RESUMEN

OBJECTIVE: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and risk stratification indicators as well as thrombus burden in patients with moderate-to-high risk acute pulmonary embolism (APE), and to assess the changes in these parameters following interventional therapy. METHODS: This study retrospectively included patients with moderate-to-high risk APE who were admitted to the Department of Interventional Vascular Surgery at Putian First Hospital from May 2020 to May 2024. All patients received anticoagulation therapy, pulmonary artery catheter-directed thrombolysis, and/or mechanical thrombectomy. Patients were further divided into subgroup A if they did not present with any of the following conditions at admission: a) acute inflammatory diseases (including lung infections); b) malignant tumors; c) history of trauma or surgery within the past 2 months. Patients with any of the aforementioned conditions were classified as subgroup B. Additionally, 50 healthy individuals were randomly selected as the healthy control group. RESULTS: The NLR and PLR in subgroup A were significantly lower than those in subgroup B (P < .01). Compared with the healthy control group, the NLR in the APE group and subgroup A was significantly higher (P < .001). There were no significant differences in NLR and PLR between the troponin I-negative and troponin I-positive groups (P > .05), or between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-negative and NT-proBNP-positive groups (P > .05). There were no significant correlations between NLR and PLR with risk stratification indicators and pulmonary artery embolism index (P > .05). Compared with before treatment, NLR, troponin I, NT-proBNP, right ventricular diameter/left ventricular diameter ratio, and pulmonary artery embolism index were significantly reduced after treatment (P < .05), while there was no significant difference in PLR before and after treatment (P > .05). CONCLUSION: Elevated NLR in patients with APE, which decreases after effective treatment, may be used for assessing disease status and treatment efficacy. However, there is no correlation between NLR and risk stratification indicators or thrombus burden. PLR does not demonstrate significant value in assessing APE.

Asunto(s)

Plaquetas , Linfocitos , Neutrófilos , Embolia Pulmonar , Humanos , Embolia Pulmonar/sangre , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedad Aguda , Anciano , Trombosis/sangre , Trombosis/etiología , Medición de Riesgo/métodos , Adulto

RESUMEN

Sepsis and atherosclerotic cardiovascular disease (ASCVD) are major health challenges involving complex processes like inflammation, renin-angiotensin system (RAS) dysregulation, and thrombosis. Despite distinct clinical symptoms, both conditions share mechanisms mediated by bradykinin. This review explores bradykinin's role in inflammation, RAS modulation, and thrombosis in sepsis and ASCVD. In sepsis, variable kininogen-bradykinin levels may correlate with disease severity and progression, though the effect of bradykinin receptor modulation on inflammation remains uncertain. RAS activation is present in both diseases, with sepsis showing variable or low levels of Ang II, ACE, and ACE2, while ASCVD consistently exhibits elevated levels. Bradykinin may act as a mediator for ACE2 and AT2 receptor effects in RAS regulation. It may influence clotting and fibrinolysis in sepsis-associated coagulopathy, but evidence for an antithrombotic effect in ASCVD is insufficient. Understanding bradykinin's role in these shared pathologies could guide therapeutic and monitoring strategies and inform future research.

Asunto(s)

Aterosclerosis , Coagulación Sanguínea , Bradiquinina , Sistema Renina-Angiotensina , Sepsis , Transducción de Señal , Humanos , Bradiquinina/metabolismo , Sepsis/fisiopatología , Sepsis/metabolismo , Sepsis/sangre , Aterosclerosis/fisiopatología , Aterosclerosis/metabolismo , Aterosclerosis/sangre , Animales , Coagulación Sanguínea/efectos de los fármacos , Receptores de Bradiquinina/metabolismo , Trombosis/fisiopatología , Trombosis/sangre , Trombosis/metabolismo

Asunto(s)

COVID-19 , Monocitos , SARS-CoV-2 , Tromboplastina , Trombosis , Humanos , COVID-19/inmunología , COVID-19/sangre , COVID-19/complicaciones , Monocitos/inmunología , Monocitos/metabolismo , Tromboplastina/metabolismo , Trombosis/sangre , Trombosis/inmunología , Trombosis/etiología , SARS-CoV-2/inmunología

RESUMEN

Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway-miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p-in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 (F3) and tissue factor pathway inhibitor 2 (TFPI2)) and miR-616-3p (targeting TFPI2) predicted VTE after OC diagnosis (χ2, p < 0.05). Regarding patients' prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients' survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice.

