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2.
Thromb Haemost ; 119(6): 894-898, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30934105

RESUMO

BACKGROUND: Parturient women are healthy individuals who require special consideration. Parturient women are considered to be in a hyper-coagulable state. For example, the fibrinogen (FIB) levels are often higher than the upper limit of normal reference intervals (RIs) in parturient women than in non-parturient healthy individuals (2-4 g/L). OBJECTIVE: The aim of this study is to establish the RIs of pro-thrombin time (PT), activated partial thromboplastin time (aPTT), FIB levels and thrombin time (TT) for parturient women. MATERIALS AND METHODS: Blood levels of PT, aPTT, FIB and TT were assayed on an ACL TOP 700 automatic coagulation analyser using plasma samples from 10,472 parturient women. Outlier results were excluded by using Tukey's test. The RIs were calculated by the Clinical and Laboratory Standards Institute C28-A3 guideline. RESULTS: The RIs of PT, aPTT, FIB and TT were 8.7 to 12.1 seconds (8.7-12.2 seconds for 16-20 years old, 8.7-12.1 second for 21-25 years old, 8.6-12.0 second for 26-30 years old, 8.7-12.0 second for 31-35 years old, 8.7-12.6 second for 36-40 years old and 8.8-12.2 second for 41 years old), 22.9 to 42.3 seconds, 1.98 to 5.82 g/L and 9.9 to 16.7 seconds, respectively. PT levels were found to be positively associated with aging. CONCLUSION: The above-established age-specific RIs, defined by using a large dataset, may assist clinicians in making accurate medical decisions. This was the first study in which the RIs of PT, aPTT, FIB and TT were established for parturient women in different age groups.


Assuntos
Fatores Etários , Envelhecimento/fisiologia , Fibrinogênio/metabolismo , Tempo de Tromboplastina Parcial/métodos , Tempo de Protrombina/métodos , Tempo de Trombina/métodos , Adolescente , Adulto , Coagulação Sanguínea , Feminino , Humanos , Parto , Gravidez , Valores de Referência , Adulto Jovem
3.
APMIS ; 127(7): 515-528, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31009118

RESUMO

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB) - a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender-age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p < 0.05), elevated antithrombin III at day 90 (p < 0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p < 0.05), and enhanced thrombin-antithrombin complex at day 4 (p < 0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin-antithrombin complex at day 4 (p < 0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p < 0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D-dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS-SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.


Assuntos
Bacteriemia/complicações , Endocardite Bacteriana/etiologia , Hemostasia/fisiologia , Infecções Estafilocócicas/complicações , Tromboembolia/etiologia , Antitrombina III/metabolismo , Bacteriemia/metabolismo , Plaquetas/metabolismo , Plaquetas/fisiologia , Fator VIII/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Meticilina/farmacologia , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , Peptídeo Hidrolases/metabolismo , Estudos Prospectivos , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/patogenicidade , Tempo de Trombina/métodos , Tromboembolia/metabolismo
5.
J Clin Pathol ; 72(2): 177-180, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30463936

RESUMO

Most fibrinogen replacement strategies focus on quantitative deficiencies. A thrombin time (TT) mixing study helped to assess qualitative defects caused by dysfibrinogens. Plasma samples were collected from non-anticoagulated subjects (n=6) meeting laboratory criteria for suspected dysfibrinogenaemia (TT > 22 s; fibrinogen activity <180) and from a control group. TT mixing studies were performed on subject plasma with increasing volumes of pooled normal plasma at 1:2, 1:4 and 1:5 dilutions. No subjects with dysfibrinogenaemia demonstrated a complete TT correction at 1:2, but 50% corrected at 1:4 and 100% at 1:5 dilution. Based on these data, a correction factor (CF), defined as the reciprocal dilution yielding complete correction, was incorporated into our clinical practice formula for fibrinogen dosing in patients with dysfibrinogenaemias. Our study incorporates TT mixing studies for assessment of dysfibrinogens. The addition of a mix-derived CF to classical formulae may better approximate dosing in patients with dysfibrinogenaemia.


