Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Cell ; 187(10): 2393-2410.e14, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38653235

RESUMEN

SARS-CoV-2 and other sarbecoviruses continue to threaten humanity, highlighting the need to characterize common mechanisms of viral immune evasion for pandemic preparedness. Cytotoxic lymphocytes are vital for antiviral immunity and express NKG2D, an activating receptor conserved among mammals that recognizes infection-induced stress ligands (e.g., MIC-A/B). We found that SARS-CoV-2 evades NKG2D recognition by surface downregulation of MIC-A/B via shedding, observed in human lung tissue and COVID-19 patient serum. Systematic testing of SARS-CoV-2 proteins revealed that ORF6, an accessory protein uniquely conserved among sarbecoviruses, was responsible for MIC-A/B downregulation via shedding. Further investigation demonstrated that natural killer (NK) cells efficiently killed SARS-CoV-2-infected cells and limited viral spread. However, inhibition of MIC-A/B shedding with a monoclonal antibody, 7C6, further enhanced NK-cell activity toward SARS-CoV-2-infected cells. Our findings unveil a strategy employed by SARS-CoV-2 to evade cytotoxic immunity, identify the culprit immunevasin shared among sarbecoviruses, and suggest a potential novel antiviral immunotherapy.


Asunto(s)
COVID-19 , Evasión Inmune , Células Asesinas Naturales , Subfamilia K de Receptores Similares a Lectina de Células NK , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , COVID-19/inmunología , COVID-19/virología , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Animales , Citotoxicidad Inmunológica , Regulación hacia Abajo , Pulmón/inmunología , Pulmón/virología , Pulmón/patología
2.
Blood ; 143(12): 1193-1197, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38237140

RESUMEN

ABSTRACT: Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors.


Asunto(s)
Síndrome Antifosfolípido , Humanos , Neutrófilos , Anticuerpos Antifosfolípidos , Plaquetas
3.
J Thromb Thrombolysis ; 55(4): 770-774, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37000318

RESUMEN

Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder that can precede the diagnosis of multiple myeloma. MGUS is characterized by the presence of a monoclonal paraprotein without evidence of multiple myeloma or other lymphoplasmacytic malignancies. Even though MGUS is an asymptomatic condition that does not require management strategies other than periodic follow-up to prevent complications, secondary nonmalignant diseases may arise, requiring control of the plasma cell clone. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that occurs in patients with no prior personal or family history of bleeding. It is associated with several other disorders, such as neoplasia, mainly hematological (including MGUS and other lymphoproliferative disorders), autoimmune, infectious and cardiac diseases. At diagnosis, patients usually present with cutaneous and mucosal bleeding, including gastrointestinal bleeding. Here, we report a case of a patient with MGUS who developed AVWS after one year of follow-up. The patient was refractory to glucocorticoids and cyclophosphamide and achieved remission only after monoclonal paraprotein was eradicated following treatment with bortezomib and dexamethasone. Our report sdemonstrates that, for refractory cases, eradication of the monoclonal paraprotein may be necessary to treat bleeding complications due to MGUS-associated AVWS.


Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Paraproteinemias , Enfermedades de von Willebrand , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Gammopatía Monoclonal de Relevancia Indeterminada/tratamiento farmacológico , Bortezomib/uso terapéutico , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Paraproteinemias/complicaciones , Paraproteinemias/tratamiento farmacológico , Enfermedades de von Willebrand/complicaciones , Enfermedades de von Willebrand/tratamiento farmacológico , Proteínas de Mieloma
4.
J Thromb Thrombolysis ; 53(2): 390-398, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34417945

RESUMEN

Although dyslipidemia is associated with poorer prognosis in antiphospholipid syndrome (APS), the management of lipid disorders can be challenging. While statins may increase the bleeding risk associated with anticoagulation, the effectiveness of hypolipid diet (HD) has not yet been established in patients with autoimmune disorders. In this study, we evaluated whether HD is associated with decreases in cholesterol levels in patients with thrombotic primary APS (t-PAPS) and dyslipidemia. Nutritional and lipid profiles were assessed before HD was initiated (baseline) and after 3 and 6 months with HD. A 24-h dietary recall was applied to assess the adherence to the diet. Forty-four patients were included, mean age was 43 years (± 12.93) and 65% were female. After HD was started, the intake of carbohydrates, lipids, saturated fats and cholesterol decreased, whereas dietary fiber intake increased. Levels of total cholesterol (TC) and non-high density lipoprotein cholesterol (non-HDL-C) decreased after 3 and 6 months of HD, as compared to baseline (P = 0.007 and P = 0.008). Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) values did not change during the study period. The mean body mass index (BMI) decreased from 28.4 to 27.8 kg/m2 after six months of HD (p < 0.0001). In subgroup analysis, the effects of HD were more pronounced in patients with high TC, LDL-C or non-HDL-C levels at baseline and in those without obesity or hypertension. Nutritional intervention is feasible among t-PAPS and could be an alternative therapy to modulate lipid metabolism in this population.


