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1.
Sci Rep ; 10(1): 14042, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820210

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in thousands of deaths in the world. Information about prediction model of prognosis of SARS-CoV-2 infection is scarce. We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). The maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator logistic regression model were used for selection of laboratory features. Seven laboratory features selected in the model were: prothrombin activity, urea, white blood cell, interleukin-2 receptor, indirect bilirubin, myoglobin, and fibrinogen degradation products. The signature constructed using the seven features had 98% [93%, 100%] sensitivity and 91% [84%, 99%] specificity in predicting outcome of SARS-CoV-2 pneumonia. Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/sangue , Modelos Estatísticos , Pneumonia Viral/sangue , Idoso , Bilirrubina/sangue , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Confiabilidade dos Dados , Estudos de Viabilidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Previsões/métodos , Humanos , Leucócitos , Aprendizado de Máquina , Masculino , Mioglobina/sangue , Pandemias , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Prognóstico , Protrombina/análise , Receptores de Interleucina-2/sangue , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Ureia/sangue
2.
Cochrane Database Syst Rev ; 6: CD008482, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32497260

RESUMO

BACKGROUND: Malabsorption and deficiency of fat-soluble vitamins K may occur in cystic fibrosis, a genetic disorder affecting multiple organs. Vitamin K is known to play an important role in both blood coagulation and bone formation, hence the role of supplementation of vitamin K in this category needs to be reviewed. This is an updated version of the review. OBJECTIVES: To assess the effects of vitamin K supplementation in people with cystic fibrosis and to investigate the hypotheses that vitamin K will decrease deficiency-related coagulopathy, increase bone mineral density, decrease risk of fractures and improve quality of life in people with CF. Also to determine the optimal dose and route of administration of vitamin K for people with CF (for both routine and therapeutic use). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 12 August 2019. SELECTION CRITERIA: Randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two authors independently screened papers, extracted trial details and assessed their risk of bias. The quality of the evidence was assessed using the GRADE criteria. MAIN RESULTS: Three trials (total 70 participants, aged 8 to 46 years) assessed as having a moderate risk of bias were included. One trial compared vitamin K to placebo, a second to no supplementation and the third compared two doses of vitamin K. No trial in either comparison reported our primary outcomes of coagulation and quality of life or the secondary outcomes of nutritional parameters and adverse events. Vitamin K versus control Two trials compared vitamin K to control, but data were not available for analysis. One 12-month trial (n = 38) compared 10 mg vitamin K daily or placebo in a parallel design and one trial (n = 18) was of cross-over design with no washout period and compared 5 mg vitamin K/week for four-weeks to no supplementation for four-weeks. Only the 12-month trial reported on the primary outcome of bone formation; we are very uncertain whether vitamin K supplementation has any effect on bone mineral density at the femoral hip or lumbar spine (very low-quality evidence). Both trials reported an increase in serum vitamin K levels and a decrease in undercarboxylated osteocalcin levels. The cross-over trial also reported that levels of proteins induced by vitamin K absence (PIVKA) showed a decrease and a return to normal following supplementation, but due to the very low-quality evidence we are not certain that this is due to the intervention. High-dose versus low-dose vitamin K One parallel trial (n = 14) compared 1 mg vitamin K/day to 5 mg vitamin K/day for four weeks. The trial did report that there did not appear to be any difference in serum undercarboxylated osteocalcin or vitamin K levels (very low-quality evidence). While the trial reported that serum vitamin K levels improved with supplementation, there was no difference between the high-dose and low-dose groups. AUTHORS' CONCLUSIONS: There is very low-quality evidence of any effect of vitamin K in people with cystic fibrosis. While there is no evidence of harm, until better evidence is available the ongoing recommendations by national CF guidelines should be followed.


Assuntos
Fibrose Cística/sangue , Osteogênese/efeitos dos fármacos , Deficiência de Vitamina K/tratamento farmacológico , Vitamina K/administração & dosagem , Vitaminas/administração & dosagem , Adolescente , Adulto , Biomarcadores/sangue , Coagulação Sanguínea/efeitos dos fármacos , Densidade Óssea , Criança , Fibrose Cística/complicações , Suplementos Nutricionais , Fraturas Ósseas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Osteocalcina/sangue , Precursores de Proteínas/sangue , Protrombina , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina K/sangue , Deficiência de Vitamina K/complicações
3.
Zhonghua Gan Zang Bing Za Zhi ; 28(4): 319-325, 2020 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-32403884

