Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.461
Filtrar
1.
Neurol India ; 70(3): 1238-1239, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35864677

RESUMO

Herein, we report two acute ischemic stroke cases that we used prothrombin complex to reverse the effects of warfarin in order to apply intravenous thrombolytic treatment. To the best of our knowledge, there are only limited amount of cases that prothrombin complex concentrates were applied prior to intravenous thrombolytic treatment administration. As one of the biggest acute stroke clinics in our country, we aim to open a discussion for this treatment to be fully researched and understood.


Assuntos
AVC Isquêmico , Protrombina , Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Estudos Retrospectivos , Vitamina K
2.
PLoS One ; 17(7): e0271527, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35839244

RESUMO

Decreased platelet count is an early phenomenon in asexual Plasmodium falciparum parasitemia, but its association with acute or long-term functional changes in platelets and coagulation is unknown. Moreover, the impact of gametocytemia on platelets and coagulation remains unclear. We investigated the changes in platelet number and function during early asexual parasitemia, gametocytemia and convalescence in 16 individuals participating in a controlled human malaria infection study, and studied its relationship with changes in total and active von Willebrand factor levels (VWF) and the coagulation system. Platelet activation and reactivity were determined by flow cytometry, and the coagulation system was assessed using different representative assays including antigen assays, activity assays and global functional assays. Platelet count was decreased during asexual blood stage infection but normalized during gametocytemia. Platelet P-selectin expression was slightly increased during asexual parasitemia, gametocytemia and at day 64. In contrast, platelet reactivity to different agonists remained unchanged, except a marked decrease in reactivity to low dose collagen-related peptide-XL. Thrombin generation and antigen assays did not show a clear activation of the coagulation during asexual parasitemia, whereas total and active VWF levels were markedly increased. During gametocytemia and on day 64, the endogenous thrombin potential, thrombin peak and velocity index were increased and prothrombin conversion and plasma prothrombin levels were decreased. We conclude that the decreased platelet count during asexual parasitemia is associated with increased active VWF levels (i.e. endothelial activation), but not platelet hyperreactivity or hypercoagulability, and that the increased platelet clearance in asexual parasitemia could cause spontaneous VWF-platelet complexes formation.


Assuntos
Hemostasia , Malária , Parasitemia , Plaquetas/metabolismo , Hemostasia/fisiologia , Humanos , Malária/complicações , Malária/metabolismo , Parasitemia/complicações , Parasitemia/metabolismo , Protrombina/metabolismo , Trombina/metabolismo , Fator de von Willebrand/metabolismo
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(7): 817-820, 2022 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-35894199

RESUMO

A boy, aged 2 years and 5 months, had recurrent epistaxis, and the coagulation function examination showed that activated partial thromboplastin time (APTT) was significantly prolonged. Further laboratory examinations showed that the prolonged APTT was not immediately corrected in the APTT correction test, with positive lupus anticoagulant and low prothrombin activity. The boy was diagnosed with hypoprothrombinemia-lupus anticoagulant syndrome. The condition was improved after treatment with glucocorticoid, immunoglobulin, and vitamin K1. The boy has been followed up for 6 months, and no epistaxis was observed. Prothrombin activity returned to normal, and lupus anticoagulant remained positive. This is a relatively rare disease, and for patients with bleeding symptoms and coagulation disorders, it is recommended to perform the tests such as APTT correction test, lupus anticoagulant testing, and coagulation factor dilution test, which can improve the detection rate of this disease, so as to achieve early diagnosis, provide rational treatment in the early stage, and improve the prognosis.


Assuntos
Síndrome Antifosfolipídica , Transtornos da Coagulação Sanguínea , Hipoprotrombinemias , Síndrome Antifosfolipídica/diagnóstico , Pré-Escolar , Epistaxe/etiologia , Humanos , Hipoprotrombinemias/diagnóstico , Inibidor de Coagulação do Lúpus , Masculino , Tempo de Tromboplastina Parcial , Protrombina
4.
Transfusion ; 62 Suppl 1: S98-S104, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35748674

