Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.857
Filtrar
1.
Int J Radiat Biol ; 96(1): 155-166, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31216213

RESUMO

Purpose: Evaluation of the pharmacodynamics (PD) and pharmacokinetics (PK) of romiplostim alone and in combination with pegfilgrastim in a non-human primate (NHP) model of acute radiation syndrome (ARS).Materials and methods: Male and female rhesus macaques were subjected to Cobalt-60 γ irradiation, at a dose of 550 cGy 24 h prior to subcutaneous administration of either romiplostim alone as a single (2.5 or 5.0 mg/kg on Day 1) or repeat dose (5.0 mg/kg on Days 1 and 8), pegfilgrastim alone as a repeat dose (0.3 µg/kg on Day 1 and 8), or a combination of both agents (romiplostim 5.0 mg/kg on Day 1; pegfilgrastim 0.3 µg/kg on Days 1 and 8). Clinical outcome, hematological parameters and PK were assessed throughout the 45 d study period post-irradiation.Results: Administration of romiplostim, pegfilgrastim or the combination of both resulted in significant improvements in hematological parameters, notably prevention of severe thrombocytopenia, compared with irradiated, vehicle control-treated NHPs. The largest hematologic benefit was observed when romiplostim and pegfilgrastim were administered as a combination therapy with much greater effects on both platelet and neutrophil recovery following irradiation compared to single agents alone.Conclusions: These results indicate that romiplostim alone or in combination with pegfilgrastim is effective at improving hematological parameters in an NHP model of ARS. This study supports further study of romiplostim as a medical countermeasure to improve primary hemostasis and survival in ARS.


Assuntos
Filgrastim/farmacologia , Neutropenia/tratamento farmacológico , Polietilenoglicóis/farmacologia , Lesões Experimentais por Radiação/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacologia , Trombocitopenia/tratamento farmacológico , Trombopoetina/farmacologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/efeitos da radiação , Relação Dose-Resposta a Droga , Interações de Medicamentos , Feminino , Macaca mulatta , Masculino , Neutropenia/sangue , Neutropenia/metabolismo , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/metabolismo , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/farmacocinética , Proteínas Recombinantes de Fusão/uso terapêutico , Trombocitopenia/sangue , Trombocitopenia/metabolismo , Trombopoetina/farmacocinética , Trombopoetina/uso terapêutico , Fatores de Tempo
2.
J Agric Food Chem ; 68(1): 176-184, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31850760

RESUMO

Thrombin can be used as a target for its inhibitors to prevent blood coagulation. A novel peptide (TKLTEEEKNR, PfCN) identified from αS2-casein (fragments 211-220) with high anticoagulant activity was screened and prepared. The activated partial thromboplastin time, prothrombin time, and thrombin time, at the concentration of 4 mM, prolonged about 19, 2.5 and 5.5 s, respectively. At the same concentration, the fibrinogen clotting time prolonged from 25.5 ± 0.7 to 38.3 ± 1.3 s. The thrombin inhibitory efficiency in vitro (IC50 value of 29.27 mM) and antithrombosis effect in vivo were determined. The secondary structure of thrombin, which was influenced by PfCN, indicates that PfCN can bind to thrombin. Isothermal titration calorimetry and the chromogenic substrate test showed that PfCN belongs to the bivalent thrombin inhibitor like bivalirudin. Although the effect was not as good as bivalirudin, in the animal experiment, bleeding occurred in the bivalirudin group but not in the PfCN group. Moreover, molecular docking illustrates the mechanism for the antithrombin activity of PfCN. These results indicated that PfCN could be used as an effective thrombin inhibitor with broad potential for the prevention of thrombotic acute pulmonary embolism and other thrombotic events.


Assuntos
Anticoagulantes/química , Peptídeos/química , Trombina/química , Animais , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Domínio Catalítico , Bovinos , Humanos , Cinética , Simulação de Acoplamento Molecular , Tempo de Tromboplastina Parcial , Peptídeos/farmacologia , Tempo de Protrombina
3.
Artigo em Russo | MEDLINE | ID: mdl-31793543

RESUMO

AIM: To detect plasma procoagulant activity in patients with schizophrenia at admission to the hospital in a state of exacerbation before (point 1) and after (point 2) pharmacotherapy and evaluate plasma and platelet hemostasis abnormalities. MATERIAL AND METHODS: The study included 80 women, aged from 16 to 57 years, median age 28 years, with schizophrenia with continuous, paroxysmal-progressive or paroxysmal course (F20.00, F20.01, F20.02 according to ICD-10). In 42 of 80 patients, depressive disorders in the structure of schizophrenia were observed. The thrombodynamic test (TD) was performed on T-2 Trombodynamis device according to the manufacturer's instructions (Hemacore LLC, Moscow, Russia). Blood for the TD test was taken in admission to the hospital (point 1) and on discharge (point 2). All patients received standard pharmacotherapy according to their condition. RESULTS: For the first time, it was established that in the whole group of patients (n=46) thrombodynamic indicators of the rate of growth of the clot: initial velocity (Vin), stationary velocity (Vst) and adjusted for spontaneous clots velocity (V) and the amount of clot for 30 minutes test TD (ClotSize, CS) were significantly higher compared to normal values. The mean time of occurrence of spontaneous thrombosis (Tsp) was significantly less than 30 min (p<0.0001), indicating rapid, spontaneous thrombosis. Other parameters of TD did not differ significantly from the norm. As a result of treatment, the initial growth rate of the clot from the activator (Vi) decreased from 58,5 µm/min to 54,5 µm/min; V speed from 37,4 µm/min to 33,5 µm/min; CS clot size from 1249 µm to 1219 µm; clot density - from 24 874 units up to 23 658 units. All these changes are significant. Such dynamics of plasma hemostasis clearly indicates a significant decrease in the coagulation activity of the blood plasma of patients as a result of treatment. An increase in the time of appearance of spontaneous clots after treatment (from 23.5 minutes to 30.5 minutes) indicates a decrease in the procoagulant activity of platelet microparticles after treatment, i.e. the reduction of platelet activation as a result of treatment. CONCLUSION: Our studies have shown for the first time that treatment of patients with antidepressants and antipsychotics reduces the generation of spontaneous clots. The treatment of patients with schizophrenia is accompanied by a decrease in the activity of plasma and platelet hemostasis. This is of great practical importance, since hypercoagulation of spontaneous clots in schizophrenic patients aggravates their chronic inflammatory disorders and affects their resistance to treatment.


Assuntos
Transtornos da Coagulação Sanguínea , Coagulação Sanguínea , Esquizofrenia , Adolescente , Adulto , Antipsicóticos/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Transtornos da Coagulação Sanguínea/induzido quimicamente , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Feminino , Hemostasia , Humanos , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico , Adulto Jovem
4.
Transplant Proc ; 51(9): 2986-2990, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31711580

RESUMO

Left ventricular assist device (LVAD) management is very challenging since many adverse events can occur in ongoing patients. Inadequate anticoagulation treatment can lead to life-threatening situations like ischemic stroke or pump thrombosis. The main intention of our study was to investigate if early identification of aspirin nonresponders by using aggregometry can improve anticoagulation management, reducing the risk of pump thrombosis. METHODS: From December 2010 to May 2018, 24 patients were implanted with a HeartMate II (HMII), 6 received a HeartWare HVAD system--full support VAD (HVAD), and 22 received a HeartMate III (HMIII). All patients were maintained with a target INR of 2.0 to 3.0. When the aggregometry test revealed a normal platelet function, 100 mg of aspirin were initiated. Only aspirin nonresponders were early identified by repeating the aggregometry after 7 days of aspirin administration. In acetylsalicylic acid nonresponder patients, 75 mg of clopidogrel was used, and the patients were tested again. Ticlopidine (250 mg) was used when clopidogrel was unsuccessful. RESULTS: Four patients required modification in antiplatelet therapy. Three patients (5%), 2 HVAD and 1 HMII, suffered from pump thrombosis. One patient died as a consequence of a large intracranial hemorrhagic event following thrombolytic treatment. One patient required a pump exchange; in 1 patient, thrombolytic infusion was conducted successfully. CONCLUSION: Reported rates of pump thrombosis at 12 months for patients implanted with commonly used LVADs were 6% to 12% for axial-flow pumps and 8% with centrifugal-flow devices. In our series, the reported 5% overall incidence of pump thrombosis encourages the routine use of an aggregometry test for early identification of aspirin nonresponders.


Assuntos
Aspirina/uso terapêutico , Testes de Coagulação Sanguínea/métodos , Coração Auxiliar/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Trombose/etiologia , Trombose/prevenção & controle , Coagulação Sanguínea/efeitos dos fármacos , Resistência a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Trombose/epidemiologia
6.
Biochem Med (Zagreb) ; 29(3): 030706, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31624459

RESUMO

Introduction: Failure to obtain complete blood clotting in serum is a common laboratory problem. Our aim was to determine whether snake proth-rombin activators are effective in clotting blood and producing quality serum for analyte measurement in anticoagulated patients. Materials and methods: Whole blood clotting was studied in a total of 64 blood samples (41 controls, 20 Warfarin patients, 3 anticoagulated patients using snake venom prothrombin activator (OsPA)) with plain tubes. Coagulation was analysed using a visual assay, Hyland-Clotek and thromboelastography. Healthy control blood was spiked with a range of anticoagulants to determine the effectiveness of OsPa-induced clotting. A paired analysis of a Dabigatran patient and a control investigated the effectiveness of the OsPA clotting tubes. Biochemical analytes (N = 31) were determined for 7 samples on chemistry and immunoassay analysers and compared with commercial tubes. Results: Snake venom prothrombin activators efficiently coagulated blood and plasma spiked with heparin and commonly used anticoagulants. Clotting was observed in the presence of anticoagulants whereas no clotting was observed in BDRST tubes containing 3 U/mL of heparin. Snake venom prothrombin activator enhanced heparinised blood clotting by shortening substantially the clotting time and improving significantly the strength of the clot. Comparison of 31 analytes from the blood of five healthy and two anticoagulated participants gave very good agreement between the analyte concentrations determined. Conclusions: Our results showed that the snake venom prothrombin activators OsPA and PtPA efficiently coagulated recalcified and fresh bloods with or without added anticoagulants. These procoagulants produced high quality serum for accurate analyte measurement.


Assuntos
Anticoagulantes/farmacologia , Protrombina/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Heparina/farmacologia , Humanos
7.
An Acad Bras Cienc ; 91(3): e20180746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576915

RESUMO

The use of ulinastatin for pancreatitis and sepsis have been described. This study was designed to evaluate the effect of ulinastatin on vascular endothelial cell damage and coagulation in pregnant women with severe pre-eclampsia (PE).From October 2015 to November 2017 at Tianjin Central Hospital of gynecology and obstetrics in China. Eighty pregnant women with severe PE, who elected to deliver by cesarean section, were randomly assigned to a control group or an ulinastatin group. The plasma concentration of von Willebrand factor (vWF) and platelet granule membrane protein (GMP-140), platelet count, fibrinogen levels, prothrombin time (PT), and partial prothrombin activation time (APTT) were recorded before combined spinal-epidural anesthesia and 40 min after administration in both groups.Ulinastatin attenuates vascular endothelial cell damage in pregnant women with PE as indicated by decreased plasma concentrations of vWF and prolonged APTT.


Assuntos
Células Endoteliais/efeitos dos fármacos , Glicoproteínas/farmacologia , Pré-Eclâmpsia/tratamento farmacológico , Inibidores da Tripsina/farmacologia , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Cesárea/efeitos adversos , Feminino , Fibrinogênio/análise , Glicoproteínas/uso terapêutico , Humanos , Selectina-P/sangue , Contagem de Plaquetas , Pré-Eclâmpsia/sangue , Gravidez , Tempo de Protrombina , Valores de Referência , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Inibidores da Tripsina/uso terapêutico , Adulto Jovem , Fator de von Willebrand/análise
8.
Mater Sci Eng C Mater Biol Appl ; 104: 109930, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500069

RESUMO

An injectable hydrogel dressing with multifunctional properties of superior hemostasis, antibacterial activity, tissue adhesive and cytocompatibility is desirable candidate in wound healing. In this study, we developed a novel hydrogel dressing composed of hydrophobically modified chitosan (hmCS) and oxidized dextran (OD). The gelation time, microstructure, injectability, self-healing and rheological properties were characterized. The in vitro ability of the precursor solution of the hydrogels to coagulate heparinized whole blood was confirmed. The in vivo hemostatic activity was demonstrated in a rat hemorrhaging liver model. The antibacterial activity against S. aureus and P. aeruginosa was evaluated in vitro through surface antibacterial test. The corresponding killing efficiencies were up to 95.0% and 96.4% at bacterial concentration of 108 CFU/mL. The cytotoxicity was examined by co-culturing with 3 T3 fibroblast cells. The wound healing functions were further verified with an infected wound model of rat skin. The aforementioned findings demonstrated that the hydrogel with multifunctional activities has potential for hemorrhagic and infected wound healing.


Assuntos
Quitosana/farmacologia , Dextranos/farmacologia , Hidrogéis/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Injeções , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quitosana/química , Hemostasia/efeitos dos fármacos , Hidrogéis/química , Masculino , Camundongos , Células NIH 3T3 , Oxirredução , Espectroscopia de Prótons por Ressonância Magnética , Pseudomonas aeruginosa/efeitos dos fármacos , Ratos Sprague-Dawley , Reologia , Staphylococcus aureus/efeitos dos fármacos , Adesivos Teciduais/farmacologia
9.
Toxicol Lett ; 316: 35-48, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31509773

RESUMO

Snake envenomation globally is attributed to an ever-increasing human population encroaching into snake territories. Responsible for many bites in Asia is the widespread genus Trimeresurus. While bites lead to haemorrhage, only a few species have had their venoms examined in detail. We found that Trimeresurus venom causes haemorrhaging by cleaving fibrinogen in a pseudo-procoagulation manner to produce weak, unstable, short-lived fibrin clots ultimately resulting in an overall anticoagulant effect due to fibrinogen depletion. The monovalent antivenom 'Thai Red Cross Green Pit Viper antivenin', varied in efficacy ranging from excellent neutralisation of T. albolabris venom through to T. gumprechti and T. mcgregori being poorly neutralised and T. hageni being unrecognised by the antivenom. While the results showing excellent neutralisation of some non-T. albolabris venoms (such as T. flavomaculaturs, T. fucatus, and T. macrops) needs to be confirmed with in vivo tests, conversely the antivenom failure T. hageni, and the very poor results against T. gumprechti and T. mcgregori, despite being conducted in the ideal scenario of preincubation of antivenom:venom, indicates that the likelihood of clinically relevant cross-reactivity for these species is low (T. gumprechti and T. mcgregori) to non-existent (T. hageni). These same latter three species were also not inhibited by the serine protease inhibitor AEBSF, suggesting that the toxins leading to a coagulotoxic effect in these species are non-serine proteases while in contrast T. albolabris coagulotoxicity was completely impeded by AEBSF, and thus driven by kallikrein-type serine proteases. There was a conspicuous lack of phylogenetic pattern in venom variation, with the most potent venoms (T. albolabris and T. hageni) being distant to each other on the organismal tree, and with the three most divergent and poorly neutralised venoms (T. gumprechti, T. hageni, and T. mcgregori) were also not each others closest relatives. This reinforces the paradigm that the fundamental dynamic evolution of venom results in organismal phylogeny being a poor predictor of venom potency or antivenom efficacy. This study provides a robust investigation on the differential venom effects from a wide range of Trimeresurus species on coagulation, highlighting differential fibrinogenolytic effects, while also investigating the relative antivenom neutralisation capabilities of the widely available Thai Red Cross Green Pit Viper antivenom. These results therefore have immediate, real-world implications for patients envenomed by Trimeresurus species.


Assuntos
Antídotos/farmacologia , Antivenenos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Venenos de Crotalídeos/antagonistas & inibidores , Hemorragia/tratamento farmacológico , Mordeduras de Serpentes/tratamento farmacológico , Trimeresurus , Animais , Testes de Coagulação Sanguínea , Reações Cruzadas , Venenos de Crotalídeos/classificação , Venenos de Crotalídeos/imunologia , Venenos de Crotalídeos/metabolismo , Fibrinólise/efeitos dos fármacos , Hemorragia/sangue , Hemorragia/imunologia , Filogenia , Mordeduras de Serpentes/sangue , Mordeduras de Serpentes/imunologia , Trimeresurus/classificação
10.
Mater Sci Eng C Mater Biol Appl ; 104: 109896, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499977

RESUMO

Zinc alloys have been explored as potential materials for biodegradable vascular stents due to their tolerable corrosion rates and tunable mechanical properties. However, the performances of Zn alloys were not supported with enough toxicity or biological compatibility evaluation, particularly hemocompatibility for vascular scaffolding application. In this work, the hemocompatibility of three zinc alloys (Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li) was evaluated with 316 L stainless steel and pure zinc as controls. The hemolysis ratios of 316 L stainless steel, pure Zn, Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li were 0.38 ±â€¯0.08%, 1.04 ±â€¯0.21%, 0.47 ±â€¯0.21%, 0.57 ±â€¯0.14% and 0.52 ±â€¯0.22%, respectively, for direct contact method. Platelets aggregation on the 316 L stainless steel was observed, while the adhered platelets on the Zn alloys exhibited round shape with few pseudopodia spreading. The number of adhered platelets on the three zinc alloys (Zn-0.8Cu, Zn-0.8Mn and Zn-0.8Li) had no statistically difference compared with 316 L stainless steel, while significant fewer than the pure Zn group. None remarkable platelet activation, hematocyte aggregation, coagulation or complement activation was observed in any Zn alloy group. Furthermore, the Zn alloys prolonged prothrombin time and partial thromboplastin time, demonstrating a potential function of anticoagulation. The results demonstrated that Zn alloys presented in this work are indeed meeting the hemocompatible requirements of implant and showing the promise for perspective application as biodegradable stent.


Assuntos
Ligas/química , Materiais Biocompatíveis/química , Lítio/química , Magnésio/química , Zinco/química , Implantes Absorvíveis , Ligas/administração & dosagem , Materiais Biocompatíveis/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Ativação do Complemento/efeitos dos fármacos , Corrosão , Hemólise/efeitos dos fármacos , Humanos , Lítio/administração & dosagem , Teste de Materiais/métodos , Ativação Plaquetária/efeitos dos fármacos , Aço Inoxidável/química , Stents , Zinco/administração & dosagem
11.
Molecules ; 24(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480278

RESUMO

The physicochemical properties and potential hemostatic application of Wenchang kaolin and Maoming kaolin were inspected and evaluated. Chemical composition analysis, Fourier transform infrared (FTIR) spectroscopy, surface area determination, X-ray diffraction, particle size, scanning electron microscopy (SEM) observations, and zeta potential analysis were performed to quantify the physical and chemical properties of the two kaolins. The results showed that both kaolins have typical FTIR bands of kaolinite with a weight fraction for kaolinite over 90 wt%. Larger conglobate aggregates of Maoming kaolin demonstrated wider particle size distributions with two peaks at 3.17 and 35.57 µm, while the book-like Wenchang kaolin had narrow particle size distribution, with a frequent size of 5.64 µm. Furthermore, thrombelastography, the whole blood clotting tests (WBCT), plasma recalcification time (PRT) measurement, and MTT assay were performed to measure the clotting activities and biocompatibility of the two kaolins. The results showed that both kaolins could promote blood coagulation with good cytocompatibility, while Wenchang kaolin had a better procoagulant activity than Maoming kaolin. These findings demonstrated Wenchang kaolin to be a more suitable local source material for application as a hemostatic agent.


Assuntos
Hemostáticos/farmacologia , Caulim/farmacologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , China , Cães , Concentração de Íons de Hidrogênio , Caulim/química , Camundongos , Tamanho da Partícula , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Tromboelastografia , Difração de Raios X
12.
BMC Complement Altern Med ; 19(1): 236, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481052

RESUMO

BACKGROUND: Syzygium cumini (L.) Skeels. is one of the very popular traditionally used medicinal plants with numerous pharmacological activities including antioxidant, hypoglycemic and anti-inflammatory. However, actions of S. cumini on blood coagulation and other parameters of blood were poorly pharmacologically studied. Therefore, aim of this present investigation is to examine the effects of methanolic extract of S. cumini on blood coagulation and anticoagulation factors in healthy white albino rabbits at different doses. METHODS: Blood samples were drawn twice during this study and biochemical assays were performed to determine the effect on different parameters such as coagulation, anticoagulation, hematological, Protein C (PC) and thrombin antithrombin (TAT) complex and platelet aggregation. RESULTS: The results showed significant increase in RBCs, hemoglobin, hematocrit and platelets counts up to 1.4 × 103/cm, 2.2 g/dl, 6%, 248.2 × 103/cm respectively. While, thrombin and bleeding time were also prolonged in dose dependent manner which is highly significant (p ≤ 0.005) as compared to control. Similarly, highly significantly increased (p ≤ 0.005) in levels of protein C, thrombin antithrombin complex at dose of 500 mg/kg were observed. Whereas, levels of platelets aggregation and fibrinogen were decreased at high doses. CONCLUSION: The obtained findings of hematological and coagulation tests concludes possibly S. cumini possess anticoagulant and antiplatelet effects.


Assuntos
Anticoagulantes/farmacologia , Extratos Vegetais/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Syzygium/química , Animais , Anticoagulantes/química , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/química , Coelhos
13.
J Clin Pharm Ther ; 44(5): 809-812, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31486123

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The off-label use of fondaparinux in patients with heparin-induced thrombocytopenia with thrombosis (HITT) has historically been controversial. We present a case of successful fondaparinux use to treat HITT confirmed by the serotonin-release assay in the setting of other significant clotting and bleeding risk factors. CASE SUMMARY: We report a 19-year-old male with a history of Factor V Leiden and recent neurosurgery treated with fondaparinux after developing HITT confirmed by the serotonin-release assay (SRA). The patient achieved full platelet recovery on fondaparinux and was successfully transitioned to warfarin therapy without further thrombotic nor bleeding complications. WHAT IS NEW AND CONCLUSION: This case demonstrates a clear example of success of fondaparinux use to treat SRA-confirmed HITT in the setting of complicating factors and adds to the existing literature supporting the use of fondaparinux for HIT.


Assuntos
Fator V/metabolismo , Inibidores do Fator Xa/uso terapêutico , Fondaparinux/uso terapêutico , Serotonina/metabolismo , Trombocitopenia/tratamento farmacológico , Trombose/tratamento farmacológico , Adulto , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/tratamento farmacológico , Hemorragia/metabolismo , Heparina/efeitos adversos , Humanos , Masculino , Trombocitopenia/induzido quimicamente , Trombocitopenia/metabolismo , Trombose/metabolismo , Adulto Jovem
14.
Am J Health Syst Pharm ; 76(6): 387-397, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31415684

RESUMO

PURPOSE: As a preliminary evaluation of the outcomes of implementing pharmacogenetic testing within a large rural healthcare system, patients who received pre-emptive pharmacogenetic testing and warfarin dosing were monitored until June 2017. SUMMARY: Over a 20-month period, 749 patients were genotyped for VKORC1 and CYP2C9 as part of the electronic Medical Records and Genomics Pharmacogenetics (eMERGE PGx) study. Of these, 27 were prescribed warfarin and received an alert for pharmacogenetic testing pertinent to warfarin; 20 patients achieved their target international normalized ratio (INR) of 2.0-3.0, and 65% of these patients achieved target dosing within the recommended pharmacogenetic alert dose (± 0.5 mg/day). Of these, 10 patients had never been on warfarin prior to the alert and were further evaluated with regard to time to first stable target INR, bleeds and thromboembolic events, hospitalizations, and mortality. There was a general trend of faster time to first stable target INR when the patient was initiated at a warfarin dose within the alert recommendation versus a dose outside of the alert recommendation with a mean (± SD) of 34 (± 28) days versus 129 (± 117) days, respectively. No trends regarding bleeds, thromboembolic events, hospitalization, or mortality were identified with respect to the pharmacogenetic alert. The pharmacogenetic alert provided pharmacogenetic dosing information to prescribing clinicians and appeared to deploy appropriately with the correct recommendation based upon patient genotype. CONCLUSION: Implementing pharmacogenetic testing as a standard of care service in anticoagulation monitoring programs may improve dosage regimens for patients on anticoagulation therapy.


Assuntos
Anticoagulantes/administração & dosagem , Monitoramento de Medicamentos/métodos , Testes Farmacogenômicos , Serviços de Saúde Rural/organização & administração , Varfarina/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Genótipo , Implementação de Plano de Saúde , Hemorragia/sangue , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Variantes Farmacogenômicos , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Padrão de Cuidado , Tromboembolia/sangue , Tromboembolia/prevenção & controle , Varfarina/efeitos adversos
15.
Vasc Health Risk Manag ; 15: 175-186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417269

RESUMO

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with cancer. Compared with the general population, cancer patients with VTE have higher rates of both VTE recurrence and bleeding. While low molecular weight heparin (LMWH) has been the mainstay of treatment for cancer-associated VTE for over a decade, direct oral anticoagulants (DOACs) have recently emerged as a new therapeutic option due to their ease of administration and because they do not require laboratory monitoring. Several large randomized clinical trials have been performed or are ongoing at the time of writing, comparing DOACs with LMWH in this population. Three of these trials have thus far been published and suggest that DOACs are a reasonable alternative to LMWH for management of cancer-associated VTE. Despite the advantages offered by DOACs, these agents may not be appropriate for certain patient groups owing to increased risk of bleeding, organ compromise, extremes of weight, and other issues. Finally, data are emerging suggesting that DOACs may be useful for primary thromboprophylaxis in cancer patients in conjunction with validated risk assessment scores. In this evidence-based review, data for the use of DOACs to treat cancer-associated VTE will be examined, focusing on efficacy, safety, and timing of treatment. Guidance on choosing the optimal anticoagulant for a given patient is also offered.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/mortalidade , Recidiva , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/mortalidade
16.
Toxicol Lett ; 316: 171-182, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31442586

RESUMO

Australian elapid snakes are some of the most venomous snakes in the world and are unique among venomous snakes in having mutated forms of the blood clotting factor X in an activated form (FXa) as a key venom component. In human bite victims, an overdose of this activated clotting enzyme results in the systemic consumption of fibrinogen due to the large amounts of endogenous thrombin generated by the conversion of prothrombin to thrombin by venom FXa. Within Australian elapids, such procoagulant venom is currently known from the tiger snake clade (Hoplocephalus, Notechis, Paroplocephalus, and Tropidechis species), brown/taipan (Oxyuranus and Pseudonaja species) clade, and the red-bellied black snake Pseudechis porphyriacus. We used a STA-R Max coagulation analyser and TEG5000 thromboelastographers to test 47 Australian elapid venoms from 19 genera against human plasma in vitro. In addition to activity being confirmed in the two clades above, FXa-driven potent procoagulant activity was found in four additional genera (Cryptophis, Demansia, Hemiaspis, and Suta). Ontogenetic changes in procoagulant function was also identified as a feature of Suta punctata venom. Phylogenetic analysis of FX sequences confirmed that snake venom FXa toxins evolved only once, that the potency of these toxins against human plasma has increased in a stepwise fashion, and that multiple convergent amplifications of procoagulant activity within Australian elapid snakes have occurred. Cofactor dependence tests revealed all procoagulant venoms in our study, except those of the tiger snake clade, to be highly calcium-dependent, whereas phospholipid dependence was less of a feature but still displayed significant variation between venoms. Antivenom testing using CSL Tiger Snake Antivenom showed broad but differential cross-reactivity against procoagulant venoms, with P. porphyriacus and S. punctata extremely well neutralised but with Cryptophis, Demansia, and Hemiaspis less well-neutralised. The relative variation was not in accordance to genetic relatedness of the species used in antivenom production (Notechis scutatus), which underscores a fundamental principle that the rapid evolution characteristic of venoms results in organismal phylogeny being a poor predictor of antivenom efficacy. Our results have direct and immediate implications for the design of clinical management plans in the event of snakebite by such lesser known Australian elapid snake species that have been revealed in this study to be as potent as the better studied, and proven lethal, species.


Assuntos
Antivenenos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Venenos Elapídicos/antagonistas & inibidores , Elapidae , Inibidores do Fator Xa/farmacologia , Fator Xa/metabolismo , Mordeduras de Serpentes/tratamento farmacológico , Animais , Reações Cruzadas , Venenos Elapídicos/genética , Venenos Elapídicos/imunologia , Venenos Elapídicos/metabolismo , Elapidae/classificação , Elapidae/genética , Elapidae/imunologia , Elapidae/metabolismo , Evolução Molecular , Fator Xa/genética , Fator Xa/imunologia , Fibrinólise/efeitos dos fármacos , Mutação , Filogenia , Mordeduras de Serpentes/imunologia , Mordeduras de Serpentes/metabolismo , Tromboelastografia
17.
Crit Care Resusc ; 21(3): 171-178, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31462204

RESUMO

OBJECTIVE: Fibrinogen is one of the first coagulation factors to be depleted during traumatic haemorrhage, and evidence suggests hypofibrinogenaemia leads to poor outcomes. A number of fibrinogen replacement products are currently available, with no clear consensus on the ideal product to use in severe traumatic haemorrhage. We hypothesised that it will be possible to rapidly administer fibrinogen concentrate (FC) guided by rotational thromboelastometry (ROTEM) FIBTEM A5 in patients presenting with trauma haemorrhage. METHODS: We examined 36 consecutive patients with trauma admitted to a level 1 trauma centre in Australia who received FC as part of their initial resuscitation. ROTEM analysis was conducted at various time points from emergency department (ED) admission to 48 hours after admission. The primary outcome was time to administration of FC after identification of hypofibrinogenaemia using ROTEM FIBTEM A5. Data were collected on quantity and timing of product transfusion, demographics, Injury Severity Score and laboratory values of coagulation. Spearman rank order correlation was used to determine the correlation between FIBTEM A5 and Clauss fibrinogen (FibC). RESULTS: Thirty-six patients received FC as their initial form of fibrinogen replacement during the study. Patients were hypofibrinogenaemic by both FIBTEM A5 (6 mm) and FibC (1.7 g/L) on presentation to the ED. It took a median of 22 minutes (IQR, 17-30 minutes) from time of a FIBTEM A5 analysis to FC administration. Both parameters increased significantly (P < 0.05) by 24 hours after admission. CONCLUSION: This study suggests that administration of FC represents a rapid and feasible method to replace fibrinogen in severe traumatic haemorrhage. However, the optimal method for replacing fibrinogen in traumatic haemorrhage is controversial and large multicentre randomised controlled trials are needed to provide further evidence. This study provided baseline data to inform the design of further clinical trials investigating fibrinogen replacement in traumatic haemorrhage.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fibrinogênio/administração & dosagem , Hemorragia/prevenção & controle , Tromboelastografia/instrumentação , Ferimentos e Lesões/tratamento farmacológico , Austrália , Transfusão de Sangue , Fibrinogênio/uso terapêutico , Hemorragia/diagnóstico , Humanos
18.
ACS Appl Mater Interfaces ; 11(34): 31411-31420, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31373785

RESUMO

Cutaneous hemorrhage often occurs in daily life which may cause infection and even amputation. This research aims to develop a novel chitosan dressing impregnated with ZnO/N-halamine hybrid nanoparticles for quick antibacterial performance, outstanding hemostatic potential, high porosity, and favorable swelling property through combining sonication and lyophilization processing. After 30 days of storage, about 90% bacterial cell viability loss could be observed toward both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli O157:H7 within 30 min of contact by colony counting method. The hybrids assembled much more platelet and red blood cell as compared with pure chitosan control. Moreover, the lower blooding clotting index value gave evidence that these composites could control hemorrhaging and reduce the probability of wound infection. No potential skin irritation and toxicity were detected using in vitro cytocompatibility and a skin stimulation test. Therefore, this work demonstrated a facile and cost-effective approach for the preparation of N-halamine-based hybrid sponges which show promising application for wound dressings.


Assuntos
Antibacterianos , Bandagens , Escherichia coli O157/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Óxido de Zinco , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Coelhos , Óxido de Zinco/química , Óxido de Zinco/farmacologia
19.
J Clin Pathol ; 72(12): 817-824, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31366633

RESUMO

AIMS: Bivalent direct thrombin inhibitors (DTIs), hirudin and bivalirudin, bind to the active site and exosite 1 of thrombin irreversibly and reversibly, respectively. The present study aims to assess in vitro effects of hirudin and bivalirudin through clot waveform analysis (CWA) and enzyme kinetics in coagulation assays. METHODS: The pooled normal plasma and its dilutions were spiked with hirudin or bivalirudin. The activated partial thromboplastin time (APTT) assay and the Clauss fibrinogen assay were performed using the CS-5100 (Sysmex). The APTT-CWA data were automatically gained by the CS-5100 programme. RESULTS: In APTT-CWA, the maximum coagulation velocity, acceleration and deceleration were decreased dependently on the drug concentrations, demonstrating evidence for the blockade of thrombin-positive feedback by hirudin or bivalirudin. The Hill plot analysis was applied to the dose-dependent curves in bivalirudin. The Hill coefficients were greater than 1, showing positive anticoagulant cooperativity. Regarding the dose-dependent curves in hirudin, all the parameters dropped to almost zero without making an asymptotic line. In the Clauss fibrinogen assay, the Lineweaver-Burk plots demonstrated that both drugs exhibit mixed inhibition mimicking uncompetitive binding. The Dixon plots in bivalirudin were linear and supported the inhibition type described above. The Dixon plots in hirudin were non-linear and inappropriate to use for determination of the inhibition type. In addition, the inverse function of the clotting time appeared to drop to zero without making an asymptotic line, suggesting complete loss of thrombin activity by irreversible binding. CONCLUSIONS: The results provide insights into anticoagulation with bivalent DTIs.


Assuntos
Antitrombinas/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Hirudinas/farmacologia , Tempo de Tromboplastina Parcial , Fragmentos de Peptídeos/farmacologia , Trombina/antagonistas & inibidores , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Fibrinogênio/metabolismo , Humanos , Cinética , Modelos Biológicos , Proteínas Recombinantes/farmacologia , Trombina/metabolismo
20.
Curr Top Med Chem ; 19(22): 1981-1989, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31376821

RESUMO

BACKGROUND: For many decades, research on snake venom toxinology focused mainly on the venoms of Viperidae and Elapidae species, which were traditionally the only ones considered as venomous. However, much less interest has been given to the venom produced by opisthoglyphous colubrid snakes, since they were typically considered of no clinical relevance. OBJECTIVE: The aim of this work is to perform a preliminary biochemical and venomic characterization of the venom of the colubrid snake Phalotris lemniscatus, a species that has been responsible for two relevant cases of envenomation in Uruguay. METHODS: We extracted venom from collected specimens and performed different biochemical and proteomic assays to understand its toxin composition. RESULTS: We found that the venom of P. lemniscatus is composed of protein families typically present in snake venoms, such as metallo and serine preoteases, L-amino acid oxidases, phospholipases A2s, Ctype lectines-like, Kunitz-type proteins and three-finger toxins. Activity assays demonstrated a highly active gelatinolytic component as well as a potent capability to induce blood coagulation. CONCLUSION: The results indicate that the venom of P. lemniscatus contains hemotoxic activities and components that resemble those found in Viperidae (Bothrops) snakes and that can induce a clinically relevant accident. Further studies are needed to better understand the venom composition of this colubrid snake and its most active compounds.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Venenos de Serpentes/toxicidade , Animais , Antivenenos/farmacologia , Colubridae , Camundongos , Venenos de Serpentes/antagonistas & inibidores , Venenos de Serpentes/isolamento & purificação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA