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1.
Biochem Med (Zagreb) ; 30(1): 011002, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839729

RESUMO

Rejection of the sample with repeated blood withdrawal is always an unwanted consequence of sample nonconformity and preanalytical errors, especially in the most vulnerable population - children. Here is presented a case with unexpected abnormal coagulation test results in a 2-year-old child with no previously documented coagulation disorder. Child is planned for tympanostomy tubes removal under the anaesthesia driven procedure, and preoperative coagulation tests revealed prolonged prothrombin time, activated partial thromboplastin time and thrombin time, with fibrinogen and antithrombin within reference intervals. From the anamnestic and clinical data, congenital coagulation disorder was excluded, and with further investigation, sample mismatch, clot presence and accidental ingestion of oral anticoagulant, heparin contamination or vitamin K deficiency were excluded too. Due to suspected EDTA carryover during blood sampling another sample was taken the same day and all tests were performed again. The results for all tests were within reference intervals confirming EDTA effect on falsely prolongation of the coagulation times in the first sample. This case can serve as alert to avoid unnecessary loss in terms of blood withdrawal repetitions and discomfort of the patients and their relatives, tests repeating, prolonging medical procedures, and probably delaying diagnosis or proper medical treatment. It is the responsibility of the laboratory specialists to continuously educate laboratory staff and other phlebotomists on the correct blood collection as well as on its importance for the patient's safety.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Coleta de Amostras Sanguíneas/normas , Testes de Coagulação Sanguínea , Pré-Escolar , Erros de Diagnóstico , Ácido Edético/química , Humanos , Tempo de Tromboplastina Parcial , Fase Pré-Analítica , Tempo de Protrombina , Valores de Referência
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.
Int Heart J ; 60(6): 1315-1320, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735780

RESUMO

Uninterrupted anticoagulation therapy during atrial fibrillation (AF) ablation minimizes the risk of periprocedural thromboembolic events. Although the use of direct oral anticoagulants (DOACs) has rapidly developed in patients undergoing AF ablation, no antidote is available for factor Xa inhibitors. We sought to investigate the feasibility of an uninterrupted DOAC protocol with temporary switching to dabigatran ("dabigatran bridge") for AF ablation.The study consisted of consecutive 137 patients in whom DOACs were interrupted on the procedural day with heparin bridging (interrupted group) and 135 in whom DOACs were uninterrupted with temporary switching to dabigatran during the periprocedural hospitalization period ("dabigatran bridge" group). The coagulation markers were measured just before and after the ablation procedure. The adverse events during and up to 8 weeks after the procedure were compared according to the definition of the International Society on Thrombosis and Hemostasis.The patients were significantly older in the "dabigatran bridge" group; however, the other baseline patient characteristics were similar between the two groups. The incidence of all adverse events was comparable between the two groups (8/137 versus 8/135, P = 0.96); however, one patient from the interrupted group experienced stroke, and another from the "dabigatran bridge" group experienced cardiac tamponade, which was safely managed with an antidote. In the "dabigatran bridge" group, the activated partial thromboplastin time was significantly longer, and coagulation markers (soluble fibrin monomer and thrombin-antithrombin complexes) were significantly lower than in the interrupted group before ablation.The "dabigatran bridge" seems to be a reasonable anticoagulation protocol to minimize the thromboembolic risk while ensuring safety in patients undergoing AF ablation and taking factor Xa inhibitors.


Assuntos
Antitrombinas/administração & dosagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Dabigatrana/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia/prevenção & controle , Administração Oral , Idoso , Protocolos Clínicos , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial
4.
Int J Nanomedicine ; 14: 7017-7038, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564863

RESUMO

Background: Fabrication of a smart drug delivery system that could dramatically increase the efficiency of chemotherapeutic drugs and reduce the side effects is still a challenge for pharmaceutical researchers. By the emergence of nanotechnology, a huge window was opened towards this goal, and a wide type of nanocarriers were introduced for delivering the chemotherapeutic to the cancer cells, among them are cyclodextrins with the ability to host different types of hydrophobic bioactive molecules through inclusion complexation process. Aim: The aim of this study is to design and fabricate a pH-responsive theranostic nanocapsule based on cyclodextrin supramolecular nano-structure. Materials and methods: This nanostructure contains iron oxide nanoparticles in the core surrounded with three polymeric layers including polymeric ß-cyclodextrin, polyacrylic acid conjugated to sulfadiazine, and polyethylenimine functionalized with ß-cyclodextrin. Sulfadiazine is a pH-responsive hydrophobic component capable of making inclusion complex with ß-cyclodextrin available in the first and third layers. Doxorubicin, as an anti-cancer drug model, was chosen and the drug loading and release pattern were determined at normal and acidic pH. Moreover, the biocompatibility of the nanocapsule (with/without drug component) was examined using different techniques such as MTT assay, complement activation, coagulation assay, and hemolysis. Results: The results revealed the successful preparation of a spherical nanocapsule with mean size 43±1.5 nm and negatively charge of -43 mV that show 160% loading efficacy. Moreover, the nanocapsule has an on/off switching release pattern in response to pH that leads to drug released in low acidic pH. The results of the biocompatibility tests indicated that this nano drug delivery system had no effect on blood and immune components while it could affect cancer cells even at very low concentrations (0.3 µg mL-1). Conclusion: The obtained results suggest that this is a "switchable" theranostic nanocapsule with potential application as an ideal delivery system for simultaneous cancer diagnosis and therapy.


Assuntos
Nanocápsulas/química , Polietilenoimina/química , Nanomedicina Teranóstica , beta-Ciclodextrinas/química , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Compostos Férricos/química , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Nanocápsulas/ultraestrutura , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Eletricidade Estática , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/química , Difração de Raios X , beta-Ciclodextrinas/síntese química
5.
Chem Commun (Camb) ; 55(78): 11790-11793, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31524903

RESUMO

Balancing and neutralizing heparin dosing after surgeries and hemodialysis treatment is of great importance in medical and clinical fields. In this study, a series of new amphiphilic multi-charged cyclodextrins (AMCD)s as anti-heparin coagulants were designed and synthesized. The AMCD assembly was capable of selective heparin binding through multivalent bonding and showed a better neutralizing effect towards both unfractionated heparin and low molecular weight heparin than protamine in plasma. Meanwhile, an AMCD and vitamin K (VK) co-assembly was prepared to realize heparin-responsive VK release and provide a novel VK deficiency treatment for hemodialysis patients. This AMCD-VK co-assembly for heparin neutralization & vitamin K supplementation synergistic coagulation represents a promising candidate as a clinical anti-heparin coagulant.


Assuntos
Coagulantes/química , Ciclodextrinas/química , Vitamina K/química , Coagulantes/metabolismo , Ciclodextrinas/metabolismo , Heparina/química , Heparina/metabolismo , Tempo de Tromboplastina Parcial , Protaminas/química , Protaminas/metabolismo , Espectrofotometria , Vitamina K/metabolismo
6.
Eur J Med Chem ; 183: 111722, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563807

RESUMO

Thrombosis is a pathological coagulation process and can lead to many serious thrombotic diseases. Here, we report a novel potent antithrombotic compound (6k) based on isosteviol with anticoagulant and antiplatelet activities. 6k selectively inhibited FXa (Ki = 0.015 µM) against a panel of serine proteases and showed excellent anticoagulant activity (significant prolongation of ex vivo PT and aPTT over the vehicle, p < 0.01). 6k also significantly inhibited ADP-induced platelet aggregation in rats relative to the vehicle (p < 0.01). Furthermore, 6k exhibited potent ex vivo and in vivo antithrombotic activity in rats relative to the vehicle (p < 0.01 and p < 0.0001, respectively). Novel structure 6k, with potent antithrombotic activity, is expected to lead a promising approach for the development of antithrombotic agents.


