 70.4%, and its specificity was 92.3%. Combination of ELISA and PRP-PAT had a 0.7% false-negative rate. CONCLUSION: This study shows that ELISA can rule out HIT with an excellent NPV, especially when combined with the 4T risk score. Nonetheless, it has low specificity; hence, it needs to be associated with a functional assay.
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Factor Plaquetario 4 , Trombocitopenia , Humanos , Estudios Retrospectivos , Factor Plaquetario 4/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/diagnóstico , Heparina/efectos adversos , Anticoagulantes/efectos adversos , Ensayo de Inmunoadsorción Enzimática , Pruebas de Función Plaquetaria , Inmunoglobulina GRESUMEN
BACKGROUND: The difficulty in interpreting somatic alterations is correlated with the increase in sequencing panel size. To correctly guide the clinical management of patients with cancer, there needs to be accurate classification of pathogenicity followed by actionability assessment. Here, we describe a specific detailed workflow for the classification of the pathogenicity of somatic variants in cancer into five categories: benign, likely benign, unknown significance, likely pathogenic and pathogenic. METHODS: Classification is obtained by combining a set of eight relevant criteria in favour of either a pathogenic or a benign effect (pathogenic stand-alone, pathogenic very strong, pathogenic strong, pathogenic moderate, pathogenic supporting, benign supporting, benign strong and benign stand-alone). RESULTS: Our guide is concordant with the ACMG/AMP 2015 guidelines for germline variants. Interpretation of somatic variants requires considering specific criteria, such as the disease and therapeutic context, co-occurring genomic events in the tumour when available and the use of cancer-specific variant databases. In addition, the gene role in tumorigenesis (oncogene or tumour suppressor gene) also needs to be taken into consideration. CONCLUSION: Our classification could contribute to homogenize best practices on somatic variant pathogenicity interpretation and improve interpretation consistency both within and between laboratories.
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Neoplasias/genética , Patología Molecular/métodos , Patología Molecular/normas , Humanos , Flujo de TrabajoRESUMEN
The intestine-specific caudal-related homeobox gene-2 (CDX2) homeobox gene, while being a tumor suppressor in the gut, is ectopically expressed in a large proportion of acute leukemia and is associated with poor prognosis. Here, we report that turning on human CDX2 expression in the hematopoietic lineage of mice induces acute monoblastic leukemia, characterized by the decrease in erythroid and lymphoid cells at the benefit of immature monocytic and granulocytic cells. One of the highly stimulated genes in leukemic bone marrow cells was BMP and activin membrane-bound inhibitor (Bambi), an inhibitor of transforming growth factor-ß (TGF-ß) signaling. The CDX2 protein was shown to bind to and activate the transcription of the human BAMBI promoter. Moreover, in a leukemic cell line established from CDX2-expressing mice, reducing the levels of CDX2 or Bambi stimulated the TGF-ß-dependent expression of Cd11b, a marker of monocyte maturation. Taken together, this work demonstrates the strong oncogenic potential of the homeobox gene CDX2 in the hematopoietic lineage, in contrast with its physiological tumor suppressor activity exerted in the gut. It also reveals, through BAMBI and TGF-ß signaling, the involvement of CDX2 in the perturbation of the interactions between leukemia cells and their microenvironment.
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Factor de Transcripción CDX2/genética , Leucemia Monocítica Aguda/genética , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Animales , Antígeno CD11b/genética , Linaje de la Célula , Humanos , Leucemia Monocítica Aguda/patología , Proteínas de la Membrana/genética , Ratones , Transducción de Señal , Microambiente TumoralRESUMEN
B-cell receptor (BCR) signaling is crucial for the pathophysiology of most mature B-cell lymphomas/leukemias and has emerged as a therapeutic target whose effectiveness remains limited by the occurrence of mutations. Therefore, deciphering the cellular program activated downstream this pathway has become of paramount importance for the development of innovative therapies. Using an original ex vivo model of BCR-induced proliferation of chronic lymphocytic leukemia cells, we generated 108 temporal transcriptional and proteomic profiles from 1 h up to 4 days after BCR activation. This dataset revealed a structured temporal response composed of 13,065 transcripts and 4027 proteins, comprising a leukemic proliferative signature consisting of 430 genes and 374 proteins. Mathematical modeling of this complex cellular response further highlighted a transcriptional network driven by 14 early genes linked to proteins involved in cell proliferation. This group includes expected genes (EGR1/2, NF-kB) and genes involved in NF-kB signaling modulation (TANK, ROHF) and immune evasion (KMO, IL4I1) that have not yet been associated with leukemic cells proliferation. Our study unveils the BCR-activated proliferative genetic program in primary leukemic cells. This approach combining temporal measurements with modeling allows identifying new putative targets for innovative therapy of lymphoid malignancies and also cancers dependent on ligand-receptor interactions.