RESUMO

BACKGROUND: There is increasing interest in leukoreduced whole blood (WB) as a transfusion product for trauma patients. In some jurisdictions, few leukoreduced filters are approved or appropriate for WB leukoreduction and quality information is therefore limited. This study assessed the impact of filtration timing of WB collected in CPDA-1 versus CPD on in vitro quality. STUDY DESIGN AND METHODS: WB was collected in CPDA-1 or CPD and leukoreduction filtered either after 3-8 h (early) or 18-24 h (late) from stop bleed time. In vitro quality was assessed after filtration and throughout 5 weeks of storage at 4°C. Cell count and hemoglobin levels were determined by hematology analyzer, platelet activation and responsiveness to ADP by surface expression of P-selectin by flow cytometry, hemolysis by HemoCue, and metabolic parameters by blood gas analyzer. Hemostatic properties were assessed by rotational thromboelastometry. Plasma protein activities and clotting times were determined by automated coagulation. RESULTS: Although there were some data points which showed statistically significant differences associated with anticoagulant choices or the filtration timing, no general trend in inferiority/performance could be discerned. After 35 days' storage, only clotting time, alpha angle and factor II in the early filtration arm comparing anticoagulants and prothrombin time and factor II in the CPDA-1 study arm comparing filtration timing showed a significant difference. CONCLUSION: In vitro WB quality seems to be independent on the choice of anticoagulant and filtration timing supporting WB hold-times to up to 24 h, increasing operational flexibility for transfusion services.


Assuntos
Preservação de Sangue , Procedimentos de Redução de Leucócitos , Anticoagulantes/metabolismo , Anticoagulantes/farmacologia , Plaquetas/metabolismo , Humanos , Protrombina
5.
Blood ; 139(24): 3451-3453, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35708725
6.
Sci Rep ; 12(1): 7842, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551494

RESUMO

Information about prevalence and associated factors of non-alcoholic fatty liver disease (NAFLD) has been scarce for the Russian, Eastern European and Central Asian world region. We assessed prevalence and associated factors of NAFLD in two population-based studies (Ural Eye and Medical Study (UEMS), Ural Very Old Study (UVOS)), which were conducted in rural and urban regions in Bashkortostan/Russia and included participants aged 40 + years and 85 + years, respectively. Defining NAFLD by an absence of regular alcohol consumption, and by abnormally high alanine transaminase (ALT) and aspartate transaminase (AST) concentrations or an AST/ALT ratio of > 1.0, 2341 out of 5852 UEMS participants (40.0%; 95% confidence intervals (CI) 38.8, 41.3) had NAFLD. A higher NAFLD prevalence correlated (multivariable analysis) with older age (odds ratio (OR) 1.02; 95%CI 1.01, 1.03; P < 0.001), female sex (OR 1.87; 95%CI 1.58, 2.21; P < 0.001), higher waist-hip circumference ratio (OR 2.64; 95%CI 1.11, 6.27; P = 0.03), lower depression score (OR 0.98; 95%CI 0.96, 0.999; P = 0.04), higher serum concentrations of creatinine (OR 1.004; 95%CI 1.000, 1.008; P = 0.03) and bilirubine (OR 1.009; 95%CI 1.002, 1.015; P = 0.008), lower prothrombin index (OR 0.99; 95%CI 0.985, 0.998; P = 0.01), lower ankle-brachial index (OR 0.49; 95%CI 0.32, 0.75; P = 0.001), higher prevalence of a grain-rich diet (OR 1.88; 95%CI 1.50, 2.36; P < 0.001) and iron deficiency-related anemia (OR 1.61; 95%CI 1.13, 2.29; P = 0.009), and lower prevalence of vigorous leisure activities (OR 0.84; 95%CI 0.72, 0.99; P = 0.04). In the UVOS, NAFLD prevalence (mean: 789/1130; 69.8%; 95%CI 67.1, 72.3) was associated with female sex (OR 2.24; 95%CI 1.66, 3.01; P < 0.001), higher serum concentrations of low-density lipoproteins (OR 1.34; 95%CI 1.17, 1.55; P < 0.001), lower prothrombin index (OR 0.98; 95%CI 0.96, 0.99; P = 0.002), and lower ankle-brachial index (OR 0.03; 95%CI 0.02, 0.29; P = 0.003). The NAFLD prevalence of 40% in the UEMS and 69.8% in the UVOS corresponds to findings obtained in other world regions and shows the importance of NAFLD, including its determinants such as age, sex, waist-hip ratio, serum creatinine concentration, prothrombin index, ankle-brachial index, and lower physical activity.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Alanina Transaminase , Aspartato Aminotransferases , Índice de Massa Corporal , Feminino , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Protrombina , Fatores de Risco , População Rural , Federação Russa/epidemiologia
7.
Physiol Res ; 71(3): 439-445, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35616044