Asunto(s)
Síndrome Antifosfolípido , Dislipidemias , Adulto , HDL-Colesterol , Dieta , Femenino , Humanos , Lípidos , Estudios Prospectivos
5.
J Thromb Thrombolysis ; 53(1): 30-42, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34449018

RESUMEN

Neutrophil activation and neutrophil extracellular traps (NETs) have been associated with the pathogenesis of venous thromboembolism (VTE). Considering VTE-associated chronic sequelae, which suggest that some pathological mechanisms remain after the acute episode, we investigated whether neutrophil activation is increased in patients with a prior VTE at least one year before this investigation. Thirty-seven patients with prior VTE and 37 individuals with no history of VTE were included. Neutrophil activity was evaluated by the expression of the adhesive molecule activation-specific epitopes LFA-1 (CD11a) and MAC-1 (CD11b), chemotaxis, reactive oxygen species (ROS) and by MPO-DNA complexes as markers of NETs. The adhesive molecules sICAM-1 and sVCAM-1, involved in the cross talk between neutrophil and endothelial cells, were also evaluated. Patient neutrophils presented increased CD11a expression before and after TNF-α stimulus, whereas increased CD11b expression was observed only after TNF-α stimulus, as compared to controls. Neutrophil chemotaxis on both, basal state and after IL-8 stimulus, on circulating levels of sICAM-1 and sVCAM-1, and on MPO-DNA complexes were also increased in VTE patients. ROS release was similar between patients and controls. This is, to our knowledge, the first study to investigate neutrophil inflammatory activity in VTE patients a long period after an acute event (approximately 2 years). The results showed altered neutrophil activation patterns in these patients. While activated neutrophils can cause endothelial activation and injury, the activated endothelium can induce the release of NETs with consequent endothelial cytotoxicity, creating a vicious cycle of activation between neutrophils and endothelium that can lead to thrombosis. VTE patients (approximately 2 years after the clinical event) present an altered neutrophil activation state evidenced by increased activity of the LFA-1 and Mac-1 adhesive molecules, as well as increased chemotaxis and circulating levels of NETs remnants. Circulating levels of ICAM-1 and VCAM-1, which are endothelial adhesive molecules, are also increased in VTE patients, suggesting not only an exacerbated endothelial activation and dysfunction, but also an interaction of the neutrophil adhesive molecules with their endothelial ligands, favoring the migration process of neutrophil.


Asunto(s)
Trampas Extracelulares , Tromboembolia Venosa , Células Endoteliales/metabolismo , Trampas Extracelulares/metabolismo , Humanos , Activación Neutrófila , Neutrófilos/metabolismo
6.
Br J Haematol ; 193(6): 1194-1202, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33748963

RESUMEN

Glucocorticoid treatment increases venous thromboembolism (VTE) risk. Whether this is due to the medication or the underlying disease, or affects the risk of VTE recurrence, has been difficult to determine. The aim of our present study was to quantify the risk for first and recurrent VTE associated with oral glucocorticoids use, considering the underlying disease. A total of 2547 patients with VTE from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study were linked to the Dutch Pharmaceutical Statistics register. The risk of first VTE during periods of exposure with oral glucocorticoids was estimated by the self-controlled case series method and that of recurrent VTE was examined in a cohort design. The incidence rate ratio (IRR) of first VTE in the period of glucocorticoid treatment was 3·51 [95% confidence interval (CI) 2·55-4·80]. This IRR was 2·53 (95% CI 1·10-5·72) in the week before treatment started, 5·28 (95% CI 2·89-9·53) in the first 7 days of treatment, remained elevated afterwards and decreased to 1·55 (95% CI 0·85-3·12) after 6 months, as compared to unexposed periods. The hazard ratio for recurrence was 2·72 (95% CI 1·64-4·78) in treatment periods as compared with no treatment. The increased risk of VTE associated with oral glucocorticoid treatment is due to a combined effect of the treatment and the underlying disease, remaining high during the first months of prescription.