Assuntos
Afibrinogenemia/diagnóstico , Afibrinogenemia/tratamento farmacológico , Fibrinogênio/análise , Fibrinogênio/uso terapêutico , Tempo de Trombina/métodos , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino
6.
Int J Biol Macromol ; 123: 335-342, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30419328

RESUMO

A sulfated polysaccharide from Globularia alypum L. (GASP) was extracted with a yield of 14.2%. GASP is composed mostly of sulfate and total sugars (13.29% and 71.56%, respectively) with small amount of proteins and lipids. The chemical and structural characterization was studied by Infra-Red spectroscopic and gas chromatography-mass spectrometry (GC-MS). GASP composed of eight carbohydrates where galactose, glucose, and mannose are the major compounds (33.47%, 26.71% and 18.21%, respectively). The in vitro and in vivo anticoagulant activities in rats were tested using the standard coagulation assays activated partial thromboplastin time (aPTT), prothrombine time (TT) and thrombin time (PT) tests. Both doses of GASP (200 and 500 mg/kg b.w) displayed a significant in vitro (1.22 and 1.33-fold, 1.17 and 1.27-fold, and 1.21 and 1.26-fold, respectively) and in vivo (1.47 and 2.52-fold; 1.20 and 1.43-fold; 1.21 and 1.40-fold, respectively) compared with the control. Toxicity studies on liver performed by the catalytic activity of transaminases in plasma, oxidative stress markers and hepatic morphological changes indicated that GASP at both doses are not toxics. The important pharmacological and toxicological profile of GASP revealed that this compound may be used as a novel and effective drug.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Plantaginaceae/química , Polissacarídeos/administração & dosagem , Animais , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Testes de Coagulação Sanguínea , Cromatografia Gasosa , Humanos , Espectrometria de Massas , Tempo de Tromboplastina Parcial/métodos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Ratos , Sulfatos/química , Tempo de Trombina/métodos
7.
Thromb Res ; 171: 62-67, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30261356

RESUMO

BACKGROUND: In patients who are receiving dabigatran, a direct oral anticoagulant, measuring the anticoagulant effect before surgery may be needed in certain circumstances. Although the dilute thrombin time (dTT) can reliably measure dabigatran levels, it is not consistently available. More commonly used coagulation tests, including the activated partial thromboplastin time (aPTT) and thrombin time (TT) might have clinical utility but their accuracy is uncertain. METHODS: 103 patients stopped dabigatran 1-4 days before an elective surgery/procedure as part of a standardized dabigatran interruption protocol. With a blood sample taken just before surgery, we assessed the accuracy of five aPTT assays (Actin FS, Stago PTT, C.K. PREST, HemosIL aPTT-SP, SynthASil) and TT to measure the residual anticoagulant effect of dabigatran. We determined the sensitivity, specificity and other accuracy indices of these assays to predict a dabigatran level > 30 ng/mL as determined by a reference standard test, the dTT (Hemoclot). RESULTS: Of five aPTT reagents, four assays had excellent (100%) and one assay had good (93%) sensitivity to detect a level of dabigatran > 30 ng/mL, but all had insufficient specificity (50-74%). A TT > 90 s had good sensitivity (93%) and excellent specificity (100%). CONCLUSION: Five aPTT assays had good sensitivity but poor specificity to detect low levels of dabigatran (≤30 ng/mL) after standardized dabigatran interruption before an elective surgery/procedure, thereby limiting the use of aPTT as an alternative to the dTT in preoperative settings.


Assuntos
Antitrombinas/sangue , Antitrombinas/farmacologia , Dabigatrana/sangue , Dabigatrana/farmacologia , Tempo de Tromboplastina Parcial/métodos , Tempo de Trombina/métodos , Antitrombinas/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Dabigatrana/uso terapêutico , Monitoramento de Medicamentos/métodos , Procedimentos Cirúrgicos Eletivos , Humanos , Indicadores e Reagentes , Estudos Prospectivos
8.
Mar Drugs ; 16(7)2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30037033

