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2.
J Am Heart Assoc ; 9(21): e017773, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-32972320

RESUMO

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.


Assuntos
Síndrome Antifosfolipídica/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Deficiência de Proteína S/epidemiologia , Trombose/epidemiologia , Idoso , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Prevalência , Prognóstico , Proteína S/análise , Deficiência de Proteína S/sangue , Deficiência de Proteína S/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/diagnóstico
3.
Eur Rev Med Pharmacol Sci ; 24(17): 9161-9168, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32965009

RESUMO

OBJECTIVE: Coronavirus Disease-2019 (COVID-19) predisposes patients to thrombosis which underlying mechanisms are still incompletely understood. We sought to investigate the balance between procoagulant factors and natural coagulation inhibitors in the critically ill COVID-19 patient and to evaluate the usefulness of hemostasis parameters to identify patients at risk of venous thromboembolic event (VTE). PATIENTS AND METHODS: We conducted an observational study recording VTEs defined as deep vein thrombosis or pulmonary embolism using lower limb ultrasound (92% of the patients), computed tomography pulmonary angiography (6%) and both tests (2%). We developed a comprehensive analysis of hemostasis. RESULTS: Ninety-two consecutive mechanically ventilated COVID-19 patients (age, 62 years [53-69] (median [25th-75th percentiles]); M/F sex ratio, 2.5; body-mass index, 28 kg/m2 [25-32]; past hypertension (52%) and diabetes mellitus (30%)) admitted to the Intensive Care Unit (ICU) from 03/11/2020 to 5/05/2020, were included. When tested, patients were receiving prophylactic (74%) or therapeutic (26%) anticoagulation. Forty patients (43%) were diagnosed with VTE. Patients displayed inflammatory and prothrombotic profile including markedly elevated plasma fibrinogen (7.7 g/L [6.1-8.6]), D-dimer (3,360 ng/mL [1668-7575]), factor V (166 IU/dL [136-195]) and factor VIII activities (294 IU/dL [223-362]). We evidenced significant discrepant protein C anticoagulant and chromogenic activities, combined with slightly decreased protein S activity. Plasma D-dimer >3,300 ng/mL predicted VTE presence with 78% (95%-confidence interval (95% CI), 62-89) sensitivity, 69% (95% CI, 55-81) specificity, 66% (95% CI, 51-79) positive predictive value and 80% (95% CI, 65-90) negative predictive value [area under the ROC curve, 0.779 (95%CI, 0.681-0.859), p=0.0001]. CONCLUSIONS: Mechanically ventilated COVID-19 patients present with an imbalance between markedly increased factor V/VIII activity and overwhelmed protein C/S pathway. Plasma D-dimer may be a useful biomarker at the bedside for suspicion of VTE.


Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/metabolismo , Fatores de Coagulação Sanguínea/metabolismo , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Área Sob a Curva , Betacoronavirus/isolamento & purificação , Índice de Massa Corporal , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Estado Terminal , Fator V/análise , Fator VIII/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Proteína C/análise , Proteína S/análise , Curva ROC , Tromboembolia Venosa/complicações , Tromboembolia Venosa/diagnóstico
5.
J Thromb Thrombolysis ; 50(3): 580-586, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32648093

