RESUMO
INTRODUCTION: COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin. METHODS: This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. RESULTS: 10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). CONCLUSIONS: Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.
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Aspirina , COVID-19 , Tromboembolia , United States Department of Veterans Affairs , Veteranos , Humanos , Aspirina/uso terapêutico , Estados Unidos/epidemiologia , COVID-19/epidemiologia , COVID-19/complicações , COVID-19/prevenção & controle , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Incidência , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle , Tromboembolia/etiologia , Tromboembolia/tratamento farmacológico , SARS-CoV-2 , Fatores de Risco , Idoso de 80 Anos ou maisAssuntos
Neoplasias , Rivaroxabana , Rivaroxabana/uso terapêutico , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Resultado do Tratamento , Tromboembolia Venosa/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Medicina Baseada em Evidências , Anticoagulantes/uso terapêutico , Tromboembolia/prevenção & controle , Tromboembolia/etiologia , Tromboembolia/tratamento farmacológico , Comorbidade , Prevalência , Fatores de RiscoRESUMO
With many available data sources, clinicians need to consider the benefit-risk profile of individual anticoagulants when balancing the need for anticoagulation, including evaluating the risks in patients with comorbidities and potential drug-drug interactions. This narrative review presents clinical data across multiple phases of drug development for the use of apixaban, a selective factor Xa inhibitor, when taken concomitantly with other agents, and evaluates the benefit-risk profile of apixaban with these interacting medications. Key subgroup analyses from the phase 3 ARISTOTLE trial (NCT00412984) are presented using data from patients who received either concomitant inhibitors or inducers of cytochrome P450 3A4 and/or Pglycoprotein. We also review the available evidence for the use of apixaban in patients with cancer-associated thromboembolism, as well as the use of apixaban in patients with COVID-19.
Assuntos
Interações Medicamentosas , Inibidores do Fator Xa , Pirazóis , Piridonas , Humanos , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Tratamento Farmacológico da COVID-19/métodos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacocinética , Neoplasias/tratamento farmacológico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/farmacocinética , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Piridonas/farmacocinética , Medição de Risco , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Ensaios Clínicos Fase III como AssuntoRESUMO
This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection.
Assuntos
Fibrinolíticos , Hemorragia , Tromboembolia , Humanos , Criança , Tromboembolia/prevenção & controle , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Resultado do Tratamento , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Rivaroxabana/uso terapêutico , Rivaroxabana/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , PiridonasRESUMO
Anticoagulants have long been fundamental in preventing and treating thromboembolic disorders, with a recent shift of focus towards direct oral anticoagulants, thanks to their ease of use, efficacy, and safety. Despite these advancements, bleeding complications remain a major concern with any anticoagulant, highlighting the need for safer drugs. Factor XI (FXI) inhibitors have emerged as promising agents in this regard, offering a novel approach by targeting upstream factors in the coagulation system. Phase II trials have shown encouraging outcomes, indicating a reduced bleeding risk compared to that associated with traditional anticoagulants, particularly in the context of cardiovascular disease management when combined with antiplatelet therapy. However, the variability in findings and limited efficacy data call for a cautious interpretation pending insights from phase III trials. These trials are essential for validating the potential of FXI inhibitors to balance bleeding risk reduction and maintain anticoagulant efficacy. This review explores the pharmacology, potential indications, clinical data, and future directions of FXI inhibitors, providing a perspective on their evolving role in anticoagulant therapy. It also provides a detailed analysis of data from published clinical trials on FXI inhibitors in various indications. Preliminary data from ongoing trials are also outlined. As the field moves forward, a cautiously optimistic outlook can be expected, focusing on comprehensive data from phase III trials to define the role of FXI inhibitors in various clinical scenarios.
Assuntos
Anticoagulantes , Fator XI , Hemorragia , Humanos , Fator XI/antagonistas & inibidores , Fator XI/metabolismo , Anticoagulantes/uso terapêutico , Hemorragia/prevenção & controle , Hemorragia/induzido quimicamente , Coagulação Sanguínea/efeitos dos fármacos , Tromboembolia/prevenção & controle , Tromboembolia/etiologia , Tromboembolia/tratamento farmacológico , Ensaios Clínicos como AssuntoAssuntos
Anticorpos Antifosfolipídeos , Síndrome de Behçet , Tromboembolia , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Inflamação/imunologia , Células Endoteliais/imunologia , Tromboembolia/tratamento farmacológico , Tromboembolia/imunologia , Tromboembolia/prevenção & controle , Anticorpos Antifosfolipídeos/imunologia , Anticoagulantes/uso terapêuticoAssuntos
Síndrome de Behçet , Tromboembolia , Humanos , Masculino , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/imunologia , Imunossupressores/uso terapêutico , Inflamação/imunologia , Tromboembolia/tratamento farmacológico , Tromboembolia/imunologia , Tromboembolia/prevenção & controle , Anticorpos Antifosfolipídeos/imunologia , Anticoagulantes/uso terapêuticoRESUMO
Direct oral anticoagulants (DOACs) revolutionized the management of thromboembolic disorders. Clinical care may be further improved as Factor XIs undergo large-scale outcome trials. What role can non-randomized database studies play in expediting understanding of these drugs in clinical practice? The RCT-DUPLICATIVE Initiative emulated the design of eight DOAC randomized clinical trials (RCT) using non-randomized claims database studies. RCT study design parameters and measurements were closely emulated by the database studies and produced highly concordant results. The results of the single database study that did not meet all agreement metrics with the specific RCT it was emulating were aligned with a meta-analysis of six trials studying similar questions, suggesting the trial result was an outlier. Well-designed database studies using fit-for-purpose data came to the same conclusions as DOAC trials, illustrating how database studies could complement RCTs for Factor XI inhibitors-by accelerating insights in underrepresented populations, demonstrating effectiveness and safety in clinical practice, and testing broader indications.
Assuntos
Anticoagulantes , Bases de Dados Factuais , Fator XI , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Anticoagulantes/uso terapêutico , Fator XI/antagonistas & inibidores , Projetos de Pesquisa , Tromboembolia/prevenção & controle , Tromboembolia/tratamento farmacológicoRESUMO
The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.
Assuntos
Anticoagulantes , Hemorragia Cerebral , Humanos , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Tromboembolia/prevenção & controle , Tromboembolia/tratamento farmacológicoRESUMO
Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.
Assuntos
Fibrinolíticos , Tromboembolia , Humanos , Fibrinolíticos/uso terapêutico , Tromboembolia/tratamento farmacológico , História do Século XXRESUMO
There are clinical situations where information about the anticoagulant effects of Apixaban could be useful. Specialised methods for measuring Apixaban concentrations are not available at all medical laboratories while methods for measuring the functional effects of Apixaban, using clot time ratio (CTR), can be performed in most medical laboratories around the clock using well-established measurement procedures. The aim of this study was to investigate CTR in trough and peak samples during Apixaban treatment of atrial fibrillation and to correlate the findings to bleeds and thrombotic events. Three trough- and three peak samples from 61 patients (31 on Apixaban 5 mg twice daily and 30 on Apixaban 2.5 mg twice daily) were analysed with MRX PT DOAC. Patients were followed for 30 + /-15 months, and bleeds and thrombotic events were documented. The effect of Apixaban could be measured with MRX PT DOAC and there was a statistically significant difference between CTR in trough samples compared to peak samples (p < 0.001). A total of 21 patients suffered bleeds during follow-up; two patients suffered major bleeds, and 19 suffered minor bleeds. Patients with major bleeds had both mean peak- and mean trough CTR above the respective first to third quartile (Q1-Q3) range. Four patients suffered thromboembolic events. Generally, the peak CTRs were below or in the lower end of the peak Q1-Q3 for these patients. The new test MRX PT DOAC can be used to measure the effect of Apixaban during the treatment of atrial fibrillation. High mean peak- and mean trough CTR were seen in 2 patients with major bleeds, and low peak CTR was seen in 4 patients with thromboembolic events.
Assuntos
Fibrilação Atrial , Pirazóis , Acidente Vascular Cerebral , Tromboembolia , Trombose , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Anticoagulantes/efeitos adversos , Testes de Coagulação Sanguínea , Piridonas/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Trombose/tratamento farmacológico , Tromboembolia/tratamento farmacológico , Resultado do Tratamento , Acidente Vascular Cerebral/tratamento farmacológico , RivaroxabanaRESUMO
Feline arterial thromboembolism has been reported to be secondary to various feline cardiomyopathies; however, it has not been described in cats with transient myocardial thickening. A previously healthy, one-year-old, castrated male cat presented with acute paraparesis and congestive heart failure. Echocardiography revealed asymmetric left ventricular free wall thickening and left atrial enlargement. Antithrombotic treatment and cardiac medication resulted in reperfusion and mobility on day seven in one limb and on day 10 in the other. Different complications were managed successfully, including worsening acute kidney injury, inflammation, pleural effusion, and anemia. After three weeks, the cat was discharged and prescribed oral antithrombotic drugs (clopidogrel and rivaroxaban) and cardiac medication. Within five months, echocardiographic findings normalized, and medical treatment was gradually discontinued. To date, the cat remains healthy at 1735 days after the initial diagnosis and 1494 days after the last antithrombotic medication. To the best of our knowledge, this is the first case report on feline arterial thromboembolism combined with transient myocardial thickening, with favorable long-term survival.
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Doenças do Gato , Tromboembolia , Gatos , Animais , Masculino , Doenças do Gato/tratamento farmacológico , Doenças do Gato/patologia , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/diagnóstico , Tromboembolia/veterinária , Tromboembolia/tratamento farmacológico , Ecocardiografia/veterinária , Cardiomiopatias/veterinária , Cardiomiopatias/complicaçõesRESUMO
OBJECTIVES: Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain. DATA SOURCES: A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome. STUDY SELECTION: Abstracts and full texts were assessed independently and in duplicate by two reviewers. DATA EXTRACTION: Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. DATA SYNTHESIS: The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies. CONCLUSIONS: A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.
Assuntos
Fatores de Coagulação Sanguínea , Tromboembolia , Humanos , Fatores de Coagulação Sanguínea/uso terapêutico , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Tromboembolia/tratamento farmacológico , Tromboembolia/prevenção & controle , Coeficiente Internacional Normatizado , Fibrinolíticos , Vitamina K , Estudos RetrospectivosRESUMO
ABSTRACT: Arterial and venous thromboses are classically considered distinct disease states, with arterial thrombosis mediated predominantly by platelets and therefore, treated with antiplatelet therapy, and venous thrombosis mediated by the plasmatic coagulation system and treated with anticoagulation. However, co-occurrence of arterial and venous events is common, and there is increasing evidence of shared risk factors and pathophysiologic overlap. This presents a management challenge: does the patient with venous and arterial thrombosis, require anticoagulation, antiplatelet therapy, or both? Herein, we present a structured approach to the evaluation and management of patients with venous thrombosis who are also at risk for or have a history of an arterial thromboembolic event. We emphasize the importance of defining the indications for antithrombotic therapy, as well as the evaluation of factors that influence both thrombotic and bleeding risk, including disorder-specific and patient-specific factors, as well as the inherent risk balance of antithrombotic therapy regimens. We illustrate this approach in 4 cases, discussing the unique considerations and recent updates in the management of venous thrombosis, acute noncardioembolic ischemic stroke, coronary artery disease and acute myocardial infarction, and peripheral artery disease after revascularization.
Assuntos
Anticoagulantes , Inibidores da Agregação Plaquetária , Tromboembolia , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Trombose Venosa/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Iatrogenic femoral artery pseudoaneurysm (IFP) incidence is increasing with increase in diagnostic and therapeutic angiography, and so, the less invasive percutaneous thrombin injection (PTI) is the most widely used treatment. Moreover, studies that minimize PTI complications and highlight therapeutic effects are lacking. OBJECTIVES: This study performed in vitro thrombosis modeling of pseudoaneurysms and analyzed thrombosis within and thromboembolism outside the sac during thrombin injection. METHODS: We evaluated PTI in terms of thrombin injection location (at the junction of the IFP sac and neck, the center, and the dome, located farthest from the neck of the sac), thrombin injection time (5 and 8 seconds), and blood flow rate (ranging from 210 mL/min to 300 mL/min). Porcine blood was used as the working fluid in this study. RESULTS: Thrombin injection at the junction of the IFP sac and the pseudoaneurysm neck led to less thrombosis within the sac but substantial thrombi consistently outside the sac, whereas thrombin injected at the sac center mostly led to complete thrombosis within the sac, preventing further blood flow into the sac and reducing likelihood of thrombi outside the sac. A longer thrombin injection time enhanced the therapeutic effect and decreased the possibility of thromboembolism. Thromboembolism occurred more frequently at flow rates of >240 mL/min. CONCLUSION: The thrombin injection site in a pseudoaneurysm significantly influences thrombogenesis within and thromboembolism outside the sac. Thus, slow and deliberate injection of thrombin into the center of the sac could potentially reduce complications and enhance treatment efficacy.
Assuntos
Falso Aneurisma , Artéria Femoral , Trombina , Trombose , Trombina/administração & dosagem , Falso Aneurisma/tratamento farmacológico , Animais , Trombose/tratamento farmacológico , Trombose/etiologia , Suínos , Injeções Intra-Arteriais , Fatores de Tempo , Humanos , Tromboembolia/tratamento farmacológico , Tromboembolia/prevenção & controle , Tromboembolia/etiologia , Doença IatrogênicaRESUMO
BACKGROUND: Data comparing the specific reversal agent andexanet alfa with non-specific treatments in patients with non-traumatic intracerebral hemorrhage (ICH) associated with factor-Xa inhibitor (FXaI) use are scarce. AIM: The study aimed to determine the association between the use of andexanet alfa compared with non-specific treatments with the rate of hematoma expansion and thromboembolic complications in patients with FXaI-associated ICH. METHODS: We performed an individual patient data analysis combining two independent, prospective studies: ANNEXA-4 (180 patients receiving andexanet alfa, NCT02329327) and TICH-NOAC (63 patients receiving tranexamic acid or placebo ± prothrombin complex concentrate, NCT02866838). The primary efficacy outcome was hematoma expansion on follow-up imaging. The primary safety outcome was any thromboembolic complication (ischemic stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis) at 30 days. We used binary logistic regression models adjusted for baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively. RESULTS: Among 243 participants included, the median age was 80 (IQR 75-84) years, baseline hematoma volume was 9.1 (IQR 3.4-21) mL and anti-Xa activity 118 (IQR 78-222) ng/mL. Times from last FXaI intake and symptom onset to treatment were 11 (IQR 7-16) and 4.7 (IQR 3.0-7.6) h, respectively. Overall, 50 patients (22%) experienced hematoma expansion (ANNEXA-4: n=24 (14%); TICH-NOAC: n=26 (41%)). After adjusting for pre-specified confounders (baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively), treatment with andexanet alfa was independently associated with decreased odds for hematoma expansion (aOR 0.33, 95% CI 0.13-0.80, p = 0.015). Overall, 26 patients (11%) had any thromboembolic complication within 30 days (ANNEXA-4: n=20 (11%); TICH-NOAC: n=6 (10%)). There was no association between any thromboembolic complication and treatment with andexanet alfa (aOR 0.70, 95% CI 0.16-3.12, p = 0.641). CONCLUSION: The use of andexanet alfa compared to any other non-specific treatment strategy was associated with decreased odds for hematoma expansion, without increased odds for thromboembolic complications.
Assuntos
Hemorragia Cerebral , Inibidores do Fator Xa , Proteínas Recombinantes , Humanos , Hemorragia Cerebral/induzido quimicamente , Masculino , Feminino , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Idoso , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Estudos Prospectivos , Fator Xa/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso de 80 Anos ou mais , Hematoma , Tromboembolia/tratamento farmacológicoRESUMO
Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TEind ) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T-cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TEind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T-cell phenotype and mortality but did not predict induction failure.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Tromboembolia , Trombose , Criança , Humanos , Adolescente , Lactente , Resultado do Tratamento , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Estudos Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Fatores de Risco , Trombose/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Tromboembolia/tratamento farmacológico , OntárioRESUMO
Cancer-related inflammation, anti-cancer treatment and other cancer-related comorbidities are proposed to affect atrial remodeling, increasing the susceptibility of lung cancer patients for developing atrial fibrillation. Moreover, cancer is assumed to modify the risk of thromboembolisms and bleeding. An association between AF and malignancy has been reported but incompletely defined. The earliest publications of cancer predisposing to AF came in the 1940s-50s with reports of neoplastic cardiac infiltration or mechanical pressure on the heart, and with oncologic thoracic surgery. Subsequently, multiple studies have reported an increased risk of AF after cancer therapy with surgery (particularly thoracic) and chemotherapy. However, the prevalence of AF appears to be higher in patients with cancer at the time of diagnosis even before undergoing therapy. The emerging field of cardio-oncology has revealed that these seemingly disparate disease processes are intertwined, owing to the cardiovascular sequelae of anticancer therapies, shared risk factors that predispose individuals to both cardiovascular disease and cancer, as well the possible potentiation of cancer growth by cardiac dysfunction. Although direct oral anticoagulants (DOAC) seem to represent a safe and effective option, compared to Vitamin K antagonists (VKA), in this population, this statement is based mainly on observational studies and sub analyses of pivotal trials of the DOAC.
Assuntos
Fibrilação Atrial , Neoplasias Pulmonares , Acidente Vascular Cerebral , Tromboembolia , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Pacientes Ambulatoriais , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/induzido quimicamente , Anticoagulantes/efeitos adversos , Tromboembolia/tratamento farmacológico , Administração Oral , Acidente Vascular Cerebral/etiologiaRESUMO
Intracranial hemorrhage (ICH) is the most feared and lethal complication of oral anticoagulant (OAC) therapy. Resumption of OAC after ICH has long posed a challenge for clinicians, complicated by the expanding range of anticoagulant agents available in modern clinical practice, including direct OACs and, more recently, factor XI and XII inhibitors. A review of the current literature found support for resuming OAC in the majority of patients after ICH based on pooled retrospective data showing that resumption is associated with a lower risk of mortality and thromboembolism without a significantly increased risk of recurrent hemorrhage. The optimal time to resume OAC is less clear; however, the available evidence suggests that the composite risk of both recurrent hemorrhage and thromboembolism is likely minimized, somewhere between 4 and 6 weeks, after ICH in most patients. Specific considerations to guide the optimal resumption time in the individual patient include ICH location, mechanism, and anticoagulant class. Patients with mechanical heart valves and intracerebral malignancy represent high-risk groups who require more nuanced decision making. Here, we appraise the literature with the aim of providing a practical guide for clinicians while also discussing priorities for future investigation.
Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia , Humanos , Estudos Retrospectivos , Fibrilação Atrial/tratamento farmacológico , Hemorragias Intracranianas/complicações , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Tromboembolia/tratamento farmacológico , Administração Oral , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/complicações , Hemorragia Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
OBJECTIVE: To assess the effects of tranexamic acid (TXA) in individuals with kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We performed a literature search of Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, grey literature, and conference proceedings. We included randomised controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients aged ≥18 years. Two review authors independently classified studies and abstracted data. Primary outcomes were blood transfusion, stone-free rate (SFR), thromboembolic events (TEE). We rated the certainty of evidence (CoE) according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach using a minimally contextualised approach with pre-defined thresholds for minimally clinically important differences (MCID). RESULTS: We included 10 RCTs assessing the effect of systemic TXA in PCNL vs placebo (or no TXA). Eight studies were published as full text. Based on an adjusted baseline risk of blood transfusion of 5.7%, systemic TXA may reduce blood transfusions (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.27-0.76). Based on an adjusted baseline SFR of 75.7%, systemic TXA may increase SFR (RR 1.11, 95% CI 0.98-1.27). There is probably no difference in TEEs (risk difference 0.001, 95% CI -0.01 to 0.01). Systemic TXA may increase adverse events (AEs) (RR 5.22, 95% CI 0.52-52.72). Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84-1.57). The CoE for most outcomes was assessed as low or very low. CONCLUSIONS: Based on a body of evidence of 10 RCTs, we found that systemic TXA in PCNL may reduce blood transfusions, major surgical complications, and hospital length of stay, as well as improve the SFR; however, it may increase AEs. These findings should inform urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.