Asunto(s)

MicroARNs , Neoplasias Ováricas , Tromboplastina , Humanos , Femenino , Neoplasias Ováricas/sangre , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/genética , MicroARNs/sangre , MicroARNs/genética , Tromboplastina/metabolismo , Tromboplastina/genética , Persona de Mediana Edad , Pronóstico , Anciano , Trombosis/sangre , Trombosis/etiología , Tromboembolia Venosa/sangre , Tromboembolia Venosa/etiología , Tromboembolia Venosa/genética , Adulto , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica

RESUMEN

OBJECTIVES: This review aims to identify biological markers associated with the risk of recurrence of thrombotic and/or obstetric events in patients with antiphospholipid syndrome (APS). METHODS: A comprehensive review of literature was conducted to evaluate established and potential novel biological markers associated with thrombosis in APS. To this end, a PubMed literature search was conducted for the last twenty years using the following keywords or their combinations: thrombotic risk, recurrence of thrombosis, risk stratification, severity, predictive value. RESULTS: Previous studies showed that multiple aPL positivity correlates with an increased risk of thrombosis in APS. Moreover, the analysis of N-glycosylation of antiphospholipid antibodies (aPL) revealed that low levels of IgG sialylation, fucosylation or galactosylation increases the pro-inflammatory activity of aPL, predisposing to thrombosis. In addition, quantification of neutrophil extracellular traps (NETs) and antibodies directed against NETs (anti-NETs) in serum demonstrates promising prognostic utility in assessing APS severity. Oxidative stress plays a role in the pathogenicity of APS and paraoxonase 1 (PON1) activity emerges as a promising biomarker of thrombotic risk in APS. Furthermore, identification of novel antigenic targets involved in the pathophysiology of APS, such as lysobisphosphatidic acid (LBPA), had led to the discovery of unconventional aPL, antibodies directed against the LBPA (aLBPA), whose clinical value could make it possible to identify APS patients at high risk of thrombotic recurrence. CONCLUSION: The immunological profile of aPL, N-glycosylation of aPL, quantification of NETs and anti-NETs, analysis of biomarkers of oxidative stress and the discovery of aLBPA offer potential prognostic tools for risk stratification in APS patients.

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Biomarcadores , Recurrencia , Trombosis , Humanos , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Biomarcadores/sangre , Trombosis/etiología , Trombosis/inmunología , Trombosis/sangre , Anticuerpos Antifosfolípidos/inmunología , Anticuerpos Antifosfolípidos/sangre , Pronóstico , Factores de Riesgo

RESUMEN

BACKGROUND: Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. METHODS: Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. RESULTS: Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] µmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. CONCLUSIONS: Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

Asunto(s)

Plaquetas , Eritritol , Glucosa , Voluntarios Sanos , Agregación Plaquetaria , Trombosis , Humanos , Eritritol/sangre , Eritritol/administración & dosificación , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Masculino , Trombosis/sangre , Trombosis/inducido químicamente , Trombosis/prevención & control , Estudios Prospectivos , Agregación Plaquetaria/efectos de los fármacos , Femenino , Adulto , Edulcorantes no Nutritivos/administración & dosificación , Edulcorantes no Nutritivos/efectos adversos , Adulto Joven , Factor Plaquetario 4/sangre , Espectrometría de Masas en Tándem , Persona de Mediana Edad , Serotonina/sangre , Edulcorantes/administración & dosificación , Pruebas de Función Plaquetaria

Asunto(s)

