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[PMID]:28034889
[Au] Autor:Kalathottukaren MT; Abraham L; Kapopara PR; Lai BF; Shenoi RA; Rosell FI; Conway EM; Pryzdial EL; Morrissey JH; Haynes CA; Kizhakkedathu JN
[Ad] Endereço:Centre for Blood Research.
[Ti] Título:Alteration of blood clotting and lung damage by protamine are avoided using the heparin and polyphosphate inhibitor UHRA.
[So] Source:Blood;129(10):1368-1379, 2017 Mar 09.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Anticoagulant therapy-associated bleeding and pathological thrombosis pose serious risks to hospitalized patients. Both complications could be mitigated by developing new therapeutics that safely neutralize anticoagulant activity and inhibit activators of the intrinsic blood clotting pathway, such as polyphosphate (polyP) and extracellular nucleic acids. The latter strategy could reduce the use of anticoagulants, potentially decreasing bleeding events. However, previously described cationic inhibitors of polyP and extracellular nucleic acids exhibit both nonspecific binding and adverse effects on blood clotting that limit their use. Indeed, the polycation used to counteract heparin-associated bleeding in surgical settings, protamine, exhibits adverse effects. To address these clinical shortcomings, we developed a synthetic polycation, Universal Heparin Reversal Agent (UHRA), which is nontoxic and can neutralize the anticoagulant activity of heparins and the prothrombotic activity of polyP. Sharply contrasting protamine, we show that UHRA does not interact with fibrinogen, affect fibrin polymerization during clot formation, or abrogate plasma clotting. Using scanning electron microscopy, confocal microscopy, and clot lysis assays, we confirm that UHRA does not incorporate into clots, and that clots are stable with normal fibrin morphology. Conversely, protamine binds to the fibrin clot, which could explain how protamine instigates clot lysis and increases bleeding after surgery. Finally, studies in mice reveal that UHRA reverses heparin anticoagulant activity without the lung injury seen with protamine. The data presented here illustrate that UHRA could be safely used as an antidote during adverse therapeutic modulation of hemostasis.
[Mh] Termos MeSH primário: Antídotos/farmacologia
Coagulação Sanguínea/efeitos dos fármacos
Hemorragia/tratamento farmacológico
Antagonistas de Heparina/farmacologia
[Mh] Termos MeSH secundário: Animais
Anticoagulantes/efeitos adversos
Hemorragia/induzido quimicamente
Heparina/efeitos adversos
Seres Humanos
Pulmão/efeitos dos fármacos
Camundongos
Poliaminas
Protaminas/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Antidotes); 0 (Heparin Antagonists); 0 (Polyamines); 0 (Protamines); 0 (polycations); 9005-49-6 (Heparin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161231
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2016-10-747915


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[PMID]:27915244
[Au] Autor:Nagao JI; Cho T; Mitarai M; Iohara K; Hayama K; Abe S; Tanaka Y
[Ad] Endereço:Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
[Ti] Título:Antifungal activity in vitro and in vivo of a salmon protamine peptide and its derived cyclic peptide against Candida albicans.
[So] Source:FEMS Yeast Res;17(1), 2017 Feb.
[Is] ISSN:1567-1364
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Protamine peptide (PP) derived from salmon is a 14-mer with 10 arginine residues. We investigated the in vitro and in vivo antifungal activity of PP against Candida albicans PP showed a concentration-dependent dual mode of action, with fungicidal activity and inhibitory activity for hyphal development in vitro. At lethal concentrations of PP, intracellular accumulation of PP was energy-dependent but independent of endocytosis, and resulted in ATP efflux and the generation of reactive oxygen species in the cells. PP at sublethal concentrations inhibited hyphal development in C. albicans by binding to the cell surface. Though antifungal activity of PP was inactivated by high concentrations of NaCl, the antifungal activity of the synthetic cyclic (via a disulfide bond) form of PP (cyclic PP) was not. Cyclic PP also showed the concentration-dependent dual mode of action, and had five-fold greater antifungal activity than PP. The advantage of antifungal activity of cyclic PP compared with PP in vitro resulted in a high in vivo efficacy in a murine oral candidiasis model. Oral treatment with cyclic PP inhibited hyphal development of C. albicans on mouse tongues and protected against the development of severe candidiasis. This study shows the therapeutic potential of cyclic PP as an antifungal peptide against C. albicans.
[Mh] Termos MeSH primário: Antifúngicos/metabolismo
Candida albicans/efeitos dos fármacos
Antagonistas de Heparina/metabolismo
Peptídeos Cíclicos/metabolismo
Protaminas/metabolismo
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Animais
Antifúngicos/uso terapêutico
Candida albicans/crescimento & desenvolvimento
Candida albicans/fisiologia
Candidíase Bucal/tratamento farmacológico
Modelos Animais de Doenças
Antagonistas de Heparina/uso terapêutico
Hifas/efeitos dos fármacos
Hifas/crescimento & desenvolvimento
Camundongos
Viabilidade Microbiana/efeitos dos fármacos
Peptídeos Cíclicos/uso terapêutico
Protaminas/uso terapêutico
Espécies Reativas de Oxigênio/metabolismo
Salmão
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Heparin Antagonists); 0 (Peptides, Cyclic); 0 (Protamines); 0 (Reactive Oxygen Species); 8L70Q75FXE (Adenosine Triphosphate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170802
[Lr] Data última revisão:
170802
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161205
[St] Status:MEDLINE


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[PMID]:27214037
[Au] Autor:Guevara C; Quijada A; Rosas C; Bulatova K; Lara H; Nieto E; Morales M
[Ad] Endereço:aFacultad de Medicina, Universidad de Chile, Santiago bFacultad de Medicina, Universidad de Valparaiso, Valparaiso cUnidad de Hematologia dUnidad de Cardiologia, Universidad de Chile, Santiago, Chile.
[Ti] Título:Acute ischemic stroke after cardiac catheterization: the protamine low-dose recombinant tissue plasminogen activator pathway.
[So] Source:Blood Coagul Fibrinolysis;28(3):261-263, 2017 Apr.
[Is] ISSN:1473-5733
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:: Intravenous thrombolysis is the preferred treatment for acute ischemic stroke; however, it remains unestablished in the area of cardiac catheterization. We report three patients with acute ischemic stroke after cardiac catheterization. After reversing the anticoagulant effect of unfractionated heparin with protamine, all of the patients were successfully off-label thrombolyzed with reduced doses of intravenous recombinant tissue plasminogen activator (0.6 mg/kg). This dose was preferred to reduce the risk of symptomatic cerebral or systemic bleeding. The sequential pathway of protamine recombinant tissue plasminogen activator at reduced doses may be safer for reducing intracranial or systemic bleeding events, whereas remaining efficacious for the treatment of acute ischemic stroke after cardiac catheterization.
[Mh] Termos MeSH primário: Cateterismo Cardíaco/efeitos adversos
Antagonistas de Heparina/uso terapêutico
Protaminas/uso terapêutico
Acidente Vascular Cerebral/etiologia
Terapia Trombolítica/métodos
Ativador de Plasminogênio Tecidual/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
Acidente Vascular Cerebral/tratamento farmacológico
Ativador de Plasminogênio Tecidual/administração & dosagem
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Heparin Antagonists); 0 (Protamines); EC 3.4.21.68 (Tissue Plasminogen Activator)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170427
[Lr] Data última revisão:
170427
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160524
[St] Status:MEDLINE
[do] DOI:10.1097/MBC.0000000000000569


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[PMID]:27871567
[Au] Autor:Freundlich RE; Duggal NM; Housey M; Tremper TT; Engoren MC; Kheterpal S
[Ad] Endereço:Department of Anesthesiology, Vanderbilt University Medical Center, 1211 21st Ave S, Suite 526, Nashville, TN 37212. Electronic address: Robert.e.freundlich@vanderbilt.edu.
[Ti] Título:Intraoperative medications associated with hemodynamically significant anaphylaxis.
[So] Source:J Clin Anesth;35:415-423, 2016 Dec.
[Is] ISSN:1873-4529
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:STUDY OBJECTIVE: To facilitate the identification of drugs and patient factors associated with hemodynamically significant anaphylaxis. DESIGN: Using an existing database containing complete perioperative records, instances of hemodynamically significant anaphylaxis were identified using a physiologic and treatment-based screening algorithm. All cases were manually reviewed by 2 clinicians, with a third adjudicating disagreements, and confirmed cases were matched 3:1 with control cases. Intraoperative medications given in instances of hemodynamically significant anaphylaxis and patient risk factors were compared with control cases. SETTING: University of Michigan Hospital, a large, tertiary care hospital. PATIENTS: All adult patients undergoing surgery between January 1, 2004, and January 5, 2015. INTERVENTIONS: None. MEASUREMENTS: Incidence of hemodynamically significant anaphylaxis during anesthesia. Patient risk factors and intraoperative medications associated with hemodynamically significant anaphylaxis. MAIN RESULTS: Hemodynamically significant anaphylaxis occurred in 55 of 461 986 cases (1 in 8400). Hemodynamically significant anaphylaxis occurred in 52 patients, with 1 patient experiencing 3 instances and another patient 2 instances. Only 1 drug was associated with an increased risk of hemodynamically significant anaphylaxis: protamine (odds ratio, 11.78; 95% confidence interval, 1.40-99.26; P=.0233). No category of drugs was associated with increased risk. Of patient risk factors, only personal history of anaphylaxis was associated with an increased risk (odds ratio, 77.1; 95% confidence interval, 10.46-567.69; P=<.0001). Postoperative follow-up and evaluation of patients were low at our institution. A serum tryptase level was sent in only 49% of cases, and 41% of levels were positive, an overall positive rate of 20% of cases. Following instances of hemodynamically significant anaphylaxis, only 29% of patients were seen and evaluated by an allergist at our institution. CONCLUSIONS: Hemodynamically significant anaphylaxis is a rare complication of anesthesia, with an incidence consistent with the existing literature. Contrary to most existing literature, only protamine was associated with increased risk. A personal history of anaphylaxis appears to best predict risk of hemodynamically significant anaphylaxis.
[Mh] Termos MeSH primário: Anafilaxia/induzido quimicamente
Antagonistas de Heparina/efeitos adversos
Cuidados Intraoperatórios/efeitos adversos
Protaminas/efeitos adversos
[Mh] Termos MeSH secundário: Bases de Dados Factuais
Feminino
Hemodinâmica/efeitos dos fármacos
Seres Humanos
Incidência
Masculino
Meia-Idade
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Heparin Antagonists); 0 (Protamines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170901
[Lr] Data última revisão:
170901
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161123
[St] Status:MEDLINE


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[PMID]:27555185
[Au] Autor:Botros MM; Mahmoud MA; Costandi AJ
[Ad] Endereço:University of Toledo College of Medicine, Toledo, OH, USA.
[Ti] Título:Reliable low-molecular-weight heparin reversal in a child undergoing emergency surgery: a case report.
[So] Source:J Clin Anesth;33:317-9, 2016 Sep.
[Is] ISSN:1873-4529
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Low-molecular-weight heparin neutralization using protamine alone can be unreliable, especially in cases of immediate reversal for emergency surgery. Here, we describe a unique case of a 17-month-old girl with a history of glioneuronal tumor and corresponding hydrocephalus status post debulking and ventriculoperitoneal shunt placement, who was placed on enoxaparin after the development of a sagittal sinus thrombosis. Patient presented for emergency craniectomy and evacuation of subdural bleed after a fall while on therapeutic dose of enoxaparin. Protamine and fresh frozen plasma were used in the patient's perioperative course providing a reliable reversal of enoxaparin.
[Mh] Termos MeSH primário: Craniectomia Descompressiva/métodos
Enoxaparina/antagonistas & inibidores
Antagonistas de Heparina/uso terapêutico
Heparina de Baixo Peso Molecular/antagonistas & inibidores
[Mh] Termos MeSH secundário: Anticoagulantes/uso terapêutico
Perda Sanguínea Cirúrgica
Neoplasias Encefálicas/complicações
Neoplasias Encefálicas/cirurgia
Serviços Médicos de Emergência
Enoxaparina/uso terapêutico
Feminino
Heparina de Baixo Peso Molecular/uso terapêutico
Seres Humanos
Lactente
Derivação Ventriculoperitoneal
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Enoxaparin); 0 (Heparin Antagonists); 0 (Heparin, Low-Molecular-Weight)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170310
[Lr] Data última revisão:
170310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160825
[St] Status:MEDLINE


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[PMID]:27536976
[Au] Autor:Bandara MK; Masoudi S; Zhu H; Bandara R; Willcox MD
[Ad] Endereço:*PhD †BSc ‡PhD, FAAO Brien Holden Vision Institute (MKB, SM, HZ, RB), and School of Optometry and Vision Science (SM, HZ, RB, MDPW), University of New South Wales, Sydney, New South Wales, Australia.
[Ti] Título:Evaluation of Protamine as a Disinfectant for Contact Lenses.
[So] Source:Optom Vis Sci;93(11):1349-1355, 2016 Nov.
[Is] ISSN:1538-9235
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To investigate the ability of protamine, alone or in combination with other antimicrobial agents, to kill bacteria and fungi associated with contact lens-related keratitis. METHODS: The International Organization for Standardization 14729:2001 procedure was used to test the antimicrobial activity of solutions of protamine (23-228 µM) with and without polyhexamethylene biguanide (PHMB) and ethylenediamine tetra-acetic acid (EDTA). The recommended ISO panel of microbes along with six clinical isolates was tested. The effect of increasing sodium chloride concentration on the antimicrobial activity was also assessed. The cytotoxicity of the final protamine/EDTA/PHMB solution was measured using ISO 10993-5 standard assays. RESULTS: Protamine gave a dose-dependent antimicrobial effect, with the highest effect for most strains being at 228 µM (≥6 log reductions of viable bacteria and ≥1 log reduction of viable fungi). Addition of EDTA and PHMB increased the antimicrobial effect for all strains except Pseudomonas aeruginosa ATCC6538, which had optimum activity (≥6 log inhibition) even in protamine alone. The optimum antimicrobial activity of all microbes was achieved in 0.2% sodium chloride, but even in 0.8% sodium chloride, the activity met or exceeded the ISO standard (>3 log reductions for bacteria and >1 log reduction for fungi). None of the formulations was cytotoxic to mammalian cells. CONCLUSIONS: This study highlights the potential for protamine to be used for the development of effective multipurpose disinfection solutions. Further investigations such as stability, compatibility with contact lenses, and in vivo toxicity are warranted.
[Mh] Termos MeSH primário: Anti-Infecciosos/farmacologia
Bactérias/efeitos dos fármacos
Lentes de Contato/microbiologia
Desinfetantes/farmacologia
Fungos/efeitos dos fármacos
Protaminas/farmacologia
[Mh] Termos MeSH secundário: Bactérias/isolamento & purificação
Biguanidas/farmacologia
Contagem de Colônia Microbiana
Soluções para Lentes de Contato/farmacologia
Desinfecção/métodos
Combinação de Medicamentos
Fungos/isolamento & purificação
Antagonistas de Heparina/farmacologia
Seres Humanos
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Biguanides); 0 (Contact Lens Solutions); 0 (Disinfectants); 0 (Drug Combinations); 0 (Heparin Antagonists); 0 (Protamines); 322U039GMF (polihexanide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE


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[PMID]:27493093
[Au] Autor:Meesters MI; Veerhoek D; de Jong JR; Boer C
[Ad] Endereço:Departments of Anesthesiology.
[Ti] Título:A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass.
[So] Source:J Cardiothorac Vasc Anesth;30(5):1190-5, 2016 Oct.
[Is] ISSN:1532-8422
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: This study investigated postoperative hemostasis of patients subjected to conventional protamine dosing compared with protamine dosing based on a pharmacokinetic (PK) model following cardiopulmonary bypass. DESIGN: Retrospective case-control study. SETTING: Tertiary university hospital. PARTICIPANTS: Patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: In 56 patients, protamine was dosed in a fixed ratio (CD), while 62 patients received protamine based on the PK model. MEASUREMENTS AND MAIN RESULTS: There was no difference in heparin administration (414±107 mg (CD) v 403±90 mg (PK); p = 0.54), whereas protamine dosing was considerably different with a protamine-to-heparin dosing ratio of 1.1±0.3 for the CD group and 0.5±0.1 for the PK group (p<0.001). The changes in activated coagulation time (ΔACT) values (ACT after protamine minus preoperative ACT;+17±77 s v+6±15 s; p = 0.31) were equal between groups. Yet, the thromboelastometric intrinsically activated coagulation test clotting time (CT; 250±76 s v 203±44 s; p<0.001) and intrinsically activated coagulation test without the heparin effect CT (275±105 v 198±32 s; p<0.001) were prolonged in the CD group. Median packed red blood cell transfusion (0 [0-2] v 0 [0-0]), fresh frozen plasma transfusion (1 [0-2] v 0 [0-0]), and platelet concentrate transfusion (0 [0-1] v 0 [0-0]) were different between the fixed ratio and PK group, respectively (all p<0.001). CONCLUSIONS: This study showed that patient-tailored protamine dosing based on a PK model was associated with a reduction in protamine dosing, with better hemostatic test results when compared with fixed-ratio protamine dosing.
[Mh] Termos MeSH primário: Procedimentos Cirúrgicos Cardíacos
Antagonistas de Heparina/farmacocinética
Cuidados Pós-Operatórios/métodos
Protaminas/farmacocinética
[Mh] Termos MeSH secundário: Idoso
Coagulação Sanguínea/efeitos dos fármacos
Testes de Coagulação Sanguínea/estatística & dados numéricos
Estudos de Casos e Controles
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Masculino
Estudos Retrospectivos
Tromboelastografia/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Heparin Antagonists); 0 (Protamines)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160806
[St] Status:MEDLINE


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[PMID]:27461795
[Au] Autor:Willems A; Savan V; Faraoni D; De Ville A; Rozen L; Demulder A; Van der Linden P
[Ad] Endereço:Pediatric Intensive Care Unit, Department of Pediatrics, Queen Fabiola University Children's Hospital, Brussels, Belgium. Electronic address: ariane.willems@huderf.be.
[Ti] Título:Heparin Reversal After Cardiopulmonary Bypass: Are Point-of-Care Coagulation Tests Interchangeable?
[So] Source:J Cardiothorac Vasc Anesth;30(5):1184-9, 2016 Oct.
[Is] ISSN:1532-8422
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Protamine is used to neutralize heparin after patient separation from cardiopulmonary bypass (CPB). Different bedside tests are used to monitor the adequacy of heparin neutralization. For this study, the interchangeability of the activated coagulation time (ACT) and thromboelastometry (ROTEM; Tem Innovations GmbH, Basel, Switzerland) clotting time (CT) ratios in children undergoing cardiac surgery was assessed. DESIGN: Single-center, retrospective, cohort study between September 2010 and January 2012. SETTING: University children's hospital. PARTICIPANTS: The study comprised children 0 to 16 years old undergoing elective cardiac surgery with CPB. Exclusion criteria were preoperative coagulopathy, Jehovah's witnesses, and children in a moribund condition (American Society of Anesthesiologists score 5). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After heparin neutralization with protamine, the ratio between ACT, with and without heparinase, and the CT measured with INTEM/HEPTEM (intrinsic test activated with ellagic acid was performed without heparinase [INTEM] and with heparinase [HEPTEM]) using tests of ROTEM were calculated. Agreement was evaluated using Cohen's kappa statistics, Passing-Bablok regression, and Bland-Altman analysis. Among the 173 patients included for analysis, agreement between both tests showed a Cohen's kappa statistic of 0.06 (95% CI: -0.02 to 0.14; p = 0.22). Bland-Altman analysis showed a bias of 0.01, with a standard deviation of 0.13, and limits of agreement between -0.24 and 0.26. Passing-Bablok regression showed a systematic difference of 0.40 (95% CI: 0.16-0.59) and a proportional difference of 0.61 (95% CI: 0.42-0.86). The residual standard deviation was 0.11 (95% CI: -0.22 to 0.22), and the test for linearity showed p = 0.10. CONCLUSION: ACT, with or without heparinase, and the INTEM/HEPTEM CT ratios are not interchangeable to evaluate heparin reversal after pediatric patient separation from CPB. Therefore, the results of these tests should be corroborated with the absence/presence of bleeding and integrated into center-specific treatment algorithms.
[Mh] Termos MeSH primário: Coagulação Sanguínea/efeitos dos fármacos
Ponte Cardiopulmonar
Antagonistas de Heparina/uso terapêutico
Sistemas Automatizados de Assistência Junto ao Leito
Cuidados Pós-Operatórios/métodos
[Mh] Termos MeSH secundário: Adolescente
Testes de Coagulação Sanguínea/métodos
Criança
Pré-Escolar
Heparina Liase/uso terapêutico
Seres Humanos
Lactente
Masculino
Protaminas/uso terapêutico
Estudos Retrospectivos
Tromboelastografia/efeitos dos fármacos
Tempo de Coagulação do Sangue Total
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Heparin Antagonists); 0 (Protamines); EC 4.2.2.7 (Heparin Lyase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160728
[St] Status:MEDLINE


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[PMID]:27389942
[Au] Autor:Kakisis JD; Antonopoulos CN; Moulakakis KG; Schneider F; Geroulakos G; Ricco JB
[Ad] Endereço:Department of Vascular Surgery, "Attikon" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: kakisis@med.uoa.gr.
[Ti] Título:Protamine Reduces Bleeding Complications without Increasing the Risk of Stroke after Carotid Endarterectomy: A Meta-analysis.
[So] Source:Eur J Vasc Endovasc Surg;52(3):296-307, 2016 Sep.
[Is] ISSN:1532-2165
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The aim was to evaluate the safety and efficacy of heparin reversal with protamine after completion of carotid endarterectomy (CEA), summarising the available data from both randomised and non-randomised studies. METHODS: The study was a meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated for the outcomes of stroke and wound haematoma among patients receiving or not receiving protamine after CEA. Meta-regression analysis was performed to examine whether the documented differences were modified by potentially meaningful patient related or procedure related predictors, namely publication year, general anesthesia used, number of patients treated, mean age (years), males, neurological symptoms, use of patch, and use of shunt. RESULTS: Seven studies were included in the meta-analysis reporting on 3,817 patients receiving protamine after CEA and 6,070 patients not receiving protamine for heparin reversal. Only one study was randomised. A statistically significant reduction in wound haematoma requiring re-operation was recorded after heparin reversal with protamine in patients undergoing CEA (OR, 0.42, 95% CI, 0.22-0.80, p = .008). In contrast, no significant difference was observed in stroke rates between groups of patients that received and did not receive protamine (OR, 0.71, 95% CI, 0.49-1.03, p = .07). Meta-regression analysis did not reveal any significant effect mediated by the modifiers examined. CONCLUSION: On the basis of the available data, heparin reversal with protamine seems to reduce the risk of wound haematoma, without increasing the risk of procedural stroke. However, taking into account the limitations of the analysis, further studies are needed to increase the level of evidence provided by the current meta-analysis.
[Mh] Termos MeSH primário: Endarterectomia das Carótidas/métodos
Antagonistas de Heparina/uso terapêutico
Hemorragia Pós-Operatória/prevenção & controle
Protaminas/uso terapêutico
Acidente Vascular Cerebral/induzido quimicamente
[Mh] Termos MeSH secundário: Endarterectomia das Carótidas/efeitos adversos
Seres Humanos
Acidente Vascular Cerebral/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Heparin Antagonists); 0 (Protamines)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE


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[PMID]:27223896
[Au] Autor:Sokolowska E; Kalaska B; Miklosz J; Mogielnicki A
[Ad] Endereço:a Department of Pharmacodynamics , Medical University of Bialystok , Bialystok , Poland.
[Ti] Título:The toxicology of heparin reversal with protamine: past, present and future.
[So] Source:Expert Opin Drug Metab Toxicol;12(8):897-909, 2016 Aug.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Unfractionated heparin is a strongly anionic anticoagulant used extensively in medicine to prevent blood clotting. In the case of an emergency bleeding in response to heparin, the protamine sulfate is administered. Despite its extensive clinical use, protamine may produce life-threatening side effects such as systemic hypotension, catastrophic pulmonary vasoconstriction or allergic reactions. Recent studies have demonstrated new organ-specific complications of the heparin reversal with protamine. AREAS COVERED: Past and present knowledge of the mechanisms responsible for the toxicity of protamine and the most promising potential replacements of protamine in the different phases of development. EXPERT OPINION: Despite of the low therapeutic index, protamine is the only registered antidote of heparins. The toxicology of protamine depends on a complex interaction of the high molecular weight, a cationic peptide with the surfaces of the vasculature and blood cells. The mechanisms involve membrane receptors and ion channels targeted by different vasoactive compounds, such as nitric oxide, bradykinin or histamine. Unacceptable side effects of protamine have led to a search for new alternatives: UHRA, LMWP, and Dex40-GTMAC3 are in the preclinical stage; the two other agents (andexanet alfa and PER977) are already in the advanced clinical phases.
[Mh] Termos MeSH primário: Antagonistas de Heparina/efeitos adversos
Heparina/efeitos adversos
Protaminas/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Anticoagulantes/efeitos adversos
Antídotos/efeitos adversos
Antídotos/uso terapêutico
Desenho de Drogas
Hemorragia/induzido quimicamente
Hemorragia/tratamento farmacológico
Antagonistas de Heparina/uso terapêutico
Seres Humanos
Protaminas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Antidotes); 0 (Heparin Antagonists); 0 (Protamines); 9005-49-6 (Heparin)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170130
[Lr] Data última revisão:
170130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160526
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2016.1194395



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