Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.084
Filtrar
1.
BMJ Open Qual ; 12(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36631136

RESUMO

Left ventricular (LV) thrombus is an increasingly recognised complication following anterior myocardial infarction and non-ischaemic cardiomyopathy. Whilst vitamin K antagonists (VKA) remain the only approved therapeutic option to reduce the risk of systemic thromboembolism including stroke, the off-label use of direct oral anticoagulants (DOACs) is becoming an attractive alternative.We aimed to improve the diagnosis and management of LV thrombus at a tertiary cardiology centre using quality improvement methodology. Outcomes included increasing the use of DOACs from 25% to 70% over a period of 1 year and shorten length of time from diagnosis to repeat imaging to within 3-6 months as recommended by guidelines.During the first Plan-Do-Study-Action (PDSA) cycle, we identified 84 patients diagnosed with LV thrombus between 1 December 2012 and 30 June 2018. The majority (74%) were prescribed VKA. Repeat imaging occurred in 89% of patients, but only 55% using the same modality. The mean duration between diagnosis and repeat imaging was 233±251 days. There were no significant differences between VKA and DOAC in terms of thrombus resolution, systemic embolisation or clinically significant bleeding. We published trust-wide guidelines on the management of LV thrombus with recommendations supporting the use of DOACs and appropriate follow-up imaging. A second PDSA cycle undertaken between 1 October 2019 and 31 March 2020 identified a further 20 patients. DOAC use increased to 70% and 70% of patients underwent follow-up imaging following a mean duration of 140±61 days, although in only 36% using the same modality.Using quality improvement methodology, we confirmed safe and efficient use of DOAC in the setting of LV thrombus. We published trust guidelines supporting their use, which was associated with an increase in DOAC use and in earlier follow-up imaging in line with our recommendations.


Assuntos
Cardiologia , Trombose , Humanos , Melhoria de Qualidade , Anticoagulantes/uso terapêutico , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Trombose/induzido quimicamente , Hemorragia
2.
FASEB J ; 37(2): e22768, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36624703

RESUMO

Platelet mitochondria possess remarkable plasticity for oxidation of energy substrates, where metabolic dependency on glucose or fatty acids is higher than glutamine. Since platelets metabolize nearly the entire pool of glucose to lactate rather than fluxing through mitochondrial tricarboxylic acid cycle, we posit that majority of mitochondrial ATP, which is essential for platelet granule secretion and thrombus formation, is sourced from oxidation of fatty acids. We performed a comprehensive analysis of bioenergetics and function of stimulated platelets in the presence of etomoxir, trimetazidine and oxfenicine, three pharmacologically distinct inhibitors of ß-oxidation. Each of them significantly impaired oxidative phosphorylation in unstimulated as well as thrombin-stimulated platelets leading to a small but consistent drop in ATP level in activated cells due to a lack of compensation from glycolytic ATP. Trimetazidine and oxfenicine attenuated platelet aggregation, P-selectin externalization and integrin αIIb ß3 activation. Both etomoxir and trimetazidine impeded agonist-induced dense granule release and platelet thrombus formation on collagen under arterial shear. The effect of inhibitors on platelet aggregation and dense granule release was dose- and incubation time- dependent with significant inhibition at higher doses and prolonged incubation times. Neither of the inhibitors could protect mice from collagen-epinephrine-induced pulmonary embolism or prolong mouse tail bleeding times. However, mice pre-administered with etomoxir, trimetazidine and oxfenicine were protected from ferric chloride-induced mesenteric thrombosis. In conclusion, ß-oxidation of fatty acids sustains ATP level in stimulated platelets and is therefore essential for energy-intensive agonist-induced platelet responses. Thus, fatty acid oxidation may constitute an attractive therapeutic target for novel antiplatelet agents.


Assuntos
Trombose , Trimetazidina , Camundongos , Animais , Ácidos Graxos/metabolismo , Trimetazidina/efeitos adversos , Trimetazidina/metabolismo , Plaquetas/metabolismo , Ativação Plaquetária , Agregação Plaquetária , Trombose/induzido quimicamente , Trombose/prevenção & controle , Trombose/metabolismo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/efeitos adversos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Fosforilação Oxidativa , Colágeno/metabolismo , Trifosfato de Adenosina/metabolismo , Glucose/metabolismo
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(12): 1305-1310, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36567588

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban. METHODS: From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment. RESULTS: In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) µg×kg-1×min-1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) µg×kg-1×min-1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) µg×kg-1×min-1], but without significant difference (P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) µg×kg-1×min-1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [µg×kg-1×min-1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. CONCLUSIONS: Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.


