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1.
Medicine (Baltimore) ; 100(23): e26221, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115006

RESUMO

BACKGROUND: Vitamin K has long been regarded as a procoagulant drug by physicians, and concerns have been raised with regard to its effects on hemostasis. Although many studies have shown that vitamin K supplementation is safe for thrombotic events, the effect of vitamin K supplementation on the activities of vitamin K dependent procoagulation factors in healthy individuals is not available. OBJECTIVES: This study aimed to investigate whether vitamin K2 supplementation at recommended doses affects the activity of vitamin K dependent procoagulation factors in healthy individuals without any anticoagulation treatment. DESIGN: Forty healthy volunteers between 25 and 40 years of age were recruited. Menaquinone-7 (MK-7) was administrated at 90 µg for 30 days. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and blood coagulation factors II, VII, IX, and X activities and Protein induced by vitamin K absence or antagonist-II (PIVKA-II) were measured on days 0 and 30 after MK-7 administration. RESULTS: PT, APTT, and TT showed no significant differences on day 30 when compared with baseline. The activities of coagulation factors II, VII, IX, and X on day 30 showed no significant differences with those at baseline. PIVKA-II levels were unchanged after 30 days of MK-7 supplementation. CONCLUSIONS: MK-7 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' coagulation activity, and does not enhance the carboxylation of prothrombin in healthy individuals. This indicated that MK-7 administration does not alter hemostatic balance in healthy populations without anticoagulation treatment.


Assuntos
Fatores de Coagulação Sanguínea/efeitos dos fármacos , Suplementos Nutricionais/normas , Vitamina K 2/farmacologia , Adulto , Antifibrinolíticos/farmacologia , Antifibrinolíticos/uso terapêutico , Fatores de Coagulação Sanguínea/análise , Suplementos Nutricionais/estatística & dados numéricos , Fator IX/análise , Fator IX/efeitos dos fármacos , Fator VII/análise , Fator VII/efeitos dos fármacos , Fator X/análise , Fator X/efeitos dos fármacos , Feminino , Voluntários Saudáveis/estatística & dados numéricos , Humanos , Masculino , Tempo de Tromboplastina Parcial/métodos , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Protrombina/análise , Protrombina/efeitos dos fármacos , Tempo de Protrombina/métodos , Tempo de Protrombina/estatística & dados numéricos , Tempo de Trombina/métodos , Tempo de Trombina/estatística & dados numéricos , Vitamina K 2/uso terapêutico
2.
Lupus ; 30(4): 641-648, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33509039

RESUMO

INTRODUCTION: Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare phenomenon that leads to concomitant thrombosis and hemorrhage in children with SLE. LAHPS in pediatric SLE (pSLE) has a protracted course requiring long-term immunosuppressive therapy. Due to the rarity of this syndrome and paucity of reported cases, there is lack of standardized management. We herewith report 5 children with pSLE with LAHPS.Methodology: We retrospectively reviewed clinical features, laboratory features, treatment and outcome for 5 children with lupus anticoagulant hypoprothrombinemia syndrome with SLE and a review of literature of similar cases published. RESULTS: Mean age of presentation was 10.2 ± 2.38 years (mean ± SD) and female to male ratio was 4:1. All children presented with mild to severe bleeding manifestations like gum bleed, epistaxis, hematuria, menorrhagia and subarachnoid bleed. Coagulation profile revealed prolonged PT and aPTT, with low prothrombin levels and positive Lupus anticoagulant in all children. Mixing studies were characteristic in these children. On comparing laboratory parameters majority had low C3, C4 levels, ANA and anti-DsDNA antibody positivity and three children had anticardiolipin positivity. One child had lupus nephritis along with LAHPS at presentation. All responded well to steroids and supportive measures. CONCLUSION: High index of suspicion is needed when child with lupus presents with bleeding manifestations for early diagnosis and treatment.