Assuntos
Diterpenos de Caurano/química , Diterpenos de Caurano/farmacologia , Fibrinolíticos/química , Fibrinolíticos/farmacologia , Inibidores da Agregação de Plaquetas/química , Inibidores da Agregação de Plaquetas/farmacologia , Trombose/tratamento farmacológico , Animais , Descoberta de Drogas , Inibidores do Fator Xa/química , Inibidores do Fator Xa/farmacologia , Feminino , Humanos , Masculino , Tempo de Tromboplastina Parcial , Agregação Plaquetária/efeitos dos fármacos , Ratos , Ratos Wistar , Trombina/metabolismo
7.
Pan Afr Med J ; 33: 39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384354

RESUMO

Hageman factor (factor XII) has a key role in activation of intrinsic coagulation system gauged by activated partial thromboplastin time (aPPT). Hageman factor deficiency is more often an autosomal recessive condition, but an autosomal dominant inheritance is also reported. This condition in its own is not known to cause bleeding complications rather is associated with paradoxical fatal thromboembolic complications. Exact prevalence of this condition is not known, as under normal conditions they are asymptomatic. In literature, a prevalence of 2.3% has been reported in one study on 300 patients presenting with complications. Homozygous patients has non-detectable levels of factor XII, while heterozygous individuals has variable levels ranging from 20-60%. Hageman factor is a pro-coagulation protein initiating intrinsic pathway. Intrinsic pathway is activated either by direct contact with a negative charged surface or by proteolytic activation on the endothelial cells via prekallikerin/kallikerin system. Factor XII as an integral part of this system leads to factor XI activation resulting in production of thrombin orchestrated by intrinsic system. In addition, there is concomitant activation of complement components C3 and C5 via C1-estrase activation. Patients with this condition are known to have spontaneous thromboembolic complications although less common but are prone to life threatening complications under provocating circumstances. The aim of this case report is to study the relation of factor XII deficiency and isolated raised activated partial thromboplastin time (aPPT) and how it can be prevented. We are presenting a Saudi female patient, 29 years of age who presented to accident and emergency room (A&E room) of our hospital with sudden severe breathlessness and chest pain.


Assuntos
Deficiência do Fator XII/diagnóstico , Fator XII/análise , Tempo de Tromboplastina Parcial , Adulto , Dor no Peito/etiologia , Dispneia/etiologia , Serviço Hospitalar de Emergência , Deficiência do Fator XII/complicações , Feminino , Humanos
9.
Am J Vet Res ; 80(9): 846-851, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31449444

RESUMO

OBJECTIVE: To evaluate coagulation factors in units of leukoreduced (LR) and nonleukoreduced (non-LR) canine fresh-frozen plasma (cFFP). ANIMALS: 8 healthy research dogs. PROCEDURES: In a crossover study, dogs were randomly assigned to 1 of 2 groups from which blood was collected and either did or did not undergo leukoreduction. After a recovery period of ≥ 28 days, the dogs were switched between protocols. After each collection, blood samples were centrifuged, and cFFP was stored frozen for later comparative analysis of coagulation factors, antithrombin, and protein C activities (reported as comparative percentages of the corresponding activities determined in a canine pooled plasma standard); prothrombin and activated partial thromboplastin times; and fibrinogen concentration. RESULTS: There were no significant differences detected between results for LR cFFP, compared with those for non-LR cFFP. CONCLUSIONS AND CLINICAL RELEVANCE: Although there was variation among residual activities of coagulation factors in LR and non-LR cFFP, the variations and differences were considered unlikely to impact the efficacy of LR cFFP transfused for coagulation factor replacement in dogs. However, owing to the small sample size and high variability of results in the present study, additional research with a larger sample size is required for definitive conclusions on the effects of leukoreduction on coagulation factors in cFFP and to develop treatment guidelines for LR cFFP use in dogs with congenital and acquired coagulopathies.