Assuntos
Oxigenação por Membrana Extracorpórea , Trombose , Humanos , Heparina/uso terapêutico , Estudos de Casos e Controles , Anticoagulantes/uso terapêutico , Hemorragia/etiologia , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Estudos Retrospectivos
4.
Hematology Am Soc Hematol Educ Program ; 2022(1): 515-521, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36485108

RESUMO

Direct oral anticoagulants (DOACs) are commonly used oral factor Xa inhibitors in recent years. However, in some special clinical situations, the appropriate use of these anticoagulants may be of concern. In this article, we address the 5 commonly asked questions regarding their use for the treatment of venous thromboembolism, including in the setting of obesity, renal impairment, gastrointestinal (GI) malignancy, catheter-related thrombosis, and drug-drug interactions. Data on the use of DOACs in the presence of significant obesity or renal failure are mainly observational. Some DOACs are shown to have an increased risk of bleeding in patients with unresected luminal GI malignancy but not others, so selection of appropriate patients is the key. Furthermore, literature on the use of DOACs for catheter-related thrombosis or when drug-drug interactions are of concern is limited, and more research is welcome.


Assuntos
Neoplasias , Trombose , Tromboembolia Venosa , Humanos , Inibidores do Fator Xa/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/induzido quimicamente , Anticoagulantes/efeitos adversos , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Trombose/induzido quimicamente , Neoplasias/tratamento farmacológico , Obesidade , Administração Oral
5.
BMC Cancer ; 22(1): 1322, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36526992

RESUMO

BACKGROUND: Although initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at high risk of bleeding. METHODS: In this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration. RESULTS: Of the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who experienced MB or CRNMB recovered. CONCLUSIONS: The risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.


Assuntos
Neoplasias Gastrointestinais , Trombose , Humanos , Inibidores do Fator Xa/efeitos adversos , Estudos Prospectivos , Estudos de Viabilidade , Anticoagulantes/efeitos adversos , Hemorragia/tratamento farmacológico , Heparina , Trombose/prevenção & controle , Trombose/induzido quimicamente , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/tratamento farmacológico
6.
Nutrients ; 14(19)2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36235814

RESUMO

BACKGROUND: Folate is a water-soluble vitamin and is essential for maintaining cell functions. Dialysis removes folate, and folate deficiency is reported in patients with end-stage kidney disease (ESKD). However, there is no consensus as to the appropriate dosage of folate supplements and their advantages and disadvantages for patients with ESKD. METHODS: This study was based on the electronic medical records of the Chang Gung Research Database (CGRD) of the Chang Gung Medical Foundation. We included patients who were diagnosed with ESKD, initiated hemodialysis, and were given folic acid supplements at any point from 1 January 2001 to 31 December 2019. The patients were divided into weekly and daily folic acid supplementation groups. We reduced the effects of confounding through the inverse probability of treatment weighting based on the propensity score. RESULTS: We identified 2081 and 954 newly diagnosed patients with ESKD, who received daily and weekly folic acid supplements. The mean follow-up time was 5.8 years, and the event rates of arteriovenous access thrombosis were 17.0% and 23.6% in the daily and weekly folic acid supplementation groups (sub-distribution hazard ratio = 0.69, 95% confidence interval = 0.61 to 0.77), respectively. Neither group significantly differed in the occurrence of other clinical events, such as major cardiovascular cardiac events (e.g., myocardial infarction and ischemic stroke), all-cause mortality, cardiovascular death, infection death, malignancy, and adverse effects. CONCLUSION: a daily 5 mg folic acid supplementation might result in a lower event rate of arteriovenous access thrombosis in patients with ESKD than weekly folic acid supplementation. Further prospective studies are warranted to explore the preventive effect of folate on thrombosis.