RESUMO

The outbreak of novel coronavirus disease 2019 (COVID-19) has now become a global pandemic. Coagulopathy has been reported widely in critically ill COVID-19 patients and was related to high mortality. However, the comprehensive coagulation profiles have not been examined and the underlying mechanism of the coagulopathy in COVID-19 patients is unclear. To study the coagulation profiles of routine hemostasis tests, natural anticoagulants, coagulant factors and antiphospholipid antibodies in critically ill COVID-19 patients. This single-center and cross-section study included 19 patients with COVID-19, who were admitted to intensive care unit (ICU) at Tongji hospital in Wuhan, China, from Feb 23 to Mar 3, 2020. Demographic data, laboratory parameters, treatments and clinical outcomes of the patients were collected and analyzed. The final date of follow-up was Mar 31, 2020. In this study, 12 thrombotic events occurred in 9 patients, including 4 cerebral infarctions, 7 acro-ischemia and 1 internal jugular vein thrombosis. The common abnormalities of routine coagulation tests included evelated D-Dimer level (100%), prolonged prothrombin time (73.7%) and hyperfibrinogenemia (73.7%). The median activities of natural anticoagulants including protein C, protein S and antithrombin were all below the normal range. Factor VIII activities were significantly above normal range (median value 307%, IQR 198-441) in all patients. Factor V and factor VII activities were significantly lower in near-terminal stage patients. Anti-phospholipid antibodies were present in 10 patients. Strikingly, 4 cerebral infarction events were in patients had anti-phospholipid antibodies of multiple isotypes. Sustained hypercoagulable status and thrombotic events were common in critically ill patients with COVID-19. The low activities of natural anticoagulants, elevated factor VIII level and the presence of antiphospholipid antibodies, together, may contribute to the etiopathology of coagulopathy in COVID-19 patients.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Betacoronavirus/patogenicidade , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/análise , Coagulação Sanguínea , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Trombose/sangue , Idoso , Proteínas Antitrombina/análise , Biomarcadores/sangue , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Estado Terminal , Estudos Transversais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Proteína C/análise , Proteína S/análise , Fatores de Risco , Trombose/diagnóstico , Trombose/virologia
6.
Rev. clín. esp. (Ed. impr.) ; 220(3): 162-166, abr. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-198988

RESUMO

ANTECEDENTES Y OBJETIVO: La β-talasemia mayor (β-TM) se define como una enfermedad hereditaria relacionada con las células rojas sanguíneas. En los pacientes adultos, los eventos trombóticos se asocian con la talasemia. Así, el objetivo de esta investigación fue examinar algunos de los parámetros hemostáticos, incluyendo la antitrombina III (AT-III), la proteína C (PRC) y la proteína S (PRS), en pacientes β-TM. MÉTODOS: Se seleccionó a 30pacientes β-TM remitidos para un ingreso de seguimiento de rutina en la clínica de talasemia del Centro Especial de Enfermedades Kerman, junto con otros 30 sujetos sanos. Tras el registro y 3 semanas después de la última transfusión, se recogieron especímenes de sangre periférica, y se midió la concentración plasmática de AT-III, PRC y PRS. RESULTADOS: Hemos observado que la concentración de inhibidores naturales de la coagulación (PRC y PRS) estaba ligeramente disminuida en los pacientes β-TM (p < 0,05), mientras que el nivel plasmático de AT-III no era muy diferente en los pacientes β-TM cuando se los comparaba con los sujetos sanos. CONCLUSIÓN: Conforme a los hallazgos obtenidos en el presente trabajo, podríamos considerar los cambios significativos en las PRC, PRS y AT-III, que se observan en pacientes β-TM multitransfundidos, como factores de riesgo críticos para el desarrollo de eventos tromboembólicos futuros a lo largo de su vida


BACKGROUND AND AIM: The β-thalassemia major (β-TM) is defined as a hereditary red blood cell-related disease. Thrombotic events are associated with thalassemia in adult patients. Thus, the present investigation was aimed to examine some hemostatic parameters, including anti thrombin-III (AT-III), protein-C (PRC) and protein-S (PRS) in β-TM patients. METHODS: Thirty B-TM patients who referred for routine follow-up admission to the thalassemia clinic of Kerman Special Disease Center alongside with 30 healthy subjects were selected and enrolled in the present study. Further registration, the peripheral blood specimens were collected after 3 weeks of last transfusion and then the plasma concentrations of AT-III, PRC and PRS were measured in them. RESULTS: We have observed that the concentrations of natural coagulation inhibitors (PRC and PRS) were significantly attenuated in β-TM patients (P<0.05), while the plasma level of AT-III was not remarkably differed in β-TM patients in compare to healthy subjects. CONCLUSION: According to the findings of present work, significant changes in the PRC, PRS and AT-III which could be observed in multi transfused β-TM patients may attribute as critical risk factors for the development of upcoming thromboembolic events in their future life


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Talassemia beta/complicações , Tromboembolia/etiologia , Transtornos Plaquetários/etiologia , Transtornos Plaquetários/sangue , Tromboembolia/sangue , Ativação Plaquetária , Antitrombina III/análise , Proteína C/análise , Proteína S/análise
8.
Clin Lab ; 65(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625376

RESUMO

BACKGROUND: Protein Z is a glycoprotein which acts as an anticoagulant factor. A deficiency of protein Z is associated with thrombotic events and adverse obstetric outcomes. The association between protein Z deficiency and adverse obstetric outcomes has previously been demonstrated in several studies. However, none of them have investigated each complication independently. The aim of this study was to evaluate serum levels of protein Z in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: Pregnant and nonpregnant healthy women between the ages of 18 and 40 years were included in the study. There were three groups: One: Study group: pregnant women with IUGR fetuses; Two: Control group 1: pregnant women with normal fetuses; Three: Control group 2: nonpregnant, healthy women. Plasma protein levels of protein Z, protein S, and protein C were measured for each group. RESULTS: Women with IUGR had significantly higher mean plasma concentrations of protein Z compared to women with normal pregnancies. This is in contrast to previous studies. CONCLUSIONS: The results of this study indicate that the association between protein Z levels and IUGR is still controversial.


Assuntos
Proteínas Sanguíneas/análise , Retardo do Crescimento Fetal/sangue , Complicações na Gravidez/sangue , Terceiro Trimestre da Gravidez/sangue , Adolescente , Adulto , Feminino , Retardo do Crescimento Fetal/diagnóstico , Humanos , Gravidez , Complicações na Gravidez/diagnóstico , Proteína C/análise , Proteína S/análise , Adulto Jovem
9.
Transfusion ; 59(11): 3468-3477, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31618457

RESUMO

BACKGROUND: There is renewed interest in administering whole blood (WB) for the resuscitation of patients with bleeding trauma. The shelf life of WB was established decades ago based on the viability of red blood cells. However, plasma quality during WB storage is not established. STUDY DESIGN AND METHODS: White blood cell- and platelet-reduced WB (WB-PLT) was prepared using standard processes and compared to WB processed using a platelet-sparing WBC reduction (WB + PLT) filter. WB (± PLT) was held at 2 to 6°C for 35 days alongside control units of red blood cells (RBCs) in saline, adenine, glucose, and mannitol and liquid plasma. A series of assays explored the coagulation potential and RBC quality. RESULTS: While fibrinogen and α2-antiplasmin remained unaffected by storage, other factors varied between components or over time at 2 to 6°C. At 14 days factor V, factor VII, α2 -antiplasmin and free protein S antigen remained on average greater than 0.50 IU/mL or 50%, as appropriate, in WB ± PLT. Factor VIII was on average 0.49 IU/mL in WB+PLT, and 0.56 IU/mL for WB-PLT. Free protein S activity decreased significantly in all arms but remained on average greater than 40% at Day 14. Contact activation was not demonstrated before Day 14. Thrombin generation in plasma remained relatively stable to Day 35 in all arms. CONCLUSIONS: Clotting factor activity remained at or above a mean of 0.5 IU/mL, or 50%, at Day 14 for factor V, factor VII, factor VIII, free protein S, fibrinogen, and α2-antiplasmin in all arms. Further data on platelet function in WB+PLT is needed to inform its shelf life.


Assuntos
Plaquetas/fisiologia , Preservação de Sangue/métodos , Eritrócitos/fisiologia , Plasma , Trifosfato de Adenosina/sangue , Coagulação Sanguínea , Coleta de Amostras Sanguíneas , Humanos , Procedimentos de Redução de Leucócitos , Proteína S/análise , Tromboelastografia , alfa 2-Antiplasmina/análise
10.
PLoS One ; 14(9): e0223171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31560710