RESUMO

Great diversity and metabolite complexity of seaweeds offer a unique and exclusive source of renewable drug molecules. Polysaccharide from seaweed has potential as a promising candidate for marine drug development. In the present study, seaweed polysaccharide (SPm) was isolated from Monostroma angicava, the polymeric repeat units and anticoagulant property in vitro and in vivo of SPm were investigated. SPm was a sulfated polysaccharide which was mainly constituted by 3-linked, 2-linked-α-l-rhamnose residues with partially sulfate groups at C-2 of 3-linked α-l-rhamnose residues and C-3 of 2-linked α-l-rhamnose residues. Small amounts of xylose and glucuronic acid exist in the forms of ß-d-Xylp(4SO4)-(1→ and ß-d-GlcA-(1→. SPm effectively prolonged clotting time as evaluated by the activated partial thromboplastin time and thrombin time assays, and exhibited strong anticoagulant activity in vitro and in vivo. The fibrin(ogen)olytic and thrombolytic properties of SPm were evaluated by plasminogen activator inhibitior-1, fibrin degradation products, D-dimer and clot lytic rate assays using rats plasma, and the results showed that SPm possessed high fibrin(ogen)olytic and thrombolytic properties. These results suggested that SPm has potential as a novel anticoagulant agent.


Assuntos
Anticoagulantes/farmacologia , Desoxiaçúcares/química , Mananas/química , Alga Marinha/química , Sulfatos/química , Animais , Clorófitas/química , Fibrinolíticos/farmacologia , Masculino , Tempo de Tromboplastina Parcial/métodos , Inibidor 1 de Ativador de Plasminogênio/farmacologia , Polissacarídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Tempo de Trombina/métodos , Trombose/tratamento farmacológico
9.
Sci Rep ; 8(1): 8847, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891906

RESUMO

Our objective was to evaluate the efficacy and safety of natural hirudin and low molecular weight heparin (LMWH) in the prevention of perioperative deep venous thrombosis (DVT) in elderly patients with intertrochanteric fracture. From June 2014 to June 2017, 96 patients with intertrochanteric fractures were treated with proximal femoral nail antirotation (PFNA) were randomly divided into two groups. For DVT prevention, 45 patients were treated with oral natural hirudin and subcutaneous LMWH-calcium (test group) and 51 patients were treated with subcutaneous LMWH-calcium (control group). The mean intraoperative bleeding, wound drainage and incisional hematoma were higher in the test group, with no significant differences between the groups. There were significant differences in distal intramuscular venous thrombosis (P = 0.043). Both activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) lengthened in both groups postoperatively, and there was a significant difference between the two groups two weeks postoperatively. D-dimer were significantly different and platelet count (PLT) did not differ between groups two weeks postoperatively. In elderly patients with unilateral intertrochanteric fracture after PFNA on anticoagulant therapy, the combination of natural hirudin and LMWH was more effective than that of LMWH-calcium alone, with no significant difference with regard to safety.


Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Fraturas do Quadril/complicações , Fraturas do Quadril/cirurgia , Terapia com Hirudina , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/métodos , Contagem de Plaquetas , Período Pós-Operatório , Tempo de Protrombina/métodos , Distribuição Aleatória , Tempo de Trombina/métodos , Resultado do Tratamento
10.
J Thromb Haemost ; 15(12): 2377-2387, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28976630

RESUMO

Essentials Routine monitoring is unnecessary but measuring dabigatran levels is helpful in certain situations. We compared ecarin chromogenic assay (STA-ECA-II) and dilute thrombin time (dTT) in patient samples. Both tests provided accurate measurements over a wide range of dabigatran concentrations. Adoption of STA-ECA-II and dTT into routine clinical practice will improve patient care. SUMMARY: Background Although routine coagulation monitoring is unnecessary, measuring plasma dabigatran concentrations can be useful for detecting drug accumulation in renal failure or overdose, assessing the contribution of dabigatran to serious bleeding, planning the timing of urgent surgery or intervention, or determining the suitability for thrombolytic therapy for acute ischemic stroke. Dabigatran concentrations can be quantified using chromogenic or clot-based tests, such as the ecarin chromogenic assay (ECA) and the diluted thrombin time (dTT), respectively. Objective The purpose of this study was to compare the results of these assays with dabigatran concentrations measured by the reference standard of mass spectrometry in samples from 50 dabigatran-treated patients collected at peak and trough after at least 4 months of drug intake. Methods Drug levels measured with either the STA Ecarin Chromogenic Assay-II (STA-ECA-II) or dTT were linearly correlated with those determined by mass spectrometry over a wide range of concentrations. Results and Conclusions For detection of levels below 50 ng mL-1 both tests have specificities of at least 96%, suggesting that they accurately detect even low levels of drug. Therefore, regardless of whether a chromogenic or clot-based platform is preferred, the STA-ECA-II and dTT are useful tests for measuring dabigatran concentrations. Unfortunately, neither test is licensed by the United States Food and Drug Administration. Although approved in other jurisdictions, the dTT and STA-ECA-II are not widely or rapidly available in most hospitals. Therefore, cooperation between regulators and hospitals is urgently needed to render these tests readily available to inform patient care.


Assuntos
Análise Química do Sangue/métodos , Testes de Coagulação Sanguínea/métodos , Dabigatrana/sangue , Tempo de Trombina/métodos , Anticoagulantes/sangue , Anticoagulantes/normas , Anticoagulantes/uso terapêutico , Fibrilação Atrial/sangue , Fibrilação Atrial/tratamento farmacológico , Análise Química do Sangue/estatística & dados numéricos , Testes de Coagulação Sanguínea/estatística & dados numéricos , Cromatografia Líquida de Alta Pressão , Compostos Cromogênicos , Dabigatrana/normas , Dabigatrana/uso terapêutico , Endopeptidases , Humanos , Espectrometria de Massas em Tandem , Tempo de Trombina/estatística & dados numéricos
11.
Methods Mol Biol ; 1646: 105-110, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28804822

RESUMO

Fibrinogen is measured in plasma most commonly using the Clauss method, based on the comparison of thrombin clotting times of dilutions of plasma against a plasma standard. Thrombin time (TT) is a coagulation assay, which reflects the conversion of fibrinogen to fibrin after addition of thrombin reagent. Measurement of clottable fibrinogen and TT allows detecting inborn (congenital) and acquired qualitative and quantitative disorders of fibrinogen that can lead to thrombotic or bleeding events.


Assuntos
Coagulação Sanguínea , Fibrinogênio/análise , Tempo de Trombina/métodos , Afibrinogenemia/sangue , Afibrinogenemia/diagnóstico , Fibrinogênio/metabolismo , Humanos , Trombina/metabolismo
12.
Methods Mol Biol ; 1646: 217-225, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28804832

RESUMO

Direct oral anticoagulants (DOACs) can be quantified using methods that can be performed in any clinical or research laboratory using manual or automated instrument platforms. Dabigatran etexilate, the oral direct thrombin inhibitor, can be quantified by drug-calibrated clot or chromogenic-based assays using either thrombin or ecarin as substrates. Oral direct anti-Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban, can be quantified with drug-calibrated anti-Xa kits or reagents as typically used for measuring heparins (unfractionated, low molecular weight, or pentasaccharides).


Assuntos
Antitrombinas/sangue , Antitrombinas/uso terapêutico , Monitoramento de Medicamentos/métodos , Inibidores do Fator Xa/sangue , Inibidores do Fator Xa/uso terapêutico , Tempo de Trombina/métodos , Administração Oral , Antitrombinas/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Dabigatrana/administração & dosagem , Dabigatrana/sangue , Dabigatrana/uso terapêutico , Endopeptidases/administração & dosagem , Endopeptidases/sangue , Endopeptidases/uso terapêutico , Inibidores do Fator Xa/administração & dosagem , Fibrinolíticos/administração & dosagem , Fibrinolíticos/sangue , Fibrinolíticos/uso terapêutico , Humanos , Pirazóis/administração & dosagem , Pirazóis/sangue , Pirazóis/uso terapêutico , Piridinas/administração & dosagem , Piridinas/sangue , Piridinas/uso terapêutico , Piridonas/administração & dosagem , Piridonas/sangue , Piridonas/uso terapêutico , Rivaroxabana/administração & dosagem , Rivaroxabana/sangue , Rivaroxabana/uso terapêutico , Tiazóis/administração & dosagem , Tiazóis/sangue , Tiazóis/uso terapêutico , Tromboembolia Venosa/sangue , Tromboembolia Venosa/tratamento farmacológico
13.
Bioanalysis ; 9(9): 693-705, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28488882

RESUMO

AIM: Variegin is an anticoagulant peptide that will be tested in porcine models of percutaneous coronary intervention. We developed three bioanalytical assays for variegin quantitation and utilized these methods to evaluate pharmacokinetics of variegin in pigs. Results & methodology: The LC-MS/MS, thrombin amidolytic and modified thrombin time assays had a quantitation range of 21.6-5541.7, 10.8-5541.7 and 5.4-5541.7 nM in human plasma, respectively. The elimination half-lives obtained using the LC-MS/MS, modified thrombin time and thrombin amidolytic assays were 52.3 ± 4.4, 50.4 ± 5.9 and 67.7 ± 6.3 min, respectively. CONCLUSION: We developed three bioanalytical assays for a novel direct thrombin inhibitor, variegin. The thrombin time assay is optimized for variegin quantitation during future porcine studies and clinical trials.


Assuntos
Antitrombinas/sangue , Cromatografia Líquida/métodos , Proteínas e Peptídeos Salivares/sangue , Espectrometria de Massas em Tandem/métodos , Tempo de Trombina/métodos , Animais , Antitrombinas/farmacologia , Humanos , Limite de Detecção , Masculino , Proteínas e Peptídeos Salivares/farmacologia , Suínos , Trombina/antagonistas & inibidores , Trombina/metabolismo
14.
Int J Lab Hematol ; 39(3): 301-307, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28318107

RESUMO

INTRODUCTION: Thrombin time (TT) tests are useful for diagnosing coagulation disorders involving abnormal fibrinogen but do not allow us to distinguish between qualitative and quantitative defects. However, with the widening availability of optical coagulation automates, more information about the coagulation process is becoming increasingly accessible. METHODS: In this study, we compared the coagulation curves of TT tests carried out with plasma from healthy donors with those from patients with acquired low Clauss fibrinogen levels or with dysfibrinogenemia caused by a heterozygous point mutation in the fibrinogen γ-chain that results in a p.Arg301(275)Cys substitution. The functional fibrinogen levels of these three groups of samples were also measured with the Clauss method, and their fibrinogen protein levels were determined by ELISA. RESULTS: Our data indicate that the amplitude and maximal velocity of coagulation curves from plasma samples from FGG p.Arg301(275)Cys dysfibrinogenemic patients were comparable to those from plasma samples with fibrinogen in the normal range, whereas the amplitude of coagulation curves from patients with acquired low fibrinogen levels was lower. CONCLUSIONS: Examination of the amplitude of coagulation curves generated during TT tests may provide additional information to enable the differential diagnoses of diseases following a low fibrinogen measurement by the Clauss method.


Assuntos
Afibrinogenemia/sangue , Afibrinogenemia/genética , Fibrinogênios Anormais/genética , Fibrinogênios Anormais/metabolismo , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Feminino , Humanos , Masculino , Tempo de Trombina/métodos
15.
Crit Care ; 21(1): 32, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28196509

RESUMO

BACKGROUND: Point-of-care testing (POCT) of coagulation has been proven to be of great value in accelerating emergency treatment. Specific POCT for direct oral anticoagulants (DOAC) is not available, but the effects of DOAC on established POCT have been described. We aimed to determine the diagnostic accuracy of Hemochron® Signature coagulation POCT to qualitatively rule out relevant concentrations of apixaban, rivaroxaban, and dabigatran in real-life patients. METHODS: We enrolled 68 patients receiving apixaban, rivaroxaban, or dabigatran and obtained blood samples at six pre-specified time points. Coagulation testing was performed using prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and activated clotting time (ACT+ and ACT-low range) POCT cards. For comparison, laboratory-based assays of diluted thrombin time (Hemoclot) and anti-Xa activity were conducted. DOAC concentrations were determined by liquid chromatography-tandem mass spectrometry. RESULTS: Four hundred and three samples were collected. POCT results of PT/INR and ACT+ correlated with both rivaroxaban and dabigatran concentrations. Insufficient correlation was found for apixaban. Rivaroxaban concentrations at <30 and <100 ng/mL were detected with >95% specificity at PT/INR POCT ≤1.0 and ≤1.1 and ACT+ POCT ≤120 and ≤130 s. Dabigatran concentrations at <30 and <50 ng/mL were detected with >95% specificity at PT/INR POCT ≤1.1 and ≤1.2 and ACT+ POCT ≤100 s. CONCLUSIONS: Hemochron® Signature POCT can be a fast and reliable alternative for guiding emergency treatment during rivaroxaban and dabigatran therapy. It allows the rapid identification of a relevant fraction of patients that can be treated immediately without the need to await the results of much slower laboratory-based coagulation tests. TRIAL REGISTRATION: Unique identifier, NCT02371070 . Retrospectively registered on 18 February 2015.


Assuntos
Anticoagulantes/análise , Testes de Coagulação Sanguínea/normas , Tempo de Tromboplastina Parcial/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito/normas , Tempo de Protrombina/instrumentação , Tempo de Trombina/instrumentação , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Testes de Coagulação Sanguínea/métodos , Dabigatrana/análise , Dabigatrana/uso terapêutico , Inibidores do Fator Xa/análise , Inibidores do Fator Xa/uso terapêutico , Humanos , Tempo de Tromboplastina Parcial/métodos , Estudos Prospectivos , Tempo de Protrombina/métodos , Pirazóis/análise , Pirazóis/uso terapêutico , Piridonas/análise , Piridonas/uso terapêutico , Rivaroxabana/análise , Rivaroxabana/uso terapêutico , Tempo de Trombina/métodos
16.
Semin Thromb Hemost ; 43(3): 270-276, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28052306

RESUMO

Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion. Argatroban is primarily eliminated by the liver, while bivalirudin is removed by a combination of proteolytic cleavage by thrombin and renal clearance mechanisms. Several laboratory tests are available for monitoring the anticoagulant effects of the DTIs: the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) are the most commonly used assays, but on occasion, the thrombin time may be useful. Other coagulation assays such as the dilute thrombin time (dTT), chromogenic anti-IIa assays, and the ecarin clotting time (ECT) can be used. The intensity of anticoagulation with DTIs depends on the indication for use. For patients with HIT, the target aPTT is 1.5 to 3.0 and 1.5 to 2.5 times the patient's baseline value for argatroban and bivalirudin, respectively. DTI anticoagulation used during percutaneous coronary intervention can be measured using ACT. Both DTIs may cause an elevation in the international normalized ratio depending on their plasma concentration. This article will review the use of parenteral DTIs and related laboratory assays for assessing the anticoagulant effect of these drugs.


Assuntos
Antitrombinas/uso terapêutico , Monitoramento de Medicamentos/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Trombina/antagonistas & inibidores , Antitrombinas/administração & dosagem , Hirudinas/administração & dosagem , Humanos , Infusões Parenterais , Tempo de Tromboplastina Parcial/métodos , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/uso terapêutico , Ácidos Pipecólicos/administração & dosagem , Ácidos Pipecólicos/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Trombina/metabolismo , Tempo de Trombina/métodos
17.
Clin Appl Thromb Hemost ; 22(4): 322-6, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25354749

RESUMO

We evaluated the correlation between thrombin generation (TG) parameters with bleeding symptoms and disease severity in patients with hemophilia. In this cross-sectional study, 59 patients with hemophilia without inhibitors and regardless of their severity were randomly selected from southern Iran and TG assays were conducted. Bleeding score (BS) was calculated by performing a clinical evaluation using Tosetto questionnaire. Only lag time showed a statistically significant correlation with BS (rs = .316,P= .016). All TG parameters except peak showed association with disease severity (P< .05). Endogenous thrombin potential showed a significant correlation with factor activity level (rs = .459,P< .001). Both lag time and start tail showed significant negative correlations with factor activity level (rs = -0.488,P< .001 andrs = - .289,P< .026, respectively). Although most of the TG parameters evaluated were not significantly correlated with the BS of patients with hemophilia, the majority of TG parameters were significantly associated with factor activity level and disease severity.


Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Hemofilia A/sangue , Índice de Gravidade de Doença , Trombina/metabolismo , Feminino , Humanos , Irã (Geográfico) , Masculino , Tempo de Trombina/métodos
18.
Semin Thromb Hemost ; 42(1): 30-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26595153

RESUMO

Hemophilia treatment relies upon replacement of the deficient factor to restore physiological levels in plasma. The development of inhibitors is the main complication of replacement therapy, which renders replacement therapy ineffective and requires the use of alternative hemostatic drugs known as bypassing agents. The hemostatic response to bypassing agents is different from patient to patient and even in the same patient during different bleeding episodes. Up to now, no routine laboratory test has been found suitable to monitor efficacy and safety of these drugs. The unpredictable clinical response to bypassing therapy and the lack of a monitoring laboratory tool renders surgery in inhibitor patients a big challenge for the risk of both bleeding and thromboembolic complications. The thrombin generation assay (TGA) has been proposed as a monitoring tool in this patient population on the basis of the results obtained both in vitro and ex vivo. This review aims to summarize the current published evidence on the use of TGA as a laboratory monitoring tool in patients with hemophilia complicated by inhibitors.


Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Hemofilia A , Monitorização Fisiológica/métodos , Trombina/metabolismo , Enxerto Vascular/métodos , Hemofilia A/sangue , Hemofilia A/cirurgia , Hemorragia/sangue , Hemorragia/prevenção & controle , Humanos , Tempo de Trombina/métodos , Tromboembolia/sangue , Tromboembolia/prevenção & controle
19.
J Thromb Thrombolysis ; 41(3): 359-64, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26188585

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder resulting in the erosion of the cartilage and bone. Systemic involvement including the cardiovascular system with the risk of atherosclerosis may also occur. Calibrated automated thrombogram (CAT), a commercially available thrombin generation assay is suitable for the general assessment of the functionality of coagulation system. In this study we performed CAT assay in RA patients and in non-affected control subjects (matched for age, sex and comorbidities). Among the CAT parameters Velocity Index increased (from 60 to 83 nM/min), Lag Time and Time to Peak decreased (from 3.47 to 2.83 min and from 6.98 to 5.58 min respectively) in RA. On the other hand, Endogenous Thrombin Potential values decreased (from 1242 to 1108 nM min). The observed alterations were not associated with the applied therapy. These results indicate that the velocity of thrombin formation is increased, while the thrombin generating capability is reduced in RA.


Assuntos
Artrite Reumatoide/sangue , Trombina/metabolismo , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Tempo de Trombina/métodos
20.
Int J Lab Hematol ; 38(1): 50-3, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26406495

RESUMO

INTRODUCTION: Pre-analytical phase is a critical step in the haemostasis laboratory cycle. Numerous variations affect tests results, and it is crucial to detect them in order to reject improper specimens before reporting test results. Comparing to prior results or requesting, a repeat sample can help in pre-analytical irregularity assessment. METHODS: Each time a sample addressed to our laboratory displayed aberrant results or discordant with a prior report, another specimen was asked and both were analysed through calcium (Ca) level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration, factor II, factor VII+X and factor V coagulant activity measurements. Among these, all the primary citrated samples from inpatients without anticoagulant treatment, displaying very low calcium level ('Ca 0' samples), were selected for this 2 years study. RESULTS: A total of 17 samples could be identified. Ca level in their paired repeat samples was always >1.00 mmol/L. Coagulation testing for 'Ca 0' samples showed a significant prolongation of PT, APTT, TT and a significant decrease for fibrinogen concentration and factor V coagulant activity. CONCLUSION: We identified factor V coagulant activity, as the parameter with the most important variation in case of very low calcium level in presumed citrated sample tubes probably contaminated with EDTA.


Assuntos
Fator V , Fibrinogênio , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Tempo de Trombina , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea , Humanos , Tempo de Tromboplastina Parcial/métodos , Tempo de Tromboplastina Parcial/normas , Tempo de Protrombina/métodos , Tempo de Protrombina/normas , Tempo de Trombina/métodos , Tempo de Trombina/normas
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