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1.
PLoS One ; 19(5): e0303376, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38723003

RESUMO

The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery.


Assuntos
Heparina , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Masculino , Resultado do Tratamento , Feminino , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Angiografia Coronária , Pessoa de Meia-Idade , Adulto , Idoso
2.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731888

RESUMO

The interaction of heparin with antithrombin (AT) involves a specific sequence corresponding to the pentasaccharide GlcNAc/NS6S-GlcA-GlcNS3S6S-IdoA2S-GlcNS6S (AGA*IA). Recent studies have revealed that two AGA*IA-containing hexasaccharides, which differ in the sulfation degree of the iduronic acid unit, exhibit similar binding to AT, albeit with different affinities. However, the lack of experimental data concerning the molecular contacts between these ligands and the amino acids within the protein-binding site prevents a detailed description of the complexes. Differential epitope mapping (DEEP)-STD NMR, in combination with MD simulations, enables the experimental observation and comparison of two heparin pentasaccharides interacting with AT, revealing slightly different bound orientations and distinct affinities of both glycans for AT. We demonstrate the effectiveness of the differential solvent DEEP-STD NMR approach in determining the presence of polar residues in the recognition sites of glycosaminoglycan-binding proteins.


Assuntos
Antitrombinas , Heparina , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Oligossacarídeos , Ligação Proteica , Heparina/química , Heparina/metabolismo , Oligossacarídeos/química , Oligossacarídeos/metabolismo , Antitrombinas/química , Antitrombinas/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Sítios de Ligação , Solventes/química , Mapeamento de Epitopos/métodos , Humanos
3.
Clin Appl Thromb Hemost ; 30: 10760296241252838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711321

RESUMO

In unfractionated heparin (UFH) monitoring during extracorporeal circulation, the traditional measures of activated clotting time (ACT) or activated partial thromboplastin time (APTT) may diverge, confounding anticoagulant adjustments. We aimed to explore the factors explaining this discrepancy in children and young adults. This retrospective observational study, conducted at an urban regional tertiary hospital, included consecutive pediatric patients who received UFH during extracorporeal circulation (continuous kidney replacement therapy or extracorporeal membrane oxygenation) between April 2017 and March 2021. After patients whose ACT and APTT were not measured simultaneously or who were also taking other anticoagulants were excluded, we analyzed 94 samples from 23 patients. To explain the discrepancy between ACT and APTT, regression equations were created using a generalized linear model (family = gamma, link = logarithmic) with ACT as the response variable. Other explanatory variables included age, platelet count, and antithrombin. Compared to APTT alone as an explanatory variable, the Akaike information criterion and pseudo-coefficient of determination improved from 855 to 625 and from 0.01 to 0.42, respectively, when these explanatory variables were used. In conclusion, we identified several factors that may explain some of the discrepancy between ACT and APTT in the routinely measured tests. Evaluation of these factors may aid in appropriate adjustments in anticoagulation therapy.


Assuntos
Circulação Extracorpórea , Heparina , Humanos , Heparina/farmacologia , Heparina/uso terapêutico , Feminino , Masculino , Criança , Estudos Retrospectivos , Circulação Extracorpórea/métodos , Adolescente , Tempo de Tromboplastina Parcial/métodos , Pré-Escolar , Adulto Jovem , Adulto , Lactente , Anticoagulantes/uso terapêutico , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Tempo de Coagulação do Sangue Total/métodos
4.
Nat Commun ; 15(1): 3755, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704385

RESUMO

Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy.


Assuntos
Anticoagulantes , Escherichia coli , Heparina , Sulfotransferases , Sulfotransferases/metabolismo , Sulfotransferases/genética , Heparina/metabolismo , Heparina/biossíntese , Anticoagulantes/metabolismo , Anticoagulantes/química , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia Metabólica/métodos , Humanos , Polissacarídeos/metabolismo , Polissacarídeos/biossíntese , Polissacarídeos/química , Mutagênese Sítio-Dirigida , Engenharia de Proteínas/métodos , Dissacarídeos/metabolismo , Dissacarídeos/biossíntese , Dissacarídeos/química , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética
7.
Int J Mol Sci ; 25(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38732176

RESUMO

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.


Assuntos
Trombocitopenia , Trombose , Humanos , Trombocitopenia/diagnóstico , Trombose/etiologia , Plaquetas/metabolismo , Contagem de Plaquetas , Heparina/uso terapêutico , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/sangue
8.
ACS Biomater Sci Eng ; 10(5): 3057-3068, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38641433

RESUMO

Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL)4 coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL)4 catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL)4 catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL)4 catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.


Assuntos
Catéteres , Materiais Revestidos Biocompatíveis , Heparina , Polifenóis , Taninos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Catéteres/microbiologia , Polifenóis/química , Polifenóis/farmacologia , Heparina/química , Heparina/farmacologia , Taninos/química , Taninos/farmacologia , Silanos/química , Silanos/farmacologia , Anticoagulantes/química , Anticoagulantes/farmacologia , Propilaminas/química , Aminas/química , Aminas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Polilisina/química , Polilisina/farmacologia , Propriedades de Superfície , Interações Hidrofóbicas e Hidrofílicas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Elastômeros de Silicone/química , Adsorção , Escherichia coli/efeitos dos fármacos
9.
Transpl Int ; 37: 12752, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585623

RESUMO

Background: Extracorporeal membrane oxygenation (ECMO) is frequently used during lung transplantation. Unfractionated heparin (UFH) is mainly used as part of ECMO support for anticoagulation. One of the most common perioperative complications is bleeding, which high-dose UFH can aggravate. Methods: We retrospectively analyzed (n = 141) patients who underwent lung transplantation between 2020 and 2022. All subjects (n = 109) underwent central cannulated VA ECMO with successful intraoperative ECMO weaning. Patients on ECMO bridge, postoperative ECMO, heart-lung transplants and transplants without ECMO were excluded. The dose of UFH for the entire surgical procedure, blood loss and consumption of blood derivatives intraoperatively and 48 h after ICU admission were recorded. Surgical revision for postoperative bleeding were analyzed. Thrombotic complications, mortality and long-term survival were evaluated. Results: Lower doses of UFH administered for intraoperative ECMO anticoagulation contribute to a reduction in intraoperative blood derivates consumption and blood loss with no thrombotic complications related to the patient or the ECMO circuit. Lower doses of UFH may lead to a decreased incidence of surgical revision for hemothorax. Conclusion: Lower doses of UFH as part of intraoperative ECMO anticoagulation might reduce the incidence of complications and lead to better postoperative outcomes.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Pulmão , Trombose , Humanos , Heparina/uso terapêutico , Estudos Retrospectivos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Anticoagulantes/uso terapêutico , Transplante de Pulmão/métodos , Trombose/etiologia , Hemorragia Pós-Operatória
10.
Glycoconj J ; 41(2): 163-174, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38642280

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide COVID-19 pandemic, leading to 6.8 million deaths. Numerous variants have emerged since its outbreak, resulting in its significantly enhanced ability to spread among humans. As with many other viruses, SARS­CoV­2 utilizes heparan sulfate (HS) glycosaminoglycan (GAG) on the surface of host cells to facilitate viral attachment and initiate cellular entry through the ACE2 receptor. Therefore, interfering with virion-HS interactions represents a promising target to develop broad-spectrum antiviral therapeutics. Sulfated glycans derived from marine organisms have been proven to be exceptional reservoirs of naturally existing HS mimetics, which exhibit remarkable therapeutic properties encompassing antiviral/microbial, antitumor, anticoagulant, and anti-inflammatory activities. In the current study, the interactions between the receptor-binding domain (RBD) of S-protein of SARS-CoV-2 (both WT and XBB.1.5 variants) and heparin were applied to assess the inhibitory activity of 10 marine-sourced glycans including three sulfated fucans, three fucosylated chondroitin sulfates and two fucoidans derived from sea cucumbers, sea urchin and seaweed Saccharina japonica, respectively. The inhibitory activity of these marine derived sulfated glycans on the interactions between RBD of S-protein and heparin was evaluated using Surface Plasmon Resonance (SPR). The RBDs of S-proteins from both Omicrion XBB.1.5 and wild-type (WT) were found to bind to heparin, which is a highly sulfated form of HS. All the tested marine-sourced sulfated glycans exhibited strong inhibition of WT and XBB.1.5 S-protein binding to heparin. We believe the study on the molecular interactions between S-proteins and host cell glycosaminoglycans provides valuable insight for the development of marine-sourced, glycan-based inhibitors as potential anti-SARS-CoV-2 agents.


Assuntos
Heparina , Polissacarídeos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , Heparina/farmacologia , Heparina/química , Heparina/metabolismo , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , COVID-19/virologia , COVID-19/metabolismo , Ligação Proteica , Animais , Antivirais/farmacologia , Antivirais/química , Heparitina Sulfato/metabolismo , Heparitina Sulfato/química
11.
Am J Cardiovasc Drugs ; 24(3): 385-398, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38683263

RESUMO

AIM: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003). CONCLUSION: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.


Assuntos
Antitrombinas , Heparina , Hirudinas , Fragmentos de Peptídeos , Intervenção Coronária Percutânea , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Proteínas Recombinantes , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Hirudinas/efeitos adversos , Hirudinas/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina/administração & dosagem , Antitrombinas/uso terapêutico , Antitrombinas/efeitos adversos , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Sci Rep ; 14(1): 8572, 2024 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-38609431

RESUMO

Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin prior to heparin. We studied this phenomenon in patients undergoing cardiac artery bypass grafting (n = 17) to determine whether the effects of heparin were systemic or platelet-specific. All patients' platelets were fully inhibited by aspirin prior to surgery, but within 3 min of receiving heparin spontaneous aggregation and responses to arachidonic acid (AA) and ADP increased significantly (p ≥ 0.0002), and activated platelets were found in the circulation. While there was no rise in thromboxane in the plasma following heparin, levels of the major platelet 12-lipoxygenase product, 12-HETE, rose significantly. Mixing experiments demonstrated that the changes caused by heparin resided primarily in the platelets, while addition of AA pathway inhibitors, and analysis of oxylipins provided evidence that, following heparin, aggregating platelets regained their ability to synthesise thromboxane. These findings highlight potentially unrecognised pro-thrombotic and pro-inflammatory changes during CABG surgery, and provide further evidence of adverse effects associated with UFH.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Heparina , Humanos , Heparina/farmacologia , Ácido Araquidônico , Aspirina/farmacologia , Ponte de Artéria Coronária , Tromboxanos
13.
Molecules ; 29(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38611809

RESUMO

Nowadays, drug delivery systems (DDSs) are gaining more and more attention. Conducting polymers (CPs) are efficiently used for DDS construction as such systems can be used in therapy. In this research, a well-known CP, polypyrrole (PPy), was synthesized in the presence of the polysaccharide heparin (HEP) and chlorpromazine (CPZ) using sodium dodecyl sulfate (SDS) as electrolyte on a steel substrate. The obtained results demonstrate the successful incorporation of CPZ and HEP into the polymer matrix, with the deposited films maintaining stable electrochemical parameters across multiple doping/dedoping cycles. Surface roughness, estimated via AFM analysis, revealed a correlation with layer thickness-decreasing for thinner layers and increasing for thicker ones. Moreover, SEM images revealed a change in the morphology of PPy films when PPy is electropolymerized in the presence of CPZ and HEP, while FTIR confirmed the presence of CPZ and HEP within PPy. Due to its lower molecular mass compared to HEP, CPZ was readily integrated into the thin polymer matrix during deposition, with diffusion being unimpeded, as opposed to films with greater thickness. Finally, the resulting system exhibited the ability to release CPZ, enabling a dosing range of 10 mg to 20 mg per day, effectively covering the therapeutic concentration range.


Assuntos
Clorpromazina , Polímeros , Pirróis , Sistemas de Liberação de Medicamentos , Heparina
14.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612796

RESUMO

The development of novel anticoagulants requires a comprehensive investigational approach that is capable of characterizing different aspects of antithrombotic activity. The necessary experiments include both in vitro assays and studies on animal models. The required in vivo approaches include the assessment of pharmacokinetic and pharmacodynamic profiles and studies of hemorrhagic and antithrombotic effects. Comparison of anticoagulants with different mechanisms of action and administration types requires unification of the experiment scheme and its adaptation to existing laboratory conditions. The rodent thrombosis models in combination with the assessment of hemostasis parameters and hematological analysis are the classic methods for conducting preclinical studies. We report an approach for the comparative study of the activity of different anticoagulants in vivo, including the investigation of pharmacodynamics and the assessment of hemorrhagic effects (tail-cut bleeding model) and pathological thrombus formation (inferior vena cava stenosis model of venous thrombosis). The reproducibility and uniformity of our set of experiments were illustrated on unfractionated heparin and dabigatran etexilate (the most common pharmaceuticals in antithrombic therapy) as comparator drugs and an experimental drug variegin from the tick Amblyomma variegatum. Variegin is notorious since it is a potential analogue of bivalirudin (Angiomax, Novartis AG, Basel, Switzerland), which is now being actively introduced into antithrombotic therapy.


Assuntos
Anticoagulantes , Heparina , Animais , Preparações Farmacêuticas , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Heparina/farmacologia , Heparina/uso terapêutico , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Reprodutibilidade dos Testes
15.
J Cardiothorac Surg ; 19(1): 242, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632589

RESUMO

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. CASE PRESENTATION: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. CONCLUSION: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.


Assuntos
Anestésicos , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Masculino , Humanos , Criança , Heparina/uso terapêutico , Fondaparinux , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Anticoagulantes/uso terapêutico , Hirudinas/efeitos adversos , Eosinofilia/induzido quimicamente , Eosinofilia/tratamento farmacológico , Fragmentos de Peptídeos , Proteínas Recombinantes
16.
Perfusion ; 39(1_suppl): 77S-80S, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651576

RESUMO

PURPOSE: We aimed at assessing the correlation between TEG reaction time (TEG-R) in citrated and fresh blood samples with TEG5000 and TEG 6S during heparin administration in patients with and without ECMO support. MATERIALS AND METHODS: Paired TEG5000 (fresh and citrated whole blood, kaolin and kaolin-heparinase) and TEG6S (citrated whole blood) samples were obtained, together with standard coagulation laboratory tests. Bland-Altman analysis and Lin's concordance correlation coefficient were used to assess agreement. RESULTS: Thirteen consecutive ECMO patients and eight consecutive non-ECMO patients were enrolled and TEG was performed for a total of 84 paired samples. ECMO patients received 19.2 (12.6-25.8) U/kg/h of heparin. Five of the non-ECMO patients did not receive heparin, two of them received a very low prophylactic dose (1.6 and 2.9 IU/kg/h, respectively), and one of them 13.1 U/kg/h of heparin. Using TEG®5000, TEG-R was 21.0 (-23.4; 65.5) min longer on fresh compared to citrated blood in patients receiving heparin while only 1.58 (-5.5; 8.7) min longer in patients not-receiving heparin. These differences were reverted by heparinase. CONCLUSIONS: Using citrated-recalcified blood to perform TEG might lead to underestimation of the effect of heparin.


Assuntos
Oxigenação por Membrana Extracorpórea , Tromboelastografia , Humanos , Tromboelastografia/métodos , Oxigenação por Membrana Extracorpórea/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Heparina/administração & dosagem , Heparina/farmacologia , Adulto , Idoso
17.
J Cardiothorac Surg ; 19(1): 255, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643128

RESUMO

BACKGROUND: In lung transplantation (LTx) surgery, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide mechanical circulatory support to patients with cardiopulmonary failure. However, the use of heparin in the administration of ECMO can increase blood loss during LTx. This study aimed to evaluate the safety of heparin-free V-A ECMO strategies. METHODS: From September 2019 to April 2022, patients who underwent lung transplantation at the First Affiliated Hospital of Guangzhou Medical University were retrospectively reviewed. A total of 229 patients were included, including 117 patients in the ECMO group and 112 in the non-ECMO group. RESULT: There was no significant difference in the incidence of thrombus events and bleeding requiring reoperation between the two groups. The in-hospital survival rate after single lung transplantation (SLTx) was 81.08%in the ECMO group and 85.14% in the Non-ECMO group, (P = 0.585). The in-hospital survival rate after double lung transplantation (DLTx) was 80.00% in the ECMO group and 92.11% in the Non-ECMO groups (P = 0.095). CONCLUSIONS: In conclusion, the findings of this study suggest that the heparin-free V-A ECMO strategy in lung transplantation is a safe approach that does not increase the incidence of perioperative thrombotic events or bleeding requiring reoperation.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Pulmão , Humanos , Estudos Retrospectivos , Heparina/uso terapêutico , Coração
18.
Thromb Res ; 237: 129-137, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583310

RESUMO

BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation. METHODS: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding. RESULTS: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04. CONCLUSION: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding.


Assuntos
Anticoagulantes , Unidades de Terapia Intensiva , Neoplasias , Embolia Pulmonar , Humanos , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Estudos Retrospectivos , Masculino , Embolia Pulmonar/mortalidade , Embolia Pulmonar/tratamento farmacológico , Feminino , Neoplasias/complicações , Neoplasias/mortalidade , Neoplasias/tratamento farmacológico , Idoso , Fatores de Risco , Pessoa de Meia-Idade , Hemorragia/mortalidade , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Doença Aguda , Heparina/uso terapêutico , Heparina/efeitos adversos , França/epidemiologia
19.
J Cardiothorac Surg ; 19(1): 221, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627833

RESUMO

BACKGROUND: Alpha-gal syndrome is an allergic condition in which individuals develop an immune-mediated hypersensitivity response when consuming red meat and its derived products. Its diagnosis is important in individuals undergoing cardiac surgery, as patients frequently require large doses of unfractionated heparin or the insertion of surgical implants, both of which are porcine or bovine in origin. There are currently no guidelines for heparin administration in alpha-gal patients, with even less knowledge regarding the long-term clinical implications of these patients after receiving bioprosthetic valve replacements or other prostheses. CASE PRESENTATION: We present the case of a 31-year-old male who underwent cardiac surgery in the setting of alpha-gal syndrome for a large atrial septal defect (ASD) and mitral valve prolapse (MVP). The patient continues to do well one year after undergoing a mitral valve repair, tricuspid valve repair and an ASD closure using bovine pericardium. He sustained no adverse reaction to the use of heparin products or the presence of a bovine pericardial patch. This rare case was managed by a multidisciplinary team consisting of cardiothoracic surgery, cardiac anesthesiology, and allergy/immunology that led to an optimal outcome despite the patient's pertinent allergic history. CONCLUSIONS: This case highlights that the use of bovine pericardium and porcine heparin to close septal defects in patients with milder forms of alpha-gal allergy can be considered if other options are not available. Further studies are warranted to investigate the long-term outcomes of such potential alpha-gal containing prostheses and heparin exposure and establish the optimal decision making algorithm and prophylactic regimen.


Assuntos
Hipersensibilidade Alimentar , Comunicação Interatrial , Masculino , Humanos , Bovinos , Animais , Suínos , Adulto , Heparina/uso terapêutico , Pericárdio , Comunicação Interatrial/cirurgia , Contraindicações
20.
Saudi Med J ; 45(4): 341-348, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38657982

RESUMO

OBJECTIVES: To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. METHODS: PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. RESULTS: A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. CONCLUSION: Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.


Assuntos
Anticoagulantes , Tratamento Farmacológico da COVID-19 , COVID-19 , Hemorragia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivaroxabana , Humanos , Rivaroxabana/uso terapêutico , Rivaroxabana/efeitos adversos , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , COVID-19/complicações , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Trombose/prevenção & controle , Trombose/etiologia , Resultado do Tratamento , Heparina/uso terapêutico , Heparina/efeitos adversos , SARS-CoV-2
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