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Linfocitos B/metabolismo , Proliferación Celular/genética , Leucemia Linfocítica Crónica de Células B/genética , Receptores de Antígenos de Linfocitos B/genética , Anciano , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/metabolismo , Activación de Linfocitos/genética , Masculino , Persona de Mediana Edad , Proteoma/genética , Proteómica/métodos , Transducción de Señal/genética , Transcripción Genética/genéticaRESUMEN
FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.
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Corticoesteroides/administración & dosificación , Eosinofilia , Neoplasias Hematológicas , Trastornos Mieloproliferativos , Proteínas de Fusión Oncogénica , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Factores de Escisión y Poliadenilación de ARNm , Adulto , Supervivencia sin Enfermedad , Eosinofilia/sangre , Eosinofilia/tratamiento farmacológico , Eosinofilia/genética , Eosinofilia/mortalidad , Femenino , Francia/epidemiología , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/sangre , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/mortalidad , Proteínas de Fusión Oncogénica/sangre , Proteínas de Fusión Oncogénica/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/sangre , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Estudios Retrospectivos , Tasa de Supervivencia , Triptasas/sangre , Vitamina B 12/sangre , Factores de Escisión y Poliadenilación de ARNm/sangre , Factores de Escisión y Poliadenilación de ARNm/genéticaAsunto(s)
Arteriopatías Oclusivas , Betacoronavirus , Angiografía por Tomografía Computarizada , Infecciones por Coronavirus , Hemorragia , Leucemia Promielocítica Aguda , Pandemias , Neumonía Viral , Trombosis , Arteriopatías Oclusivas/sangre , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/terapia , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/etiología , Infecciones por Coronavirus/terapia , Resultado Fatal , Femenino , Hemorragia/sangre , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Hemorragia/terapia , Humanos , Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/complicaciones , Leucemia Promielocítica Aguda/diagnóstico por imagen , Leucemia Promielocítica Aguda/terapia , Persona de Mediana Edad , Neumonía Viral/sangre , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/etiología , Neumonía Viral/terapia , SARS-CoV-2 , Síndrome , Trombosis/sangre , Trombosis/diagnóstico por imagen , Trombosis/etiologíaRESUMEN
Disseminated intravascular coagulation (DIC) is a severe complication of septic shock. Polymorphonuclear neutrophils (PMNs) may play a key role in septic shock-induced DIC via the release of neutrophils extracellular traps (NETs). NETs capture invading pathogens, but also act as a pro-coagulant surface at the interface between immunity and thrombosis. During septic shock-induced DIC, neutrophil activation may result in excessive NET formation. Herein, we originally report the presence of circulating NETs in human blood during septic shock-induced DIC. To investigate NET formation during shock-induced DIC neutrophils were isolated from patients in septic shock associated with (nâ¯=â¯3) or without (nâ¯=â¯3) DIC. Neutrophils from healthy donors (nâ¯=â¯3) were stimulated in vitro with ionomycin as NET formation positive controls. PMNs smears were stained with mouse anti-human FITC anti-myeloperoxidase antibody and the blue-fluorescent DAPI nucleic acid stain. NETs were identified as elongated extracellular DNA fibers associated to myeloperoxidase detected by immunofluorescence. NETs were unambiguously observed in PMNs from septic shock patients with DIC but not from patients without DIC. NETs features in DIC+ patients were undistinguishable from those observed in ionomycin-induced PMNs from healthy donors. Fluorescence images of NETs were associated to extracellular cytoplasmic expansions. Our data report for the first time the direct visualization of circulating NETs in patients with septic shock-induced DIC. The in vivo relevance of previously reported indirect markers of NETosis (neutrophil side fluorescence) is confirmed.
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Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/etiología , Trampas Extracelulares/metabolismo , Fluorescencia , Neutrófilos/metabolismo , Choque Séptico/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Coagulación Intravascular Diseminada/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Choque Séptico/patologíaAsunto(s)
Médula Ósea/patología , Leucemia/patología , Adolescente , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Glicosaminoglicanos/análisis , Humanos , Quimioterapia de Inducción , Leucemia/complicaciones , Leucemia/tratamiento farmacológico , Leucemia/genética , Masculino , Proteínas de Fusión Oncogénica/genéticaAsunto(s)
Factor de Transcripción Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Enfermedad Aguda , Secuencia de Bases , Haploinsuficiencia , Humanos , Factor de Transcripción Ikaros/biosíntesis , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Eliminación de SecuenciaRESUMEN
Ruxolitinib is a JAK-1/JAK-2 inhibitor indicated for the treatment of polycythemia vera and primary or secondary myelofibrosis. Only one patient (0.2%) was diagnosed with tuberculosis among the 485 patients receiving ruxolitinib in the four pivotal trials. Fourteen cases of tuberculosis have since been reported. We observed two (3%) mycobacterial infections (one due to Mycobacterium tuberculosis and one due to Mycobacterium avium complex) in our cohort of 65 patients receiving ruxolitinib. This observation suggests that the rate of mycobacterial infection might be higher than that observed in the pivotal trials and that atypical mycobacterial infections can also occur.