RESUMO

Objective: To analyze the clinical characteristics among types of acute-on-chronic liver failure (ACLF) and explore the new classification criteria for judging the prognosis of acute-on-chronic liver failure, so as to provide a basis for the formulation of more precise therapeutic schedule. Methods: 388 cases with ACLF diagnosed in two tertiary level hospitals were included. Patients demographic characteristics, clinical examination information, diagnostic and treatment process information were collected. Laboratory examination data of day 1, 3, 7, 14, 21, 28 and of week 12 or prior to discharge after improvement and at 24 h prior to liver transplantation or death from the diagnosis of ACLF were collected. According to the change trend of the patient's prothrombin activity (PTA), the changes within 4 weeks and 12 weeks were divided into: increased to > 40 %, increase but still ≤ 40%, progressively decreasing or not continuously rising. Moreover, the change trend of total bilirubin (TBil) was divided into: decreasing degree≥50%, decreasing degree < 50%, progressively increasing or not decreasing. Patients meeting the requirements of dynamic classification were screened. PTA and TBil variation tendency of each patient at week 4 and 12 was synthesized, and prognostic condition for dynamic classification was formulated. The clinical characteristics of ACLF patients were analyzed by χ (2) test. Results: A total of 262 screened cases were enrolled. At the 4th week of the course of disease, 45% of the patients' PTA had increased to > 40%, and 40.8% of the patients' TBIL had decreased by 50%. When the course of disease was progressed to 12 weeks, 65.3% of the patients' PTA had increased to > 40%, and 63.4% of the patients' TBIL had decreased by 50%. Combined with the prognosis of the patients at the 4th and 12th week, the patients' disease evolution process was divided into five types: Type A: 60 cases (22.9%) of rapid progression; Type B: 82 cases (31.3%) of rapid recovery; Type C: 48 cases (18.3%) of slow progression; Type D: 43 cases (16.4%) of slow recovering; Type E: 29 cases (11.1%) of slow persistence. The proportions of patients with rapid progression combined with upper gastrointestinal hemorrhage, hepatic encephalopathy, and acute renal injury were 16.7%, 33.3%, and 33.3%, respectively; while the above-mentioned complications accounted for 3.7%, 7.3%, and 12.2% only in the rapid recovery type, χ (2) = 14.411, 20.060, 12.140, P < 0.05, and the differences were statistically significant. Fungal infection rates were 21.7%, and 10.4% in patients who died of disease or liver transplantation (i.e., patients with rapid progression and slow-progressing types), respectively, and 1.2%, 14%, and 6.9% in patients with rapid progression type, slow-recovering type, and slow persistence type, respectively, and the difference between the rapid progression type and the rapid recovery type was significant, χ (2) = 18.925, and the difference was statistically significant (P < 0.05). Conclusion: The course of disease progression in ACLF patients can be divided into rapid progression type, rapid recovery type, slow progression type, slow recovering type, and slow persistence type. The basis of liver disease, accompanied with fungal infection, gastrointestinal hemorrhage, hepatic encephalopathy and acute renal injury can affect the development of ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Progressão da Doença , Insuficiência Hepática Crônica Agudizada/classificação , Bilirrubina/análise , Humanos , Transplante de Fígado , Prognóstico , Protrombina/análise
4.
Gan To Kagaku Ryoho ; 47(2): 319-321, 2020 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-32381975

RESUMO

We report a case of a 75-year-old man with a-fetoprotein(AFP)-producing gastric cancer accompanied by multiple large liver metastases. The patient underwent a total gastrectomy for gastric cancer(p-T3N3H0P0M0, fStage ⅢB). The patient then underwent chemotherapy(TS-1 80m g/day)following the radical operation. However, 5 months after the radical operation, he presented with multiple large liver tumors, which were subsequently biopsied. Based on immunohistochemical examination, the liver tumors were negative for AFP protein, but were similar to hepatoid adenocarcinoma, and no fibrosis was observed in the background liver. Therefore, we diagnosed the tumors as liver metastases of AFP producing gastric cancer and metachronous liver metastasis. The patient underwent transcatheter arterial chemoembolization(TACE). TACE decreased the AFP and PIVKA-Ⅱ levels and reduced the multiple huge liver metastases. Due to the increase in AFP and the multiple liver metastases, despite intensive hepatic infusion chemotherapy, he died 5 months after admission.


Assuntos
Quimioembolização Terapêutica , Neoplasias Hepáticas , Neoplasias Gástricas , Idoso , Biomarcadores , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Precursores de Proteínas , Protrombina , alfa-Fetoproteínas
5.
Neurology ; 94(18): e1892-e1899, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32291293