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients are predisposed to several diabetes-related complications. Dysregulation of the haemostatic mechanisms have been implicated. There are however no current studies assessing the levels and activity of protein C (PC), protein S (PS), and antithrombin III (AT III), which are essential in haemostatic regulation, in a single cohort of T2DM patients. This study evaluated the effect of poorly-managed T2DM on the levels and activity of PC, PS, and AT III. METHODS: This cross-sectional study was conducted at the Diabetes Clinic, Cocoa Clinic in Kumasi, Ghana. A total of 242 T2DM patients, comprising 152 patients with poorly-managed diabetes and 90 well-managed diabetes patients, were recruited for the study. Fasting blood glucose, liver function tests and lipid profile were performed for each respondent. Glycated haemoglobin (HbA1c) was estimated by turbidimetric inhibition immunoassay. The levels and activity of PC, PS and AT III were measured by solid phase sandwich ELISA method. RESULTS: There was a negative correlation between HbA1c and the levels and activity of PC, PS and AT III. The levels and activity of PC [(5.78 vs 4.64 µg/ml, p<0.0001) and (42.22 vs 36.21 U/ml, p = 0.01) respectively], PS [(22.55 vs 20.29 µg/ml, p = 0.010) and (235.94 vs 211.67 U/ml, p<0.0001) respectively] and AT III [(16.28 vs 14.41µg/ml, p<0.0001) and (176.01 vs 160.09 U/ml, p = 0.03) respectively] were significantly increased in patients with well-managed T2DM compared to the poorly-managed diabetes patients. Likewise, the levels and activity of PC, PS, and AT III was higher among T2DM patients using statins than patients who were statin-naïve. Among patients with well-managed T2DM, those who were on statins had significantly higher levels and activities of PC, PS, and AT III compared to well-managed T2DM patients not on statins. However, there no statistically significant differences between the level and activity of PC, PS, and AT III among poorly-managed T2DM patients with respect to statin status. CONCLUSION: Poorly-managed type 2 diabetes mellitus is associated with reduced levels and activity of PC, PS and AT III compared to well-managed T2DM. Though use of statins may improve the levels and activity of the PC, PS and AT III in T2DM, their effect is limited in the presence of poorly-controlled T2DM. Proper management of diabetes is essential to reduce the likelihood of thrombotic events among T2DM patients.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipoglicemiantes/administração & dosagem , Trombose/prevenção & controle , Adulto , Idoso , Antitrombina III/análise , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Proteína C/análise , Proteína S/análise , Trombose/sangue , Trombose/etiologia , Resultado do Tratamento
11.
Methods Mol Biol ; 2009: 13-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31152392

RESUMO

The use of synthetically synthesized azide and alkyne fatty acid analogs coupled with bioorthogonal Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction-based detection methods to study protein S-acylation reactions has replaced the traditional method of using in vivo metabolic radiolabeling with tritiated palmitic acid and has greatly facilitated our understanding of this essential cellular process. Here, we describe the chemical synthesis of myristic (C:14), palmitic (C16:0), and stearic (C18:0) acid-azide probes and detail how they may be utilized as chemical reporters for the analysis of S-acylation of exogenously expressed proteins in cells.


Assuntos
Ácido Mirístico/análise , Ácido Palmítico/análise , Proteína S/análise , Ácidos Esteáricos/análise , Acilação , Reação de Cicloadição , Células HEK293 , Humanos , Ácido Mirístico/metabolismo , Ácido Palmítico/metabolismo , Proteína S/metabolismo , Ácidos Esteáricos/metabolismo
12.
J Perinatol ; 39(2): 212-219, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353081

RESUMO

ABSTARCT: OBJECTIVE: The diagnosis of neonatal-onset protein C (PC) deficiency is challenging. This study aimed to establish the neonatal screening of heritable PC deficiency in Japan. STUDY DESIGN: We determined the changes in plasma activity levels of PC and protein S (PS) in healthy neonates, and studied newborn patients with PROC mutation in the Japanese registry. RESULT: Physiological PC and PS levels increased with wide range. The PC/PS-activity ratios converged after birth. The PC/PS-activity ratios of 19 patients with biallelic mutations, but not, 9 with monoallelic mutation, were lower than those of 13 without mutation. The logistic regression analyses established a formula including two significant variables of PC activity (cut-off < 10%, odds ratio = 30.0) and PC/PS-activity ratio (cut-off < 0.35, odds ratio = 22.7), with 93% sensitivity and 44% specificity for determining patients with mutation(s). CONCLUSION: The PC/PS-activity ratio is an effective parameter for the genetic screening of neonatal-onset PC-deficiency in Japanese population.