Assuntos
Hemorragia/etiologia , Hipoprotrombinemias/complicações , Inibidor de Coagulação do Lúpus/sangue , Lúpus Eritematoso Sistêmico/complicações , Trombose/etiologia , Adolescente , Testes de Coagulação Sanguínea/estatística & dados numéricos , Transfusão de Sangue/métodos , Criança , Diagnóstico Precoce , Feminino , Hemorragia/diagnóstico , Humanos , Hipoprotrombinemias/diagnóstico , Hipoprotrombinemias/tratamento farmacológico , Hipoprotrombinemias/terapia , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Protrombina/análise , Estudos Retrospectivos , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Trombose/diagnóstico , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(43): e22926, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120848

RESUMO

RATIONALE: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies directed against the activity of factor VIII (FVIII) and presents with prolonged bleeding. 5.7% of systemic lupus erythematosus (SLE) patients are affected by AHA. PATIENT CONCERNS: A 51-year-old female patient with SLE presenting with the fatigue and spontaneous clinical bleeding symptoms such as hematuria and ecchymoses for 1 week. DIAGNOSIS: Laboratory examinations revealed prolongation of the activated partial thromboplastin time (APTT) (65.7 s), decreased FVIII activity (1.4%), and a titer of FVIII inhibitors of 8.5 Bethesda units/mL. INTERVENTIONS: Transfusion of recombinant human FVIII (ADVATE) in combination with intravenous methylprednisolone, cyclophosphamide, plasmapheresis, and fresh frozen plasma successfully stopped the bleeding and reduced the level of FVIII inhibitor. OUTCOMES: The size of the hematoma slowly decreased. The skin ecchymosis was gradually absorbed, the hemoglobin count increased, and the coagulation index gradually improved. There was no new bleeding or bleeding site. The patient was discharged and transferred to a local hospital for hospice care. LESSONS: AHA in a patient with SLE is rare. Once it occurs, it can be life-threatening. Clinicians should remain aware that because some cases of AHA may have features of SLE, appropriate distinction and diagnosis of these different but associated diseases is necessary.


Assuntos
Coagulantes/uso terapêutico , Fator VIII/uso terapêutico , Hemofilia A/etiologia , Lúpus Eritematoso Sistêmico/complicações , Administração Intravenosa , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Testes de Coagulação Sanguínea/métodos , Coagulantes/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Equimose/diagnóstico , Equimose/etiologia , Fator VIII/administração & dosagem , Feminino , Hematúria/diagnóstico , Hematúria/etiologia , Hemofilia A/terapia , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/métodos , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Plasma , Plasmaferese/métodos , Resultado do Tratamento
4.
Kaohsiung J Med Sci ; 36(11): 929-936, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32643870

RESUMO

Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non-ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin-antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 (PAI-1) levels by enzyme-linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non-ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI-1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.


Assuntos
Lesão Pulmonar Aguda/sangue , Traumatismos por Explosões/sangue , Explosões , Fibrinólise , Pulmão/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Antitrombina III/metabolismo , Traumatismos por Explosões/patologia , Plaquetas/metabolismo , Plaquetas/patologia , Líquido da Lavagem Broncoalveolar/química , Fibrinogênio/metabolismo , Gases/química , Humanos , Lipoproteínas/metabolismo , Pulmão/irrigação sanguínea , Pulmão/patologia , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Peptídeo Hidrolases/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Contagem de Plaquetas , Tempo de Protrombina/estatística & dados numéricos , Ratos , Ratos Sprague-Dawley , Tromboplastina/metabolismo
6.
CEN Case Rep ; 9(3): 225-231, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32180153

RESUMO

An 88-year-old man with congenital hemophilia A developed end-stage renal disease due to microscopic polyangiitis. He was at risk for catheter-related infection because he was taking immunosuppressive agents for the treatment of polyangiitis. He was also unable to manipulate the peritoneal dialysis device. Therefore, hemodialysis using an arteriovenous fistula was induced for renal replacement therapy. Recombinant coagulation factor VIII (1000 IU) was administered via the venous chamber of the hemodialysis circuit 10 min before the end of each hemodialysis session, and nafamostat mesylate (25 mg/h) was employed as an anticoagulant during hemodialysis. His clotting factor VIII activity level increased to > 50% and activated partial thromboplastin time decreased to 50 s at the end of each hemodialysis session. This method allowed him to achieve hemostasis at the puncture site of the arteriovenous fistula and undergo stable hemodialysis with no complications, including bleeding. This case suggests that hemodialysis using an arteriovenous fistula with coagulation factor replacement and nafamostat mesylate in each hemodialysis session is a therapeutic option for end-stage renal disease in patients of advanced age with hemophilia at high risk of bleeding.