Assuntos
Falência Renal Crônica , Trombose , Estudos de Coortes , Suplementos Nutricionais , Ácido Fólico , Humanos , Falência Renal Crônica/tratamento farmacológico , Diálise Renal , Trombose/induzido quimicamente , Vitaminas , Água
7.
BMC Cardiovasc Disord ; 22(1): 450, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307769

RESUMO

Very short duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has recently attracted a lot of attention with the introduction of newer generations stents. This is appealing, especially in patients at high bleeding risk. However, none of the trials were powered for the individual ischemic and bleeding endpoints. All randomised controlled trials (RCTs) investigating one-month versus routine duration of DAPT in patients undergoing PCI and reporting outcomes from the time of cessation of DAPT (1 month) to 1 year were eligible for inclusion in the meta-analysis. The pooled risk ratios (RR) with their 95% confidence interval (CI) were calculated with the random-effects model using the Mantel-Haenszel method. Four RCTs involving 26,576 patients were included in this meta-analysis. Cessation of DAPT after 1 month was associated with significantly less major bleeding [RR 0.70, 95%CI (0.51-0.95), P = 0.02, heterogeneity (I2) = 42%]. There was no statistically significant difference in all-cause mortality [RR 0.84 (95%CI 0.69-1.03), P = 0.10, I2 = 0%] and stroke [RR 0.71 (95%CI 0.45-1.13), P = 0.15, I2 = 42%] when compared to routine duration of DAPT. There was also no difference in myocardial infarction (MI) [RR 1.12 (95%CI 0.91-1.39), P = 0.28, I2 = 0%], and definite or probable stent thrombosis [RR 1.49 (95%CI 0.92-2.41), P = 0.11, I2 = 0%] with cessation of DAPT after 1 month. Cessation of DAPT 1 month after PCI was associated with significantly less major bleeding, but there was no difference in the rate of all-cause mortality, stroke, MI and stent thrombosis.


Assuntos
Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Infarto do Miocárdio , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Trombose/prevenção & controle , Trombose/induzido quimicamente , Resultado do Tratamento
8.
Thromb Res ; 219: 155-161, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36191535

RESUMO

INTRODUCTION: Rheumatic heart disease with mechanical heart valve (MHV) replacement is common in Africa. However, MHV requires long-life anticoagulation and managing this can be challenging. METHODS AND RESULTS: We report data of a prospective observational study conducted between August 2018 and September 2019 in MHV patients in the Salam Centre for Cardiac Surgery built in Khartoum, by Emergency, an Italian Non-Governmental Organization, to evaluate the quality of anticoagulation control and the risk of thrombotic complications. RESULTS: We studied 3647 patients (median age 25.1 years; 53.9 % female). Median Time in Therapeutic Range (TTR) was 53 % (interquartile range 37 % to 67 %) and 70 thrombotic events (rate 1.8 × 100 pt-years [95 % CI 1.38-2.23]) were recorded. Among patients in the first quartile of TTR (≤37 %), we recorded 34/70 (48.6 %) of all thrombotic events (rate 3.7 × 100 pt-years [95 % CI 2.5-5.1]), with a high mortality rate (2.2 × 100 pt-years [95 % CI 1.3-3.3]). In patients with guideline-recommended TTR (≥65 %) the event rate was 0.8 × 100 pt-years for thrombotic events [95 % CI 0.3-1.5] and 0.4 × 100 pt-years for mortality [95 % CI 0.1-0.9]. Multivariable analysis showed that having a TTR in the lowest quartile (≤37 %) and being noncompliant are significantly associated with increased thrombotic risk. Aspirin use or different valve type did not influence the thrombotic risk. Almost 40 % of all thromboembolic complications could have been potentially prevented by further improving VKA management to obtain a TTR > 37 %. CONCLUSION: The thrombotic risk of MHV patients on VKAs living in a low-income country like Sudan is associated with low quality of anticoagulation control. Efforts should be made to decrease the number of non-compliant patients and to reach a guideline-recommended TTR of ≥65 %.