COVID-19 , Monocitos , SARS-CoV-2 , Tromboplastina , Trombosis , Humanos , COVID-19/inmunología , COVID-19/complicaciones , COVID-19/sangre , Trombosis/sangre , Trombosis/inmunología , Trombosis/etiología , Monocitos/inmunología , Monocitos/metabolismo , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidad , Tromboplastina/metabolismo

RESUMEN

The use of antithrombotic agents is increasing in infants, children and adolescents. The more recent routine inclusion of children in FDA-monitored clinical trials has propelled the rapid accumulation of safety and efficacy data on these agents in pediatric patients. Antithrombotic agents in current use include indirect or antithrombin-dependent anticoagulants, intravenous direct thrombin inhibitors, direct oral anticoagulants (DOACs) targeting thrombin or factor Xa, antiplatelet agents and thrombolytic therapies. Each class of antithrombotic agent has distinct mechanisms of action, clearance routes, half-lives, safety and dosing. Anticoagulant efficacy is dependent upon the specific clinical indication and stability of the pediatric patient. Duration of anticoagulant course is also dependent upon the clinical indication as well as rate of thrombus resolution. This manuscript reviews the mechanism of action, route of administration, route of clearance and plasma half-life for the antithrombotic agents in current use in children. Use of anticoagulation in the context of thrombolytic therapy is discussed.

Asunto(s)

Anticoagulantes , Humanos , Niño , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Adolescente , Lactante , Preescolar , Resultado del Tratamiento , Factores de Edad , Coagulación Sanguínea/efectos de los fármacos , Trombosis/tratamiento farmacológico , Trombosis/sangre , Terapia Trombolítica/efectos adversos , Recién Nacido , Fibrinolíticos/efectos adversos , Fibrinolíticos/administración & dosificación , Hemorragia/inducido químicamente , Factores de Riesgo , Administración Oral

Asunto(s)

COVID-19 , Fibrinolíticos , Guías de Práctica Clínica como Asunto , Humanos , COVID-19/complicaciones , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , SARS-CoV-2 , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Trombosis/prevención & control , Trombosis/tratamiento farmacológico , Trombosis/sangre

Asunto(s)

COVID-19 , Fibrinolíticos , Guías de Práctica Clínica como Asunto , Humanos , COVID-19/complicaciones , COVID-19/sangre , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Fibrinolíticos/administración & dosificación , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Trombosis/prevención & control , Trombosis/tratamiento farmacológico , Trombosis/sangre

Asunto(s)

Anticoagulantes , Hemorragia , Trombosis , Humanos , Hemorragia/inducido químicamente , Factores de Riesgo , Medición de Riesgo , Trombosis/etiología , Trombosis/epidemiología , Trombosis/diagnóstico , Trombosis/prevención & control , Trombosis/sangre , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico

RESUMEN

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by platelet-activating antibodies targeting platelet factor 4 (PF4) and heparin complex. A higher antibody titer is reflected in a higher optical density (OD) by enzyme-linked immunosorbent assay for heparin-PF4 antibodies. This single-institution retrospective study of 116 HIT patients examined the effect of heparin-PF4 OD on time to platelet recovery, vascular thrombosis, and in-hospital mortality. Patients were divided into 3 cohorts based on heparin-PF4 OD: cohort 1 had an OD ≥ 2 and ≤ 2.4, cohort 2 had an OD > 2.4 and ≤ 2.8, and cohort 3 had an OD > 2.8. A higher OD titer was associated with significantly increased time to platelet recovery when compared between cohorts 1 versus 2 (HR = 0.599, p = 0.0221) and 1 versus 3 (HR = 0.515, p = 0.0014), as well as an increased risk of thrombosis (79.4%-cohort 3 vs 53.8%-cohort 2 vs 46.1%-cohort 1, p = 0.04), but had no impact on mortality (2.62-alive vs 2.65-deceased, p = 0.7432). A higher OD titer can inform risk assessment and support decision-making in HIT patients; however, prospective studies are needed to further clarify the impact of heparin-PF4 OD on outcomes.