Asunto(s)
Glucocorticoides , Tromboembolia Venosa , Administración Oral , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tromboembolia Venosa/sangre , Tromboembolia Venosa/inducido químicamente , Tromboembolia Venosa/epidemiología
7.
J Thromb Thrombolysis ; 52(3): 730-737, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34224066

RESUMEN

Antiphospholipid antibodies induce a pro-inflammatory and hypercoagulable state that lead to increased risk of thrombosis. Whether oxidative damage contributes thrombosis risk is a matter of debate. We evaluated the association between oxidative stress and thrombosis in primary antiphospholipid syndrome (t-PAPS). Plasma total antioxidant capacity and the levels of malondialdehyde (TBARs), carbonyl protein, and 8-isoprostane in plasma were determined in a group of patients with t-PAPS and in individuals without a history of thrombosis (controls) using commercial ELISA assays. The levels of these plasma markers of oxidative stress were compared between t-PAPS and controls using Mann-Whitney test. A total of 70 patients with t-PAPS and 74 controls were included. Overall, measurements of all plasma oxidative stress markers were similar between t-PAPS patients and controls. In a subgroup analysis, patients with t-PAPS and arterial thrombosis had a higher antioxidant capacity as compared to controls. Thrombotic PAPS was not associated with increased levels of oxidative stress markers, in comparison with individuals without thrombosis. Even though it is not possible to rule out that a mild oxidative damage, not detected by plasma markers, occurs in t-PAPS, our results suggest that measuring plasma oxidative stress markers has limited clinical relevance in t-PAPS.


Asunto(s)
Síndrome Antifosfolípido , Trombosis , Anticuerpos Antifosfolípidos , Antioxidantes , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Biomarcadores/sangre , Humanos , Estrés Oxidativo , Trombosis/sangre , Trombosis/etiología
8.
J Thromb Thrombolysis ; 50(4): 772-781, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32462539

RESUMEN

The role of inflammation in thrombotic complications of primary antiphospholipid syndrome (PAPS) is controversial. The aim of this study was to evaluate levels of inflammation and coagulation markers in patients with thrombotic PAPS (t-PAPS). Patients with t-PAPS and individuals with no history of thrombosis were enrolled. The association of t-PAPS with levels of tumor necrosis factor (TNF)-α, C-reactive protein (hs-CRP), interferon (IFN)-α, interleukins (IL)-6, -8, factor VIII (FVIII), von Willebrand factor (VWF) and tissue factor (TF) was evaluated by regression models. The levels of these markers were also compared between controls and subgroups of t-PAPS patients with triple positivity, recently diagnosed thrombosis, recurrent thrombosis and venous thrombosis. Patients with t-PAPS (n = 101) had a 8.6-fold increased levels of TNF-α, 90% increased levels of hs-CRP, 80% increased levels of IL-6, 30% increased levels of FVIIIAg, 50% increased levels of VWF and 66% increased levels of TF as compared to controls (n = 131), and the differences did not change after adjustments for sex, age and cardiovascular risk factors. Inflammatory markers were elevated in t-PAPS regardless of the aPL profile, number of previous thrombosis or time elapsed since diagnosis. TNF-α and IL-8 levels were higher in t-PAPS patients with venous thrombosis, in comparison with those with arterial thrombosis and controls. Patients with t-PAPS presented with increased levels of inflammatory and coagulation markers, which suggests that t-PAPS is associated not only with hypercoagulability but also with a persistent inflammatory state.