Assuntos
Anticoagulantes , Trombose , Adulto , Anticoagulantes/efeitos adversos , Aspirina/farmacologia , Coagulação Sanguínea , Feminino , Valvas Cardíacas , Hemorragia/induzido quimicamente , Humanos , Masculino , Trombose/induzido quimicamente , Trombose/etiologia
9.
Thromb Res ; 219: 40-48, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36113402

RESUMO

BACKGROUND: Thromboembolic events are common complications of COVID-19. Clinical study results on safety and efficacy of anticoagulation in COVID-19 are controversial. MATERIAL AND METHODS: This report updates our systematic review and random-effects meta-analysis on randomized controlled trials (RCTs) comparing standard prophylactic anticoagulation and intermediate or therapeutic anticoagulation in COVID-19 patients. We searched eligible studies for the update up to 4 February 2022 by weekly monitoring of RCTs in the Cochrane COVID-19 Study Register. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: For this update we included five new trials; a total of 13 RCTs with 7364 patients. Certainty of evidence was very low to low. We are uncertain whether low-dose prophylactic anticoagulation is favoured over placebo or no anticoagulation in the outpatient- or post-discharge-setting. In hospitalized patients with moderate and severe COVID-19, intermediate-dose anticoagulation may have little or no effect on thrombotic events or death (RR 1.03, 95 % CI 0.86-1.24), but may increase severe bleeding non-significantly (RR 1.48, 95 % CI 0.53-4.15). Therapeutic-dose anticoagulation may decrease thrombotic events or deaths in hospitalized patients with moderate COVID-19 (RR 0.64, 95 % CI 0.38-1.07; fixed-effect model RR 0.72, 95 % CI 0.57-0.91), but may have little or no effect in patients with severe disease (RR 0.98, 95 % CI 0.86-1.12). With therapeutic-dose anticoagulation, the risk of major bleeding may increase regardless of COVID-19 severity (RR 1.78, 95 % CI 1.15-2.74). CONCLUSIONS: Hospitalized, moderately ill COVID-19 patients may benefit from therapeutic-dose anticoagulation, while critically ill patients may not. Risk of major bleeding must be considered.


Assuntos
COVID-19 , Tromboembolia , Trombose , Anticoagulantes/efeitos adversos , Coagulação Sanguínea , COVID-19/complicações , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Trombose/induzido quimicamente , Trombose/etiologia
10.
J Viral Hepat ; 29(12): 1073-1078, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36103593

RESUMO

Treatment for hepatitis C virus (HCV) with direct-acting antivirals (DAA) is advantageous over previous treatment options due to high efficacy, short treatment duration, and relatively few drug interactions. Similarly, direct oral anticoagulants (DOAC) are generally preferred over warfarin for the management of thrombosis and atrial fibrillation due to a favourable safety profile. Direct-acting antivirals inhibit DOAC transport through P-glycoprotein inhibition leading to a theoretical increase in bleeding risk. We evaluated the incidence of bleeding in patients who received concurrent DAA and DOAC therapy and stratified the analysis based on the patient's cirrhosis status. We conducted a multicenter, retrospective cohort study to evaluate bleeding in patients with HCV and cirrhosis compared to patients with HCV without cirrhosis. Patients receiving at least 1 month of overlapping DAA and DOAC therapy between May 2017 and August 2020 at 11 medical centers in the United Kingdom and three medical centers in the United States were included. Charts were manually reviewed to identify baseline characteristics as well as thromboembolic or bleeding events. Bleeding events were categorized as major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). Of 204 total patients, 36 patients (18%) had cirrhosis and 168 patients (82%) did not have cirrhosis. The majority of patients were male (79%) and Caucasian (75%). Sofosbuvir/velpatasvir (32%) and rivaroxaban (57%) were the most commonly prescribed DAA and DOAC, respectively. Leading indications for anticoagulation included thrombosis (75%) and atrial fibrillation (21%). There were three MB events (1.5%) all of which occurred in patients with additional risk factors (age over 65 and on antiplatelet therapy) and no CRNMB occurred while on DOAC and DAA therapy. Of the three MB, one occurred in a patient with cirrhosis and two in patients without cirrhosis, RR 1.23 (0.56-2.76). In conclusion, in this multicenter cohort study of concurrent DAA and DOAC use, MB was uncommon and there was no CRNMB. There was no significant difference in bleeding events among patients with cirrhosis compared to those without cirrhosis. These findings support the use of DAA among patients requiring DOAC.


Assuntos
Fibrilação Atrial , Hepatite C Crônica , Trombose , Humanos , Masculino , Feminino , Antivirais/efeitos adversos , Hepacivirus , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Administração Oral , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Trombose/induzido quimicamente , Trombose/tratamento farmacológico
12.
Int J Immunopathol Pharmacol ; 36: 3946320221128534, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36123789

RESUMO

In the current international scientific panorama, rare cases of venous thrombotic complications following mRNA vaccine administration have been reported, consisting mainly of cerebral sinus thromboses and acute venous thromboembolism. The present paper describes the case of a 75-year-old woman in good health who developed cerebral venous thrombosis, deep venous thrombosis, and bilateral pulmonary emboli after receiving a second dose of Pfizer-BioNTech COVID-19 vaccine. A series of laboratory tests performed during hospitalization yielded interesting results, allowing us to exclude thrombophilic risk factors and to certify the absence of thrombocytopenia in the patient. Although COVID-19 vaccination is the most important tool in stopping the pandemic, pharmacovigilance is crucial for detecting potential multisystem thrombotic events, even for mRNA vaccines.


Assuntos
Vacina BNT162 , COVID-19 , Trombose , Idoso , Feminino , Humanos , Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , Trombocitopenia , Trombose/induzido quimicamente
13.
Lupus ; 31(12): 1485-1490, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36074077

RESUMO

Limited evidence exists to guide the management of recurrent thrombosis occurring despite therapeutic anticoagulation in patients with thrombotic antiphospholipid syndrome (APS). In this case series, fondaparinux, with or without an antiplatelet agent, provided an effective and safe option in three patients with thrombotic APS, all two triple and one single positive for antiphospholipid antibodies, who had recurrent venous and/or arterial thromboembolism. Rituximab was also used in all patients. Recurrent events occurred despite therapeutic anticoagulation, including at high-intensity, with warfarin and subsequent low-molecular-weight heparin. There were no major bleeding events. Adjunctive therapies used for thrombosis included catheter-directed thrombolysis and rituximab.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Trombose , Anticorpos Antifosfolipídeos/uso terapêutico , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Fondaparinux/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Rituximab/uso terapêutico , Trombose/induzido quimicamente , Trombose/etiologia , Varfarina/uso terapêutico
14.
J Cardiovasc Med (Hagerstown) ; 23(10): 672-677, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36099074

RESUMO

AIMS: This meta-analysis aims to compare direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in the setting of left ventricular thrombosis (LVT). METHOD AND RESULTS: We systematically searched MEDLINE, Cochrane Library, Biomed Central and Web of Science for trials comparing DOACs versus VKAs in the setting of LVT and reporting outcome data on thrombosis resolution, stroke and bleeding. Fourteen studies were finally selected. The Mantel-Haenszel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of LVT resolution. The secondary outcomes were the occurrence of stroke or bleeding during treatment. One thousand three hundred and thirty-two patients were included in the analysis for the primary outcome. Of these, 424 were treated with DOACs and 908 with VKAs. The pooled odds ratio (OR) for the primary outcome was 1.00 [95% confidence interval (95% CI) 0.77-1.31, I2 0.0%], reflecting equal effect in terms of thrombus resolution. Overall, 2290 patients, 608 on DOACs and 1682 on VKAs were included in the analysis of stroke occurrence, showing reduced risk of events in patients treated with DOACs (pooled OR 0.58, 95% CI 0.36-0.93; I2 0.0%) as well as for bleeding occurrence (number of patients included 2139; pooled OR 0.64, 95% CI 0.44-0.94; I2 0.0%). CONCLUSION: Compared with VKAs, we found DOACs to have similar efficacy on thrombus resolution and favorable effects on stroke reduction and bleedings. DOACs should be considered as an alternative treatment for LVT. Large prospective randomized clinical trials are needed to confirm this exploratory finding.


Assuntos
Cardiopatias , Acidente Vascular Cerebral , Trombose , Administração Oral , Anticoagulantes , Fibrinolíticos/uso terapêutico , Cardiopatias/tratamento farmacológico , Hemorragia/epidemiologia , Humanos , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Trombose/prevenção & controle
15.
J Thromb Haemost ; 20(11): 2646-2655, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35971886

RESUMO

BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) requires functional assays to demonstrate that platelet factor 4 (PF4)-specific antibodies activate platelets, typically when therapeutic heparin (H) concentrations are tested ("classical" pattern). Some HIT samples also activate platelets without heparin ("atypical" pattern), but with unclear clinical significance. OBJECTIVES: We aimed to assess whether platelet activation pattern and some characteristics of PF4-specific antibodies were associated with the severity of HIT. PATIENTS/METHODS: Serotonin release assay (SRA) pattern of 81 HIT patients were analyzed and compared with their clinical and biological data, including levels of anti-PF4/H immunoglobulin G (IgG) and anti-PF4 IgG in 47 of them. RESULTS: Higher anti-PF4/H IgG titers were measured in patients with an "atypical" SRA (optical density 2.52 vs. 1.94 in those with a "classical" pattern, p < .001). Patients of both groups had similar platelet count (PC) nadir and time to recovery, but those with an "atypical" SRA more frequently developed thrombotic events (69% vs. 34%, p = .037). Significant levels of anti-PF4 IgG were detected in both groups (38% and 61%, respectively). Whatever the SRA pattern, a lower PC nadir (35 vs. 53 G/L, p = .006) and a longer PC recovery time (6 vs. 3 days, p = .015) were evidenced in patients with anti-PF4 antibodies, compared with those with anti-PF4/H IgG only. CONCLUSIONS: An atypical SRA pattern with elevated anti-PF4/H IgG titers seems associated with an increased risk of thrombosis in HIT. IgG antibodies to native PF4 may contribute to more severe and persistent thrombocytopenia, and their detection could be useful in clinical practice.


Assuntos
Trombocitopenia , Trombose , Humanos , Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Imunoglobulina G , Fatores Imunológicos/efeitos adversos , Fator Plaquetário 4 , Serotonina , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombose/induzido quimicamente , Trombose/diagnóstico , Trombose/complicações
16.
PLoS One ; 17(8): e0269268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35913955

RESUMO

With the progression of global vaccination against coronavirus disease 2019 (COVID-19), embolic and thrombotic events (ETEs) following COVID-19 vaccination continue to be reported. To date, most reports on the type of COVID-19 vaccine and ETEs have been based on clinical trials, and other reports include a small number of cases. Further, the relationship between the type of COVID-19 vaccine and ETEs has not been clarified. It is important to elucidate trends in the development of ETEs after vaccination, which is a crucial concern for both prospective patients and healthcare providers. In this retrospective, pharmacovigilance study, we analyzed the Vaccine Adverse Event Reporting System (VAERS) reports from January 1, 2020 to June 18, 2021, and performed signal detection and time-to-onset analysis of adverse events by calculating the reported odds ratio (ROR) to understand ETE trends after COVID-19 vaccination based on the vaccine type. Using VAERS, we could collect data about several ETEs associated with COVID-19 vaccination. Nine adverse events associated with ETEs were reported following the administration of viral vector vaccines. The median time to ETE onset was 6 (interquartile range: 2-17) days for mRNA vaccines and 11 (interquartile range: 4-21) days for viral vector vaccines. This study suggests that VAERS aids in disequilibrium analysis to examine the association between vaccine type and ETEs after COVID-19 vaccination. Additionally, the tendency to develop ETEs and the number of days taken to develop ETEs varied depending on the type of the COVID-19 vaccine. Thus, vaccinators and healthcare providers should consider the primary diseases associated with ETEs while selecting vaccines for administration and carefully monitor patients following vaccination for potential ETEs based on the characteristics of vaccine type-specific onset period.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Embolia , Farmacovigilância , Trombose , Sistemas de Notificação de Reações Adversas a Medicamentos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Embolia/induzido quimicamente , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Trombose/induzido quimicamente , Estados Unidos , Vacinação/efeitos adversos
17.
J Thromb Haemost ; 20(11): 2579-2586, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36006172

RESUMO

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic, heparin-induced thrombocytopenia (HIT)-mimicking, adverse reaction caused by platelet-activating anti-platelet factor 4 (PF4) antibodies that occurs rarely after adenovirus vector-based COVID-19 vaccination. Strength of PF4-dependent enzyme immunoassay (EIA) reactivity-judged by optical density (OD) measurements-strongly predicts platelet-activating properties of HIT antibodies in a functional test. Whether a similar relationship holds for VITT antibodies is unknown. OBJECTIVES: To evaluate probability for positive platelet activation testing for VITT antibodies based upon EIA OD reactivity; and to investigate simple approaches to minimize false-negative platelet activation testing for VITT. METHODS: All samples referred for VITT testing were systematically evaluated by semiquantitative in-house PF4/heparin-EIA (OD readings) and PF4-induced platelet activation (PIPA) testing within a cohort study. EIA-positive sera testing PIPA-negative were retested following 1/4 to 1/10 dilution. Logistic regression was performed to predict the probability of a positive PIPA per magnitude of EIA reactivity. RESULTS: Greater EIA ODs in sera from patients with suspected VITT correlated strongly with greater likelihood of PIPA reactivity. Of 61 sera (with OD values >1.0) testing negative in the PIPA, a high proportion (27/61, 44.3%) became PIPA positive when tested at 1/4 to 1/10 dilution. CONCLUSIONS: VITT serology resembles HIT in that greater EIA OD reactivity predicts higher probability of positive testing for platelet-activating antibodies. Unlike the situation with HIT antibodies, however, diluting putative VITT serum increases probability of a positive platelet activation assay, suggesting that optimal complex formation depends on the stoichiometric ratio of PF4 and anti-PF4 VITT antibodies.


Assuntos
COVID-19 , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Trombose , Vacinas , Humanos , Heparina/efeitos adversos , Estudos de Coortes , Vacinas contra COVID-19 , Fator Plaquetário 4 , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Técnicas Imunoenzimáticas , Anticorpos , Trombose/diagnóstico , Trombose/induzido quimicamente , Púrpura Trombocitopênica Idiopática/induzido quimicamente
18.
Vaccine ; 40(38): 5585-5593, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-35989136

RESUMO

BACKGROUND: Post-marketing surveillance for COVID-19 vaccines during the pandemic identified an extremely rare thrombosis with thrombocytopenia syndrome (TTS) reported post-vaccination, requiring further characterisation to improve diagnosis and management. METHODS: We searched the AstraZeneca Global Safety Database (through April 26, 2021) for cases with co-reported thrombocytopenia and thrombosis (using standardised MedDRA queries/high-level terms) following AZD1222 (ChAdOx1 nCoV-19). Cases were adjudicated by experts as 'typical','possible', 'no' or 'unknown' according to available TTS criteria. Additional confirmatory datasets (May 20-June 20, October 1-December 28) were evaluated. FINDINGS: We identified 573 reports, including 273 (47.6 %) 'typical' and 171 (29.8 %) 'possible' TTS cases. Of these 444 cases, 275 (61.9 %) were female, median age was 50.0 years (IQR: 38.0-60.0). Cerebral venous sinus thrombosis was reported in 196 (44.1 %) cases, splanchnic venous thrombosis in 65 (14.6 %) and thromboses at multiple sites in 119 (26.8 %). Median time to onset was 12.0 days (IQR: 9.0-15.0). Comparison with a pre-pandemic reference population indicated higher rates of autoimmune disorders (13.8 %, 4.4 %), previous heparin therapy (7.4 %, 1.2 %), history of thrombosis (5.5 %, 1.4 %), and immune thrombocytopenia (6.1 %, 0.2 %). Fatality rate was 22.2 % (127/573) overall and 23.6 % (105/444) in 'typical'/'possible' TTS, which decreased from 39.0 % (60/154) in February/March to 15.5 % (45/290) in April. Overall patterns were similar in confirmatory datasets. CONCLUSIONS: The reporting rate of 'typical'/'possible' TTS post first-dose vaccination in this dataset is 7.5 per million vaccinated persons; few cases were reported after subsequent doses, including booster doses. Peak reporting coincided with media-driven attention. Medical history differences versus a reference population indicate potentially unidentified risk factors. The decreasing fatality rate correlates with increasing awareness and publication of diagnostic/treatment guidelines. Adjudication was hindered by unreported parameters, and an algorithm was developed to classify potential TTS cases; comprehensive reporting could help further improve definition and management of this extremely rare syndrome.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Trombocitopenia , Trombose , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Trombose/induzido quimicamente , Trombose/epidemiologia , Vacinação/efeitos adversos
19.
Int J Mol Sci ; 23(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36012169