Asunto(s)

Heparina , Factor Plaquetario 4 , Trombocitopenia , Trombosis , Humanos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/sangre , Trombosis/etiología , Trombosis/sangre , Masculino , Estudios Retrospectivos , Factor Plaquetario 4/inmunología , Femenino , Persona de Mediana Edad , Anciano , Plaquetas/inmunología , Anciano de 80 o más Años , Adulto , Factores de Riesgo , Autoanticuerpos/sangre , Recuento de Plaquetas , Anticuerpos/sangre , Mortalidad Hospitalaria

RESUMEN

Plasma proteins involved in coagulation and fibrinolysis are essential to hemostasis. Consequently, their circulating levels and functionality are critical in bleeding and thrombosis development. Well-established laboratory tests to assess these are available; however, said tests do not allow high multiplicity, require large volumes of plasma and are often costly. A novel technology to quantify plasma proteins is quantitative protein mass spectrometry (QPMS). Aided by stable isotope-labeled internal standards a large number of proteins can be quantified in one single analytical run requiring <30 µL of plasma. This provides an opportunity to improve insight in the etiology and prognosis of bleeding and thrombotic disorders, in which the balance between different proteins plays a crucial role. This manuscript aims to give an overview of the QPMS potential applications in thrombosis and hemostasis research (quantifying the 38 proteins assigned to coagulation and fibrinolysis by the KEGG database), but also to explore the potential and hurdles if designed for clinical practice. Advantages and limitations of QPMS are described and strategies for improved analysis are proposed, using as an example the test requirements for antithrombin. Application of this technology in the future could represent a step towards individualized patient care.

Asunto(s)

Coagulación Sanguínea , Fibrinólisis , Espectrometría de Masas , Humanos , Espectrometría de Masas/métodos , Proteínas Sanguíneas/análisis , Trombosis/sangre , Proteómica/métodos

RESUMEN

INTRODUCTION: Hutchinson-Gilford Progeria Syndrome (HGPS) is an ultra-rare premature aging genetic disorder caused by a point mutation in the lamin A gene, LMNA. Children with HGPS display short lifespans and typically die due to myocardial infarction or ischemic stroke, both acute cardiovascular events that are tightly linked to arterial thrombosis. Despite this fact, the effect of the classic HGPS LMNA gene mutation on arterial thrombosis remains unknown. METHODS: Heterozygous LmnaG609G knock-in (LmnaG609G/+) mice, yielding an equivalent classic mutation observed in HGPS patients (c.1824C>T; pG608G mutation in the human LMNA gene) and corresponding wild-type (WT) control littermates underwent photochemically laser-induced carotid injury to trigger thrombosis. Coagulation and fibrinolytic factors were measured. Furthermore, platelet activation and reactivity were investigated. RESULTS: LmnaG609G/+ mice displayed accelerated arterial thrombus formation, as underlined by shortened time to occlusion compared to WT littermates. Levels of factors involved in the coagulation and fibrinolytic system were comparable between groups, while LmnaG609G/+ animals showed higher plasma levels of thrombin-antithrombin complex and lower levels of antithrombin. Bone marrow analysis showed larger megakaryocytes in progeric mice. Lastly, enhanced platelet activation upon adenosine diphosphate, collagen-related peptide, and thrombin stimulation was observed in LmnaG609G/+ animals compared to the WT group, indicating a higher platelet reactivity in progeric animals. CONCLUSIONS: LMNA mutation in HGPS mice accelerates arterial thrombus formation, which is mediated, at least in part, by enhanced platelet reactivity, which consequently augments thrombin generation. Given the wide spectrum of antiplatelet agents available clinically, further investigation is warranted to consider the most suitable antiplatelet regimen for children with HGPS to mitigate disease mortality and morbidity.