Asunto(s)
Síndrome Antifosfolípido/sangre , Inflamación/sangre , Trombosis/sangre , Adulto , Síndrome Antifosfolípido/complicaciones , Biomarcadores/sangre , Coagulación Sanguínea , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Factor VIII/análisis , Femenino , Humanos , Inflamación/complicaciones , Interferón-alfa/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Trombosis/etiología , Factor de von Willebrand/análisis
9.
Semin Thromb Hemost ; 45(8): 825-833, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31096309

RESUMEN

Venous thromboembolism (VTE) causes a major disease burden worldwide, so that effective preventive measures are warranted. Although oral anticoagulation is effective in preventing VTE episodes, bleeding complications are a major concern that may lead to treatment avoidance. Statin therapy, which is widely used for prevention of arterial cardiovascular disease, is a promising alternative treatment for VTE prophylaxis, as the drug may affect hemostasis without increasing the risk of bleeding. In the past years, clinical studies have suggested that statins can interfere with blood coagulation and, in turn, reduce the risk of VTE. These effects, however, are still regarded with skepticism, as the underlying mechanisms by which statins may affect hemostasis in humans are not clear and data showing that statin therapy reduces VTE risk mostly came from observational studies, while only one randomized trial was conducted to evaluate this issue. In this review, the authors summarize the currently available evidence regarding the effect of statin therapy on coagulation and on VTE prevention. Recent randomized data showed that statin therapy, in particular rosuvastatin, leads to decreased levels of coagulation factors in patients with prior VTE. This evidence provides a reasonable basis for interventional studies necessary to establish the efficacy of statins on reducing the risk of incident and recurrent VTE.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Trombofilia/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Humanos
11.
Hematol Transfus Cell Ther ; 46(1): 49-57, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37451977

RESUMEN

The evolutionary conserved link between coagulation and innate immunity is a biological process characterized by the thrombosis formation stimulus of immune cells and specific thrombosis-related molecules. In physiological settings, the relationship between the immune system and thrombosis facilitates the recognition of pathogens and damaged cells and inhibits pathogen proliferation. However, when deregulated, the interplay between hemostasis and innate immunity becomes a pathological process named immunothrombosis, which is at the basis of several infectious and inflammation-related thrombotic disorders, including coronavirus disease 2019 (COVID-19). In advanced stages, alterations in both coagulation and immune cell function due to extreme inflammation lead to an increase in blood coagulability, with high rates of thrombosis and mortality. Therefore, understanding underlying mechanisms in immunothrombosis has become decisive for the development of more efficient therapies to treat and prevent thrombosis in COVID-19 and in other thrombotic disorders. In this review, we outline the existing knowledge on the molecular and cellular processes involved in immunothrombosis, focusing on the role of neutrophil extracellular traps (NETs), platelets and the coagulation pathway. We also describe how the deregulation of hemostasis is associated with pathological conditions and can significantly aggravate a patient's condition, using COVID-19 as a clinical model.

12.
Hematol Transfus Cell Ther ; 46(2): 176-185, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38341321

RESUMEN

Exacerbated inflammation and coagulation are a hallmark of COVID-19 severity. Extracellular vesicles (EVs) are intercellular transmitters involved in inflammatory conditions, which are capable of triggering prothrombotic mechanisms. Since the release of EVs is potentially associated with COVID-19-induced coagulopathy, the aim of this study was to evaluate changes in inflammation- and hypercoagulability-related EVs during the first month after symptom onset and to determine whether they are associated with disease severity. Blood samples of patients with mild or severe forms of the disease were collected on three occasions: in the second, third and fourth weeks after symptom onset for the quantification by flow cytometry of CD41A (platelet glycoprotein IIb/IIIa), CD162 (PSGL-1), CD31 (PECAM-1) and CD142 cells (tissue factor). Analysis of variance (ANOVA) with repeated measures, Kruskal-Wallis and correlation tests were used. Eighty-five patients were enrolled, 71% of whom had mild disease. Seventeen uninfected individuals served as controls. Compared to controls, both mild and severe COVID-19 were associated with higher EV-CD31+, EV-CD41+ and EV-CD142+ levels. All EV levels were higher in severe than in mild COVID-19 only after the third week from symptom onset, as opposed to C-reactive protein and D-dimer levels, which were higher in severe than in mild COVID-19 earlier during disease progression. EV levels were also associated with C-reactive protein and D-dimer levels only after the third week of symptoms. In conclusion, EVs expressing CD41A, CD31, TF, and CD162 appear as late markers of COVID-19 severity. This finding may contribute to the understanding of the pathogenesis of acute and possibly long COVID-19.