Assuntos
Fístula Arteriovenosa/cirurgia , Hemofilia A/complicações , Falência Renal Crônica/etiologia , Poliangiite Microscópica/complicações , Diálise Renal/métodos , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Benzamidinas/administração & dosagem , Coagulantes/administração & dosagem , Fator VIII/administração & dosagem , Guanidinas/administração & dosagem , Hemorragia/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Masculino , Poliangiite Microscópica/tratamento farmacológico , Tempo de Tromboplastina Parcial/estatística & dados numéricos
7.
Acta Anaesthesiol Scand ; 64(5): 628-634, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31898318

RESUMO

BACKGROUND: It is well known that low platelet count on admission to intensive care units (ICU) is associated with increased mortality. However, it is unknown whether prothrombin time (PT-INR) and activated partial thromboplastin time (APTT) on admission correlate with mortality and organ failure. Therefore, the aim of this study was to investigate whether PT-INR and APTT at admission can predict outcome in the critically ill patient after adjusting for severity of illness measured with Simplified Acute Physiology Score 3 (SAPS 3). MATERIALS AND METHODS: Data were retrospectively collected. APTT and PT-INR taken on admission and SAPS 3 score were independent variables in all regression analyses. Survival analysis was done with Cox regression. Organ failure was reported as days alive and free (DAF) of vasopressors and invasive ventilation, need of continuous renal replacement therapy (CRRT) and Acute Kidney Injury Network creatinine score (AKIN-crea). RESULTS: A total of 3585 ICU patients were included. Prolonged APTT correlated with mortality with 95% confidence interval (CI) of hazard ratio 1.001-1.010. Prolonged APTT also correlated with DAF vasopressor, CRRT and AKIN-crea with 95% CI of odds ratio (OR) 1.009-1.034, 1.016-1.037 and 1.009-1.028, respectively. Increased PT-INR correlated with DAF vasopressor and DAF ventilator with 95% CI of OR 1.112-2.014 and 1.135-1.847, respectively. CONCLUSIONS: Activated partial thromboplastin time prolongation was associated with mortality and all morbidity outcomes except the DAF ventilator. PT-INR increase at admission was associated with DAF vasopressor and DAF ventilator. APTT and PT-INR at admission correlate with morbidity, which is not accounted for in the SAPS 3 model.


Assuntos
Insuficiência de Múltiplos Órgãos/mortalidade , Tempo de Protrombina/mortalidade , Tempo de Protrombina/estatística & dados numéricos , Idoso , Testes de Coagulação Sanguínea , Estudos de Coortes , Estado Terminal/mortalidade , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/mortalidade , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Suécia/epidemiologia
8.
Acad Emerg Med ; 27(2): 117-127, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31625654

RESUMO

OBJECTIVE: The objective was to determine the proportion of patients with pulmonary embolism (PE) treated with unfractionated heparin (UFH) who achieved therapeutic activated partial thromboplastin time (aPTT) values within 48 hours of treatment. METHODS: Retrospective analysis of a PE response team (PERT) database was performed at a large, urban, academic teaching hospital. Inclusion criteria were adult patients with acute PE for whom the PERT was consulted and who received anticoagulation (AC) with UFH according to guideline standard dosing. aPTT values during 6-hour time periods during the first 48 hours of AC were collected and analyzed. RESULTS: A total of 505 patients met inclusion criteria. For patients receiving a bolus and infusion of UFH, the proportions (95% confidence interval [CI]) of patients in the therapeutic range were 19.0% (14.2% to 25.0%) at 12 hours, 26.3% (26.3% to 33.1%) at 24 hours, 28.3% (22.0% to 35.4%) at 36 hours, and 28.4% (20.8% to 37.5%) at 48 hours. For titrated infusion only, the proportions (95% CIs) of patients were 23.3% (16.2% to 32.3%) at 12 hours, 41.4% (31.6% to 51.9%) at 24 hours, 37.0% (26.8% to 48.5%) at 36 hours, and 42.1% (30.2% to 55.0%) at 48 hours. No patient had all therapeutic aPTT values. CONCLUSIONS: The majority of patients with acute PE spend most of their first 48 hours outside of the therapeutic range of AC when treated with guideline standard dosing of UFH. Over half of the patients fail to achieve any therapeutic PTT level within 24 hours of UFH initiation, and no patient had all therapeutic aPTTs. Future research should focus on identifying factors associated with achieving therapeutic AC with UFH.


Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Embolia Pulmonar/tratamento farmacológico , Doença Aguda , Adulto , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
9.
BMJ Open ; 9(11): e032306, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31780592

RESUMO

OBJECTIVES: To describe the prevalence and factors associated with preoperative haemostasis and ABO blood typing tests for children because these tests might represent low-value care. DESIGN: A retrospective observational study. SETTING: Nationwide insurance claims database in Japan. PARTICIPANTS: Patients aged 1-17 years who underwent common non-cardiac surgeries between April 2012 and March 2018 were included. Patients with high-risk comorbidities for bleeding (n=175) and those with multiple eligible surgeries were excluded (n=2121). MAIN OUTCOME MEASURES: We described the proportions of each preoperative test performed within 60 days before an index surgery, including platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and ABO blood typing tests. We also explored the associations between patient-level and institutional-level factors and any preoperative tests, using multilevel logistic regression analysis. RESULTS: We included 13 018 patients (median (IQR) age, 5.2 (2.9-7.7) years; 8276 (63.6%) boys) from 1499 institutions. The overall proportion of each test was as follows: platelet count, 78.6%; PT, 54.4%; aPTT, 56.4% and ABO blood typing tests, 50.4%. The proportion of patients undergoing any preoperative tests in the overall sample was 79.3%. Multilevel logistic regression analysis indicated that preoperative tests were associated with type of anaesthesia (general anaesthesia: adjusted OR 7.06; 95% CI 4.94 to 10.11), type of surgery (tonsillectomy: adjusted OR 3.45; 95% CI 2.75 to 4.33) and surgical setting (inpatient procedure: adjusted OR 5.41; 95% CI 3.83 to 7.66). There was one postoperative transfusion event (0.008%) in the entire cohort and 37 postoperative reoperation events for surgical bleeding after tonsillectomy (0.90%). CONCLUSIONS: In the largest Japanese cohort reported to date, preoperative haemostasis and ABO blood typing tests were performed in a majority of children prior to common paediatric surgeries. Preoperative tests were associated with anaesthesia, surgical type and surgical setting.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas/estatística & dados numéricos , Cuidados Pré-Operatórios/estatística & dados numéricos , Adolescente , Anestesia Geral , Criança , Pré-Escolar , Feminino , Hemostasia , Humanos , Lactente , Japão/epidemiologia , Masculino , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Contagem de Plaquetas/estatística & dados numéricos , Período Pré-Operatório , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios
10.
Biomarkers ; 24(4): 389-393, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30907672

RESUMO

Background: There are only limited data in the literature on the thrombotic risk of patients with Clostridium difficile (CD) colitis, although this disease is widespread throughout the world. Objective: The aim of this study was to explore thrombin generation in these patients - the best way to evaluate their coagulation. Methods: A prospective observational study was conducted during 15 months on hospitalized patients with CD colitis. Thrombin generation was performed in platelet-poor plasma using a Ceveron® alpha analyzer and was compared with a group of volunteer control subjects. Results: Thirty-three patients and 51 control subjects were enrolled in the study. Two biomarkers - mean velocity index and peak thrombin - were significantly higher in patient group, compared to the control subjects (p = 0.010, respectively, p = 0.0395). This pattern of thrombin generation suggests that patients with CD colitis without septic shock have a potential thrombotic risk. The mean velocity index significantly correlated with the estimated related risk of death according to the Charlson age-comorbidity index. Conclusions: The higher values of thrombin generation suggest that CD colitis increases the thromboembolic risk. The pattern of thrombin generation could identify patients with particularly higher thromboembolic risk. They are potential candidates for thromboprophylaxis strategies and monitorization.