Asunto(s)

Plaquetas , Progeria , Trombosis , Animales , Progeria/genética , Progeria/sangre , Progeria/complicaciones , Ratones , Trombosis/sangre , Trombosis/genética , Plaquetas/metabolismo , Activación Plaquetaria , Lamina Tipo A/genética , Modelos Animales de Enfermedad , Masculino , Humanos

RESUMEN

BACKGROUND: Post implantation syndrome (PIS) is a well-defined entity with unclear etiology, complicating a number of patients with abdominal aortic aneurysms treated with endovascular aortic repair (EVAR). The aim of this study was to assess the platelets' role and the influence of aneurysmal sac thrombus volumes in the development of PIS. A retrospective analysis of prospectively collected data was performed, and 76 patients who were treated by EVAR (2011-2013) were studied. Aneurysms with endoleak were not included in the study. Based on the criteria for systemic inflammatory response syndrome (SIRS), 17 patients (22%) developed PIS (which is considered a SIRS analogue), while 59 (78%) did not. METHODS: The 2 groups were compared in relation to the following parameters: baseline platelet count (PLT), decrease of platelet count (PLT drop), volume of the arterial flow before the procedure (V flow), volume of thrombus of the aneurysm (V thromb), ratio of thrombus volume to aneurysm sac volume (V ratio), and the volume of newly formed thrombus (V new). Volume flow measurements were calculated by Osirix software preoperatively and in the first month postoperatively. Parametric and nonparametric techniques (unpaired t-test, Mann-Whitney U test) were used accordingly. RESULTS: Baseline platelets absolute count was greater in the PIS group (239,000 ± 17,000) versus the non-PIS group (194,000 ± 6,900, P = 0.004), and the PLT drop was larger in the PIS group (74,000 ± 15,600 versus 45,000 ± 5,300, P = 0.019). No difference was found regarding the aneurysm volumes (V flow, V thromb, V ratio, and V new) between the 2 groups. CONCLUSIONS: Platelets, in terms of their absolute baseline count and their decrease after the procedure, seem to be an important factor in developing PIS after EVAR. Further, more tailored studies are needed to elucidate the role of platelets and flow or thrombus volumes in the development of PIS.

Asunto(s)

Aneurisma de la Aorta Abdominal , Plaquetas , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Trombosis , Humanos , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/sangre , Estudios Retrospectivos , Procedimientos Endovasculares/efectos adversos , Trombosis/etiología , Trombosis/diagnóstico por imagen , Trombosis/sangre , Trombosis/fisiopatología , Implantación de Prótesis Vascular/efectos adversos , Resultado del Tratamiento , Masculino , Recuento de Plaquetas , Femenino , Anciano , Factores de Tiempo , Anciano de 80 o más Años , Factores de Riesgo , Aortografía , Síndrome , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Flujo Sanguíneo Regional

RESUMEN

Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.

Asunto(s)

Janus Quinasa 2 , Neutrófilos , Policitemia Vera , Trombocitemia Esencial , Trombosis , Humanos , Trombosis/etiología , Trombosis/sangre , Femenino , Masculino , Persona de Mediana Edad , Janus Quinasa 2/genética , Anciano , Estudios Retrospectivos , Trombocitemia Esencial/sangre , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/genética , Policitemia Vera/sangre , Policitemia Vera/complicaciones , Policitemia Vera/genética , Adulto , Trastornos Mieloproliferativos/sangre , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Recuento de Leucocitos , Valor Predictivo de las Pruebas , Anciano de 80 o más Años

RESUMEN

BACKGROUND: Cardiovascular diseases are the dominant cause of morbidity in hemodialysis (HD) patients. Unless sufficient anticoagulation is used during HD, clotting may appear. The objective was to investigate if levels of fibrin degradation products (D-dimer) were increased before and during HD. METHODS: The combined observational study included 20 patients performing a total of 60 hemodialysis divided into three sessions of low-flux dialysis. None of the patients suffered from any clinically evident thromboembolic event before or during the study. Median bolus anticoagulation (mainly tinzaparin) doses were 84 Units/kg bow. Blood samples were drawn before HD (predialysis), and at 30min and 180min during HD with focus on analyzing D-dimer levels and its relation to interdialytic weight gain (IDWG) and speed of fluid elimination by HD (UF-rate). RESULTS: Predialysis, D-dimer levels (mean 0.767 ±0.821, min 0.136mg/L) were above the upper reference value in 95% of the sessions. D-dimer levels were lowered at 30min (p<0.001) and returned to predialysis levels at 180min. Predialysis D-dimer correlated with NT-pro-BNP, Troponin T, IDWG and UF-rate. Multiple regression analysis revealed that the D-dimer levels were significantly related to IDWG and the UF-rate. CONCLUSIONS: D-dimer levels were elevated in a high proportion predialysis and during HD and related to the IDWG and the UF-rate. Awareness of D-dimer levels and future studies will help clarify if optimization of those variables, besides anticoagulation and biocompatibility measures, will eradicate the repeated subclinical thromboembolic events related to each HD; one reason that may explain organ damage and shortened life span of these patients.

Asunto(s)

Productos de Degradación de Fibrina-Fibrinógeno , Diálisis Renal , Humanos , Diálisis Renal/efectos adversos , Femenino , Masculino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Persona de Mediana Edad , Anciano , Trombosis/etiología , Trombosis/sangre , Fallo Renal Crónico/terapia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Anticoagulantes/uso terapéutico , Adulto

RESUMEN

The high thrombus burden of the infarct-related artery (IRA) is associated with the adverse prognosis in ST-segment elevation myocardial infarction (STEMI) patients. Our objectives were to investigate the predictors and evaluate the prognosis of refractory thrombus in STEMI patients. A total of 1305 consecutive patients with STEMI who underwent primary percutaneous coronary intervention (pPCI) were screened. The refractory thrombus group (n = 15) was defined as IRA thrombolysis in myocardial infarction flow < grade 2 after multiple thrombus aspiration (TA). The control group (n = 45) was age- and sex-matched and was selected from the same batch of patients. Baseline hematologic indices were measured before the pPCI. The major adverse cardiovascular events (MACE) were recorded during follow-up. The refractory thrombus group had significantly higher red cell distribution width (RDW) at baseline compared with the control group (13.1 [12.4-13.7] vs 12.6 [12.3-12.8], P = .008). In multivariate logistic regression analysis, RDW was an independent predictor of refractory thrombus (odds ratio: 8.799, 95% CI: 1.240-62.454, P = .030). The area under the receiver-operating characteristic curve of the RDW was 0.730 (95%CI: 0.548-0.912, P = .008). During a mean period of 26 months follow-up, patients in the refractory thrombus group tended to have higher percent MACEs compared with patients in the control group (53.3% vs 6.7%, P < .001). In the present study, we found that the refractory thrombus in STEMI patients was associated with the worse prognosis and the increased RDW might be a potential independent predictor.

Asunto(s)

Índices de Eritrocitos , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Femenino , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios de Casos y Controles , Intervención Coronaria Percutánea/métodos , Anciano , Trombosis/etiología , Trombosis/sangre , Curva ROC , Trombosis Coronaria/sangre , Trombectomía/métodos

