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1.
Ann Transplant ; 27: e936937, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36097403

RESUMO

BACKGROUND This study analyzed pretransplant alpha-fetoprotein (AFP) and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) in liver transplantation (LT) candidates. MATERIAL AND METHODS A total of 3,273 LT recipients enrolled at the Korean Organ Transplantation Registry were divided according to hepatocellular carcinoma (HCC) status and background liver disease, and AFP and PIVKA-II were compared. RESULTS In all patients, the median AFP and PIVKA-II were 6.3 ng/mL and 29 mAU/mL in the viable-HCC group and 3.3 ng/mL and 35 mAU/mL, respectively, in the no-HCC group (P<0.001 for AFP and p=0.037 for PIVKA-II). In patients with hepatitis B virus infection, they were 6.0 ng/mL and 26 mAU/mL in the HCC group and 3.2 ng/mL and 21 mAU/mL in the no-HCC group, respectively (P<0.001 and P<0.001). In patients with hepatitis C virus infection, they were 10.7 ng/mL and 37 mAU/mL in the HCC group and 2.6 ng/mL and 21 mAU/mL in the no-HCC group, respectively (P<0.001 and P=0.117). In alcoholic liver disease patients, they were 5.2 ng/mL and 61 mAU/mL in the HCC group and 6.4 ng/mL and 75 mAU/mL in the no-HCC group, respectively (P<0.001 and P=0.419). In patients with other diseases, they were 7.1 ng/mL and 32 mAU/mL in the HCC group and 3.3 ng/mL and 28 mAU/mL in the no-HCC group, respectively (P<0.001 and P=0.822). CONCLUSIONS The results of the present study indicate that pretransplant serum AFP and PIVKA-II were highly variably expressed in LT candidates with end-stage liver diseases; therefore, their values should be cautiously interpreted because their role in HCC diagnosis is limited.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Biomarcadores Tumorais , Humanos , Precursores de Proteínas/metabolismo , Protrombina , Sistema de Registros , República da Coreia , alfa-Fetoproteínas/metabolismo
3.
Thromb Res ; 218: 171-176, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36057167

RESUMO

BACKGROUND: Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) results in respiratory syndromes but also in vascular complications such as thromboembolism (TE). In this regard, immunothrombosis, resulting from inflammation in SARS-CoV-2 infected tissues, has been described. Data on TE in COVID-19 are mainly based on clinical observational and/or incomplete autopsy studies. The true burden of TE and the relevance of genetic predisposition, however, have not been resolved. OBJECTIVES: Here, we report on a consecutive cohort of 100 fully autopsied patients deceased by SARS-CoV-2 infections during the first wave of the pandemic (March to April 2020). We investigated the localization of TE, potential clinical risk factors, and the prothrombotic gene mutations, factor V Leiden and prothrombin G20210A, in postmortem blood or tissue samples. RESULTS: TE was found in 43/100 autopsies. 93 % of TE events were venous occlusions, with 23 patients having pulmonary thromboembolism (PT) with or without lower-extremity deep vein thrombosis. Of these, 70 % showed PT restricted to (sub)segmental arteries, consistent with in situ immunothrombosis. Patients with TE had a significantly higher BMI and died more frequently at an intensive care unit. Hereditary thrombophilia factors were not associated with TE. CONCLUSIONS: Our autopsy results show that a significant proportion of SARS-CoV-2 infected patients suffer from TE, affecting predominantly the venous system. Orthotopic peripheral PT was the most frequent finding. Hereditary thrombophilia appears not to be a determinant for TE in COVID-19. However, obesity and the need for intensive care increase the risk of TE in these patients.