RESUMO

Endothelial cells are highly sensitive to ionizing radiation, and exposure leads to multiple adaptive changes. Remarkably, part of this response is the translocation of normally intracellular proteins to the cell surface. It is unclear whether this ectopic expression has a protective or deleterious function, but, regardless, these surface-exposed proteins may provide unique discriminatory targets for radiation-guided drug delivery to vascular malformations or tumor vasculature. We investigated the ability of an antibody-thrombin conjugate targeting mitochondrial PDCE2 (E2 subunit of pyruvate dehydrogenase) to induce precision thrombosis on irradiated endothelial cells in a parallel-plate flow system. Click-chemistry was used to create antibody-thrombin conjugates targeting PDCE2 as the vascular targeting agent (VTA). VTAs were injected into the parallel-plate flow system with whole human blood circulating over irradiated cells. The efficacy and specificity of fibrin-thrombus formation was assessed relative to non-irradiated controls. The PDCE2-targeting VTA dose-dependently increased thrombus formation: minimal thrombosis was induced in response to 5 Gy radiation; doses of 15 and 25 Gy induced significant thrombosis with equivalent efficacy. Negligible VTA binding or thrombosis was demonstrated in the absence of radiation or with non-targeted thrombin. PDCE2 represents a unique discriminatory target for radiation-guided drug delivery and precision thrombosis in pathological vasculature.


Assuntos
Células Endoteliais , Complexo Piruvato Desidrogenase/metabolismo , Trombose , Células Endoteliais/metabolismo , Endotélio/patologia , Endotélio Vascular/metabolismo , Humanos , Radiação Ionizante , Trombina/metabolismo , Trombose/induzido quimicamente , Trombose/etiologia
20.
Phytomedicine ; 104: 154271, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35777120

RESUMO

BACKGROUND: Coronary thrombosis and its correlated disorders are main healthcare problems globally. The therapeutic effects of current treatments involving antiplatelet drugs are not fully satisfactory. Danshensu (DSS) is an important monomer obtained from Salvia miltiorrhiza roots that have been widely employed for vascular diseases in medicinal practices. Nonetheless, the underlying mechanisms of DSS are not fully unraveled. PURPOSE: The objective of this study was to penetrate the antithrombotic and antiplatelet mechanisms of DSS. METHODS: Network pharmacology assay was used to forecast the cellular mechanisms of DSS for treating thrombosis. The work focused the impacts of DSS on platelet activation by analyzing aggregation and adhesion in vitro. Flow cytometry, western blotting, CM-H2DCFDA staining and mitochondrial function assays were performed to reveal the molecular mechanisms. The model of common carotid artery thrombus induced by ferric chloride was established. The wet weight of thrombus was measured, and the thrombosis was observed by hematoxylin and eosin (H&E) staining, in order to support the inhibitory effect of DSS on thrombosis. RESULTS: Data mining found the antithrombotic effect of DSS is related to platelet activation and the core target is silent information regulator 1 (SIRT1). We confirmed that DSS dose-dependently inhibited platelet activation in vitro. DSS was further demonstrated to induce the expression of SIRT1 and decreased reactive oxygen species (ROS) burden and thereby prevented mitochondrial dysfunction. Mitochondrial function tests further indicated that DSS prevented mitochondrial DNA (mtDNA) release, which induced activation of platelet in a dendritic cell specific intercellular-adhesion-molecule-3 grabbing non-integrin (DC-SIGN)-dependent manner. In carotid artery injury model induced by ferric chloride, DSS inhibited the development of carotid arterial thrombosis. More encouragingly, in tail bleeding time assay, DSS did not augment bleeding risk. CONCLUSION: These findings indicated that DSS effectively inhibited platelet activation by depressing the collection of ROS and the release of platelet mtDNA without arousing hemorrhage risk. DSS might represent a promising candidate drug for thrombosis and cardiovascular disease therapeutics.


Assuntos
Sirtuína 1 , Trombose , DNA Mitocondrial , Fibrinolíticos/farmacologia , Humanos , Lactatos , Mitocôndrias/metabolismo , Ativação Plaquetária , Agregação Plaquetária , Inibidores da Agregação Plaquetária/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Trombose/prevenção & controle
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...