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Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Mielofibrosis Primaria/tratamiento farmacológico , Pirazoles/uso terapéutico , Tuberculosis/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Mycobacterium avium/efectos de los fármacos , Mycobacterium avium/aislamiento & purificación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Nitrilos , Policitemia Vera/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , PirimidinasRESUMEN
A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies.
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Linfocitos B/patología , Proliferación Celular , Leucemia Linfocítica Crónica de Células B/patología , Receptores de Antígenos de Linfocitos B/metabolismo , Factor de Transcripción STAT6/metabolismo , Quinasa Syk/metabolismo , Proteína Tirosina Quinasa ZAP-70/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Linfocitos B/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/metabolismo , Masculino , Persona de Mediana Edad , Fosforilación , Células Tumorales CultivadasRESUMEN
The prognosis of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains unsatisfactory and, despite major advances in genomic studies, the biological mechanisms underlying chemoresistance are still poorly understood. We conducted for the first time a large-scale differential multi-omics investigation on DLBCL patient's samples in order to identify new biomarkers that could early identify patients at risk of R/R disease and to identify new targets that could determine chemorefractoriness. We compared a well-characterized cohort of R/R versus chemosensitive DLBCL patients by combining label-free quantitative proteomics and targeted RNA sequencing performed on the same tissues samples. The cross-section of both data levels allowed extracting a sub-list of 22 transcripts/proteins pairs whose expression levels significantly differed between the two groups of patients. In particular, we identified significant targets related to tumor metabolism (Hexokinase 3), microenvironment (IDO1, CXCL13), cancer cells proliferation, migration and invasion (S100 proteins) or BCR signaling pathway (CD79B). Overall, this study revealed several extremely promising biomarker candidates related to DLBCL chemorefractoriness and highlighted some new potential therapeutic drug targets. The complete datasets have been made publically available and should constitute a valuable resource for the future research.
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Resistencia a Antineoplásicos/genética , Genómica , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Metabolómica , Proteómica , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biología Computacional/métodos , Femenino , Perfilación de la Expresión Génica , Ontología de Genes , Genómica/métodos , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Proteómica/métodos , Retratamiento , Resultado del Tratamiento , Microambiente Tumoral , Adulto JovenAsunto(s)
Aberraciones Cromosómicas , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Anciano , Biomarcadores , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Femenino , Inestabilidad Genómica , Humanos , Inmunofenotipificación , Hibridación Fluorescente in SituRESUMEN
INTRODUCTION: Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity, and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic shock-induced DIC. METHODS: Twenty patients with septic shock (10 without and 10 with DIC according to JAAM 2006 score) were prospectively included in our study. Vascular cell activation was assessed by microparticle (MP) measurement. NETosis was investigated at days 1, 3, and 7 using two different approaches: probing and measurement of neutrophil DNA decompaction by neutrophil-side fluorescence light (NEUT-SFL) as recorded by an automated blood cell cytometer and the assessment of nucleosomes and NETs (DNA-bound myeloperoxidase, DNA-MPO). RESULTS: Endothelial-derived CD105-MPs, leucocyte-derived CD11a-MPs/leucocyte, and neutrophil-derived CD66b-MPs/neutrophil count ratios significantly increased in DIC compared with non-DIC patients, indicating on-going cell activation (Pâ<0.05). NEUT-SFL, indicating DNA decompaction, was significantly higher in DIC patients. Circulating nucleosomes and DNA-MPO were increased in DIC patients (Pâ<0.05). There were significant correlations between: nucleosomes and NETs (râ=â0.397, Pâ=â0.004), NEUT-SFL and nucleosomes (râ=â0.243, Pâ=â0.032), NEUT-SFL and DNA-MPO (râ=â0.266, Pâ=â0.024). CONCLUSION: NEUT-SFL, NETs, and elevated nucleosome concentrations were all correlated to DIC (Pâ<0.05). We have shown that NETosis is significantly correlated to septic shock-induced DIC.