Assuntos
COVID-19 , Embolia Pulmonar , Tromboembolia , Trombofilia , COVID-19/complicações , Humanos , Protrombina/genética , Embolia Pulmonar/complicações , Fatores de Risco , SARS-CoV-2 , Tromboembolia/complicações , Trombofilia/complicações , Trombofilia/genética
4.
Thromb Res ; 218: 17-23, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35973396

RESUMO

BACKGROUND: Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are the major contributor to activated Protein C resistance (APC-R) in tetra-positive thrombotic high-risk patients with Antiphospholipid Syndrome (APS). OBJECTIVES: To evaluate the role of phospholipids (PL) on aPS/PT mediated APC-R. PATIENTS/METHODS: Total IgG were purified from plasma of 6 tetra-positive patients and IgG aPS/PT were affinity-purified from 3 of these patients. Purified material was spiked into Normal Pooled Plasma (NPP) and tested for APC-R in thrombin generation assay and in Factor Va inactivation assay using increasing amounts of phospholipids. RESULTS AND CONCLUSIONS: Total IgG showed APC-R at low PL concentration (1.5 µg/mL) that disappeared at increasing PL concentrations (5.8, 11.6 and 46.6 µg/mL). In the same way, affinity purified aPS/PT showed a robust (59 %, 52 %, 36 %) APC-R in patients #4, #5 and #6, respectively at low PL concentration (1.5 µg/mL) that was completely reversed at higher concentration (11.6 µg/mL). The inactivation of FVa by activated Protein C (aPC) was impaired in the presence of aPS/PT at low aPL concentration and reversed by increasing amounts of PL. These data point out the relevance of PL in reversing APC-R in this 'in vitro' system. The mechanism for reversal might be explained by loss of PL availability for aPC. These results may give some insight into the pathogenesis of thrombosis or suggestions for alternative treatments.


Assuntos
Resistência à Proteína C Ativada , Síndrome Antifosfolipídica , Trombose , Anticorpos Antifosfolipídeos , Fator Va , Humanos , Imunoglobulina G , Fosfatidilserinas , Proteína C , Protrombina , Trombina
5.
Int J Surg ; 105: 106843, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35995351

RESUMO

BACKGROUND: Alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) are two commonly used biomarkers for detection and prognostic prediction of hepatocellular carcinoma (HCC). This study sought to evaluate and compare the use of these two biomarkers to detect HCC, as well as predict postoperative early recurrence (within 2 years after HCC resection). METHODS: Data on consecutive patients who underwent curative resection for HCC between 2014 and 2020 was prospectively collected and reviewed. Serum AFP and PIVKA-II levels within one week before surgery or at the time of detection of early recurrence were assessed; preoperative AFP positivity (≥20 ng/ml) and preoperative PIVKA-II positivity (≥40 mAU/ml) were examined relative to recurrence using univariate and multivariate Cox-regression analyses. RESULTS: Among 751 patients who underwent curative HCC resection, 589 (78.4%) patients had preoperative PIVKA-II positivity versus 498 (66.3%) patients had preoperative AFP positivity (P < 0.001). With a median follow-up of 41.6 months, 370 (50.1%) patients had an early HCC recurrence; among patients with an early recurrence, the proportion of patients with PIVKA-II positivity versus AFP positivity (76.5% vs. 60.0%, P = 0.002) was higher. On multivariate analysis, preoperative PIVKA-II positivity, but not preoperative AFP positivity was an independent risk factor to predict early recurrence after HCC resection. CONCLUSIONS: AFP and PIVKA-II are useful biomarkers to detect resectable HCC and predict early recurrence after HCC resection, with the latter showing higher rates of positivity. Preoperative PIVKA-II positivity was independently associated with early recurrence following HCC resection.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Precursores de Proteínas , Protrombina , Curva ROC , Estudos Retrospectivos , Vitamina K , alfa-Fetoproteínas/análise
6.
Int J Mol Sci ; 23(16)2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-36012233

RESUMO

Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against ß2-glycoprotein-I (anti-ß2GPI), but also non-criteria antibodies such as antibodies against ß2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-ß2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.