RESUMO

High incidence of thrombosis and venous thromboembolism was reported in patients with COVID-19. In this study, we focused on analysis of thrombophilic mutations performed without a standard DNA extraction step. In one hundred of COVID-19 positive outpatients, real-time PCR for Leiden mutation in the FV gene and G20210A mutation in the FII gene was carried out from DNA extracts and modified whole blood samples, and their cycle threshold (Ct) values were evaluated. In the extracts, healthy homozygotes (wt/wt), heterozygotes (M/wt), and homozygous carriers of Leiden mutation (M/M) provided median Ct values of 18.5, 19.4/22.0, and 20.9. In the whole blood, Ct values were 25.3 (wt/wt), 24.8/27.2 (M/wt), and 26.9 (M/M). Median Ct values for G20210A in the extracts were 19.6 for homozygotes (wt/wt), and 19.7/20.4 for heterozygous carriers. The whole blood samples provided Ct values of 23.9 in healthy homozygotes and 26.3/27.2 in heterozygotes for G20210A mutation. No homozygous subjects for G20210A and no double heterozygotes (for Leiden and G20210A mutations) were found. Despite significant differences in the Ct values, genotyping showed complete result concordance of the DNA extracts and the whole blood samples. The integrity and amplificability of DNA molecules in the whole blood samples during 28 days of deep freezing, interrupted by four cycles of thawing, did not significantly change. In conclusion, we demonstrated a new protocol for the detection of the thrombophilic mutations via real time PCR on the modified whole blood of COVID-19 positive patients. The blood modification was reliable, easy, cheap, and saving costs and turnaround time of the whole laboratory process.


Assuntos
COVID-19 , Trombofilia , COVID-19/diagnóstico , COVID-19/genética , Teste para COVID-19 , DNA , Fator V/genética , Humanos , Mutação , Protrombina/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , SARS-CoV-2/genética , Trombofilia/genética
8.
Zhonghua Gan Zang Bing Za Zhi ; 30(4): 407-412, 2022 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-35545566

RESUMO

Objective: To investigate the effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors. Methods: 127 cases with liver cirrhosis accompanied with esophageal and gastric varices without bleeding history were included in the endoscopic and non-endoscopic treatment group, respectively. Informed consent was obtained from both groups. Gastric varices (Lgf) and esophageal varices (Leg) were diagnosed according to LDRf classification criteria, and the corresponding treatment scheme was selected according to the recommended principle of this method.The incidence rate of bleeding from ruptured esophageal varices were observed at 3, 6 months, and 1, and 2 years in the treated and the untreated group, and the patients with different Child-Pugh scores were followed-up for 2 years. Gender, age, etiology, varicose degree, Child-Pugh grade, platelet count, prothrombin activity, portal vein thrombosis, collateral circulation, portal vein width and other factors affecting the bleeding rate were assessed. Measurement data were described as mean ± standard deviation (x¯±s), and qualitative data of categorical variables were expressed as percentage (%), and χ2 test was used. Results: 127 cases were followed up for 2 years. There were 55 cases in the endoscopic treatment group (18 cases underwent band ligation, 2 cases underwent band ligation combined with tissue adhesive embolization, 28 cases underwent sclerotherapy, and 7 cases underwent sclerotherapy combined with tissue adhesive embolization). Recurrent bleeding and hemorrhage was occurred in 5 (9.1%) and 28 cases (38.9%), respectively (P<0.05). In addition, there were 72 cases in the untreated group (P<0.05). Severe varicose veins proportions in treated and untreated group were 91.1% and 85.1%, respectively (P>0.05). There was no statistically significant difference in liver cirrhosis-related medication and ß-blocker therapy between the treated and untreated group (P>0.05). There was no statistically significant difference in the bleeding rate between the different treated groups (P>0.05). The bleeding rates at 3, 6 months, 1, and 2 years in endoscopic treated and untreated group were 2.00% vs. 2.59% (P>0.05), 2.30% vs. 5.88% (P>0.05), 3.10% vs. 7.55% (P>0.05) and 4.00% vs. 21.62% (P<0.05), respectively. All patients with Child-Pugh grade A, B and C in the treated and the untreated group were followed-up for 2 years, and the bleeding rates were 1.8% vs. 8.1% (P<0.05), 1.1% vs. 9.4% (P<0.05) and 9.1% vs. 10.1% (P>0.05), respectively. There were statistically significant differences in the rupture and bleeding of esophageal and gastric varices, varices degree, Child-Pugh grade and presence or absence of thrombosis formation in portal vein (P<0.05); however, no statistically significant differences in gender, age, etiology, platelet count, prothrombin activity, collateral circulation and portal vein width (P>0.05). There was no intraoperative bleeding and postoperative related serious complications in the treated group. Conclusion: The risk of initial episodes of bleeding from esophageal and gastric varices is significantly correlated with the varices degree, Child-Pugh grade, and portal vein thrombosis. Primary preventive treatment under endoscope is safe and effective for reducing the long-term variceal bleeding risk from esophageal and gastric varices.