Assuntos
Clostridioides difficile/patogenicidade , Enterocolite Pseudomembranosa/diagnóstico , Trombina/metabolismo , Trombose/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Coagulação Sanguínea , Estudos de Casos e Controles , Clostridioides difficile/fisiologia , Enterocolite Pseudomembranosa/sangue , Enterocolite Pseudomembranosa/complicações , Enterocolite Pseudomembranosa/microbiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Projetos Piloto , Estudos Prospectivos , Tempo de Protrombina/estatística & dados numéricos , Tempo de Trombina/estatística & dados numéricos , Trombose/sangue , Trombose/complicações , Trombose/microbiologia , Tempo de Coagulação do Sangue Total/estatística & dados numéricos
11.
Clin Transplant ; 33(3): e13478, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30636073

RESUMO

INTRODUCTION: Thromboelastography (TEG) is gaining increasing acceptance in liver transplantation (LT) with conventional coagulation tests (CCTs) such as prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III (ATIII), platelet count (PLT), and fibrinogen concentration. The purpose of this study was to evaluate the clinical utility of TEG in LT and investigate the correlation between TEG and CCT values during each phase of LT. MATERIALS AND METHODS: Medical records of patients who underwent deceased donor LT at a single, university hospital between October 2010 and July 2015 were retrospectively reviewed. Blood samples were obtained at each phase of LT (pre-anhepatic, anhepatic, and neo-hepatic phase) according to our institutional LT protocol and utilized for analysis of TEG and CCTs. The Spearman correlation coefficient between TEG and CCT values were obtained. RESULTS: During the pre-anhepatic phase, the reaction time (R), PT, and aPTT did not correlate with each other, but demonstrated a negative correlation with PLT. Clot formation time (K) demonstrated a similar correlation with R and a negative correlation with fibrinogen. The maximal amplitude (MA) and α-angle (α) were positively correlated with PLT and fibrinogen and inversely correlated with aPTT. During the anhepatic phase, MA was significantly correlated with PLT and inversely correlated with aPTT; other parameters had weak or indistinct correlation. During the neo-hepatic phase, R and K were significantly correlated with aPTT and inversely correlated with PLT and fibrinogen. A correlation of MA and α with PLT, aPTT, and fibrinogen was also observed. Clot lysis at 30 minutes and estimated percent lysis were inversely correlated with levels of ATIII and fibrinogen. CONCLUSIONS: Conventional coagulation tests and TEG show particularly poor comparability during the anhepatic period of liver transplantation. TEG can be most reliable in the anhepatic phase, during which dynamic hemostatic changes occur.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea/métodos , Rejeição de Enxerto/diagnóstico , Transplante de Fígado/efeitos adversos , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Complicações Pós-Operatórias , Tromboelastografia/métodos , Transtornos da Coagulação Sanguínea/etiologia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
12.
J Extra Corpor Technol ; 50(3): 161-166, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30250342

RESUMO

Anticoagulation with unfractionated heparin during extracorporeal membrane oxygenation (ECMO) is common, but alternative agents are being evaluated for safety and efficacy. The objective of this analysis was to assess if a comprehensive bivalirudin dosing and monitoring protocol effectively guides dose adjustments and monitoring of bivalirudin in patients during ECMO. Our analysis included 11 patients who received bivalirudin during ECMO therapy and had dosing managed using our hospital derived protocol. Patients treated over a 1-year period were included in this retrospective analysis. Clinical characteristics and changes in activated partial thromboplastin time (aPTT) were evaluated from medical records to determine the efficacy of the dosing protocol. ECMO was initiated for acute respiratory distress syndrome in eight (72.7%) patients and for cardiac arrest in three (27.3%) patients. A total of 178 protocol guided dose adjustments were made during the study. Among the dose adjustments, 56 (31.5%) attained the protocol predicted aPTT level change, 96 (53.9%) of the measured aPTT changes were less than predicted, and 26 (14.6%) of the measured aPTT changes were more than predicted. On average, patients were within their defined therapeutic aPTT target range 66.3% of the time. All patients reached their designated aPTT target range within the first 24 hours of therapy. Significant bleeding was documented in eight (72.7%) patients. No clinically evident thromboembolic events were identified in vivo while cannulated. This analysis suggests that bivalirudin can be managed using a dosing protocol to provide anticoagulation therapy to patients during ECMO and can provide foundational guidance for dose adjustment and monitoring for other institutions.


Assuntos
Anticoagulantes/uso terapêutico , Oxigenação por Membrana Extracorpórea/métodos , Fragmentos de Peptídeos/uso terapêutico , Adolescente , Adulto , Idoso , Hirudinas , Humanos , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
13.
Dis Markers ; 2018: 5214376, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29511389

RESUMO

It would be important to predict type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). This study was aimed at evaluating the predicting significance of hemostatic parameters for T2DM and DN. Plasma coagulation and hematologic parameters before treatment were measured in 297 T2DM patients. The risk factors and their predicting power were evaluated. T2DM patients without complications exhibited significantly different activated partial thromboplastin time (aPTT), platelet (PLT), and D-dimer (D-D) levels compared with controls (P < 0.01). Fibrinogen (FIB), PLT, and D-D increased in DN patients compared with those without complications (P < 0.001). Both aPTT and PLT were the independent risk factors for T2DM (OR: 1.320 and 1.211, P < 0.01, resp.), and FIB and PLT were the independent risk factors for DN (OR: 1.611 and 1.194, P < 0.01, resp.). The area under ROC curve (AUC) of aPTT and PLT was 0.592 and 0.647, respectively, with low sensitivity in predicting T2DM. AUC of FIB was 0.874 with high sensitivity (85%) and specificity (76%) for DN, and that of PLT was 0.564, with sensitivity (60%) and specificity (89%) based on the cutoff values of 3.15 g/L and 245 × 109/L, respectively. This study suggests that hemostatic parameters have a low predicting value for T2DM, whereas fibrinogen is a powerful predictor for DN.


Assuntos
Coagulação Sanguínea , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Fibrinogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Plaquetas/metabolismo , Plaquetas/patologia , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/diagnóstico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Contagem de Plaquetas , Curva ROC , Estudos Retrospectivos , Fatores de Risco
14.
Br J Clin Pharmacol ; 84(5): 876-887, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29346838

RESUMO

AIMS: The aims of the present study were to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a randomized, placebo-controlled, double-blind, sequential, ascending-dose study of 2-h (part A) and 5-day (part B) intravenous (IV) infusions of BMS-962212. Part A used four doses (1.5, 4, 10 and 25 mg h-1 ) of BMS-962212 or placebo in a 6:2 ratio per dose. Part B used four doses (1, 3, 9 and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese (n = 4 active, n = 1 placebo) subjects per dose. The PK, PD, safety and tolerability were assessed throughout the study. RESULTS: BMS-962212 was well tolerated; there were no signs of bleeding, and adverse events were mild. In parts A and B, BMS-962212 demonstrated dose proportionality. The mean half-life in parts A and B ranged from 2.04 to 4.94 h and 6.22 to 8.65 h, respectively. Exposure-dependent changes were observed in the PD parameters, activated partial thromboplastin time (aPTT) and factor XI clotting activity (FXI:C). The maximum mean aPTT and FXI:C change from baseline at 20 mg h-1 in part B was 92% and 90%, respectively. No difference was observed in weight-corrected steady-state concentrations, aPTT or FXI:C between Japanese and non-Japanese subjects (P > 0.05). CONCLUSION: BMS-962212 has tolerability, PK and PD properties suitable for investigational use as an acute antithrombotic agent in Japanese or non-Japanese subjects.


Assuntos
Isoquinolinas/efeitos adversos , Isoquinolinas/farmacologia , Isoquinolinas/farmacocinética , para-Aminobenzoatos/efeitos adversos , para-Aminobenzoatos/farmacologia , para-Aminobenzoatos/farmacocinética , Adolescente , Adulto , Povo Asiático/estatística & dados numéricos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Fibrinolíticos/farmacologia , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Isoquinolinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adulto Jovem , para-Aminobenzoatos/administração & dosagem
16.
Acta pediatr. esp ; 75(11/12): e195-e199, nov.-dic. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-170221

RESUMO

Introducción: La presencia de un tiempo de cefalina (APTT) alargado en niños con fiebre y petequias es un hallazgo descrito en la bibliografía. La causa de esta alteración se desconoce, pero se postula que puede deberse a la formación de anticuerpos antifosfolípidos (Ac AFL). El objetivo de este estudio es determinar si el alargamiento del APTT se asocia con la formación Ac AFL. Pacientes y métodos: Estudio observacional, prospectivo, de casos y controles, realizado en niños que consultaron por fiebre y petequias en el servicio de urgencias de un hospital de tercer nivel durante un periodo de 13 meses. Se recogieron variables epidemiológicas, clínicas y analíticas. Se describieron las características de los grupos con APTT alargado y normal, y se comparó la asociación entre las concentraciones de los diferentes anticuerpos y el APTT. Resultados: Se incluyeron 36 pacientes, 12 casos y 24 controles. No se encontraron diferencias significativas respecto a la positividad de Ac AFL entre los casos y los controles (odds ratio [OR]= 1,67; intervalo de confianza [IC] del 95%: 0,31-9,04). No se observó ninguna asociación entre los diferentes tipos de anticuerpos y el APTT, cuyos coeficientes de regresión fueron de 0,04 seg (IC del 95%: -0,31 a 0,40) para anticardiolipina IgG, de 1,11 seg (IC del 95%: -1,24 a 3,46) para la IgM, y de -0,02 seg (IC del 95%: -0,35 a 0,31) y 0,64 seg (IC del 95%: -1,40 a 2,68) para antibeta 2 GPI, IgG e IgM, respectivamente. Conclusión: Ante los resultados de nuestro estudio, no podemos concluir que el alargamiento de APTT se relacione con la presencia de Ac AFL (AU)


Introduction: The presence of a longer time of cephalin (APTT) extended in children who come to emergency department with fever and petechiae is a result previously described in the literature. The cause of this alteration in coagulation is unknown, it is presumed that may be due to the formation of antiphospholipids antibodies. The aim of this study is to determine if the length of APTT is associated to the formation of antiphospholipids antibodies. Patients and methods: Observational, prospective case-control study in children who consulted for fever and petechiae in the emergency department of a tertiary hospital over a 13-month period epidemiological; clinical and laboratory variables were collected. The characteristics of groups with elongated and normal APTT were described and the association between concentrations of different antibodies and APTT were compared. Results: 36 patients, 12 cases and 24 controls, were included. No significant differences were found regarding the positivity of antiphospholipid antibodies between cases and controls (OR= 1.67; 95%CI: 0.31 to 9.04). No association was observed between the different types of antibodies and APTT, resulting regression coefficients in 0.04 s (95%CI: -0.31 to 0.40) for cardiolipin IgG, 1.11 s (95%CI: -1.24 to 3.46) for IgM and -0.02 s (95%CI: -0.35 to 0.31) and 0,64 s (95%CI: -1.40 to 2.68) for antibeta 2 GPI, IgG and IgM, respectively. Conclusion: Given the results of our study we can not conclude that the elongation of APTT is related with the presence of antiphospholipids antibodies (AU)


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Febre/etiologia , Púrpura/etiologia , Síndrome Antifosfolipídica/epidemiologia , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Anticorpos Antifosfolipídeos/isolamento & purificação , Biomarcadores/análise , Anticorpos Anticardiolipina/isolamento & purificação , Estudos Prospectivos , Estudos de Casos e Controles
17.
J Cardiothorac Vasc Anesth ; 31(3): 901-908, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28365134

RESUMO

OBJECTIVES: To assess the utility of Sonoclot in prediction of postoperative bleeding in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass for congenital cyanotic heart disease. DESIGN: Prospective, observational study. SETTING: Single university hospital. PARTICIPANTS: Eighty-seven pediatric patients undergoing cardiac surgery for congenital cyanotic heart disease. INTERVENTIONS: Laboratory coagulation parameters (prothrombin time, international normalization ratio, activated partial thromboplastin time, fibrinogen, D-dimer) as well as point-of-care Sonoclot glass bead activation time, clot rate, and platelet function (gbPF) were done before induction of anesthesia and following heparin reversal after termination of cardiopulmonary bypass (CPB) in all patients. MEASUREMENTS AND MAIN RESULTS: Postoperative blood loss was monitored by the amount of chest tube drainage. The primary outcome was to define Sonoclot parameters for prediction of postoperative bleeding. Secondary outcomes studied were amount of postoperative blood loss, transfusion requirement of various blood products, incidence of surgical re-exploration, duration of postoperative mechanical ventilation, intensive care unit and hospital stay. Among studied subjects, 37.9% (33 of 87 patients) were designated as bleeders while 62.1% (54 of 87 patients) were non-bleeders. Lower age, D-dimer, and gbPF test after termination of CPB following heparin neutralization were predictive for postoperative bleeders. Among these, post-protamine gbPF had the highest area under the curve (0.725), 95% confidence interval (0.619-0.831) for prediction of postoperative bleeders. Duration of mechanical ventilation (26.41±36.44 v 8.25±6.36 h, respectively, p = 0.001), intensive care unit stay (7.36 ± 4.05 v 4.96 ± 2.49, p = 0.001), and hospital stay (11.69±4.82 v 8.63±3.48 p = 0.001) were higher in bleeders; however, incidence of re-exploration was comparable between both groups. CONCLUSION: Postoperative bleeders may be predicted independently by post-CPB gbPF, postoperative D-dimer, and lower age of patients. Among these, post-CPB gbPF has maximum predictive value.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/cirurgia , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/diagnóstico , Tempo de Protrombina/estatística & dados numéricos , Adolescente , Testes de Coagulação Sanguínea/estatística & dados numéricos , Procedimentos Cirúrgicos Cardíacos/tendências , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Hemorragia Pós-Operatória/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos
18.
J Neurosurg Anesthesiol ; 29(1): 8-13, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26580123

RESUMO

BACKGROUND: The authors investigated the effect of equiosmolar, equivolemic solutions of 3% hypertonic saline (HS) and 20% mannitol on blood coagulation assessed by rotational thromboelastometry (ROTEM) and standard coagulation tests during elective craniotomy. METHODS: In a prospective, randomized, double-blind trial, 40 patients undergoing elective craniotomy were randomized to receive 5 mL/kg of either 20% mannitol or 3% HS for intraoperative brain relaxation. Fibrinogen, activated partial thromboplastin time, prothrombin time, hemoglobin, hematocrit, and platelet count were simultaneously measured intraoperatively with ROTEM for EXTEM, INTEM, and FIBTEM analysis. ROTEM parameters were: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and α-angle. RESULTS: No significant differences between groups were found in ROTEM variables CT, CFT, MCF, α-angle (EXTEM and INTEM), and MCF (FIBTEM) nor standard coagulation tests. ROTEM parameters did not show changes after administration of hyperosmolar solutions relating to basal values, except for an increase of CFT EXTEM (118±28 vs. 128±26 s) and decrease of CT INTEM (160±18 vs. 148±15 s) with values within normal range. Significant decreases from baseline levels were observed for hematocrit (-7%), platelet count (-10%), and fibrinogen (-13%) after HS infusion, and hematocrit (-9%), platelet count (-13%), and fibrinogen (-9%) after mannitol infusion, but remaining normal. CONCLUSIONS: The use of 5 mL/kg of equiosmolar solutions of 3% HS and 20% mannitol applied to reach a brain relaxation during elective craniotomy does not induce coagulation impairment as evidenced by ROTEM and standard coagulation tests.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Craniotomia , Diuréticos Osmóticos/farmacologia , Procedimentos Cirúrgicos Eletivos , Manitol/farmacologia , Solução Salina Hipertônica/farmacologia , Testes de Coagulação Sanguínea/estatística & dados numéricos , Método Duplo-Cego , Feminino , Fibrinogênio/efeitos dos fármacos , Hematócrito/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Estudos Prospectivos , Tromboelastografia/estatística & dados numéricos
19.
Klin Lab Diagn ; 61(2): 87-90, 2016 Feb.
Artigo em Russo | MEDLINE | ID: mdl-27455561

RESUMO

The study was carried out to diferentiate reference values for kaolin-activated thromboelastography in newborns with congenital heart disease. The study included two groups ofpatients. The first one consisted of 62 newborns with congenital heart disease and the second one consisted of 35 healthy newborns. The results of kaolin-activated thromboelastography implemented in groups are evaluated as condition of normal coagulation. The valuable diferences of homeostasis system in healthy newborns and newborns with congenital heart disease (without severe concomitant pathology) are not established. They have similar indicators of kaolin-activated thromboelastography. The derived results can be applied as standards in full-term newborns with congenital heart disease.


Assuntos
Coagulação Sanguínea , Cardiopatias Congênitas/sangue , Tromboelastografia/métodos , Estudos de Casos e Controles , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/patologia , Humanos , Recém-Nascido , Caulim/química , Masculino , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Tempo de Protrombina/estatística & dados numéricos , Valores de Referência , Tempo de Trombina/estatística & dados numéricos , Tempo de Coagulação do Sangue Total/estatística & dados numéricos
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