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2.
Proc Natl Acad Sci U S A ; 121(17): e2314450121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38621133

RESUMO

Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer's disease (AD). Vascular deficits include a compromised blood-brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen's interaction with the amyloid-beta (Aß) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears Aß plaque from the brain and slows cognitive decline. Here, we show that lecanemab blocks fibrinogen's binding to Aß protofibrils, preventing Aß/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the Aß/fibrinogen complex and prevents fibrinogen from exacerbating Aß-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD.


Assuntos
Doença de Alzheimer , Anticorpos Monoclonais Humanizados , Trombose , Camundongos , Humanos , Animais , Fibrinogênio/metabolismo , Sistemas Microfisiológicos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo
3.
Langenbecks Arch Surg ; 409(1): 116, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592545

RESUMO

INTRODUCTION: Isolated splenic vein thrombosis (iSVT) is a common complication of pancreatic disease. Whilst patients remain asymptomatic, there is a risk of sinistral portal hypertension and subsequent bleeding from gastric varices if recanalisation does not occur. There is wide variation of iSVT treatment, even within single centres. We report outcomes of iSVT from tertiary referral hepatobiliary and pancreatic (HPB) units including the impact of anticoagulation on recanalisation rates and subsequent variceal bleeding risk. METHODS: A retrospective cohort study including all patients diagnosed with iSVT on contrast-enhanced CT scan abdomen and pelvis between 2011 and 2019 from two institutions. Patients with both SVT and portal vein thrombosis at diagnosis and isolated splenic vein thrombosis secondary to malignancy were excluded. The outcomes of anticoagulation, recanalisation rates, risk of bleeding and progression to portal vein thrombosis were examined using CT scan abdomen and pelvis with contrast. RESULTS: Ninety-eight patients with iSVT were included, of which 39 patients received anticoagulation (40%). The most common cause of iSVT was acute pancreatitis n = 88 (90%). The recanalisation rate in the anticoagulation group was 46% vs 15% in patients receiving no anticoagulation (p = 0.0008, OR = 4.7, 95% CI 1.775 to 11.72). Upper abdominal vascular collaterals (demonstrated on CT scan angiography) were significantly less amongst patients who received anticoagulation treatment (p = 0.03, OR = 0.4, 95% CI 0.1736 to 0.9288). The overall rate of upper GI variceal-related bleeding was 3% (n = 3/98) and it was independent of anticoagulation treatment. Two of the patients received therapeutic anticoagulation. CONCLUSION: The current data supports that therapeutic anticoagulation is associated with a statistically significant increase in recanalisation rates of the splenic vein, with a subsequent reduction in radiological left-sided portal hypertension. However, all patients had a very low risk of variceal bleeding regardless of anticoagulation. The findings from this retrospective study should merit further investigation in large-scale randomised clinical trials.


Assuntos
Varizes Esofágicas e Gástricas , Pancreatite , Trombose , Humanos , Doença Aguda , Anticoagulantes/efeitos adversos , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal , Estudos Retrospectivos , Medição de Risco , Veia Esplênica/diagnóstico por imagem
4.
BMJ Case Rep ; 17(4)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627047

RESUMO

We present a case of a man in his 30s presenting with ST-segment elevation myocardial infarction and eosinophilia. The patient underwent thrombus aspiration and initially echocardiographic evaluation was normal. The patient was discharged after 2 days, but was hospitalised again after 6 days. Echocardiographic evaluation now revealed a thrombus formation on the aortic valve. Laboratory data revealed increasing eosinophilia, and treatment with high-dosage corticosteroids and hydroxyurea was initiated as eosinophilic disease with organ manifestations could not be precluded. Eosinophils normalised and the patient was discharged again. The combination of hypereosinophilia and absence of infection, rheumatological disorders and malignancy, led to reactive or idiopathic hypereosinophilic syndrome being the most plausible diagnoses. The patient was closely monitored in the cardiology and haematology outpatient clinics. Echocardiographic evaluation, performed 6 weeks after the patient was discharged, showed significant regression in the size of the thrombus mass.