Assuntos
Varizes Esofágicas e Gástricas , Hipertensão Portal , Adesivos Teciduais , Varizes , Trombose Venosa , Endoscópios , Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Hemorragia Gastrointestinal/cirurgia , Humanos , Hipertensão Portal/complicações , Ligadura , Cirrose Hepática/complicações , Protrombina , Escleroterapia , Trombose Venosa/complicações
9.
Clin Appl Thromb Hemost ; 28: 10760296221097383, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535394

RESUMO

OBJECTIVE: To investigate the diagnostic values of D-dimer, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin (TAT), and prothrombin fragment F1 + 2 (F1 + 2) for predicting venous thromboembolism (VTE) after total knee arthroplasty (TKA). METHODS: Ultrasonography and CTPA were performed to diagnose VTE in 252 patients who underwent TKAs. Plasma D-dimer, PAI-1, TAT, and F1 + 2 levels were assessed 1-3 days prior to operation (T1), second hour (T2), first (T3), and third day (T4) after the operation. Receiver-operating characteristic curves (ROC) analysis was conducted and pairwise compared to evaluate the diagnostic value of those biomarkers. RESULTS: Plasma D-dimer levels differed between patients with and without VTE significantly on T4, PAI-1, TAT, and F1 + 2 levels differed on T3 and T4. The areas under ROC of D-dimer, PAI-1, TAT and F1 + 2 levels were 0.645, 0.773, 0.771 and 0.797, respectively. The most feasible cutoff values of D-dimer, PAI-1, TAT and F1 + 2 in predicting VTE after TKA were 2.24 ug/ml, 35.96 ng/ml, 13.36 ng/mg and 11.1 ng/ml, respectively. Pairwise comparison of ROC curves revealed that D-dimer level had the lowest diagnostic accuracy, whereas PAI-1, TAT and F1 + 2 level had similar diagnostic accuracy. There were significant differences in duration of tourniquet time and duration of anesthesia between patients with and without VTE. CONCLUSION: After TKA, using 2.24ug/mL as the threshold value of D-dimer is more accurate than using 0.5ug/mL in the monitoring of VTE, PAI-1, TAT and F1 + 2 are more valuable than D-dimer in predicting VTE. Duration of tourniquet and duration of anesthesia are risk factors for the development of VTE.


Assuntos
Artroplastia do Joelho , Tromboembolia Venosa , Antitrombinas , Artroplastia do Joelho/efeitos adversos , Biomarcadores , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Inibidor 1 de Ativador de Plasminogênio , Protrombina , Trombina , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia
10.
Thromb Res ; 214: 106-114, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35526513

RESUMO

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs) and thrombotic events. The association of aPLs with thrombotic events depends on the number of positive tests. Besides the three classical tests to classify APS, phosphatidylserine/prothrombin complex autoantibodies (aPS/PT) are increasingly used to better define this condition. The aim of this systematic review was to evaluate the prevalence of aPS/PT in general and according to antiphospholipid antibody profiles in patients with APS. METHODS: A systematic search of PubMed, Web of Science, and the Cochrane Library from January 1990 to September 2021 was carried out according to PRISMA guidelines. Proportions and 95% confidence intervals (CIs) were calculated using random-effects model. Publication biases were evaluated via visualization of funnel plots along with Egger's and Begg's tests. RESULTS: Twenty-one articles about the prevalence of aPS/PT in 1853 patients with APS were deemed eligible and analyzed according to the inclusion criteria. Pooled prevalence of aPS/PT IgG alone, IgM alone, and IgG/M were 50.0%, 45.0%, and 65.0%, respectively. No significant publication bias was detected from funnel plots or Egger's and Begg's tests. When the prevalence of aPS/PT was calculated in homogeneous aPLs, a much higher rate of pooled prevalence of aPS/PT IgG/M in patients positive for Lupus Anticoagulant (84.5%) and in those with triple positivity (83.4%) was found. CONCLUSIONS: These data show a high rate of aPS/PT positivity in patients with APS (especially in those positive for LAC) but further studies are needed to ascertain whether this test might be useful in the laboratory classification criteria of APS.