RESUMO

OBJECTIVE: To test the hypothesis that markers of coagulation and hemostatic activation (MOCHA) help identify causes of cryptogenic stroke, we obtained serum measurements on 132 patients and followed them up to identify causes of stroke. METHODS: Consecutive patients with cryptogenic stroke who met embolic stroke of undetermined source (ESUS) criteria from January 1, 2017, to October 31, 2018, underwent outpatient cardiac monitoring and the MOCHA profile (serum D-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) obtained ≥2 weeks after the index stroke; abnormal MOCHA profile was defined as ≥2 elevated markers. Prespecified endpoints monitored during routine clinical visits included new atrial fibrillation (AF), malignancy, venous thromboembolism (VTE), or other defined hypercoagulable states (HS). RESULTS: Overall, 132 patients with ESUS (mean age 64 ± 15 years, 61% female, 51% nonwhite) met study criteria. During a median follow-up of 10 (interquartile range 7-14) months, AF, malignancy, VTE, or HS was identified in 31 (23%) patients; the 53 (40%) patients with ESUS with abnormal MOCHA were significantly more likely than patients with normal levels to have subsequent new diagnoses of malignancy (21% vs 0%, p < 0.001), VTE (9% vs 0%, p = 0.009), or HS (11% vs 0%, p = 0.004) but not AF (8% vs 9%, p = 0.79). The combination of 4 normal MOCHA and normal left atrial size (n = 30) had 100% sensitivity for ruling out the prespecified endpoints. CONCLUSION: The MOCHA profile identified patients with cryptogenic stroke more likely to have new malignancy, VTE, or HS during short-term follow-up and may be useful in direct evaluation for underlying causes of cryptogenic stroke.


Assuntos
Biomarcadores/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Antitrombina III , Coagulação Sanguínea , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemostasia , Humanos , Pessoa de Meia-Idade , Neoplasias/complicações , Fragmentos de Peptídeos/sangue , Peptídeo Hidrolases/sangue , Protrombina , Estudos Retrospectivos , Trombofilia/complicações , Tromboembolia Venosa/complicações
6.
Vascular ; 28(4): 368-377, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32252612

RESUMO

OBJECTIVE: Peripheral artery disease patients have been shown to be more susceptible to thrombotic events compared to non-peripheral artery disease patients. Therefore, the aim of this study was to investigate the coagulation profile in peripheral artery disease patients with chronic limb threatening ischemia, moderate peripheral artery disease patients with claudication, and non-peripheral artery disease controls. METHODS: Chronic limb threatening ischemia patients were matched to peripheral artery disease patients with claudication and non-peripheral artery disease controls in a 1:1:1 ratio. Each patient had their cytokines, markers of thrombin generation, coagulation factors, natural anti-coagulants, fibrinolysis, and endothelial injury markers assessed. RESULTS: Markers of thrombin activation, thrombin Fragments F1 + 2 (Frag 1 + 2), and thrombin-anti-thrombin complex were found to be significantly elevated in all peripheral artery disease and chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Similarly, relative to non-peripheral artery disease controls, inflammatory markers including C-reactive protein, soluble platelet factor 4, and neutrophil gelatinase-associated lipocalin were also found to be significantly upregulated in chronic limb threatening ischemia patients, but not in peripheral artery disease patients with claudication. Furthermore, our data demonstrated significant increases in markers of endothelial injury in chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Finally, decreases in natural anti-coagulants (protein C and protein S) and coagulation factors FIX, FXI, and FXII were also observed in chronic limb threatening ischemia patients when compared with non-peripheral artery disease controls. CONCLUSIONS: Our data suggest that in relation to non-peripheral artery disease controls, chronic limb threatening ischemia patients are more hypercoagulable. However, peripheral artery disease patients with claudication appear to have similar levels of circulating procoagulant markers as non-peripheral artery disease patients. This may explain the increased risk of thrombotic events observed in chronic limb threatening ischemia patients.


Assuntos
Coagulação Sanguínea , Claudicação Intermitente/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Idoso , Antitrombina III , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/análise , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Mediadores da Inflamação/sangue , Claudicação Intermitente/diagnóstico , Isquemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeo Hidrolases/sangue , Doença Arterial Periférica/diagnóstico , Projetos Piloto , Protrombina
7.
Wiad Lek ; 73(3): 471-477, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285816

RESUMO

OBJECTIVE: The aim is the analysis of the relationship between the polymorphism of thrombophilic genes, in particular Serpin 1 (PAI-1), F2-prothrombin and ITGB3-α integrin, and the incidence of stroke, as well as the study of factor effects of this polymorphism in association with controlled risk factors (hypertonic disease, smoking, alcohol consumption, diabetes mellitus, obesity, atrial fibrillation). PATIENTS AND METHODS: Materials and methods: A total of 134 patients were examined (men accounted for 44.8%, women 55.2%, average age 62.5 ± 2.1). The statistical analysis was carried out using the following criteria: χ2-Pearson, Fisher's exact criterion (reversible), Chuprov's coefficient of conjugation and dispersion analysis (alternative complex). RESULTS: Results: The relationship between the frequency of a specific allele of thrombophilia and the incidence of stroke is absent. The reason for such results can be a significant effect of random factors (hypertension, diabetes ...), a significant variability of risk factors, their different frequency in groups (inter- and intra-group differences), a significant (95%) total effect of these factors. CONCLUSION: Conclusions:Identification of biochemical or genetic markers of thrombophilic conditions, including polymorphism of the hemostasis system genes, will significantly increase the possibility of adequate pathogenetic treatment and timely prevention of acute cerebrovascular disorders, especially persons of working age, which has great medical and social importance.


Assuntos
Acidente Vascular Cerebral , Trombofilia , Fator V , Feminino , Humanos , Integrina beta3 , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio , Protrombina , Fatores de Risco , Serpinas
8.
Clin Chem Lab Med ; 58(7): 1116-1120, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: covidwho-8776

RESUMO

Background As the number of patients increases, there is a growing understanding of the form of pneumonia sustained by the 2019 novel coronavirus (SARS-CoV-2), which has caused an outbreak in China. Up to now, clinical features and treatment of patients infected with SARS-CoV-2 have been reported in detail. However, the relationship between SARS-CoV-2 and coagulation has been scarcely addressed. Our aim is to investigate the blood coagulation function of patients with SARS-CoV-2 infection. Methods In our study, 94 patients with confirmed SARS-CoV-2 infection were admitted in Renmin Hospital of Wuhan University. We prospectively collect blood coagulation data in these patients and in 40 healthy controls during the same period. Results Antithrombin values in patients were lower than that in the control group (p < 0.001). The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. Moreover, D-dimer and FDP values in patients with severe SARS-CoV-2 infection were higher than those in patients with milder forms. Compared with healthy controls, prothrombin time activity (PT-act) was lower in SARS-CoV-2 patients. Thrombin time in critical SARS-CoV-2 patients was also shorter than that in controls. Conclusions The coagulation function in patients with SARS-CoV-2 is significantly deranged compared with healthy people, but monitoring D-dimer and FDP values may be helpful for the early identification of severe cases.


Assuntos
Testes de Coagulação Sanguínea/métodos , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Adulto , Anticoagulantes , Betacoronavirus/patogenicidade , Biomarcadores/sangue , China/epidemiologia , Infecções por Coronavirus/fisiopatologia , Surtos de Doenças , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/fisiopatologia , Protrombina/análise , Síndrome Respiratória Aguda Grave/epidemiologia
9.
Clin Chem Lab Med ; 58(7): 1116-1120, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32172226

RESUMO

Background As the number of patients increases, there is a growing understanding of the form of pneumonia sustained by the 2019 novel coronavirus (SARS-CoV-2), which has caused an outbreak in China. Up to now, clinical features and treatment of patients infected with SARS-CoV-2 have been reported in detail. However, the relationship between SARS-CoV-2 and coagulation has been scarcely addressed. Our aim is to investigate the blood coagulation function of patients with SARS-CoV-2 infection. Methods In our study, 94 patients with confirmed SARS-CoV-2 infection were admitted in Renmin Hospital of Wuhan University. We prospectively collect blood coagulation data in these patients and in 40 healthy controls during the same period. Results Antithrombin values in patients were lower than that in the control group (p < 0.001). The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. Moreover, D-dimer and FDP values in patients with severe SARS-CoV-2 infection were higher than those in patients with milder forms. Compared with healthy controls, prothrombin time activity (PT-act) was lower in SARS-CoV-2 patients. Thrombin time in critical SARS-CoV-2 patients was also shorter than that in controls. Conclusions The coagulation function in patients with SARS-CoV-2 is significantly deranged compared with healthy people, but monitoring D-dimer and FDP values may be helpful for the early identification of severe cases.


Assuntos
Testes de Coagulação Sanguínea/métodos , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Adulto , Anticoagulantes , Betacoronavirus/patogenicidade , Biomarcadores/sangue , China/epidemiologia , Infecções por Coronavirus/fisiopatologia , Surtos de Doenças , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/fisiopatologia , Protrombina/análise , Síndrome Respiratória Aguda Grave/epidemiologia
10.
Arterioscler Thromb Vasc Biol ; 40(4): 901-913, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32102568

RESUMO

OBJECTIVE: Cardiac myosin (CM) is structurally similar to skeletal muscle myosin, which has procoagulant activity. Here, we evaluated CM's ex vivo, in vivo, and in vitro activities related to hemostasis and thrombosis. Approach and Results: Perfusion of fresh human blood over CM-coated surfaces caused thrombus formation and fibrin deposition. Addition of CM to blood passing over collagen-coated surfaces enhanced fibrin formation. In a murine ischemia/reperfusion injury model, exogenous CM, when administered intravenously, augmented myocardial infarction and troponin I release. In hemophilia A mice, intravenously administered CM reduced tail-cut-initiated bleeding. These data provide proof of concept for CM's in vivo procoagulant properties. In vitro studies clarified some mechanisms for CM's procoagulant properties. Thrombin generation assays showed that CM, like skeletal muscle myosin, enhanced thrombin generation in human platelet-rich and platelet-poor plasmas and also in mixtures of purified factors Xa, Va, and prothrombin. Binding studies showed that CM, like skeletal muscle myosin, directly binds factor Xa, supporting the concept that the CM surface is a site for prothrombinase assembly. In tPA (tissue-type plasminogen activator)-induced plasma clot lysis assays, CM was antifibrinolytic due to robust CM-dependent thrombin generation that enhanced activation of TAFI (thrombin activatable fibrinolysis inhibitor). CONCLUSIONS: CM in vitro is procoagulant and prothrombotic. CM in vivo can augment myocardial damage and can be prohemostatic in the presence of bleeding. CM's procoagulant and antifibrinolytic activities likely involve, at least in part, its ability to bind factor Xa and enhance thrombin generation. Future work is needed to clarify CM's pathophysiology and its mechanistic influences on hemostasis or thrombosis.


Assuntos
Coagulação Sanguínea , Miosinas Cardíacas/metabolismo , Hemostasia , Trombina/biossíntese , Trombose/fisiopatologia , Animais , Plaquetas/metabolismo , Miosinas Cardíacas/fisiologia , Modelos Animais de Doenças , Fator Va/metabolismo , Fator Xa/metabolismo , Hemorragia/fisiopatologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Protrombina/metabolismo
11.
Clin Chem ; 66(2): 379-389, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040579

RESUMO

BACKGROUND: Thrombosis is a major global disease burden with almost 60% of cases related to underlying heredity and most cases still idiopathic. Synonymous single nucleotide polymorphisms (sSNPs) are considered silent and phenotypically neutral. Our previous study revealed a novel synonymous FII c.1824C>T variant as a potential risk factor for pregnancy loss, but it has not yet been associated with thrombotic diseases. METHODS: To determine the frequency of the FII c.1824C>T variant we have sequenced patients' DNA. Prothrombin RNA expression was measured by quantitative PCR. Functional analyses included routine hemostasis tests, western blotting and ELISA to determine prothrombin levels in plasma, and global hemostasis assays for thrombin and fibrin generation in carriers of the FII c.1824C>T variant. Scanning electron microscopy was used to examine the structure of fibrin clots. RESULTS: Frequency of the FII c.1824C>T variant was significantly increased in patients with venous thromboembolism and cerebrovascular insult. Examination in vitro demonstrated increased expression of prothrombin mRNA in FII c.1824T transfected cells. Our ex vivo study of FII c.1824C>T carriers showed that the presence of this variant was associated with hyperprothrombinemia, hypofibrinolysis, and formation of densely packed fibrin clots resistant to fibrinolysis. CONCLUSION: Our data indicate that FII c.1824C>T, although a synonymous variant, leads to the development of a prothrombotic phenotype and could represent a new prothrombotic risk factor. As a silent variant, FII c.1824C>T would probably be overlooked during genetic screening, and our results show that it could not be detected in routine laboratory tests.


Assuntos
Protrombina/genética , Trombose/genética , Adulto , Animais , Testes de Coagulação Sanguínea , Células COS , Estudos de Casos e Controles , Chlorocebus aethiops , Éxons/genética , Feminino , Hemostasia , Heterozigoto , Humanos , Masculino , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Protrombina/metabolismo , Estudos Retrospectivos , Fatores de Risco , Mutação Silenciosa/genética , Trombina/metabolismo , Trombofilia/genética , Trombofilia/metabolismo , Trombose/metabolismo , Tromboembolia Venosa/genética , Tromboembolia Venosa/metabolismo
12.
Vasc Health Risk Manag ; 16: 53-56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021228

RESUMO

Introduction: Factor V Leiden (G1691A), prothrombin (G20210A) and MTHFR (C677T) gene mutations were investigated in many studies for their association with Deep Venous Thrombosis. Case Presentation: A North Lebanese family has been examined, from an index case, a 40-year-old woman, who had a history of venous thrombosis with unexplained recurrent miscarriage. The index case was found to be heterozygous for factor V Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T gene variants. Her family members were heterozygous for at least two of the three-point mutations, and multiple risk factors associated with thrombophilia were identified. Conclusion: Our findings emphasize the need for clarifying the utility and futility of thrombophilia testing in the era of molecular diagnostics.


Assuntos
Aborto Habitual/etiologia , Resistência à Proteína C Ativada/genética , Coagulação Sanguínea/genética , Fator V/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Protrombina/genética , Trombofilia/genética , Trombose Venosa/etiologia , Aborto Habitual/sangue , Aborto Habitual/diagnóstico , Resistência à Proteína C Ativada/sangue , Resistência à Proteína C Ativada/complicações , Resistência à Proteína C Ativada/diagnóstico , Adulto , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Líbano , Linhagem , Fenótipo , Gravidez , Fatores de Risco , Trombofilia/sangue , Trombofilia/complicações , Trombofilia/diagnóstico , Trombose Venosa/sangue , Trombose Venosa/diagnóstico
13.
Am J Cardiol ; 125(5): 751-758, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31889526

RESUMO

Recent findings in atrial fibrillation (AF) patients receiving oral anticoagulation showed that diabetes without insulin therapy has a thromboembolic risk comparable to nondiabetic patients, whereas only diabetic patients on insulin have a heightened thromboembolic risk. We explored possible pathophysiological correlates of such finding on 90 AF patients on oral anticoagulation, divided according to diabetes status (n = 30 without diabetes; n = 29 with diabetes on oral antidiabetic drugs; n = 31 with insulin-requiring diabetes). We assessed von Willebrand Factor (VWF) concentration (VWF:Ag) and activity (VWF R:Co) as measures of endothelial dysfunction; and thrombin-activatable fibrinolysis inhibitor (TAFI) and prothrombin fragment 1 + 2 (F1+2) levels as markers of fibrinolytic activity and thrombin generation. Values of VWF:Ag, VWF:RCo, and TAFI were similar in the 3 groups. Patients with diabetes requiring insulin had significantly higher levels of F1+2 (median 23.1 pg/ml [interquartile range 17.6; 33.5]) than those without diabetes (16.3 pg/ml [11.5; 22.5], p = 0.036) and diabetic patients on oral antidiabetic drugs (20.6 pg/ml [13.3; 29], p = 0.046). Thus, in AF patients receiving oral anticoagulation, those with diabetes, regardless of the diabetes type (with or without insulin therapy), and those without diabetes have comparable indices of the explored parameters of endothelial dysfunction and fibrinolytic activity. Despite anticoagulant therapy, thrombin generation is selectively higher in diabetic patients' on insulin than in those without diabetes or with diabetes on oral antidiabetic drugs, with no differences between these latter 2 conditions. Thrombin generation might thus be a predominant contributor to the excess of thromboembolic risk in AF patients on insulin-requiring diabetes.


Assuntos
Fibrilação Atrial/metabolismo , Carboxipeptidase B2/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Endotélio Vascular/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Fragmentos de Peptídeos/metabolismo , Protrombina/metabolismo , Fator de von Willebrand/metabolismo , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Dabigatrana/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Endotélio Vascular/fisiopatologia , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Itália/epidemiologia , Masculino , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico
14.
Clin Exp Rheumatol ; 38 Suppl 124(2): 161-165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994486

RESUMO

OBJECTIVES: We investigated the relationship between lysosomal-associated membrane protein-2 (LAMP-2) and anti-phosphatidylserine/prothrombin (PS/PT) antibody in the pathogenesis of cutaneous vasculitis. METHODS: Cell surface LAMP-2 expression of human neutrophils was measured using flow cytometry. Twenty inbred wild-type Wistar-King-Aptekman-Hokudai (WKAH) rats were divided into four groups: Group 1, rabbit IgG injection only as negative control (n=5); Group 2, both histone and rabbit IgG injection (n=5); Group 3, anti-LAMP-2 antibody injection only (n=5); and Group 4, both histone and anti-LAMP-2 antibody injection (n=5). Ten WKAH rats were divided into two groups: Group A, histone, anti-PS/PT antibody, and anti-LAMP-2 antibody injection (n=5), and Group B, histone, anti-PS/PT antibody, and rabbit IgG injection as control (n=5). RESULTS: LAMP-2 expression on human neutrophils was induced by cell-free histone exposure in a dose- and time-dependent manner. Histopathological examination revealed the recruitment of neutrophils in cutaneous small vessels in all Group 4 rats. These observations were not evident in systemic organs other than the skin. LAMP-2 expression on the surface of vascular endothelial cells was evident in Group 2, exclusively in the skin, but not in Group 1. Thrombi were detected in various organs in all Groups A and B rats. However, no apparent thrombi were observed in the skin. CONCLUSIONS: Anti-PS/PT and anti-LAMP-2 antibodies are responsible for independent effector mechanisms in the rats given intravenous injection of cell-free histones. We considered that undetermined factors other than cell-free histones could be required for the induction of cutaneous vasculitis by anti-PS/PT and anti-LAMP-2 antibodies.


Assuntos
Imunoglobulina G/imunologia , Proteína 2 de Membrana Associada ao Lisossomo/imunologia , Fosfatidilserinas/imunologia , Protrombina/imunologia , Vasculite/imunologia , Animais , Células Endoteliais , Humanos , Neutrófilos , Ratos , Ratos Wistar
15.
Am J Clin Pathol ; 153(2): 229-234, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31598704

RESUMO

OBJECTIVES: Lupus anticoagulant (LAC) is typically associated with thrombosis but also rarely with hemorrhage. Some patients exhibit a prozone effect on LAC testing. Antiphosphatidylserine/prothrombin (aPS/PT) antibodies may provide a mechanism for both hemorrhage and prozone effect. Our goal was to evaluate whether antibody specificities, isotypes, and titers were associated with LAC prozone effect, factor II levels, hemorrhage, and thrombosis. METHODS: Patients with prozone effect noted on LAC testing were entered into a database over 3 years. Factor II activity and aPS/PT antibody testing were performed when a sufficient residual sample was available. RESULTS: All patients with LAC prozone effect and antibody testing were positive for at least 1 class of aPS/PT antibodies. In addition, aPS/PT IgG titers were significantly associated with thrombosis and significantly inversely associated with factor II levels. CONCLUSIONS: In prozone effect patients, aPS/PT antibodies are associated with LAC prozone effect as well as thrombosis and decreased factor II levels.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Inibidor de Coagulação do Lúpus/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Protrombina/análise , Trombose/etiologia , Adulto Jovem
16.
J Clin Pathol ; 73(2): 70-75, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862867

RESUMO

Vitamin K is required for the É£-carboxylation of specific glutamic acid residues within the Gla domain of the 17 vitamin K-dependent proteins (VKDPs). The timely detection and correction of vitamin K deficiency can protect against bleeding. Vitamin K also plays a role in bone metabolism and vascular calcification. Patients at increased risk of vitamin K deficiency include those with a restricted diet or malnutrition, lipid malabsorption, cancer, renal disease, neonates and the elderly. Coagulation assays such as the prothrombin time have been used erroneously as indicators of vitamin K status, lacking sufficient sensitivity and specificity for this application. The measurement of phylloquinone (K1) in serum is the most commonly used marker of vitamin K status and reflects abundance of the vitamin. Concentrations <0.15 µg/L are indicative of deficiency. Disadvantages of this approach include exclusion of the other vitamin K homologues and interference from recent dietary intake. The cellular utilisation of vitamin K is determined through measurement of the prevalence of undercarboxylated VKDPs. Most commonly, undercarboxylated prothrombin (Protein Induced by Vitamin K Absence/antagonism, PIVKA-II) is used (reference range 17.4-50.9 mAU/mL (Abbott Architect), providing a retrospective indicator of hepatic vitamin K status. Current clinical applications of PIVKA-II include supporting the diagnosis of vitamin K deficiency bleeding of the newborn, monitoring exposure to vitamin K antagonists, and when used in combination with α-fetoprotein, as a diagnostic marker of hepatocellular carcinoma. Using K1 and PIVKA-II in tandem is an approach that can be used successfully for many patient cohorts, providing insight into both abundance and utilisation of the vitamin.


Assuntos
Análise Química do Sangue , Deficiência de Vitamina K/diagnóstico , Vitamina K/sangue , Biomarcadores/sangue , Análise Química do Sangue/normas , Testes de Coagulação Sanguínea , Humanos , Valor Preditivo dos Testes , Precursores de Proteínas/sangue , Protrombina , Reprodutibilidade dos Testes , Vitamina K 1/sangue , Deficiência de Vitamina K/sangue , Sangramento por Deficiência de Vitamina K/sangue , Sangramento por Deficiência de Vitamina K/diagnóstico
17.
Artigo em Inglês | MEDLINE | ID: mdl-31634575

RESUMO

Dispholidus typus and Thelotornis mossambicanus are closely related rear-fanged colubrid snakes that both possess strongly procoagulant venoms. However, despite similarities in overall venom biochemistry and resulting clinical manifestations, the underlying venom composition differs significantly between the two species. As a result, the only available antivenom-which is a monovalent antivenom for D. typus-has minimal cross reactivity with T. mossambicanus and is not a clinically viable option. It was hypothesised that this lack of cross reactivity is due to the additional large metalloprotease protein within T. mossambicanus venom, which may also be responsible for faster coagulation times. In this study, we found that T. mossambicanus venom is a more powerful activator of prothrombin than that of D. typus and that the SVMP transcripts from T. mossambicanus form a clade with those from D. typus. The sequences from D. typus and T. mossambicanus were highly similar in length, with the calculated molecular weights of the T. mossambicanus transcripts being significantly less than the molecular weights of some isoforms on the 1D SDS-PAGE gels. Analyses utilising degylcosylating enzymes revealed that T. mossambicanus SVMPs are glycosylated during post-translational modification, but that this does not lead to the different molecular weight bands observed in 1D SDS-PAGE gels. However, differences in glycosylation patterns may still explain some of the difference between the enzymatic activities and neutralization by antivenom that have been observed in these venoms. The results of this study provide new information regarding the treatment options for patients envenomated by T. mossambicanus as well as the evolution of these dangerous snakes.


Assuntos
Colubridae/fisiologia , Metaloproteases/metabolismo , Protrombina/metabolismo , Venenos de Serpentes/química , Venenos de Serpentes/metabolismo , Animais , Colubridae/genética , Ativação Enzimática , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glicosilação , Metaloproteases/genética , Filogenia , Protrombina/química , Protrombina/farmacologia , Transcriptoma
18.
Carbohydr Polym ; 227: 115312, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590876

RESUMO

Low molecular weight heparin (LMWH) possesses a dual function of anticoagulation and anti-inflammation. While the structures and mechanisms on its anticoagulation have been widely studied, the structural features responsible for the anti-inflammatory activity of LMWH remain to be explored. In the present study, guided by an anti-inflammation assay, a non-anticoagulant species was generated from partial desulfation of LMWH to fully retain the anti-inflammatory activity, from which five fractions were further separated and three of them were characterized by enzymatic degradation, hydrophobic labeling, C18-based HPLC and LC-MS/MS analyses. The structure-activity relationship revealed that the sulfate groups in LMWH are critical to distinguish and separate the activities of anticoagulation and anti-inflammation, leading to the identification of a synthetic heparosan-type heptasaccharide as a potent anti-inflammatory agent. The present strategy enables the simplification of complex polysaccharides to bioactive synthetic oligosaccharides for therapeutic utility.


Assuntos
Anti-Inflamatórios/farmacologia , Anticoagulantes/química , Dissacarídeos/farmacologia , Heparina de Baixo Peso Molecular/química , Sulfatos/química , Animais , Anti-Inflamatórios/química , Dissacarídeos/química , Fator Xa/química , Heparina Liase/química , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/metabolismo , Protrombina/química , Células RAW 264.7
19.
Arterioscler Thromb Vasc Biol ; 40(2): 483-494, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31875702

RESUMO

OBJECTIVE: Defective PC (protein C) pathway predisposes patients to venous thromboembolism (VTE) and is mostly, but not exclusively, attributed to hereditary PC or PS (protein S) deficiencies and activated PC resistance caused by factor V Leiden mutation. Approach and Results: In a patient with acute mesenteric venous thrombosis and positive family history of VTE associated with the impaired PC pathway function determined by thrombin generation test, we identified a novel heterozygous prothrombin mutation p.Arg541Trp. Two more patients with positive family history of VTE carrying the same mutation were identified in a cohort of another 373 unrelated patients, making an overall prevalence of 0.8%. Family investigation revealed 11 individuals in the 3 pedigrees harboring the heterozygous prothrombin p.Arg541Trp mutation, and 8 of them (72%) had experienced episodes of VTE. Functional studies indicated the mutation moderately decreased procoagulant activity of prothrombin and had mild impact on the inactivation of thrombin by its inhibitor antithrombin. However, the amino acid residue substitution significantly compromised PC activation by thrombin, both in the absence and presence of soluble thrombomodulin, and thus rendered prothrombin function procoagulant biased. CONCLUSIONS: In summary, the prothrombin p.Arg541Trp mutation constitutes a new genetic risk factor of VTE by impairing function of PC pathway and tilting thrombin's procoagulant activity over anticoagulant function.


Assuntos
DNA/genética , Predisposição Genética para Doença , Isquemia Mesentérica/genética , Mutação , Proteína C/metabolismo , Protrombina/genética , Adulto , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Isquemia Mesentérica/sangue , Pessoa de Meia-Idade , Linhagem , Protrombina/metabolismo , Risco
20.
Zhonghua Yi Xue Za Zhi ; 99(44): 3456-3460, 2019 Nov 26.
Artigo em Chinês | MEDLINE | ID: mdl-31826561

RESUMO

Objective: To explore the possibility of using coagulation factor Ⅱ and Ⅹ (FⅡ and FⅩ) for warfarin monitoring among Chinese pulmonary embolism patients. Methods: Blood samples were collected from pulmonary embolism patients who were taking warfarin as anticoagulant and who were from Peking Union Medical Collaege Hospital during Mar 2016 and Oct 2018. Activity of coagulation factor Ⅱ/Ⅹ and International Normalized Ratio (INR) level were detected. Correction analysis was used to investigate the relationship between activity of coagulation factor Ⅱ/Ⅹ and INR. Receiver Operating Characteristic (ROC) curve was used to analyze the diagnostic ability of FⅡ and FⅩ. Results: A total of 157 blood samples were collected in this research. When 1.5≤INR≤3.0, FⅡ (r=-0.768, P<0.001) and FⅩ(r=-0.690, P<0.001) were in inverse correlations with INR. Area under ROC curve (AUC) for FⅡ and FⅩ was 0.961 and 0.965 (P<0.001) when we used INR<2.0 as the criteria of anticoagulant inadequacy. AUC of ROC for FⅡ and FⅩ was 0.885 and 0.890 (P<0.001) when we used INR≤3.0 as the criteria of not over-anticoagulation. Conclusion: FⅡ and FⅩ activity can be used as the therapeutic markers of warfarin in Chinese pulmonary embolism patients.


Assuntos
Anticoagulantes/uso terapêutico , Fator X/uso terapêutico , Protrombina/uso terapêutico , Embolia Pulmonar , Varfarina/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Embolia Pulmonar/tratamento farmacológico
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