Assuntos
Síndrome Hipereosinofílica , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombose , Masculino , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Valva Aórtica/diagnóstico por imagem , Síndrome Hipereosinofílica/complicações , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológico , Hidroxiureia , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Trombose/etiologia
5.
Vasc Health Risk Manag ; 20: 177-181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38623542

RESUMO

Cerebral sinovenous thrombosis (CSVT) encompasses a spectrum of disorders involving thrombosis of the cerebral venous system. As shown by previous epidemiological studies, the prevalence of cerebral sinovenous thrombosis is 4-7 cases per million people. Nephrotic syndrome was very rarely associated with thrombosis cerebral veins or sinuses. Hypercoagulability and thrombotic complications in nephrotic syndrome are most commonly seen in deep veins of the lower extremities and renal veins. Our case highlights a unique scenario in which cerebral sinovenous thrombosis was the initial presentation of nephrotic syndrome in a patient that was not an important past medical or surgical problem. The patient was brought to the emergency department with severe headache, vomiting, altered mental status, and generalized body swelling. Laboratory results showed proteinuria, hypoalbuminemia and hyperlipidemia. Non-contrast brain CT demonstrated hemorrhagic venous infarct associated with vasogenic edema. A subsequent brain MR venogram demonstrated occlusion of superior sagittal and right transverse sinuses. She was managed with low molecular weight heparin and intervenous corticosteroids then shifted to rivaroxaban and oral steroids, respectively, which resulted in massive clinical improvement and resolution of thrombus.


Assuntos
Síndrome Nefrótica , Trombose dos Seios Intracranianos , Trombose , Feminino , Humanos , Síndrome Nefrótica/complicações , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Encéfalo , Veias , Trombose dos Seios Intracranianos/complicações , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/tratamento farmacológico
7.
J Cardiothorac Surg ; 19(1): 188, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589945

RESUMO

Pulmonary embolism is the most common cardiovascular disease after myocardial infarction and stroke. Konstantinides (Eur Heart J 41(4):543-603, 2020) Current guidelines categorize patients with PE as being at low, intermediate, and high risk of early death, with the intermediate-risk group experiencing the greatest uncertainty regarding treatment recommendations. Rapid reduction of the thrombus load by thrombolysis significantly reduces symptoms and decreases mortality, but is accompanied by a high risk of bleeding. Meyer (N Engl J Med 370(15):1402-11, 2014) Mechanical thrombectomy (CDTE) have been proven safe and efficient, yet current ESC guidelines suggest the utilization of catheter interventions only for hypotensive patients with high bleeding risk, failed systemic thrombolysis, and cardiogenic shock or if a patient does not respond to conservative therapy Konstantinides (Eur Heart J 41(4):543-603, 2020). Here, we report a case of an intermediate-risk patient with pulmonary embolism who underwent thrombus aspiration and showed significant improvement in symptoms after treatment.


Assuntos
Compostos de Cádmio , Embolia Pulmonar , Pontos Quânticos , Trombose , Humanos , Trombectomia , Resultado do Tratamento , Telúrio , Embolia Pulmonar/terapia , Hemorragia , Terapia Trombolítica
8.
PeerJ ; 12: e17039, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590700

RESUMO

Background: Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Methods: Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. Results: R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. Conclusion: R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.


Assuntos
Hominidae , Hipertensão Pulmonar , Embolia Pulmonar , Trombose , Ratos , Animais , Hipertensão Pulmonar/tratamento farmacológico , Ratos Sprague-Dawley , Hirudinas/farmacologia , Peróxido de Hidrogênio/uso terapêutico , Embolia Pulmonar/complicações , Trombose/tratamento farmacológico
9.
Rinsho Ketsueki ; 65(3): 164-168, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38569860