Assuntos
Síndrome Antifosfolipídica , Trombose , Anticorpos Anticardiolipina , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/complicações , Feminino , Humanos , Fosfatidilserinas , Gravidez , Proteína C , Protrombina , Trombina , Trombose/etiologia , beta 2-Glicoproteína I
7.
Medicina (Kaunas) ; 58(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36013482

RESUMO

Background and Objectives: We aim to compare the diagnostic performance of Protein induced by vitamin K absence-II (PIVKA-II), a biomarker for hepatocellular carcinoma (HCC), and alpha-fetoprotein (AFP) in differentiating HCC and non-malignant high-risk (NMHR) groups and to determine their cut-off values. Materials and Methods: A total of 163 patients, including 40 with HCC and 123 with NMHR (100 with liver cirrhosis and 23 with non-cirrhotic high-risk patients) were prospectively enrolled. The levels of AFP and PIVKA-II were measured, and their cut-off values were determined. We calculated and compared the areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP, and their combination. Results: The levels of PIVKA-II and AFP were found to be significantly higher in the HCC compared to NMHR patients (p < 0.0001). For the differentiation of HCC from NMHR, the optimal cutoff values for PIVKA-II and AFP were 36.7 mAU/mL (90% sensitivity; 82.1% specificity) and 14.2 ng/mL (75% sensitivity; 93.5% specificity), respectively. The AUROC of PIVKA-II (0.905, p < 0.0001) was higher compared to AFP (0.869, p < 0.0001), but the combination of PIVKA-II and AFP gave the highest AUROC value (0.911, p < 0.0001). However, their differences were not statistically significant (AFP vs. PIVKA; p = 0.4775, AFP vs. Combination; p = 0.3808, PIVKA vs. Combination; p = 0.2268). Conclusions: PIVKA-II and AFP showed equal performance in detecting HCC in high-risk patients. AFP as a screening marker for HCC may be adequate, and replacing or adding the PIVKA-II test in current clinical practice may be of little value.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Protrombina , alfa-Fetoproteínas , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Precursores de Proteínas , Protrombina/metabolismo , alfa-Fetoproteínas/metabolismo
8.
Int J Lab Hematol ; 44(5): 952-958, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35815444

RESUMO

INTRODUCTION: The aim of our study was to establish reference ranges for neonatal coagulation and fibrinolysis parameters and to investigate their relationship with gestational age (GA) and birth weight (BW). METHODS: A single-centre prospective study was conducted in all healthy neonates born in our hospital during the study period, excluding those with maternal or neonatal disorders and diseases that affect haemostasis. The following parameters were measured: fibrinogen, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) as well as factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (vWF), protein C, free protein S, antithrombin (AT), activated protein C resistance (APCr), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). RESULTS: Study population consisted of 327 neonates. Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII were positively correlated, while PT, aPPT, INR, APCr and tPA were negatively correlated with GA and BW. Proteins C and S, factors II, VIII, IX, XI and vWF, as well AT III and PAI-1 had a significant positive linear correlation with GA, while aPTT had a significant negative one. Fibrinogen, and factors V, VII and XII had a significant positive linear correlation with BW, while factor VIII, tPA, as well PT and INR had a significant negative one. CONCLUSION: Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII increase with GA and BW.


Assuntos
Hemostáticos , Inibidor 1 de Ativador de Plasminogênio , Peso ao Nascer , Fatores de Coagulação Sanguínea/metabolismo , Fator V , Fibrinogênio , Idade Gestacional , Hemostasia , Humanos , Recém-Nascido , Estudos Prospectivos , Proteína C/metabolismo , Protrombina , Ativador de Plasminogênio Tecidual , Fator de von Willebrand
9.
Transfusion ; 62(8): 1652-1661, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35834523

RESUMO

BACKGROUND: Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures. STUDY DESIGN AND METHODS: Network meta-analysis for comparing the safety and efficacy of warfarin reversal strategies including plasma and prothrombin complex concentrates (PCCs). RESULTS: Seven studies including 594 subjects using reversal agents plasma, 3-factor-PCC (Uman Complex and Konyne), and 4-factor-PCC (Beriplex/KCentra, Octaplex, and Cofact) met inclusion criteria. Compared with plasma, patients receiving Cofact probably have a higher rate of international normalized ratio (INR) correction (risk difference [RD] 499 more per 1000 patients, 95% confidence interval [CI], 176-761, low certainty[LC]); higher reversal of bleeding (323 more per 1000 patients, 11-344 more, LC); and fewer transfusion requirements (0.96 fewer units, 1.65-0.27 fewer, LC). Patients receiving Beriplex/KCentra probably have a higher rate of INR correction (476 more per 1000 patients, 332-609 more, LC); higher reversal of bleeding (127 more per 1000 patients, 43 fewer to 236 more); and similar transfusion requirements (0.01 fewer units, 0.31 fewer to 0.28 more, high/moderate certainty). Patients receiving Octaplex probably have a higher rate of INR correction (RD 579 more per 1000 patients, 189-825 more, LC). CONCLUSIONS: PCCs probably provide an advantage in INR reversal compared to plasma. There was no added risk of adverse events with PCCs.


Assuntos
Anticoagulantes , Fatores de Coagulação Sanguínea , Anticoagulantes/efeitos adversos , Fatores de Coagulação Sanguínea/uso terapêutico , Fator IX , Fator X , Fibrinolíticos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Coeficiente Internacional Normatizado , Metanálise em Rede , Protrombina , Estudos Retrospectivos , Vitamina K/uso terapêutico , Varfarina
10.
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 , Humanos , Hipoprotrombinemias/diagnóstico , Inibidor de Coagulação do Lúpus , Masculino , Tempo de Tromboplastina Parcial , Protrombina
11.
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
Malária , Parasitemia , Plaquetas/metabolismo , Hemostasia , Humanos , Malária/metabolismo , Parasitemia/metabolismo , Protrombina/metabolismo , Trombina/metabolismo , Fator de von Willebrand/metabolismo
12.
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
13.
Transfusion ; 62 Suppl 1: S98-S104, 2022 08.
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
14.
Rev Med Interne ; 43(9): 545-551, 2022 Sep.
Artigo em Francês | MEDLINE | ID: mdl-35752484

RESUMO

Antiphospholipid syndrome (APS) is an autoimmune disease and one of the most common causes of acquired thrombophilia. It is characterised by the occurrence of thrombotic or obstetric events associated with the presence of persistent antiphospholipid antibodies. The diagnosis can be challenging, particularly because some biological tests can be disturbed by anticoagulant treatment or inflammation. In the recent years, new antiphospholipid antibodies, including anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT), have emerged but their clinical significance and causality remain uncertain. Biologically, several studies have found a strong correlation between the presence of lupus anticoagulant (LA) and anti-PS/PT antibodies. Clinically, the presence of anti-PS/PT antibodies is associated with an increased risk of thrombosis and obstetric complications. There is also an association with thrombocytopenia, suggesting that the presence of anti-PS/PT antibodies may be associated with more severe clinical APS. Among seronegative APS patients, 6-17% of patients are positive for anti-PS/PT antibodies. This might influence the therapeutic management of patients. This article aims to provide an update on contribution of anti-PS/PT antibodies detection for the diagnosis and management of APS.


Assuntos
Síndrome Antifosfolipídica , Trombose , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Feminino , Humanos , Inibidor de Coagulação do Lúpus , Fosfatidilserinas , Gravidez , Protrombina
15.
Blood ; 139(24): 3451-3453, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35708725
16.
J Thromb Haemost ; 20(9): 2070-2074, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35722911