13.
BMC Infect Dis ; 13: 350, 2013 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-23890510

RESUMEN

BACKGROUND: Dengue cases have been classified according to disease severity into dengue fever (DF) and dengue hemorrhagic fever (DHF). Although DF is considered a non-severe manifestation of dengue, it has been recently demonstrated that DF represents a heterogeneous group of patients with varied clinical complications and grades of severity. Particularly, bleeding complications, commonly associated to DHF, can be detected in half of the patients with DF. Although a frequent complication, the causes of bleedings in DF have not been fully addressed. Thus, the aim of this study was to perform a comprehensive evaluation of possible pathophysiological mechanisms that could contribute to the bleeding tendency observed in patients with DF. METHODS: This is a case-control study that enrolled adults with DF without bleeding and adults with DF and bleeding complications during the defervescence period. Healthy controls were also included. Peripheral blood counts, inflammatory, fibrinolysis and endothelial cell activation markers, and thrombin generation were evaluated in patients and controls. RESULTS: We included 33 adults with DF without complications, 26 adults with DF and bleeding and 67 healthy controls. Bleeding episodes were mild in 15 (57.6%) and moderate in 11 (42.4%) patients, 8 (30.7%) patients had bleedings in multiple sites. Patients with DF and bleedings had lower platelet counts than DF without bleeding (median = 19,500 vs. 203,500/mm3, P < 0,0001). Levels of TNF-α, thrombomodulin and VWF were significantly increased in the two dengue groups than in healthy controls, but similar between patients with and without bleedings. Plasma levels of tPA and D-dimer were significantly increased in patients with bleedings (median tPA levels were 4.5, 5.2, 11.7 ng/ml, P < 0.0001 and median D-dimer levels were 515.5, 1028 and 1927 ng/ml, P < 0.0001). The thrombin generation test showed that patients with bleeding complications had reduced thrombin formation (total thrombin generated were 3753.4 in controls, 3367.5 in non-bleeding and 2274.5nM in bleeding patients, P < 0.002). CONCLUSIONS: DF can manifest with spontaneous bleedings, which are associated with specific coagulation and fibrinolysis profiles that are not significantly present in DF without this complication. Particularly, thrombocytopenia, excessive fibrinolysis and reduced thrombin formation may contribute to the bleeding manifestations in DF.


Asunto(s)
Fibrinólisis/fisiología , Dengue Grave/sangre , Trombina/biosíntesis , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Femenino , Hemorragia/sangre , Hemorragia/virología , Humanos , Masculino , Persona de Mediana Edad , Trombina/metabolismo , Adulto Joven
14.
Clin Appl Thromb Hemost ; 29: 10760296231175656, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37203167

RESUMEN

Thrombosis occurrence in coronavirus disease 2019 (COVID-19) has been mostly compared to historical cohorts of patients with other respiratory infections. We retrospectively evaluated the thrombotic events that occurred in a contemporary cohort of patients hospitalized between March and July 2020 for acute respiratory distress syndrome (ARDS) according to the Berlin Definition and compared those with positive and negative real-time polymerase chain reaction results for wild-type severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using descriptive analysis. The association between COVID-19 and thrombotic risk was evaluated using logistic regression. 264 COVID-19-positive (56.8% male, 59.0 years [IQR 48.6-69.7], Padua score on admission 3.0 [2.0-3.0]) and 88 COVID-19-negative patients (58.0% male, 63.7 years [51.2-73.5], Padua score 3.0 [2.0-5.0]) were included. 10.2% of non-COVID-19 and 8.7% of COVID-19 patients presented ≥ 1 clinically relevant thrombotic event confirmed by imaging exam. After adjustment for sex, Padua score, intensive care unit stay, thromboprophylaxis, and hospitalization length, the odds ratio for thrombosis in COVID-19 was 0.69 (95% CI, 0.30-1.64). We, therefore, conclude that infection-induced ARDS carries an inherent thrombotic risk, which was comparable between patients with COVID-19 and other respiratory infections in our contemporary cohort.