RESUMO

Congenital protein C (PC) deficiency is one type of hereditary thrombosis. Patients with hereditary thrombosis are at high risk for thrombosis in the perioperative period, but a standard management strategy has not been established. Here we report a case of perioperative management of a fracture in a child with homozygous congenital PC deficiency. The patient was a 3-year-old boy who was diagnosed with congenital PC deficiency at birth. He sustained a traumatic supracondylar fracture of the right humerus and underwent emergency surgery. To prepare for open surgery for fixation of the fracture, warfarin was discontinued, and an activated PC (APC) concentrate was used in combination with vitamin K antagonism. However, warfarin was administered during the scheduled nail extraction because the operation was minimally invasive. No thrombotic or bleeding complications occurred in either operation. In emergency surgery in patients with congenital PC deficiency, the combination of vitamin K and APC concentrate is considered a maintenance option for PC deficiency. Postoperative PT-INR control was difficult in our patient due to the administration of vitamin K and withdrawal of warfarin, and this issue must be addressed in the future. Further case experience is desirable to standardize perioperative management.


Assuntos
Fraturas Ósseas , Deficiência de Proteína C , Trombose , Pré-Escolar , Humanos , Recém-Nascido , Masculino , Anticoagulantes , Fraturas Ósseas/complicações , Deficiência de Proteína C/complicações , Trombose/complicações , Vitamina K , Varfarina/uso terapêutico
10.
Eur Radiol Exp ; 8(1): 52, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38575701

RESUMO

BACKGROUND: Nowadays, there is no method to quantitatively characterize the material composition of acute ischemic stroke thrombi prior to intervention, but dual-energy CT (DE-CT) offers imaging-based multimaterial decomposition. We retrospectively investigated the material composition of thrombi ex vivo using DE-CT with histological analysis as a reference. METHODS: Clots of 70 patients with acute ischemic stroke were extracted by mechanical thrombectomy and scanned ex vivo in formalin-filled tubes with DE-CT. Multimaterial decomposition in the three components, i.e., red blood cells (RBC), white blood cells (WBC), and fibrin/platelets (F/P), was performed and compared to histology (hematoxylin/eosin staining) as reference. Attenuation and effective Z values were assessed, and histological composition was compared to stroke etiology according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Histological and imaging analysis showed the following correlation coefficients for RBC (r = 0.527, p < 0.001), WBC (r = 0.305, p = 0.020), and F/P (r = 0.525, p < 0.001). RBC-rich thrombi presented higher clot attenuation in Hounsfield units than F/P-rich thrombi (51 HU versus 42 HU, p < 0.01). In histological analysis, cardioembolic clots showed less RBC (40% versus 56%, p = 0.053) and more F/P (53% versus 36%, p = 0.024), similar to cryptogenic clots containing less RBC (34% versus 56%, p = 0.006) and more F/P (58% versus 36%, p = 0.003) than non-cardioembolic strokes. No difference was assessed for the mean WBC portions in all TOAST groups. CONCLUSIONS: DE-CT has the potential to quantitatively characterize the material composition of ischemic stroke thrombi. RELEVANCE STATEMENT: Using DE-CT, the composition of ischemic stroke thrombi can be determined. Knowledge of histological composition prior to intervention offers the opportunity to define personalized treatment strategies for each patient to accomplish faster recanalization and better clinical outcomes. KEY POINTS: • Acute ischemic stroke clots present different recanalization success according to histological composition. • Currently, no method can determine clot composition prior to intervention. • DE-CT allows quantitative material decomposition of thrombi ex vivo in red blood cells, white blood cells, and fibrin/platelets. • Histological clot composition differs between stroke etiology. • Insights into the histological composition in situ offer personalized treatment strategies.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/patologia , Trombose/terapia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/terapia , Fibrina/análise , Tomografia Computadorizada por Raios X/métodos
11.
Medicine (Baltimore) ; 103(14): e37692, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579050

