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1.
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
2.
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
3.
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
4.
J Clin Neuromuscul Dis ; 25(4): 171-177, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38771226

RESUMO

OBJECTIVES: Small fiber neuropathy presents a significant diagnostic and therapeutic challenge. To solve this challenge, efforts have been made to identify autoantibodies associated with this condition. Previous literature has often considered tri-sulfated heparin disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR3) as a singular seropositive group and/or focused primarily on symptomatic associations. METHODS: One hundred seventy-two small fiber neuropathy patients with a Washington University Sensory Neuropathy panel were selected for TS-HDS seropositivity, FGFR-3 seropositivity, and seronegative controls. Data were collected to on the demographic, symptomatic, and laboratory profiles of each subgroup. RESULTS: Percent female (P = 0.0043), frequency of neuropathic pain symptoms (P = 0.0074), and erythrocyte sedimentation rate (P = 0.0293), vitamin D (P < 0.0001), and vitamin B12 (P = 0.0033) differed between the groups. Skin biopsy was more frequently normal within both the FGFR-3 and the TS-HDS cohort (P = 0.0253). CONCLUSIONS: TS-HDS and FGFR-3 display a distinct phenotype from both controls and one another. Immunoglobulin M (IgM) against FGFR-3 and IgM against TS-HDS may be individually valuable markers for the development of distinct clinical phenotypes.


Assuntos
Autoanticorpos , Condução Nervosa , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Neuropatia de Pequenas Fibras , Humanos , Feminino , Neuropatia de Pequenas Fibras/diagnóstico , Pessoa de Meia-Idade , Masculino , Condução Nervosa/fisiologia , Idoso , Adulto , Autoanticorpos/sangue , Heparina/análogos & derivados , Imunoglobulina M/sangue , Heparitina Sulfato/sangue , Estudos de Condução Nervosa , Dissacarídeos
5.
J Clin Neuromuscul Dis ; 25(4): 184-196, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38771228

RESUMO

OBJECTIVES: To demonstrate treatment efficacy on composite and non-length-dependent (NLD) punch biopsy specimens from intravenous immunoglobulin (IVIG) in pure small-fiber neuropathy (SFN) with trisulfated heparin disaccharide (TS-HDS), fibroblast growth factor-3 (FGFR-3), or Plexin D1 antibodies. SFN has an increasing prevalence, and over 30% of cases may be immune-mediated. TS-HDS, FGFR-3, and Plexin D1 autoantibodies have been shown to be present in 44%-55% of cryptogenic SFN cases, suggesting an immune mechanism. Reports have shown IVIG to be effective for this condition, but some controversy exists based on length-dependent (LD) post-IVIG treatment data in a recent trial. METHODS: In a retrospective review, all pure SFN cases tested for the 3 antibodies from January 2021 to May 2022 were tabulated, and patients who underwent IVIG treatment were separated and analyzed for changes in epidermal nerve fiber density (ENFD) on skin biopsy, as well as SFN-specific questionnaire and pain scores. RESULTS: Ninety-one patients with pure SFN had antibody testing. Sixty of these (66%) were seropositive, and 31 (34%) were seronegative. Seventeen seropositive patients (13 female patients, 4 male patients, 6 FGFR-3, 2 TS-HDS, 4 Plexin D1, 2 with all 3 antibodies, 1 with FGFR-3 and Plexin D1, 1 with FGFR-3 and TS-HDS, and 1 with TS-HDS and Plexin D1) underwent IVIG treatment. Of these, 2 patients stopped treatment due to side effects, and the remaining 15 completed at least 6 months of IVIG. Of these, 12 had a post-IVIG skin biopsy, and of these, 11 (92%) had a 55.1% improved mean composite ENFD (P = 0.01). NLD-ENFD specimens improved by 42.3% (P = 0.02), and LD-ENFD specimens improved by 99.7% (P = 0.01). Composite ENFD in Plexin D1-SFN patients improved by 139% (P = 0.04). In addition, 14 patients had questionnaires pre-IVIG/post-IVIG, and average pain decreased by 2.7 (P = 0.002). CONCLUSIONS: IVIG shows disease-modifying effect in immune SFN with novel antibodies, especially Plexin D1-SFN, as well as significantly improved pain. NLD-ENFD should be examined as well as LD-ENFD to see this effect. Further randomized controlled trials looking at NLD-ENFD as well as LD-ENFD improvement, along with pain and SFN-specific questionnaires, are needed to confirm these findings.


Assuntos
Autoanticorpos , Imunoglobulinas Intravenosas , Pele , Neuropatia de Pequenas Fibras , Humanos , Neuropatia de Pequenas Fibras/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Retrospectivos , Autoanticorpos/sangue , Adulto , Idoso , Biópsia , Pele/patologia , Heparina/uso terapêutico , Heparina/análogos & derivados , Proteínas do Tecido Nervoso/imunologia , Resultado do Tratamento , Receptores de Superfície Celular , Fatores Imunológicos/uso terapêutico , Dissacarídeos
6.
Am J Nurs ; 124(6): 40-46, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38780339

RESUMO

BACKGROUND: Unfractionated heparin (UFH) is a high-risk medication that can cause bleeding and/or thrombotic complications if not managed appropriately. Between January and July 2019, our institution experienced a high number of patient safety events related to UFH infusion for the treatment of venous thromboembolism (VTE). PURPOSE: The aim of this quality improvement (QI) initiative was to prevent these safety events by improving compliance with our institution's nurse-driven VTE UFH infusion protocol. METHODS: Baseline data for patients on the VTE UFH protocol were collected to identify improvement opportunities. Compliance with eight standards of care related to the VTE UFH infusion protocol was measured. Time to first therapeutic activated partial thromboplastin time (aPTT) was recorded to assess the benefit of improved compliance. INTERVENTIONS: Institutional policy updates were made to clarify the management of UFH infusions and documentation in the electronic health record. A multidisciplinary workgroup implemented order set changes, nursing communication orders, UFH infusion reports, and a nursing education module to promote compliance with the protocol. RESULTS: The overall rate of compliance with the VTE UFH infusion protocol increased from 79.4% at baseline to 85.2% following implementation of the QI initiative, and the median time to first therapeutic aPTT decreased from 831.5 minutes to 808 minutes over the same period. CONCLUSIONS: A multidisciplinary initiative to address improvement opportunities in a nurse-driven UFH protocol for VTE treatment increased compliance with the protocol and decreased the time to first therapeutic aPTT.


Assuntos
Anticoagulantes , Fidelidade a Diretrizes , Heparina , Melhoria de Qualidade , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/enfermagem , Tromboembolia Venosa/prevenção & controle , Heparina/administração & dosagem , Heparina/uso terapêutico , Heparina/efeitos adversos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos , Fidelidade a Diretrizes/estatística & dados numéricos , Infusões Intravenosas , Feminino , Masculino , Pessoa de Meia-Idade , Segurança do Paciente/normas
7.
Antimicrob Resist Infect Control ; 13(1): 53, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764050

RESUMO

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacterium that can cause hospital infections and outbreaks within hospitals. This study aimed to evaluate an outbreak of Stenotrophomonas maltophilia, caused by ready-to-use commercial syringes containing liquid lithium and heparin for arterial blood gas collection in a university hospital. METHODS: Upon detecting an increase in Stenotrophomonas maltophilia growth in blood cultures between 15.09.2021 and 19.11.2021, an outbreak analysis and a case-control study (52 patients for the case group, 56 patients for the control group) were performed considering risk factors for bacteremia. Samples from possible foci for bacteremia were also cultured. Growing bacteria were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The genetic linkage and clonal relationship isolates were investigated with pulsed-field gel electrophoresis (PFGE) in the reference laboratory. RESULTS: In the case-control study, the odds ratio for the central venous catheter [3.38 (95% confidence interval [CI]: 1.444, 8.705 ; p = 0.006)], for surgery [3.387 (95% confidence interval [CI]: 1.370, 8.373 ; p = 0.008)] and for arterial blood gas collection history [18.584 (95% confidence interval [CI]:4.086, 84.197; p < 0.001)] were identified as significant risk factors. Stenotrophomonas maltophilia growth was found in ready-to-use commercial syringes used for arterial blood gas collection. Molecular analysis showed that the growths in the samples taken from commercial syringes and the growths from blood cultures were the same. It was decided that the epidemic occurred because the method for sterilization of heparinized liquid preparations were not suitable. After discontinuing the use of the kits with this lot number, the outbreak was brought under control. CONCLUSIONS: According to our results, disposable or sterile medical equipment should be included as a risk factor in outbreak analyses. The method by which injectors containing liquids, such as heparin, are sterilized should be reviewed. Our study also revealed the importance of the cooperation of the infection control team with the microbiology laboratory.


Assuntos
Infecção Hospitalar , Surtos de Doenças , Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Stenotrophomonas maltophilia/isolamento & purificação , Humanos , Estudos de Casos e Controles , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Masculino , Feminino , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Pessoa de Meia-Idade , Idoso , Adulto , Fatores de Risco , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Hospitais Universitários , Seringas/microbiologia , Eletroforese em Gel de Campo Pulsado , Idoso de 80 Anos ou mais , Heparina/farmacologia
8.
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
11.
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
12.
Mar Drugs ; 22(5)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38786623

RESUMO

Mycoplasma pneumoniae, a notable pathogen behind respiratory infections, employs specialized proteins to adhere to the respiratory epithelium, an essential process for initiating infection. The role of glycosaminoglycans, especially heparan sulfate, is critical in facilitating pathogen-host interactions, presenting a strategic target for therapeutic intervention. In this study, we assembled a glycan library comprising heparin, its oligosaccharide derivatives, and a variety of marine-derived sulfated glycans to screen the potential inhibitors for the pathogen-host interactions. By using Surface Plasmon Resonance spectroscopy, we evaluated the library's efficacy in inhibiting the interaction between M. pneumoniae adhesion proteins and heparin. Our findings offer a promising avenue for developing novel therapeutic strategies against M. pneumoniae infections.


Assuntos
Heparina , Mycoplasma pneumoniae , Polissacarídeos , Mycoplasma pneumoniae/efeitos dos fármacos , Heparina/farmacologia , Heparina/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Organismos Aquáticos , Humanos , Adesinas Bacterianas/metabolismo , Adesinas Bacterianas/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Interações Hospedeiro-Patógeno , Sulfatos/química , Sulfatos/farmacologia
13.
Nanoscale ; 16(17): 8352-8360, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563277

RESUMO

Detection and characterization of protein-protein interactions are essential for many cellular processes, such as cell growth, tissue repair, drug delivery, and other physiological functions. In our research, we have utilized emerging solid-state nanopore sensing technology, which is highly sensitive to better understand heparin and fibroblast growth factor 1 (FGF-1) protein interactions at a single-molecule level without any modifications. Understanding the structure and behavior of heparin-FGF-1 complexes at the single-molecule level is very important. An abnormality in their formation can lead to life-threatening conditions like tumor growth, fibrosis, and neurological disorders. Using a controlled dielectric breakdown pore fabrication approach, we have characterized individual heparin and FGF-1 (one of the 22 known FGFs in humans) proteins through the fabrication of 17 ± 1 nm nanopores. Compared to heparin, the positively charged heparin-binding domains of some FGF-1 proteins translocationally react with the pore walls, giving rise to a distinguishable second peak with higher current blockade. Additionally, we have confirmed that the dynamic FGF-1 is stabilized upon binding with heparin-FGF-1 at the single-molecule level. The larger current blockades from the complexes relative to individual heparin and the FGF-1 recorded during the translocation ensure the binding of heparin-FGF-1 proteins, forming binding complexes with higher excluded volumes. Taken together, we demonstrate that solid-state nanopores can be employed to investigate the properties of individual proteins and their complex interactions, potentially paving the way for innovative medical therapies and advancements.


Assuntos
Fator 1 de Crescimento de Fibroblastos , Heparina , Nanoporos , Ligação Proteica , Fator 1 de Crescimento de Fibroblastos/química , Fator 1 de Crescimento de Fibroblastos/metabolismo , Heparina/química , Heparina/metabolismo , Humanos
17.
Lipids Health Dis ; 23(1): 92, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561841

RESUMO

BACKGROUND: Lipoprotein lipase (LPL) plays a crucial role in triglyceride hydrolysis. Rare biallelic variants in the LPL gene leading to complete or near-complete loss of function cause autosomal recessive familial chylomicronemia syndrome. However, rare biallelic LPL variants resulting in significant but partial loss of function are rarely documented. This study reports a novel occurrence of such rare biallelic LPL variants in a Chinese patient with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) during pregnancy and provides an in-depth functional characterization. METHODS: The complete coding sequences and adjacent intronic regions of the LPL, APOC2, APOA5, LMF1, and GPIHBP1 genes were analyzed by Sanger sequencing. The aim was to identify rare variants, including nonsense, frameshift, missense, small in-frame deletions or insertions, and canonical splice site mutations. The functional impact of identified LPL missense variants on protein expression, secretion, and activity was assessed in HEK293T cells through single and co-transfection experiments, with and without heparin treatment. RESULTS: Two rare LPL missense variants were identified in the patient: the previously reported c.809G > A (p.Arg270His) and a novel c.331G > C (p.Val111Leu). Genetic testing confirmed these variants were inherited biallelically. Functional analysis showed that the p.Arg270His variant resulted in a near-complete loss of LPL function due to effects on protein synthesis/stability, secretion, and enzymatic activity. In contrast, the p.Val111Leu variant retained approximately 32.3% of wild-type activity, without impacting protein synthesis, stability, or secretion. Co-transfection experiments indicated a combined activity level of 20.7%, suggesting no dominant negative interaction between the variants. The patient's post-heparin plasma LPL activity was about 35% of control levels. CONCLUSIONS: This study presents a novel case of partial but significant loss-of-function biallelic LPL variants in a patient with HTG-AP during pregnancy. Our findings enhance the understanding of the nuanced relationship between LPL genotypes and clinical phenotypes, highlighting the importance of residual LPL function in disease manifestation and severity. Additionally, our study underscores the challenges in classifying partial loss-of-function variants in classical Mendelian disease genes according to the American College of Medical Genetics and Genomics (ACMG)'s variant classification guidelines.


Assuntos
Hiperlipidemias , Hipertrigliceridemia , Pancreatite , Humanos , Lipase Lipoproteica/genética , Doença Aguda , Células HEK293 , Pancreatite/genética , Heparina
18.
Eur J Anaesthesiol ; 41(5): 327-350, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38567679

RESUMO

BACKGROUND: Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding. DESIGN: A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process. RESULTS: So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%. DISCUSSION: DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50 ng ml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given. CONCLUSION: In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings.


Assuntos
Hemostáticos , Heparina , Humanos , Heparina/uso terapêutico , Estudos Prospectivos , Hemorragia/prevenção & controle , Anticoagulantes , Hemostáticos/uso terapêutico , Administração Oral
20.
A A Pract ; 18(4): e01767, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578015

RESUMO

Pulmonary embolism is a common complication after intracranial hemorrhage. As thrombolysis is contraindicated in this situation, surgical pulmonary embolectomy may be indicated in case of high-risk pulmonary embolism but requires transient anticoagulation with heparin during cardiopulmonary bypass. We report the case of a patient with a history of heparin-induced thrombocytopenia who presented with a high-risk pulmonary embolism 10 days after the spontaneous onset of a voluminous intracerebral hematoma. Despite high doses of heparin required to run the cardiopulmonary bypass and subsequent anticoagulation by danaparoid sodium, the brain hematoma remained stable and the patient was discharged without complications 30 days after surgery.


Assuntos
Embolia Pulmonar , Trombocitopenia , Humanos , Anticoagulantes/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Heparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/cirurgia , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/cirurgia , Embolia Pulmonar/complicações , Hemorragias Intracranianas/cirurgia , Hemorragias Intracranianas/complicações , Hemorragia Cerebral , Embolectomia/efeitos adversos , Hematoma/cirurgia
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