Assuntos
Fatores de Coagulação Sanguínea/análise , Cães/sangue , Leucócitos , Plasma/química , Animais , Estudos Cross-Over , Feminino , Fibrinogênio/análise , Contagem de Leucócitos/veterinária , Masculino , Tempo de Tromboplastina Parcial , Distribuição Aleatória
10.
Blood Coagul Fibrinolysis ; 30(6): 281-290, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31369408

RESUMO

: Thrombelastography (TEG) parameters and prothrombin time (PT), activated partial thromboplastin time (APTT) are compared and analysed. According to change of TEG parameters and assessment of haemostatic state of each patient, we try to explore the feasibility of individualized anticoagulant therapies. 87 people with hip or knee diseases awaiting arthroplasty were recruited. Haemoglobin levels and TEG parameters including R, K, α-angle, maximum amplitude, coagulation index were assessed in perioperative period. PT and APTT were assessed preoperatively. For 65 patients with normal TEG parameters, PT and APTT, we use tranexamic acid (TXA) to reduce blood loss during operation. As hypercoagulability group, 12 patients awaiting unilateral total knee arthroplasty with hypercoagulable state assessed by TEG parameters or risks for venous thromboembolism received daily 10-mg rivaroxaban until 24 h preoperatively and did not receive TXA during operation. All patients received intravenous administration of argatroban after 8 h postoperatively until day 3 and oral administration of rivaroxaban (10 mg) subsequently to prevent deep vein thrombosis or/and pulmonary embolism until 35 days postoperatively. TEG parameters have significant relationships with fibrinogen, platelet and APTT. The number of patients with abnormal haemostatic state assessed by TEG parameters is higher than that assessed by PT, APTT. TEG show hypercoagulability develops throughout perioperative period. There was no significant difference in haemoglobin concentration between hypercoagulability group and normal group in patients receiving unilateral total knee arthroplasty. TEG have higher sensitivity of perioperative abnormal haemostatic state than PT, APTT in primary arthroplasty. For patients with hypercoagulability, individualized anticoagulant therapies such as preoperative administration of rivaroxaban and not using TXA in operation is safe and effective.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Tromboelastografia/métodos , Anticoagulantes/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/normas , Assistência Perioperatória , Ácidos Pipecólicos/uso terapêutico , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Estudos Prospectivos , Tempo de Protrombina/normas , Embolia Pulmonar/prevenção & controle , Rivaroxabana/uso terapêutico , Tromboelastografia/normas , Trombofilia/diagnóstico , Trombofilia/tratamento farmacológico , Trombose Venosa/prevenção & controle
11.
Fitoterapia ; 138: 104345, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31470063

RESUMO

The present study reports the phytochemical investigation of n-butanol-soluble extracts of Glechoma longituba. Five new oleanane-type triterpenoid saponins with an 11α, 12α-epoxy unit, named glechomanosides A - E, were isolated from the n-butanol soluble fraction of G. longituba. Their chemical structures were established using HRESIMS, IR, 1D NMR, and 2D NMR techniques. The compounds were all evaluated for their antithrombus activities by monitoring thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), and antiplatelet aggregation assays. These results suggest that G. longituba might be a candidate plant source of an interesting antithrombotic activity.


Assuntos
Plaquetas/efeitos dos fármacos , Lamiaceae/química , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Animais , China , Feminino , Masculino , Camundongos , Estrutura Molecular , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Tempo de Tromboplastina Parcial , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Agregação Plaquetária , Tempo de Protrombina , Coelhos , Saponinas/isolamento & purificação , Tempo de Trombina
12.
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
13.
Clin Appl Thromb Hemost ; 25: 1076029619867137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364394

RESUMO

To describe the effect of dabigatran on thrombin time (TT) reagents at different concentrations of thrombin. Pooled normal plasma enriched with dabigatran was dissolved in dimethylsulfoxide (DMSO) at concentrations of 0, 20, 50, 100, 200, 300, and 500 ng/mL. Samples with each concentration were evaluated using a semiautomatic coagulation analyzer to assess the effect of dabigatran on internal normalized ratio (INR), thromboplastin time (APTT), and TT, which were purchased from Instrument Laboratory (IL), Sysmex (SYS), and Stago (STA), respectively. Regarding INR, no reagent showed good sensitivity to increasing concentration of dabigatran, despite all reagents showing good linear response curves (P = .012). Regarding APTT, all reagents had low sensitivity to increasing dabigatran concentration, but SYS-APTT showed a better linear response curve (P = .001). Regarding TT, all reagents had a good linear response to the concentration of dabigatran; however, SYS-TT was very sensitive at low concentrations of dabigatran (0-100 ng/mL), while IL (TT-5 mL) and STA-TT were sensitive at medium concentrations of dabigatran (0-300 ng/mL), and IL (TT-2 mL) was less sensitive for a wide concentration of dabigatran (0-500 ng/mL; P = .007). Internal normalized ratio and APTT showed low sensitivity and SYS-TT showed high sensitivity to concentrations of dabigatran that were unsuitable to monitor. Both IL (TT-5 mL) and STA-TT were useful at medium concentrations of dabigatran by semiautomatic coagulation analyzer, which calculated results using the end point method of coagulation. Instrument Laboratory (TT-2 mL), which contains a higher concentration of thrombin, had better sensitivity to the concentration of dabigatran than APTT and was suitable for routine monitoring by an automatic analyzer.


Assuntos
Dabigatrana/farmacocinética , Monitoramento de Medicamentos/métodos , Tempo de Trombina , Antitrombinas/sangue , Antitrombinas/farmacocinética , Testes de Coagulação Sanguínea , Dabigatrana/sangue , Dabigatrana/normas , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/normas , Humanos , Indicadores e Reagentes/farmacologia , Tempo de Tromboplastina Parcial , Sensibilidade e Especificidade , Trombina/farmacologia
14.
Blood Coagul Fibrinolysis ; 30(6): 300-303, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31318719

RESUMO

: Activated partial thromboplastin time is a test assessing the intrinsic and common pathways of the coagulation cascade. We presented an asymptomatic case with isolated activated partial thromboplastin time prolongation. After excluding coagulation factor deficiency and lupus anticoagulant, the patient was diagnosed with plasma prekallikrein (PPK) deficiency. We reviewed the literature regarding effects of PPK deficiency which could have both antithrombotic and prothrombotic effects. At the moment, research supports that PPK deficiency in healthy adults rarely causes bleeding as it is not a major contributor of hemastasis; whereas in adults with multiple comorbidities or with predominant systemic inflammation, effects of PPK deficiency remain debatable. Further research is needed to clarify impacts of PPK deficiency in clinical settings.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Tempo de Tromboplastina Parcial , Pré-Calicreína/deficiência , Adulto , Transtornos da Coagulação Sanguínea/diagnóstico , Comorbidade , Diagnóstico Diferencial , Hemorragia/etiologia , Humanos
15.
Transfus Apher Sci ; 58(4): 512-514, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31272859

RESUMO

A 31-year-old man with mild hemophilia B developed a herniated disc treated with prednisolone for back pain. Surprisingly, hemostasis result tests performed before epidural infiltration were a normal activated partial thrombin time at 36.1 s. (normal range 27.9-37.7 s.) and factor IX (FIX) level 76% (normal range>70%), 13 days after prednisolone introduction. After a second control with a normal FIX level and a second genetic confirmation of hemophilia, no FIX concentrates was administered to perform the infiltration, which occurred without hemorrhagic complication. This new case of FIX normalization showed the necessity to have a perfect knowledge of patient's treatment to avoid misdiagnosis and a temporary normal hemostasis permit to perform epidural infiltration without replacement therapy.


Assuntos
Fator IX/metabolismo , Hemofilia B/sangue , Deslocamento do Disco Intervertebral/sangue , Deslocamento do Disco Intervertebral/terapia , Prednisolona/administração & dosagem , Adulto , Humanos , Masculino , Tempo de Tromboplastina Parcial
16.
Rev Med Chil ; 147(3): 334-341, 2019 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-31344171

RESUMO

Acquired hemophilia A (AHA) is a rare and life-threatening autoimmune hemorrhagic disorder where autoantibodies are developed against factor VIII. An early diagnosis is challenging and mandatory: an immediate hemostatic control is required to reduce morbidity and mortality. Laboratory features of AHA are: presence of autoantibodies against factor VIII, prolonged activated partial thromboplastin time (with normal prothrombin time and thrombin time) and decreased factor VIII levels. In some cases, the results of laboratory tests may be incorrect due to errors in analysis, blood extraction or manipulation of samples; also worth of consideration are limitations in the measurement range and low sensitivity of the tests. This review highlights the importance of adequate screening in patients with suspected AHA to make an adequate diagnosis and reduce overall fatal outcomes.


Assuntos
Hemofilia A/diagnóstico , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/fisiopatologia , Testes de Coagulação Sanguínea , Diagnóstico Precoce , Fator VIII , Hemofilia A/fisiopatologia , Humanos , Tempo de Tromboplastina Parcial
17.
Biomed Res Int ; 2019: 8759231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360727

RESUMO

Introduction. Subarachnoid hemorrhage (SAH) is currently one of the most serious diseases of the central nervous system. To reduce the negative consequences of SAH and help clinicians to assess the patient's condition, there are attempts to search for new diagnostic markers, which quickly and accurately allow for the proper diagnosis. The aim of this research was the concentration and activity of Vascular Endothelial Growth Factor A (VEGF-A) and selected parameters of coagulation and fibrinolysis in the blood of patients with SAH. Serum levels of VEGF-A in patients diagnosed with SAH are measured to assess the correlation between VEGF-A and the clinical condition of patient. This may help with proper therapeutics and better prognosis. Methods. The study involved 85 patients with subarachnoid hemorrhage. The control group consisted of 45 healthy subjects, sex and age matched. The following parameters were determined: APTT (Activated Partial Thromboplastin Time), INR (International Normalized Ratio), D-dimers and fibrinogen concentration, and the concentration of VEGF-A by ELISA (R&D USA). Results. The average concentration of VEGF-A in the study group was significantly lower compared to the control group. The D-dimer concentration was higher in patients with SAH but the difference was not significant. Coagulation parameters such as INR, APTT, and fibrinogen did not show significant differences between investigated groups. Conclusions. VEGF-A cannot be an independent marker of SAH. Selected parameters of coagulation and fibrinolysis such as D-dimers, INR, APTT, and fibrinogen should not be used as markers of SAH.


Assuntos
Fibrinólise , Hemorragia Subaracnóidea/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial
18.
Molecules ; 24(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174390

RESUMO

Pentamidine is bis-oxybenzamidine-based antiprotozoal drug. The parenteral use of pentamidine appears to affect the processes of blood coagulation and/or fibrinolysis resulting in rare but potentially life-threatening blood clot formation. Pentamidine was also found to cause disseminated intravascular coagulation syndrome. To investigate the potential underlying molecular mechanism(s) of pentamidine's effects on coagulation and fibrinolysis, we studied its effects on clotting times in normal and deficient human plasmas. Using normal plasma, pentamidine isethionate doubled the activated partial thromboplastin time at 27.5 µM, doubled the prothrombin time at 45.7 µM, and weakly doubled the thrombin time at 158.17 µM. Using plasmas deficient of factors VIIa, IXa, XIa, or XIIa, the concentrations to double the activated partial thromboplastin time were similar to that obtained using normal plasma. Pentamidine also inhibited plasmin-mediated clot lysis with half-maximal inhibitory concentration (IC50) value of ~3.6 µM. Chromogenic substrate hydrolysis assays indicated that pentamidine inhibits factor Xa and plasmin with IC50 values of 10.4 µM and 8.4 µM, respectively. Interestingly, it did not significantly inhibit thrombin, factor XIa, factor XIIIa, neutrophil elastase, or chymotrypsin at the highest concentrations tested. Michaelis-Menten kinetics and molecular modeling studies revealed that pentamidine inhibits factor Xa and plasmin in a competitive fashion. Overall, this study provides quantitative mechanistic insights into the in vitro effects of pentamidine isethionate on coagulation and fibrinolysis via the disruption of the proteolytic activity of factor Xa and plasmin.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Pentamidina/farmacologia , Trombose/tratamento farmacológico , Testes de Coagulação Sanguínea , Fator VIIa/genética , Fator XIIa/genética , Fator XIa/genética , Fator Xa/genética , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Trombina/química , Trombina/genética , Tempo de Trombina , Trombose/sangue , Trombose/patologia
19.
Vestn Otorinolaringol ; 84(2): 18-22, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31198210