RESUMEN

Inflammation including immunothrombosis by neutrophil extracellular traps (NETs) has important implications in acute ischemic stroke and can affect reperfusion status, susceptibility to stroke associated infections (SAI) as well as functional clinical outcome. NETs were shown to be prevalent in stroke thrombi and NET associated markers were found in stroke patients' blood. However, little is known whether blood derived NET markers reflect the amount of NETs in thrombi. Conclusions from blood derived markers to thrombus composition might open avenues for novel strategies in diagnostic and therapeutic approaches. We prospectively recruited 166 patients with acute ischemic stroke undergoing mechanical thrombectomy between March 2018 and May 2021. Available thrombi (n = 106) were stained for NET markers DNA-histone-1 complexes and myeloperoxidase (MPO). Cell free DNA (cfDNA), deoxyribonuclease (DNase) activity, MPO-histone complexes and a cytokine-panel were measured before thrombectomy and after seven days. Clinical data, including stroke etiology, reperfusion status, SAI and functional outcome after rehabilitation, were collected of all patients. NET markers were present in all thrombi. At onset the median concentration of cfDNA in blood was 0.19 µg/ml increasing to 0.30 µg/ml at 7 days. Median DNase activity at onset was 4.33 pmol/min/ml increasing to 4.96 pmol/min/ml at 7 days. Within thrombi DNA-histone-1 complexes and MPO correlated with each other (ρ = 0.792; p < 0.001). Moreover, our study provides evidence for an association between the amount of NETs and endogenous DNase activity in blood with amounts of NETs in cerebral thrombi. However, these associations need to be confirmed in larger cohorts, to investigate the potential clinical implications for individualized therapeutic and diagnostic approaches in acute ischemic stroke.

Asunto(s)

Biomarcadores , Trampas Extracelulares , Accidente Cerebrovascular Isquémico , Humanos , Trampas Extracelulares/metabolismo , Biomarcadores/sangre , Masculino , Femenino , Anciano , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/diagnóstico , Persona de Mediana Edad , Estudios Prospectivos , Peroxidasa/sangre , Anciano de 80 o más Años , Ácidos Nucleicos Libres de Células/sangre , Trombectomía , Trombosis/sangre , Trombosis/diagnóstico , Neutrófilos/metabolismo

RESUMEN

BACKGROUND: Aging is an independent risk factor for the development of cardiovascular, thrombotic, and other chronic diseases. However, mechanisms of platelet hyperactivation in aging remain poorly understood. OBJECTIVES: Here, we examine whether and how aging alters intracellular signaling in platelets to support platelet hyperactivity and thrombosis. METHODS: Quantitative mass spectrometry with tandem mass tag labeling systematically measured protein phosphorylation in platelets from healthy aged (>65 years) and young human (<45 years) subjects. The role of platelet mechanistic target of rapamycin (mTOR) in aging-induced platelet hyperreactivity was assessed using pharmacologic mTOR inhibition and a platelet-specific mTOR-deficient mouse model (mTORplt-/-). RESULTS: Quantitative phosphoproteomics uncovered differential site-specific protein phosphorylation within mTOR, Rho GTPase, and MAPK pathways in platelets from aged donors. Western blot confirmed constitutive activation of the mTOR pathway in platelets from both aged humans and mice, which was associated with increased aggregation compared with that in young controls. Inhibition of mTOR with either Torin 1 in aged humans or genetic deletion in aged mice reversed platelet hyperreactivity. In a collagen-epinephrine pulmonary thrombosis model, aged wild-type (mTORplt+/+) mice succumbed significantly faster than young controls, while time to death of aged mTORplt-/- mice was similar to that of young mTORplt+/+ mice. Mechanistically, we noted increased Rac1 activation and levels of mitochondrial reactive oxygen species in resting platelets from aged mice, as well as increased p38 phosphorylation upstream of thromboxane generation following agonist stimulation. CONCLUSION: Aging-related changes in mTOR phosphorylation enhance Rac1 and p38 activation to enhance thromboxane generation, platelet hyperactivity, and thrombosis.

Asunto(s)

Envejecimiento , Plaquetas , Activación Plaquetaria , Transducción de Señal , Serina-Treonina Quinasas TOR , Trombosis , Proteína de Unión al GTP rac1 , Animales , Plaquetas/metabolismo , Plaquetas/efectos de los fármacos , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Trombosis/sangre , Trombosis/metabolismo , Fosforilación , Persona de Mediana Edad , Proteína de Unión al GTP rac1/metabolismo , Anciano , Masculino , Activación Plaquetaria/efectos de los fármacos , Adulto , Ratones Noqueados , Agregación Plaquetaria/efectos de los fármacos , Factores de Edad , Femenino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Proteómica/métodos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Inhibidores mTOR/farmacología , Neuropéptidos