Assuntos
Deficiência de Proteína C/diagnóstico , Proteína C/análise , Proteína S/análise , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Testes Genéticos , Humanos , Recém-Nascido , Japão , Modelos Logísticos , Masculino , Fenótipo , Valor Preditivo dos Testes , Deficiência de Proteína C/sangue , Deficiência de Proteína C/genética , Fatores de Risco , Sensibilidade e Especificidade
13.
Pregnancy Hypertens ; 13: 116-120, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30177037

RESUMO

BACKGROUND: Preeclampsia (PE) is a multifactorial dysfunction characterized by hypertension with characteristics of systematic endothelial activation. It is widely accepted that vascular disorder and deficient trophoblast invasion are involved in PE. Tyro3/Axl/MerTK (TAM) family receptors are tyrosine-kinase receptors and may exert a diverse range of functions such as cell proliferation, migration, and vascular angiogenesis. The role of TAM signaling in severe PE patients remains unclear. Therefore, the aim of this study was to investigate involvement of the TAM axis in the pathogenesis of PE. METHODS: A total of 36 severe PE patients and 40 age- and gender-matched healthy pregnant women (controls) were enrolled in this study. Plasma levels of soluble TAM receptors (Tyro3, Axl, MerTK) and ligands (Gas6 and ProS) were then measured using an enzyme-linked immunosorbent assay (ELISA). We evaluated the association between the expression of these proteins and the clinical features of PE. RESULTS: Plasma levels of sMerTK and sAxl were significantly higher in severe PE patients than in control women during pregnancy. The plasma concentrations of sMerTK and sAxl in severe PE patients correlated positively with systolic and diastolic blood pressure, and plasma sAxl levels demonstrated a significant correlation to proteinuria. In contrast, reduced levels of Gas6 were inversely associated with urine protein in PE patients. CONCLUSIONS: Elevated expression of the plasma levels of sMerTK and sAxl, as well as the reduction of Gas6 were observed in severe PE patients. Furthermore, these changes were correlated with disease activity. TAM signaling might play a role in the pathogenesis of PE.


Assuntos
Pré-Eclâmpsia/sangue , Proteínas Proto-Oncogênicas/sangue , Receptores Proteína Tirosina Quinases/sangue , c-Mer Tirosina Quinase/sangue , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Ligantes , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/fisiopatologia , Valor Preditivo dos Testes , Gravidez , Proteína S/análise , Índice de Gravidade de Doença
14.
Med J Malaysia ; 73(4): 185-189, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30121679

RESUMO

BACKGROUND: It is being increasingly recognised that thalassemia major patients, like intermedia, have increased propensity for thromboembolism. Deficiency of natural anticoagulants is more recently defined finding contributing to the hypercoagulable state. The aim this study is to determine natural anticoagulants levels and their correlation with maternal characteristics, haematological and biochemical markers. METHODS: This is a prospective case-control study. We registered 80 patients and 60 healthy controls from Jan 2009 to Dec 2013. Complete blood counts, prothrombin time, activated partial thromboplastin time, protein C, protein S, antithrombin, serum ferritin, liver enzymes; HbsAg and Anti- HCV were evaluated. RESULT: There were 42 males and 38 females with mean age of 12.30±5.50 years. The mean protein C, protein S and antithrombin in patients and control were 58.25±22.5 versus 110.67±22.60, 67.90±19.58 versus 98.70±21.54 and 89.73±18.09 versus 104.0±10.98 (p<0.001) respectively. Protein C was predominantly deficient in 65% followed by protein S and antithrombin in 35% and 20% respectively. Protein C deficiency divulged positive correlation with protein S deficiency (p = 0.035) and antithrombin deficiency with hemoglobin of ≤8gm% (p<0.0025). No significant correlation of prothrombotic markers was established with maternal characteristics, hepatic dysfunction, hepatitis and serum ferritin. CONCLUSION: Substantial decrement in prothrombotic markers, primarily protein C, may be implicated in elevated thrombosis; however follow-up data is required to establish definitive thromboembolic events.