RESUMO

Reperfusion therapy of acute myocardial infarction (AMI) refers to physical or chemical recanalization and restoration of blood flow to an occluded coronary artery, and current techniques for reperfusion therapy include intravenous thrombolysis, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The number of patients receiving emergency CABG in the real world is decreasing due to the disadvantages of CABG and the improvement in PCI procedures. Thrombolytic therapy has some disadvantages such as low recanalization rate, high risk of reocclusion and bleeding, and short time window. On the other hand, intracoronary interventional therapy may meet the requirements of "early, complete and persistent" patency of coronary arteries at different time points. However, in the emergency PCI, although thrombus aspiration via a catheter or balloon dilation is performed, residual thrombus with heavy or low TIMI (thrombolysis in myocardial infarction) myocardial perfusion grading is still observed in some patients, suggesting disordered microcirculation. Currently, the treatment of microcirculatory disturbance in emergency PCI mainly employed injection of tirofiban, adenosine, thrombolytic agent or other drugs into the local area via a microcatheter in a short time, all of which can significantly reduce the thrombus load and improve TIMI perfusion. Herein, we report that a microcatheter was indwelled in the coronary artery for continuous pumping of low-dose thrombolytic drugs as reperfusion therapy in 12 patients with acute and subacute MI.


Assuntos
Angioplastia Coronária com Balão , Infarto do Miocárdio , Intervenção Coronária Percutânea , Trombose , Humanos , Fibrinolíticos , Microcirculação , Angioplastia Coronária com Balão/métodos , Infarto do Miocárdio/etiologia , Terapia Trombolítica/efeitos adversos , Reperfusão , Trombose/etiologia , Resultado do Tratamento , Reperfusão Miocárdica
12.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612791

RESUMO

Neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, are released by neutrophils in response to pathogens but are also recognized for their involvement in a range of pathological processes, including autoimmune diseases, cancer, and cardiovascular diseases. This review explores the intricate roles of NETs in different cardiovascular conditions such as thrombosis, atherosclerosis, myocardial infarction, COVID-19, and particularly in the pathogenesis of abdominal aortic aneurysms. We elucidate the mechanisms underlying NET formation and function, provide a foundational understanding of their biological significance, and highlight the contribution of NETs to inflammation, thrombosis, and tissue remodeling in vascular disease. Therapeutic strategies for preventing NET release are compared with approaches targeting components of formed NETs in cardiovascular disease. Current limitations and potential avenues for clinical translation of anti-NET treatments are discussed.


Assuntos
Aneurisma da Aorta Abdominal , Sistema Cardiovascular , Armadilhas Extracelulares , Infarto do Miocárdio , Trombose , Humanos
13.
Med Sci Monit ; 30: e943587, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38615190

RESUMO

BACKGROUND Deep vein thrombosis is a common pre- and post-operative complication in older patients with osteoporotic hip fractures. Pre-operative thrombus can increase the risk of surgery. This study examined the association between the time from fracture to admission (injury-admission time) and deep vein thrombosis in older patients with osteoporotic hip fractures. MATERIAL AND METHODS Doppler ultrasound screening of deep lower-extremity veins was performed in patients with osteoporotic hip fractures between June 2019 and December 2021. Clinical data, including medical history, injury-admission time, and laboratory tests, were collected retrospectively. RESULTS Of the 439 patients, deep vein thrombosis was found in 139 (31.66%). The injury-admission time was significantly longer in the thrombosis group, which was positively associated with deep vein thrombosis (odds ratio 1.010, 95% confidence interval 1.003-1.017). The area under the curve to predict deep vein thrombosis was 0.619. The best cut-off value, sensitivity, and specificity were 21 h, 46.76%, and 75%, respectively. When the injury-admission period exceeded 21 h, the prevalence of deep vein thrombosis was 45.8% and the thrombosis incidence was significantly higher than in the <21 h group (24.9%). CONCLUSIONS Our results suggest that screening for deep vein thrombosis should be routinely performed for patients with osteoporotic hip fractures, particularly for those with injury-admission time ≥21 h.


Assuntos
Fraturas do Quadril , Fraturas por Osteoporose , Trombose , Trombose Venosa , Humanos , Idoso , Estudos Retrospectivos , Fraturas do Quadril/complicações , Fatores de Risco , Trombose Venosa/complicações , Trombose Venosa/epidemiologia
14.
15.
Methodist Debakey Cardiovasc J ; 20(1): 23-25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618609

RESUMO

A 51-year-old male with a complicated medical history presented with shortness of breath. Preoperative workup confirmed the presence of a large atrial mass. However, delayed gadolinium enhancement CMR with long inversion time (TI 600) showed lack of enhancement, which was suggestive of a thrombus. During cardiac magnetic resonance imaging, delayed gadolinium enhancement sequences with long inversion time (TI 600) are commonly used to distinguish between an avascular thrombus versus a vascular tumor.


Assuntos
Mixoma , Trombose , Masculino , Humanos , Pessoa de Meia-Idade , Meios de Contraste , Gadolínio , Imageamento por Ressonância Magnética , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Mixoma/complicações , Mixoma/diagnóstico por imagem , Mixoma/cirurgia , Trombose/diagnóstico por imagem , Trombose/cirurgia
16.
Artigo em Inglês | MEDLINE | ID: mdl-38618610

RESUMO

Left ventricular assist devices serve as a salvage therapy for patients with advanced heart failure. Complications such as thrombosis and obstruction can lead to acute device malfunction, posing significant clinical risks. A multidisciplinary approach is crucial for management. Few cases in the literature have demonstrated the safety and efficacy of percutaneous intervention, which holds significant value due to its less invasive nature and minimal risk of morbidity, especially in high-risk surgical patients.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Trombose , Humanos , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia
17.
J Vis Exp ; (205)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38619265

RESUMO

Reactive oxygen species (ROS) are highly unstable oxygen-containing molecules. Their chemical instability makes them extremely reactive and gives them the ability to react with important biological molecules such as proteins, nucleic acids, and lipids. Superoxide anions are important ROS generated by the reduction of molecular oxygen reduction (i.e., acquisition of one electron). Despite their initial implication exclusively in aging, degenerative, and pathogenic processes, their participation in important physiological responses has recently become apparent. In the vascular system, superoxide anions have been shown to modulate the differentiation and function of vascular smooth muscle cells, the proliferation and migration of vascular endothelial cells in angiogenesis, the immune response, and the activation of platelets in hemostasis. The role of superoxide anions is particularly important in the dysregulation of platelets and the cardiovascular complications associated with a plethora of conditions, including cancer, infection, inflammation, diabetes, and obesity. It has, therefore, become extremely relevant in cardiovascular research to be able to effectively measure the generation of superoxide anions by human platelets, understand the redox-dependent mechanisms regulating the balance between hemostasis and thrombosis and, eventually, identify novel pharmacological tools for the modulation of platelet responses leading to thrombosis and cardiovascular complications. This study presents three experimental protocols successfully adopted for the detection of superoxide anions in platelets and the study of the redox-dependent mechanisms regulating hemostasis and thrombosis: 1) dihydroethidium (DHE)-based superoxide anion detection by flow cytometry; 2) DHE-based superoxide anion visualization and analysis by single platelet imaging; and 3) spin probe-based quantification of superoxide anion output in platelets by electron paramagnetic resonance (EPR).


Assuntos
Superóxidos , Trombose , Humanos , Espécies Reativas de Oxigênio , Células Endoteliais , Oxigênio
18.
Zhonghua Xue Ye Xue Za Zhi ; 45(2): 184-189, 2024 Feb 14.
Artigo em Chinês | MEDLINE | ID: mdl-38604796

RESUMO

Objective: To evaluate the efficacy and safety of eculizumab in the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in China. Methods: Data from PNH patients who received at least 3 months of full-dose eculizumab and were followed for at least 3 months between December 2022 and July 2023 were retrospectively collected. We evaluated changes in clinical and laboratory parameters after 1, 2, 3, and 6 months of eculizumab treatment. The rates of breakthrough hemolysis (BTH), extravascular hemolysis (EVH), and the occurrence of adverse reactions were also monitored. Results: The study included nine patients, six males and three females, with a median age of 54 (28-69) years. 5 of the patients had classic PNH, while 4 had PNH/AA. The number of episodes of hemoglobinuria was 5 (1-25) per month before eculizumab. 4 patients required blood transfusion, 5 had thrombosis and one had renal impairment before eculizumab. The median time to eculizumab was 6 (3-7) months and the followup period was 3 (3-6) months after treatment. The number of episodes of hemoglobinuria following eculizumab was 0 (0-1). During the followup period, no additional thrombotic events occurred. LDH at any time after eculizumab was lower than at baseline, and some patients' HGB increased. All transfused patients became transfusion-independent after receiving eculizumab. The FACIT-Fatigue score improved by an average of 17.3 points following treatment. 2 patients developed BTH and improved with symptomatic treatment. There were three adverse events that caused mild symptoms. There are no serious adverse events or deaths. Conclusion: Eculizumab can effectively control the hemolytic-related symptoms of PNH in China, reducing the need for blood transfusions to some extent, while also demonstrating a higher safety profile.


Assuntos
Anticorpos Monoclonais Humanizados , Hemoglobinúria Paroxística , Trombose , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria , Estudos Retrospectivos , Hemólise , China
19.
Nat Commun ; 15(1): 3129, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605050

RESUMO

The essence of difference between hemostasis and thrombosis is that the clotting reaction is a highly fine-tuned process. Vascular protein disulfide isomerase (PDI) represents a critical mechanism regulating the functions of hemostatic proteins. Herein we show that histidine-rich glycoprotein (HRG) is a substrate of PDI. Reduction of HRG by PDI enhances the procoagulant and anticoagulant activities of HRG by neutralization of endothelial heparan sulfate (HS) and inhibition of factor XII (FXIIa) activity, respectively. Murine HRG deficiency (Hrg-/-) leads to delayed onset but enhanced formation of thrombus compared to WT. However, in the combined FXII deficiency (F12-/-) and HRG deficiency (by siRNA or Hrg-/-), there is further thrombosis reduction compared to F12-/- alone, confirming HRG's procoagulant activity independent of FXIIa. Mutation of target disulfides of PDI leads to a gain-of-function mutant of HRG that promotes its activities during coagulation. Thus, PDI-HRG pathway fine-tunes thrombosis by promoting its rapid initiation via neutralization of HS and preventing excessive propagation via inhibition of FXIIa.


Assuntos
Isomerases de Dissulfetos de Proteínas , Trombose , Animais , Camundongos , Isomerases de Dissulfetos de Proteínas/genética , Dissulfetos , Proteínas/metabolismo , Trombose/genética , Trombose/metabolismo , Heparitina Sulfato , Fator XII/metabolismo
20.
J Int Med Res ; 52(4): 3000605241240999, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606734

RESUMO

OBJECTIVE: This study aimed to assess the association of the neutrophil-to-lymphocyte ratio (NLR) with the occurrence of venous thromboembolism (VTE) and arterial thrombosis (AT). METHODS: This was a retrospective cross-sectional study including 585 medical records obtained from all consecutive patients who were suspected of having thrombosis. RESULTS: The AT group had a higher neutrophil count and NLR and a lower lymphocyte count than the non-thrombosis group. Receiver operating characteristic curve analysis showed the ability of the NLR to predict the presence of AT. The cut-off value for the NLR was 4.44. No distinction was found in the NLR between the VTE and non-thrombosis groups. Regression analysis showed that a high NLR was an independent factor related to the presence of AT. Patients with an NLR ≥ 4.44 had a higher risk of AT than those with an NLR < 4.44 (odds ratio = 2.015, 95% confidence interval: 1.180-3.443). CONCLUSION: A high NLR may be considered a predictive factor for the occurrence of AT, but an association with the presence of VTE was not found.


Assuntos
Trombose , Tromboembolia Venosa , Humanos , Neutrófilos , Tromboembolia Venosa/diagnóstico , Estudos Retrospectivos , Estudos Transversais , Linfócitos , Curva ROC , Prognóstico
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