RESUMO

BACKGROUND: Anti-phosphatidylserine prothrombin antibodies (aPSPT) are reported to be highly associated with the lupus anticoagulant (LAC) in established antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) cohorts. Further, aPSPT has been suggested to be a useful surrogate LAC marker. However, validation studies replicating this relationship in an all-comer study population in the diagnostic clinical setting are lacking. OBJECTIVES: To determine the sensitivity and specificity of aPSPT to the LAC in an all-comer population undergoing evaluation for suspected APS. METHODS: An assembled cross-sectional cohort from June 2017 to December 2018 undergoing APS evaluations across all medical specialties were reviewed for LAC, aPSPT, anti-cardiolipin (aCL), and anti-ß2 glycoprotein-1 (ß2GP1). Sensitivities, specificities, and negative and positive predictive values were calculated. RESULTS AND CONCLUSIONS: A cohort of 166 eligible patients was identified. Seventy-one percent were female, 89% White, 15% with SLE, and 21% with APS. The aPSPT was found to be the most specific to the LAC. Specificity of IgG aPSPT was 100% (96%-100%) and IgM aPSPT was 97% (91%-100%) to the LAC. Corresponding positive predictive value for IgG aPSPT was 100% (89%-100%) and IgM aPSPT was 95% (84%-99%). In contrast, the sensitivities of aPSPT to the LAC were less robust, only in the 40%-50% range. The findings validate previously reported findings and lends extension to an all-comer population. These findings corroborate aPSPT as a potentially useful clinical marker of the LAC.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Anticorpos Anticardiolipina , Biomarcadores , Estudos Transversais , Feminino , Humanos , Imunoglobulina G , Imunoglobulina M , Inibidor de Coagulação do Lúpus , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Fosfatidilserinas , Protrombina
17.
J Thromb Haemost ; 20(9): 2136-2150, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35713971

RESUMO

BACKGROUND: Diagnosis of antiphospholipid syndrome (APS) requires persistent presence of lupus anticoagulant (LAC), anticardiolipin (aCL) IgG/IgM, or anti-ß2 glycoprotein I (aß2GPI) IgG/IgM antibodies. Other antiphospholipid antibodies (aPL) such as antiphosphatidylserine/prothrombin antibodies (aPS/PT) are promising in assessment of thrombotic APS (TAPS). AIM: To evaluate the added value of aPS/PT IgG and IgM in TAPS. MATERIAL AND METHODS: aPS/PT IgG/IgM, aCL IgG/IgM, aß2GPI IgG/IgM, and LAC were determined in 757 patients (TAPS and controls). aPS/PT cut-off values were calculated, and aPS/PT titers and positivity were compared between TAPS and controls, type of thrombosis, and antibody profiles. Likelihood ratios (LR), odds ratios (OR), and aPL score were determined. RESULTS: aPS/PT IgG and IgM were associated with TAPS and triple positivity. In-house calculated cut-offs were higher for IgM (43 units), compared to manufacturer's cut-off (30 units). Thresholds of 90 (IgG) and 200 (IgM) units were determined as high-titer cut-off. Higher aPS/PT titers were observed in triple positive patients and showed higher LR and OR for TAPS. aPS/PT was independently associated with TAPS when adjusted for aCL/aß2GPI, but not when adjusted for LAC. In isolated LAC positive patients, aPS/PT was positive in 27.1% TAPS patients and in 77.3% patients with autoimmune disease. Diagnostic value of aPL score did not differ with and without including aPS/PT. CONCLUSION: aPS/PT positivity, especially with high antibody titer, is associated with TAPS diagnosis. Analysis on top of current laboratory criteria is not essential in TAPS diagnosis, but aPS/PT could be useful in patients with thrombosis and a double positive aPL profile (aCL+/aß2GPI+).


Assuntos
Síndrome Antifosfolipídica , Trombose , Anticorpos Antifosfolipídeos , Comunicação , Humanos , Imunoglobulina G , Imunoglobulina M , Inibidor de Coagulação do Lúpus , Fosfatidilserinas , Protrombina , beta 2-Glicoproteína I
18.
Physiol Res ; 71(3): 439-445, 2022 07 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
19.
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
20.
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
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