Assuntos
Talassemia beta/sangue , Adolescente , Antitrombinas/sangue , Biomarcadores/sangue , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Ferritinas/sangue , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Tempo de Tromboplastina Parcial , Estudos Prospectivos , Proteína C/análise , Proteína S/análise , Tempo de Protrombina , Adulto Jovem
15.
Thromb Haemost ; 118(4): 647-653, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29618151

RESUMO

BACKGROUND: Anabolic androgenic steroid (AAS) abusers are considered at increased risk of cardiovascular morbidity and mortality. We hypothesized that current and former AAS abuse would induce a procoagulant shift in the haemostatic balance. METHODS: Men 18 to 50 years of age were included as current AAS abusers, former AAS abusers or controls. Morning blood samples were collected after overnight fasting. Thrombin generation (lag time, time to peak, peak height, and endogenous thrombin potential [ETP]) and coagulation factor II (prothrombin), VII and X, antithrombin, protein C, free protein S and tissue factor pathway inhibitor (TFPI) were assessed. Groups were compared by ANOVA or Kruskal-Wallis test and probabilities were corrected for multiple comparisons. Associations were evaluated using linear regression models. RESULTS: ETP was increased around 15% in current (n = 37) and former (n = 33) AAS abusers compared with controls (n = 30; p < 0.001). Prothrombin and factor X were increased ≥10% in AAS abusers and prothrombin was a predictor of ETP (p < 0.0005). Lag time and time to peak were increased 10 to 30% in current AAS abusers (p < 0.001) and associated with higher concentrations of TFPI, antithrombin, protein C and protein S (p < 0.0005; = 0.005). Multivariate linear regression, with all coagulation inhibitors as covariates, identified TFPI to be independently associated with lag time and time to peak (p < 0.0005). CONCLUSION: Thrombin generation is augmented in current and former AAS abusers, reflecting a procoagulant state, with altered concentrations of coagulation proteins. Prospective studies are needed to clarify whether these findings translate into an increased thrombotic risk in AAS abusers potentially even after cessation.


Assuntos
Androgênios/efeitos adversos , Coagulantes/sangue , Esteroides/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/sangue , Adolescente , Adulto , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Usuários de Drogas , Fator VII/análise , Fator X/análise , Humanos , Modelos Lineares , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Proteína C/análise , Proteína S/análise , Protrombina/análise , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Trombina/análise , Trombose , Adulto Jovem
16.
Int J Lab Hematol ; 40(4): 466-472, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29704446

RESUMO

INTRODUCTION: Protein C (PrC), a physiological anticoagulant, regulates inflammation and cell death and has known predictive/therapeutic roles in sepsis. Accumulating evidences suggest plasma hypercoagulability results in progression of fibrosis and formation of microclots causing end-organ dysfunction. We investigated a possible association between natural anticoagulants-PrC, protein S (PrS) and antithrombin III (AT)-and clinical outcomes in cirrhotics. METHODS: Functional PrC, PrS and AT were analysed in 515 cirrhotic patients and compared with 229 noncirrhotics. Among those with cirrhosis, we conducted multivariable predictive model on 3-month survival to assess the prognostic ability of anticoagulants. RESULTS: Protein C (P < .001), PrS (P < .001) and AT (P < .001) levels were lower in cirrhotics compared with noncirrhotics. In addition, patients with Child-Pugh (CP)-C had significantly lower (P < .05) functional PrC, PrS and AT levels than CP-B, CP-A and noncirrhotic patients. Low PrC function correlated with markers of liver dysfunction and inflammation: INR(r = -.72, P < .001), bilirubin (r = -.620, P < .001), albumin (r = .539, P < .001), creatinine (r = -.417, P < .001), ferritin (r = -.68, P = .035), procalcitonin (r = -.79, P = .01), raised ESR (r = .56, P < .001) and liver fibrosis (r = -.840, P < .001). Patients who died (n = 160) had significantly lower median PrC function (23.8%, 16.3-33.0]) compared with those who remained alive (74.9%, [59.7-92.5]); P < .001. In a multivariable predictive model using PrC, and MELD score, we found a significant impact of low PrC levels on survival (P < .001, IRR = 0.97, 95% CI = 0.96-0.98). Receiver operating characteristic (ROC) curve analysis revealed that functional PrC levels <52% were associated with increased mortality (P < .001). CONCLUSION: Low functional protein C level correlated with markers of liver dysfunction, inflammation and sepsis and independently predicted mortality at 3 months in cirrhotics, especially if functional levels were <52%.


Assuntos
Cirrose Hepática/diagnóstico , Proteína C/análise , Adulto , Idoso , Antitrombina III/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Proteína S/análise , Curva ROC
17.
Arch Pathol Lab Med ; 142(1): 70-74, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28920711

RESUMO

CONTEXT: - Rivaroxaban causes a false increase in activated protein C resistance (APCR) ratios and protein S activity. OBJECTIVE: - To investigate whether this increase masks a diagnosis of factor V Leiden (FVL) or protein S deficiency in a "real-world" population of patients undergoing rivaroxaban treatment and hypercoagulation testing. DESIGN: - During a 2.5-year period, we compared 4 groups of patients (n = 60): FVL heterozygous (FVL-HET)/taking rivaroxaban, wild-type/taking rivaroxaban, FVL-HET/no rivaroxaban, and normal APCR/no rivaroxaban. Patients taking rivaroxaban were tested for protein S functional activity and free antigen (n = 32). RESULTS: - The FVL-HET patients taking rivaroxaban had lower APCR ratios than wild-type patients ( P < .001). For FVL-HET patients taking rivaroxaban, mean APCR was 1.75 ± 0.12, versus 1.64 ± 0.3 in FVL-HET patients not taking rivaroxaban ( P = .005). Activated protein C resistance in FVL-HET patients fell more than 3 SDs below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. No cases of FVL were missed despite rivaroxaban. In contrast, rivaroxaban falsely elevated functional protein S activity, regardless of the presence or absence of FVL ( P < .001). A total of 4 of 32 patients (12.5%) had low free protein S antigen (range, 58%-67%), whereas their functional protein S activity appeared normal (range 75%-130%). Rivaroxaban would have caused a missed diagnosis of all cases of protein S deficiency during the study if testing relied on the protein S activity assay alone. CONCLUSIONS: - Despite rivaroxaban treatment, APCR testing can distinguish FVL-HET from normal patients, rendering indiscriminate FVL DNA testing of all patients on rivaroxaban unnecessary. Free protein S should be tested in patients taking rivaroxaban to exclude hereditary protein S deficiency.


Assuntos
Resistência à Proteína C Ativada/diagnóstico , Fator V/genética , Inibidores do Fator Xa/uso terapêutico , Deficiência de Proteína S/diagnóstico , Rivaroxabana/uso terapêutico , Resistência à Proteína C Ativada/tratamento farmacológico , Resistência à Proteína C Ativada/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea , Inibidores do Fator Xa/efeitos adversos , Reações Falso-Negativas , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteína S/análise , Deficiência de Proteína S/sangue , Rivaroxabana/efeitos adversos , Adulto Jovem
18.
Afr Health Sci ; 18(3): 681-688, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30603001