Assuntos
Síndrome Antifosfolipídica , Trombose , Anticorpos Antifosfolipídeos , Humanos , Imunoglobulina G , Fosfatidilserinas , Prevalência , Protrombina , Trombose/complicações
11.
Blood ; 139(24): 3463-3473, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35427420

RESUMO

The intrinsic and extrinsic pathways of the coagulation cascade converge to a common step where the prothrombinase complex, comprising the enzyme factor Xa (fXa), the cofactor fVa, Ca2+ and phospholipids, activates the zymogen prothrombin to the protease thrombin. The reaction entails cleavage at 2 sites, R271 and R320, generating the intermediates prethrombin 2 and meizothrombin, respectively. The molecular basis of these interactions that are central to hemostasis remains elusive. We solved 2 cryogenic electron microscopy (cryo-EM) structures of the fVa-fXa complex, 1 free on nanodiscs at 5.3-Å resolution and the other bound to prothrombin at near atomic 4.1-Å resolution. In the prothrombin-fVa-fXa complex, the Gla domains of fXa and prothrombin align on a plane with the C1 and C2 domains of fVa for interaction with membranes. Prothrombin and fXa emerge from this plane in curved conformations that bring their protease domains in contact with each other against the A2 domain of fVa. The 672ESTVMATRKMHDRLEPEDEE691 segment of the A2 domain closes on the protease domain of fXa like a lid to fix orientation of the active site. The 696YDYQNRL702 segment binds to prothrombin and establishes the pathway of activation by sequestering R271 against D697 and directing R320 toward the active site of fXa. The cryo-EM structure provides a molecular view of prothrombin activation along the meizothrombin pathway and suggests a mechanism for cleavage at the alternative R271 site. The findings advance our basic knowledge of a key step of coagulation and bear broad relevance to other interactions in the blood.


Assuntos
Fator Xa , Protrombina , Microscopia Crioeletrônica , Fator V , Fator Va/metabolismo , Fator Xa/metabolismo , Protrombina/metabolismo , Tromboplastina/metabolismo
12.
BMC Gastroenterol ; 22(1): 202, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461226

RESUMO

BACKGROUND: Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease. METHODS: This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods. RESULTS: Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child-Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR). CONCLUSIONS: The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Bilirrubina , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/patologia , Humanos , Cirrose Hepática , Neoplasias Hepáticas/patologia , Precursores de Proteínas , Protrombina , Curva ROC , alfa-Fetoproteínas/metabolismo , gama-Glutamiltransferase
13.
J Investig Med High Impact Case Rep ; 10: 23247096211058486, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35426321

RESUMO

Inherited thrombophilia is an important cause of venous thrombosis. The Factor V Leiden (FVL) is the most commonly encountered mutation, followed by the prothrombin G20210A gene mutation (PTM). The typical venous thrombotic events (VTEs) associated with PTM mutations are deep vein thrombosis (DVT) and pulmonary embolisms (PE). The PTM is inherited in an autosomal dominant pattern with variable penetrance. While heterozygous PTM mutations are more frequent and well documented in the literature, rare cases of homozygous PTM mutations are also reported. In this report, we discuss a 56-year-old male with a past medical history of homozygous prothrombin gene mutation (G20210A) who presented with an unprovoked DVT of the right lower extremity involving both the proximal and distal veins associated with multiple bilateral PEs. This case is unique in terms of the homozygous PTM inheritance, the age at which the patient presented (usually presentation is earlier in life), and the fact that he had a recurrence of both DVT and PE simultaneously.


Assuntos
Embolia Pulmonar , Trombofilia , Trombose Venosa , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Protrombina/genética , Embolia Pulmonar/complicações , Embolia Pulmonar/genética , Fatores de Risco , Trombofilia/complicações , Trombofilia/genética , Trombose Venosa/complicações , Trombose Venosa/genética
14.
Int J Hematol ; 116(2): 276-287, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35416587

RESUMO

An 8-year-old Japanese boy with no underlying disease presented with severe intramuscular hematoma of the hip, and was admitted for a disseminated intravascular coagulation-like state with fibrinolytic dominance. Laboratory examinations revealed severe hyper-fibrinolysis with elevated markers, markedly shortened euglobulin clot lysis time, mildly decreased prothrombin, and severely decreased fibrinogen and factor XIII. Natural fibrin precipitates rapidly appeared in citrate-treated, ethylene-diamine-tetra-acetic-treated, and heparin-treated samples, but not in argatroban-treated samples, indicating that the mechanism of thrombin and fibrin formation was Ca2+-independent. The precipitates were physically similar to thrombin-triggered plasma fibrin. A global coagulation assay revealed that thrombin generation potentials were normal throughout the clinical course, whereas plasmin generation was already detected before initiation of fibrin formation in the acute phase. This phenomenon disappeared with time. Changes in coagulation abnormalities and nature of fibrinolysis paralleled those seen in specific markers for streptococcal infections. Streptokinase was possibly involved in this disease, as SDS-polyacrylamide gel electrophoresis revealed that plasmin derived from streptokinase-plasminogen complex proteolyzed the prothrombin to approximately 35-kDa α-thrombin consisting of the A-B single chain, which was identified by NH2-terminal sequence analysis. The involvement of streptokinase-plasminogen-prothrombin caused by streptococcal infection may be one mechanism that produces marked hyper-fibrinolysis associated with natural fibrin precipitates.


Assuntos
Fibrina , Fibrinólise , Criança , Tempo de Lise do Coágulo de Fibrina , Fibrinolisina , Humanos , Masculino , Protrombina , Estreptoquinase , Trombina
16.
Mult Scler Relat Disord ; 60: 103720, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35294920

RESUMO

BACKGROUND: The interaction of central nervous system inflammation and coagulation system activation in multiple sclerosis (MS) receives increasing attention for its diagnostic and therapeutic potential. During blood-brain barrier (BBB) disruption, fibrinogen migrates into the CNS and contributes to inflammation. In the coagulation cascade, fibrinogen is converted into fibrin by thrombin, which itself is cleaved from prothrombin by activated factor XII. We hypothesized that the conversion of prothrombin to thrombin can be quantified by prothrombin fragment 1+2 (PF1.2) in cerebrospinal fluid (CSF). Primary endpoint was the correlation between PF1.2, D-dimer and fibrinogen in CSF of patients with neuroinflammatory diseases. Secondary endpoints were PF1.2 levels depending on presence of contrast enhancement (CE) on MRI, and correlation between PF1.2 with serum-CSF albumin quotient (Qalb). Additionally, an exploratory analysis of CSF PF1.2 levels to distinguish between MS-patients and controls without neurological disease was performed. METHODS: Patients admitted for a suspected inflammatory CNS disease were prospectively recruited from October 2017 to December 2020. Citrated CSF samples were obtained and analyzed for PF1.2, fibrinogen and D-dimer using a highly sensitive luminescent oxygen channeling immunoassay. Patient clinical data and final diagnoses were retrospectively collected and analyzed. RESULTS: 187 patients were included, of whom 116 received diagnoses of relapsing-remitting (RRMS), primary-progressive MS, clinically or radiologically isolated syndrome, or anti-aquaporin-4-/anti-myelin-oligodendrocyte-glycoprotein-antibody-related diseases. CSF analysis of those 116 patients revealed a correlation between PF1.2 and CSF fibrinogen (ρ=.315; p<.001) as well as between PF1.2 and CSF D-dimer (ρ=.531; p<.001). Among all 187 patients, CSF PF1.2 was increased in patients with CE on MRI (n=71; 147.38 pmol/l; IQR 83.68-215.36) compared to patients without CE (n=86; 100.03 pmol/l; IQR 33.87-162.80; p=.008). CSF PF1.2 correlated significantly with Qalb (ρ=.445; p<.001). No differences of CSF PF1.2 levels were observed between RRMS (131.48 pmol/l, IQR 42.75-204.10) and disease controls (102.28 pmol/l; IQR 55.60-159.94; p=.606). CONCLUSION: In patients with autoimmune inflammatory CNS diseases PF1.2 correlated strongly with fibrinogen and D-dimer in CSF, indicating coagulation system activation. The findings suggest that thrombin generation might require acute BBB dysfunction to exert autoimmune effects in the CNS.


Assuntos
Doenças do Sistema Nervoso Central , Esclerose Múltipla , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Fibrinogênio , Humanos , Inflamação , Esclerose Múltipla/diagnóstico por imagem , Fragmentos de Peptídeos , Precursores de Proteínas , Protrombina , Estudos Retrospectivos , Trombina
17.
Aging (Albany NY) ; 14(6): 2645-2664, 2022 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-35307694

RESUMO

We conducted a comprehensive meta-analysis of the utility of AFP-L3 for the diagnosis of hepatocellular carcinoma, to provide a more accurate estimation for the clinical utility of AFP-L3. We performed online searches in five databases (PubMed, China National Knowledge Infrastructure, Wanfang, Web of Science, and Embase), from inception to December 31, 2021. Pooled sensitivity, specificity, and area under the curve (AUC) with the matching 95% confidence intervals (95% CIs) were calculated to estimate the diagnostic value of AFP-L3. Thirty-four studies were included in the meta-analysis. The pooled sensitivity was 0.70 [95% confidence interval (CI): 0.63-0.77], and the specificity was 0.91 (95% CI: 0.88-0.94). The estimated area under the curve (AUC) was 0.90 (95% CI: 0.87-0.92). The positive likelihood ratio and negative likelihood ratio were 7.78 (95% CI: 5.7-10.7) and 0.33 (95% CI: 0.26-0.41), respectively. The diagnostic odds ratio was 24 (95% CI: 16-37). The subgroup analysis indicated moderate sensitivity (0.79) and high specificity (0.89) for the Asian population (AUC = 0.89), and similar specificity (0.95) but lower sensitivity (0.35) for Caucasians (AUC = 0.80). Deeks' funnel plot asymmetry test detected no publication bias (P = 0.460). The sensitivity analysis showed that the pooled results were stable. Taken together, our results indicated that AFP-L3 demonstrates high diagnostic ability for HCC, especially among Asian populations. AFP-L3 is a useful means for high-volume screening, which can help doctors optimize diagnosis workflow, reduce workload, and improve detection sensitivity. The combination of multiple biomarkers may provide more accurate diagnostic tools for HCC in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Protrombina , Curva ROC , Tamanho da Amostra , Sensibilidade e Especificidade , alfa-Fetoproteínas/análise
18.
PLoS One ; 17(3): e0265235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35271670

RESUMO

BACKGROUND: Prothrombin induced by vitamin K absence-II (PIVKA-II) was reported as a diagnosis and prognosis marker for hepatocellular carcinoma (HCC). Although the development of systemic therapies for advanced HCC has been remarkable, the role of PIVKA-II is unclear. This prospective study aimed to verify Elecsys PIVKA-II compared with Lumipulse PIVKA-II in a cohort with advanced HCC undergoing systemic therapy. METHODS: A total of 62 HCC patients who were treated with atezolizumab and bevacizumab (ATZ+BEV) and molecular targeted agents (MTAs) were prospectively enrolled at Musashino Red Cross Hospital from January 2020 to December 2020. A total of 208 serum samples from 52 patients were tested using Elecsys PIVKA-II and Lumipulse PIVKA-II assays. Furthermore, the relationship of Elecsys PIVKA-II and progression-free survival (PFS) was investigated with 48 patients (24 ATZ+BEV and 24 MTAs) whose Lumipulse PIVKA-II levels were >40 mAU/mL. RESULTS: In the test accuracy analysis, the Elecsys assay has a correlation coefficient (R) of 0.92 compared with that of the Lumipulse assay (ATZ+BEV, 0.95; MTAs, 0.91). In the PFS analysis, the number of patients who received ATZ+BEV and MTAs as first- and late-line therapy were 9 and 13, and 15 and 11, respectively. The PIVKA-II response was defined for patients who had a reduction in the Elecsys PIVKA-II level on the first month of treatment evaluation. The PFS of patients with Elecsys PIVKA-II response was significantly longer than that of nonresponse patients (5.8 months vs 3.8 months, p = 0.0205). CONCLUSION: The Elecsys PIVKA-II was not only as useful as the Lumipulse PIVKA-II but also for stratifying the PFS of patients with advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Mieloma Múltiplo , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Estudos Prospectivos , Precursores de Proteínas , Protrombina , Vitamina K , alfa-Fetoproteínas/análise
19.
Lupus ; 31(5): 565-574, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35266798

RESUMO

INTRODUCTION: The standard of care for thrombotic antiphospholipid syndrome (APS) is anticoagulation with vitamin K antagonists (VKAs). Prothrombin time, and its corresponding international normalized ratio (INR), is the laboratory test routinely performed to assess anticoagulation. Self-management of VKA therapy using point-of-care (POC) devices seems to be an attractive option. PURPOSE/OBJECTIVE: To evaluate the accuracy of a POC device (CoaguChek XS) in APS patients by comparing it with venous laboratory INR. Furthermore, we analyzed whether other clinical and laboratory features could interfere with the CoaguChek XS results. PATIENTS AND METHODS: This is a single-center cross-sectional study with 94 APS patients from a tertiary rheumatology clinic performed from August 2014 to March 2015. The comparison between CoaguChek XS and venous laboratory INR results was evaluated using the coefficient of determination (r) followed by the Bland-Altman test. A paired t-test was also applied. A difference of up to ±0.5 INR unit between the two systems was considered clinically acceptable. RESULTS: The mean CoaguChek-INR was 2.94 ± 1.41 and venous laboratory INR was 2.43±0.86, with a correlation coefficient (r) of 0.95. Categorizing INR values in ranges (INR <2, INR 2-3, INR 3-4, and INR >4), we found that the INR >4 group presented a lower correlation (r = 0.64) compared to the other ranges (p < 0.05). Although both methods were highly correlated, CoaguChek XS showed higher values than the venous laboratory INR, with an increased average of 0.42 ± 0.54. Therefore, we proposed a simple linear regression model to predict the venous laboratory INR values, using results obtained from CoaguChek XS. A difference ≤0.5 INR unit between the two systems was observed in 57.4% of patients, and the aPL profile did not influence the results. CONCLUSION: Although CoaguChek XS and venous laboratory INR demonstrated a good linear correlation in the group of INR ≤4, extra caution should be taken in APS patients, since a reasonable proportion of patients can present differences in INR results that are not acceptable. We do not recommend routine POC in APS patients.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Estudos Transversais , Monitoramento de Medicamentos/métodos , Humanos , Coeficiente Internacional Normatizado/métodos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Sistemas Automatizados de Assistência Junto ao Leito , Protrombina , Tempo de Protrombina/métodos
20.
Blood ; 139(19): 2972-2982, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35148539

RESUMO

The prothrombinase complex processes prothrombin to thrombin through sequential cleavage at Arg320 followed by Arg271 when cofactor, factor (f) Va, protease, fXa, and substrate, prothrombin, are all bound to the same membrane surface. In the absence of the membrane or cofactor, cleavage occurs in the opposite order. For the less favorable cleavage site at Arg320 to be cleaved first, it is thought that prothrombin docks on fVa in a way that presents Arg320 and hides Arg271 from the active site of fXa. Based on the crystal structure of the prothrombinase complex from the venom of the Australian eastern brown snake, pseutarin C, we modeled an initial prothrombin docking mode, which involved an interaction with discrete portions of the A1 and A2 domains of fV and the loop connecting the 2 domains, known as the a1-loop. We interrogated the proposed interface by site-directed PEGylation and by swapping the a1-loop in pseutarin C with that of human fV and fVIII and measuring the effect on rate and pathway of thrombin generation. PEGylation of residues within our proposed binding site greatly reduced the rate of thrombin generation, without affecting the pathway, whereas those outside the proposed interface had no effect. PEGylation of residues within the a1-loop also reduced the rate of thrombin generation. The sequence of the a1-loop was found to play a critical role in prothrombin binding and in the presentation of Arg320 for initial cleavage.


Assuntos
Venenos Elapídicos , Protrombina , Trombina , Austrália , Sítios de Ligação , Fator Va/metabolismo , Fator Xa/metabolismo , Humanos , Protrombina/metabolismo , Trombina/metabolismo , Tromboplastina/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...