Asunto(s)
COVID-19 , Síndrome de Dificultad Respiratoria , Trombosis , Tromboembolia Venosa , Humanos , Masculino , Femenino , COVID-19/complicaciones , SARS-CoV-2 , Anticoagulantes/uso terapéutico , Estudios Retrospectivos , Tromboembolia Venosa/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/etiología
15.
Res Pract Thromb Haemost ; 6(7): e12816, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36246480

RESUMEN

Background: The magnitude of venous thromboembolism (VTE) risk in severe COVID-19 is a matter of debate because of study heterogeneity, changes in VTE management, and scarce evidence of VTE risk in critically ill patients with pneumonia in the pre-COVID-19 era. Objectives: To evaluate VTE risk in the pre-COVID-19 era in a large intensive care unit (ICU) database. Patients/Methods: Data from consecutive pneumonia patients admitted to the ICU were retrieved from the Medical Information Mart for Intensive Care III. VTE risk was described in the entire cohort and in subgroups. Results: Among 6842 pneumonia patients admitted to the ICU, 486 patients were diagnosed with VTE after a median of 3 (IQR 1-11) days in the ICU. The 30-day cumulative incidence of VTE was 7% and remained at this level across different age groups, sex, and type of ICU. After adjusting for death, the overall cumulative incidence of VTE was 5%. A total of 1788 patients received thromboprophylaxis (of 2958 for whom that data were available). VTE occurred in 10.7% (95% CI 9.0-12.6) of patients without thromboprophylaxis and in 6.4% (95% CI 5.4-7.6) of those with thromboprophylaxis. Mortality was 20.6% among patients with VTE and 19.2% among those without VTE. Conclusions: In the pre-COVID-19 era, VTE risk in ICU patients with pneumonia was high and decreased with thromboprophylaxis. These findings can serve as comparators for future studies aiming at evaluating the impact of COVID-19 or other emerging infections on VTE risk.

16.
J Thromb Haemost ; 19(9): 2275-2286, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34018665

RESUMEN

BACKGROUND: The optimum second-line treatment or best sequence of treatments for immune thrombocytopenia (ITP) are yet to be determined. Our institution has accumulated extensive experience regarding the use of dapsone as second-line therapy for ITP. OBJECTIVES: We aimed to assess the efficacy rate and safety of dapsone treatment in ITP patients. PATIENTS/METHODS: Here we report our experience in a retrospective study, including 122 patients, with a median treatment duration with dapsone of 6 months and a median follow-up period of 3.4 years. RESULTS: The overall response rate in this cohort was 66%, including 24% of complete responses. Among responders, in 24% a relapse occurred while on treatment. Therefore, a sustained response was observed in 51% of patients. Interestingly, 81% of the responders maintained the response after the interruption of treatment, for a median time of 26 months. Side effects were reported in 16% of the patients in this cohort and treatment was interrupted due to side effects in 11% of patients. The main cause in these cases was hemolytic anemia and methemoglobinemia. Reductions in hemoglobin levels during the use of dapsone were seen in 94% of the patients. Responders presented significantly greater reductions in their hemoglobin levels than nonresponders did: median hemoglobin drop of 1.9 g/dl vs. 1.2 g/dl (p = .004). CONCLUSIONS: Our findings suggest that dapsone has adequate efficacy and is well tolerated. Although the mechanism of action is still unclear, our observation that the degree in the drop of hemoglobin is greater in responders suggest a possible role of the blockage of the reticuloendothelial system in the therapeutic effect of the drug.


Asunto(s)
Dapsona , Púrpura Trombocitopénica Idiopática , Humanos , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Inducción de Remisión , Estudios Retrospectivos , Esplenectomía , Resultado del Tratamiento
17.
Res Pract Thromb Haemost ; 8(1): 102328, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38404938
18.
Hematol., Transfus. Cell Ther. (Impr.) ; 46(1): 49-57, Jan.-Mar. 2024. graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1557876

RESUMEN

Abstract The evolutionary conserved link between coagulation and innate immunity is a biological process characterized by the thrombosis formation stimulus of immune cells and specific thrombosis-related molecules. In physiological settings, the relationship between the immune system and thrombosis facilitates the recognition of pathogens and damaged cells and inhibits pathogen proliferation. However, when deregulated, the interplay between hemostasis and innate immunity becomes a pathological process named immunothrombosis, which is at the basis of several infectious and inflammation-related thrombotic disorders, including coronavirus disease 2019 (COVID-19). In advanced stages, alterations in both coagulation and immune cell function due to extreme inflammation lead to an increase in blood coagulability, with high rates of thrombosis and mortality. Therefore, understanding underlying mechanisms in immunothrombosis has become decisive for the development of more efficient therapies to treat and prevent thrombosis in COVID-19 and in other thrombotic disorders. In this review, we outline the existing knowledge on the molecular and cellular processes involved in immunothrombosis, focusing on the role of neutrophil extracellular traps (NETs), platelets and the coagulation pathway. We also describe how the deregulation of hemostasis is associated with pathological conditions and can significantly aggravate a patient's condition, using COVID-19 as a clinical model.