RESUMO

Background: Hemophilia is an inherited genetic disease characterized by the inability to coagulate blood after injury. The rationale of the current study was to evaluate serum proteins S and C and correlate to kidney function test in hemophilic patients for early diagnosis of abnormality in renal function. Subjects and Methods: This study was conducted on 80 males subjects divided into four groups. Group I: Control: Healthy subjects. Group II: Renal dysfunction (serum Creatinine >2mg/dl): Group III: Hemophilic patients. Group IV: Hemophilic patients with renal disorder. Serum urea, creatinine, sodium, potassium, protein C and protein S level were determined. Resuts: Protein C and S levels showed a significant decrease in hemophilic/and with renal dysfunction (P < 0.001, p<0.001). The level of plasma protein C and S levels were positively correlated with increased urinary albumin (P < 0.01). Urinary albumin was increased about 15 folds in hemophilic patients with renal dysfunction and nephrotic patients as compared with the control group. The cut-off value in 90% patients at the hemophilic patients with renal dysfunction 70%. Positive correlations were observed between urinary albumin (r=0.66), and creatinine (r=0.73). Conclusion: These biomarkers showed good predictive values with regard to ROC-AUC (0.41 and 0.75 for Proteins C and S, respectively).


Assuntos
Hemofilia A/complicações , Nefropatias/sangue , Proteína C/análise , Proteína S/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Creatinina/sangue , Hemofilia A/sangue , Humanos , Nefropatias/etiologia , Masculino , Potássio/sangue , Sódio/sangue , Ureia/sangue
19.
J Thromb Thrombolysis ; 44(4): 507-515, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28914415

RESUMO

Guidelines suggest restarting warfarin at known maintenance doses, although this may result in a delay to achieving therapeutic anticoagulation. As such, we compared the time to achieve an INR ≥ 2.0 between those restarting warfarin maintenance vs loading doses after transient interruption, and the impact on protein C, S and factor II levels. Patients requiring interruption of warfarin for elective procedures without hospitalization were randomized 1:1 to receive warfarin maintenance or loading doses (1.5 times the maintenance dose for 3 days followed by pre-procedural warfarin maintenance dosing). Protein C, S and Factor II were drawn at baseline (prior to warfarin interruption), 7 and 14 days after restarting warfarin. Among 19 patients randomized to maintenance and 20 to loading doses, nearly half in each group had mechanical heart valves with gastrointestinal endoscopic procedures most commonly performed (41%). The median number of days to reach an INR ≥ 2.0 was 7.8 days in the loading and 9.0 in the maintenance group (difference between medians 1.2 days, 95% CI -3.1 to 4.9; P = 0.19). Although levels of protein C, S and factor II were lower in the loading vs maintenance dose group, all remained above that of baseline. Warfarin resumption with loading doses shortened the time to achieve a therapeutic INR by a median of 1.2 days. Prompt warfarin dose escalation should be done in response to the INR. Protein C and S remained above pre-warfarin interruption levels, implying a lack of depletion with restarting warfarin.


Assuntos
Procedimentos Cirúrgicos Eletivos/métodos , Varfarina/administração & dosagem , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Proteína C/análise , Proteína S/análise , Protrombina/análise , Fatores de Tempo
20.
Methods Mol Biol ; 1646: 153-160, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28804826

RESUMO

Protein S (PS) is a Vitamin K-dependent protein that functions as a cofactor for the regulation of the coagulation system. PS works in conjunction with Activated Protein C to inactivate factors V and VIII. PS circulates in plasma either complexed to the complement protein, C4b Binding Protein or unbound. The unbound (or free) component is the functional form for the regulation of the coagulation system. PS can be measured in plasma by functional activity, the free (or unbound form) or both free and bound fractions (Total PS). The test most widely used for clinical evaluations is the Free PS Antigen assay (which is the surrogate of PS anticoagulant activity) and represents the protocol described in this chapter. The Free PS Antigen assay is an immunologic assay which specifically measures the unbound fraction of PS in test plasma. Other methods for assessing PS are also available, including PS activity and total PS Antigen assays, but protocols for these assays are not provided.


Assuntos
Imunoturbidimetria/métodos , Proteína S/análise , Trombofilia/sangue , Trombofilia/diagnóstico , Proteína de Ligação ao Complemento C4b/metabolismo , Humanos , Ligação Proteica , Proteína S/metabolismo , Trombofilia/metabolismo
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