RESUMO

The analysis (1998-2018) of the causes of early postoperative bleeding in 68 children with chronic lymphoproliferative syndrome and late postoperative bleeding (on the 7-10th day) in 3 children aged 3 to 17 years was performed. It was found the disorder of the platelet functional activity (adrenaline-induced platelet aggregation, adrenaline concentration - 2.5 µmol/l) in 83.8% cases (57 children). Late postoperative bleedings were developed due to the uncontrolled intake of nonsteroidal anti-inflammatory painkillers, which led to the platelet dysfunction. It has been established the decrease in the prothrombin percent by Quick in 73.5% children, and the elongation of the activated partial thromboplastin time (APTT) in the quarter of children amid the bleeding. Half of the children showed the increase of D-dimer concentration to 1.5-2 fold amid the bleeding. We offer preoperative examination: platelet count, prothrombin percent by Quick (prothrombin time), APTT and fibrinogen level. We recommend an extended hemostasis study with the detection of adhesive, aggregative and secretory functions of platelets in the children with chronic lymphoproliferative syndrome if the results of the integral screening tests differ from normal range.


Assuntos
Hemostasia , Hemostáticos , Transtornos Linfoproliferativos , Procedimentos Cirúrgicos Otorrinolaringológicos , Adolescente , Criança , Pré-Escolar , Humanos , Transtornos Linfoproliferativos/complicações , Tempo de Tromboplastina Parcial , Hemorragia Pós-Operatória/diagnóstico , Tempo de Protrombina
20.
Int J Pediatr Otorhinolaryngol ; 124: 210-214, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31229837

RESUMO

OBJECTIVES: There is currently no standard for screening children with post-tonsillectomy bleeds (PTB) for coagulopathy disorders. This study aims to identify children with occult coagulopathy diagnosed at PTB and to identify factors associated with diagnosis. A systematic review of the literature further identified trends in this topic. METHODS: A retrospective chart review of patients returning to the operating room for PTB at a tertiary children's hospital was undertaken from 2012 to 2016. A systematic review using Medline OVID was subsequently performed. RESULTS: Of 12,503 tonsillectomies, 311 children (52% male, mean age 8 years) required surgery for PTB (2.5% rate). Twenty-one patients (7%) had multiple episodes. Only two patients (0.6%) (both with known coagulopathy) underwent pre-tonsillectomy labs and 260 (84%) had labs at PTB. Six patients (2%) were diagnosed with a new coagulopathy, most commonly von Willebrand's Disease (vWD) in five (2%). Three patients (1%) were diagnosed at first PTB and three (1%) at second PTB. Of the three diagnosed at second PTB, two had normal partial thromboplastin time (PTT). In systematic review, 1243 manuscripts were reviewed and 8 papers discussing this topic are presented. CONCLUSION: Occult coagulopathy was rarely diagnosed at PTB, but this may be limited by inconsistent screening. PT and PTT are not sensitive tests for vWD, and normal coagulation labs may lead to delayed diagnosis. The literature reveals occult coagulopathy is rare but often diagnosed after severe or recurrent hemorrhage. In order to provide efficient care and medical management, a standardized algorithm and sensitive labs for screening PTB patients are needed.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos Hemorrágicos/diagnóstico , Hemorragia Pós-Operatória/diagnóstico , Tonsilectomia/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Tempo de Tromboplastina Parcial , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos
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