19.
Clin Epidemiol ; 11: 625-633, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31413640

RESUMEN

PURPOSE: Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterial thrombotic diseases. We investigated whether these apolipoproteins have prothrombotic properties and are associated with risk of venous thromboembolism (VTE). PATIENTS AND METHODS: A total of 127 VTE patients and 299 controls were randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (1999-2004), in the Netherlands. The apolipoproteins were quantified using mass spectrometry (LC/MS/MS), and their levels were analyzed as continuous variable (per SD increase). RESULTS: In controls, increases in levels of apolipoproteins were associated with increases in levels of vitamin K-dependent factors, factor XI, antithrombin and clot lysis time. Additionally, increasing apolipoproteins C-III and E levels were associated with higher factor VIII and von Willebrand factor levels. Levels of C-reactive protein were not associated with any apolipoprotein. The age- and sex-adjusted odds ratios of apolipoproteins E, C-III, CII and CI to the risk of venous thrombosis were 1.21 (95% CI, 0.98-1.49), 1.19 (95% CI, 0.99-1.44), 1.24 (95% CI, 0.95-1.61) and 1.06 (95% CI, 0.87-1.30) per SD increase, respectively. These odds ratios did not attenuate after adjustments for statin use, estrogen use, BMI, alcohol use, and self-reported diabetes. CONCLUSIONS: Levels of apolipoproteins C-I, C-II, C-III and E are associated with those of several coagulation factors. However, whether these apolipoproteins are also associated with an increased risk of VTE remains to be established.

20.
J Thromb Haemost ; 17(2): 319-328, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30565854

RESUMEN

Essentials The role of statins in hemostasis and venous thromboembolism (VTE) prophylaxis is not clear. This trial assessed whether rosuvastatin use affects thrombin generation in patients with VTE. Endogenous thrombin potential and peak were decreased by 10% and 5% with rosuvastatin therapy. These results provide basis for trials on the efficacy of statins in reducing recurrent VTE risk. SUMMARY: Background Statin therapy could form an alternative prophylactic treatment for venous thromboembolism (VTE) if statins are proven to downregulate hemostasis and prevent recurrent VTE, without increasing bleeding risk. Objectives The STAtins Reduce Thrombophilia (START) trial investigated whether statin affects coagulation in patients with prior VTE. Patients/methods After anticoagulation withdrawal, patients were randomized to rosuvastatin 20 mg day-1 for 4 weeks or no intervention. Plasma samples taken at baseline and at the end of the study were analyzed employing thrombin generation assay. Results and conclusions The study comprised 126 rosuvastatin users and 119 non-users. Mean age was 58 years, 61% were men, 49% had unprovoked VTE and 75% had cardiovascular (CV) risk factors. Endogenous thrombin potential (ETP) increased from baseline to end of study in non-statin users (mean 97.22 nm*min; 95% CI, 40.92-153.53) and decreased in rosuvastatin users (mean -24.94 nm*min; 95% CI, -71.81 to 21.93). The mean difference in ETP change between treatments was -120.24 nm*min (95% CI, -192.97 to -47.51), yielding a 10.4% ETP reduction by rosuvastatin. The thrombin peak increased in both non-statin (mean 20.69 nm; 95% CI, 9.80-31.58) and rosuvastatin users (mean 8.41 nm; 95% CI -0.86 to 17.69). The mean difference in peak change between treatments was -11.88 nm (95% CI, -26.11 to 2.35), yielding a 5% peak reduction by rosuvastatin. Other thrombin generation parameters did not change substantially. The reduction in ETP and peak by rosuvastatin was more pronounced in the subgroups of participants with CV risk factors and with unprovoked VTE. We conclude that rosuvastatin reduces thrombin generation potential in patients who had VTE.


Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Fibrinolíticos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Rosuvastatina Cálcica/uso terapéutico , Trombina/metabolismo , Tromboembolia Venosa/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fibrinolíticos/efectos adversos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Masculino , Persona de Mediana Edad , Países Bajos , Recurrencia , Rosuvastatina Cálcica/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/sangre , Tromboembolia Venosa/diagnóstico , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA