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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.
Eur Rev Med Pharmacol Sci ; 24(12): 7077-7082, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32633402

RESUMO

OBJECTIVE: ApoE alleles have been shown to significantly correlate with vitamin K status, however, data concerning this phenomenon in cystic fibrosis (CF) are scarce. This study aimed to investigate the effect of ApoE polymorphism on vitamin K status in a unique group of CF patients who had never received vitamin K supplementation. PATIENTS AND METHODS: The study group consisted of 93 CF patients aged from 3 months to 32 years. Vitamin K status was assessed by the concentration of prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). The clinical status was evaluated in all patients. RESULTS: Fifty-four (65.1%) out of 83 patients had a pathological PIVKA-II concentration (≥2 ng/ml) and an abnormal percentage of u-OC (≥20%). There were no differences in the clinical parameters, including PIVKA-II concentration (p=0.7752) and u-OC percentage (p=0.8395), between patients with genotypes ApoE2/3, ApoE3/3 and ApoE3/4. Moreover, the frequency of vitamin K deficiency did not significantly differ in CF patients with ApoE2/3, ApoE3/3 and ApoE3/4 genotypes (66.7 vs. 69.9 vs. 80%, p=0.8411; 87.5 vs. 89.6 vs. 100%, p=1.000, respectively). CONCLUSIONS: The presence of the ApoE4 allele does not influence the vitamin K status in CF patients who have never received vitamin K supplementation.


Assuntos
Apolipoproteínas E/genética , Fibrose Cística/genética , Fibrose Cística/metabolismo , Polimorfismo Genético/genética , Vitamina K/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Fibrose Cística/diagnóstico , Suplementos Nutricionais , Feminino , Genótipo , Humanos , Lactente , Masculino , Protrombina/análise , Adulto Jovem
3.
Bioorg Med Chem Lett ; 27(2): 208-211, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27955810

RESUMO

Vitamin K is the collective term for compounds that share a 2-methyl-1,4-naphthoquinone ring, but differ in the side-chain at the 3-position. We synthesized novel 2-methyl-1,4-naphthoquinone derivatives with different side chain length at the 3-position. Derivatives with C-14 and C-16 tails showed the highest in vitro bioactivity resulting in 2.5 and 2-fold higher carboxylated osteocalcin synthesis in MG63 cells than menaquinone-4 (MK-4, form of vitamin K2). Longer side chain lengths resulted in lower bioactivity. The in vivo vitamin K activity of the C-14 tail derivative was further tested in WKY rats receiving a vitamin K-deficient diet that resulted in a 40% decrease of prothrombin activity. The C-14 tail derivative was able to counteract the effects on vitamin K deficiency induced by the diet and resulted in the complete restoration of prothrombin activity. Compared to naturally occurring forms of vitamin K, synthetic vitamin K derivatives may have higher bioactivity and different pharmacological characteristics that are more favorable for use as supplements or in clinical settings.


Assuntos
Carbono-Carbono Ligases/metabolismo , Ativadores de Enzimas/farmacologia , Vitamina K/análogos & derivados , Vitamina K/farmacologia , Animais , Linhagem Celular Tumoral , Ativadores de Enzimas/síntese química , Humanos , Estrutura Molecular , Osteocalcina/biossíntese , Protrombina/análise , Ratos Endogâmicos WKY , Vitamina K/síntese química , Vitamina K 2/análogos & derivados , Vitamina K 2/farmacologia , Deficiência de Vitamina K/tratamento farmacológico
4.
Sci Rep ; 5: 12000, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-26160248

RESUMO

Cystic fibrosis (CF) patients are at high risk for vitamin K deficiency. The effects of vitamin K supplementation are very ambiguous. Therefore, we aimed to define the determinants of vitamin K deficiency in a large cohort of supplemented - 146 (86.9%) and non-supplemented - 22 (13.1%) CF patients. Vitamin K status was assessed using prothrombin inducted by vitamin K absence (PIVKA-II) and undercarboxylated osteocalcin (u-OC). The pathological PIVKA-II concentration (≥ 2 ng/ml) and abnormal percentage of osteocalcin (≥ 20%) were found in 72 (42.8%) and 60 (35.7%) subjects, respectively. We found that liver involvement, diabetes, and glucocorticoid therapy were potential risk factors for vitamin K deficiency. Pathological concentrations of PIVKA-II occurred more frequently in patients with pancreatic insufficiency and those who have two severe mutations in both alleles of the CFTR gene. Pathological percentage of u-OC was found more frequently in adult CF patients and those not receiving vitamin K. However, it seems that there are no good predictive factors of vitamin K deficiency in CF patients in everyday clinical care. Early vitamin K supplementation in CF patients seems to be warranted. It is impossible to clearly determine the supplementation dose. Therefore, constant monitoring of vitamin K status seems to be justified.


Assuntos
Fibrose Cística/patologia , Vitamina K/análise , Adolescente , Adulto , Antibacterianos/uso terapêutico , Biomarcadores/análise , Criança , Pré-Escolar , Estudos de Coortes , Fibrose Cística/tratamento farmacológico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Suplementos Nutricionais , Feminino , Genótipo , Glucocorticoides/uso terapêutico , Humanos , Imunoensaio , Lactente , Coeficiente Internacional Normatizado , Masculino , Estado Nutricional , Osteocalcina/análise , Osteocalcina/química , Polimorfismo de Nucleotídeo Único , Precursores de Proteínas/análise , Protrombina/análise , Infecções por Pseudomonas/tratamento farmacológico , Análise de Regressão , Fatores de Risco , Deficiência de Vitamina K/etiologia , Adulto Jovem
5.
Thromb Haemost ; 114(2): 258-67, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25925992

RESUMO

Patients on rivaroxaban requiring percutaneous coronary intervention (PCI) represent a clinical conundrum. We aimed to investigate whether rivaroxaban, with or without an additional bolus of unfractionated heparin (UFH), effectively inhibits coagulation activation during PCI. Stable patients (n=108) undergoing elective PCI and on stable dual antiplatelet therapy were randomised (2:2:2:1) to a short treatment course of rivaroxaban 10 mg (n=30), rivaroxaban 20 mg (n=32), rivaroxaban 10 mg plus UFH (n=30) or standard peri-procedural UFH (n=16). Blood samples for markers of thrombin generation and coagulation activation were drawn prior to and at 0, 0.5, 2, 6-8 and 48 hours (h) after start of PCI. In patients treated with rivaroxaban (10 or 20 mg) and patients treated with rivaroxaban plus heparin, the levels of prothrombin fragment 1 + 2 at 2 h post-PCI were 0.16 [0.1] nmol/l (median) [interquartile range, IQR] and 0.17 [0.2] nmol/l, respectively. Thrombin-antithrombin complex values at 2 h post-PCI were 3.90 [6.8]µg/l and 3.90 [10.1] µg/l, respectively, remaining below the upper reference limit (URL) after PCI and stenting. This was comparable to the control group of UFH treatment alone. However, median values for thrombin-antithrombin complex passed above the URL with increasing tendency, starting at 2 h post-PCI in the UFH-alone arm but not in rivaroxaban-treated patients. In this exploratory trial, rivaroxaban effectively suppressed coagulation activation after elective PCI and stenting.


Assuntos
Doença das Coronárias/cirurgia , Inibidores do Fator Xa/uso terapêutico , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/prevenção & controle , Rivaroxabana/uso terapêutico , Trombose/prevenção & controle , Idoso , Anticoagulantes/uso terapêutico , Antitrombina III/análise , Biomarcadores/sangue , Quimioterapia Combinada , Procedimentos Cirúrgicos Eletivos , Inibidores do Fator Xa/administração & dosagem , Feminino , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Inibidores da Agregação Plaquetária/uso terapêutico , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/sangue , Protrombina/análise , Fatores de Risco , Rivaroxabana/administração & dosagem , Método Simples-Cego , Stents , Trombina/biossíntese , Trombose/sangue
6.
J Matern Fetal Neonatal Med ; 25(9): 1660-3, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22280352

RESUMO

BACKGROUND: As the vitamin K content of human milk is low and the newborn infant's stores of vitamin K are small, vitamin K deficiency with hemorrhage in the newborn is a worldwide problem. Proteins Induced by Vitamin K Absence (PIVKA-II) are the inactive under-γ-carboxylated forms of vitamin K-dependent clotting factors and they could be useful in predicting subclinical vitamin K deficiency (VKD). OBJECTIVES: To demonstrate that PIVKA-II are earlier markers of subclinical VKD than Prothrombin time (PT) in exclusively breast-fed newborns. METHODS: A prospective, controlled, randomized study, including 53 term newborns receiving vitamin K prophylaxis (0.5 mg i.m.) at birth, was performed. At 30 days newborns were divided into three groups (G) receiving respectively: 25 µg/die of vitamin K (G I), 12 µg/die (G II) or placebo (G III). PIVKA-II and PT were measured on 30th and 90th days of life. RESULTS: G III and GII showed a significant increase in PIVKA-II from 30 to 90 days of life respectively from 2.6 to 4.7 (p = 0.001) and from 2.3 to 3.5 (p < 0.001). No significant changes were found in GI. PT showed no significant changes among groups. CONCLUSIONS: PT is a less sensitive marker than PIVKA II. Oral supplementation with 25 µg/die avoids an increase of PIVKA-II. Despite increased PIVKA-II do not mean an impending occurrence of bleeding, they highlight a subclinical VKD and its relative risk.


Assuntos
Biomarcadores/sangue , Precursores de Proteínas/sangue , Nascimento a Termo/sangue , Deficiência de Vitamina K/diagnóstico , Doenças Assintomáticas , Biomarcadores/análise , Suplementos Nutricionais , Diagnóstico Precoce , Sangue Fetal/química , Humanos , Lactente , Recém-Nascido , Precursores de Proteínas/análise , Precursores de Proteínas/fisiologia , Protrombina/análise , Protrombina/fisiologia , Tempo de Protrombina , Fatores de Tempo , Vitamina K/administração & dosagem , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/tratamento farmacológico
9.
J Am Coll Surg ; 209(2): 206-14, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19632597

RESUMO

BACKGROUND: The aim of this study was to evaluate the safety of predeposit autologous plasma donation (PAPD) and its efficacy in avoiding allogenic blood transfusions and albumin infusion in liver resection for hepatocellular carcinoma. STUDY DESIGN: PAPD was adopted in 20 patients in whom liver function remained within Child-Pugh's class A and an indocyanine green retention rate at 15 minutes was < or = 15% (PAPD group). Up to 1,200 mL of autologous fresh frozen plasma was collected through three blood donation sessions. Allogenic blood transfusion rates, albumin infusion rates, and postoperative courses were compared between the PAPD group and a historic control (no PAPD) group (n = 36). RESULTS: Serum albumin levels after the last blood donation session were not significantly different from those before PAPD. The prothrombin activity even increased through the blood donation sessions (from median 80.9% [range 70.0% to 100%] to median 89.2% [range 71.2% to 100%]; p < 0.001). Allogenic blood transfusion rate and albumin infusion rate were lower in the PAPD group than in the no PAPD group (11% versus 75%; p < 0.001 and 16% versus 47%; p = 0.038, respectively). Wastage rate of the autologous fresh frozen plasma products was 9%. CONCLUSIONS: PAPD was safe in patients with underlying liver disease and can be beneficial in simulating the liver synthetic function in advance of operation. Autologous fresh frozen plasma transfusion was effective for avoiding allogenic blood products in liver resection for hepatocellular carcinoma.


Assuntos
Transfusão de Sangue Autóloga/métodos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Plasma , Adulto , Idoso , Biomarcadores/sangue , Perda Sanguínea Cirúrgica , Estudos de Casos e Controles , Feminino , Hepatectomia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Protrombina/análise , Albumina Sérica/análise , Estatísticas não Paramétricas , Resultado do Tratamento
10.
Nutrition ; 24(2): 120-6, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18065202

RESUMO

OBJECTIVE: We evaluated the effects of soy isoflavone supplementation on hemostasis in healthy postmenopausal women. METHODS: In this double-blinded, placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg of soy isoflavone (n = 25) or 40 mg of casein placebo (n = 22) once a day for 6 mo. Levels of factors VII and X, fibrinogen, thrombin-antithrombin complex, prothrombin fragments 1 plus 2, antithrombin, protein C, total and free protein S, plasminogen, plasminogen activator inhibitor-1, and D-dimers were measured at baseline and 6 mo. Urinary isoflavone concentrations (genistein and daidzein) were measured as a marker of compliance and absorption using high-performance liquid chromatography. Baseline characteristics were compared by unpaired Student's t test. Within-group changes and comparison between the isoflavone and casein placebo groups were determined by a mixed effects model. RESULTS: The levels of hemostatic variables did not change significantly throughout the study in the isoflavone group; however, the isoflavone group showed a statistically significant reduction in plasma concentration of prothrombin fragments 1 plus 2; both groups showed a statistically significant reduction in antithrombin, protein C, and free protein S levels. A significant increase in D-dimers was observed only in the isoflavone group. Plasminogen activator inhibitor-1 levels increased significantly in the placebo group. However, these changes were not statistically different between groups. CONCLUSION: The results of the present study do not support a biologically significant estrogenic effect of soy isoflavone on coagulation and fibrinolysis in postmenopausal women. However, further research will be necessary to definitively assess the safety and efficacy of isoflavone.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Pós-Menopausa , Idoso , Antitrombina III/análise , Biomarcadores/urina , Coagulação Sanguínea/fisiologia , Suplementos Nutricionais , Método Duplo-Cego , Fator VII/análise , Fator X/análise , Feminino , Fibrinogênio/análise , Fibrinólise/efeitos dos fármacos , Fibrinólise/fisiologia , Genisteína/sangue , Genisteína/farmacologia , Genisteína/urina , Hemostasia/efeitos dos fármacos , Hemostasia/fisiologia , Humanos , Isoflavonas/sangue , Isoflavonas/urina , Pessoa de Meia-Idade , Cooperação do Paciente , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Fitoestrógenos/sangue , Fitoestrógenos/urina , Pós-Menopausa/sangue , Pós-Menopausa/urina , Precursores de Proteínas/análise , Protrombina/análise
11.
Br J Haematol ; 132(5): 604-7, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16445834

RESUMO

Patients with a supratherapeutic international normalised ratio (ST-INR) are at risk for bleeding. ST-INR is corrected by withholding warfarin therapy and often by supplementing vitamin K or providing vitamin K-dependent factors; the exact therapeutic decision is based on the extent of the prolonged INR. Currently, ST-INRs are frequently observed in clinical practice due to the use of sensitive recombinant tissue thromboplastin reagents and automation. However, there are scant data correlating an ST-INR with various vitamin K-dependent factors. This prospective cohort study, set in a large tertiary care teaching hospital for the University of Texas Southwestern Medical Center at Dallas, defined the relationship between ST-INR (>5.0) and measured vitamin K-dependent procoagulant factors. Prothrombin time, INR and vitamin K-dependent factors II, VII, IX and X were measured in 78 patients with an INR > 5.0 (ST-INR) who were on warfarin therapy for more than 2 months. There was no significant relationship between the ST-INR and levels of important vitamin K-dependent factors II and X. These data support the recent guidelines that the management of an INR > 5.0 should be driven by the clinical determinants rather than specific INR values per se.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Fatores de Coagulação Sanguínea/análise , Vitamina K/uso terapêutico , Varfarina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/sangue , Fibrilação Atrial/tratamento farmacológico , Transtornos da Coagulação Sanguínea/sangue , Fator X/análise , Feminino , Humanos , Coeficiente Internacional Normatizado , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Protrombina/análise , Análise de Regressão , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Trombose Venosa/sangue , Trombose Venosa/tratamento farmacológico
12.
J Clin Endocrinol Metab ; 90(4): 1936-41, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15657372

RESUMO

The soybean is rich in isoflavone phytoestrogens, which are ligands for estrogen receptors, but it is unknown whether soy/phytoestrogens have similar procoagulant effects to estrogen. In this randomized double-blind trial, 40 healthy postmenopausal women of age 50-75 yr received soy protein isolate (40 g soy protein, 118 mg isoflavones) (n = 19) or casein placebo (n = 21). Plasma markers of coagulation, fibrinolysis, and endothelial dysfunction were measured at baseline and 3 months. The baseline characteristics of the two groups were similar. Compared with casein placebo, soy decreased triglycerides (P < 0.005) and low-density lipoprotein/high-density lipoprotein ratio (P < 0.001) and increased lipoprotein (a) (P < 0.05). Activity of coagulation factor VII (VIIc) decreased similarly in both groups (P < 0.005). Prothrombin fragments 1 + 2 (a marker of thrombin generation) decreased in the soy group (P < 0.005), but the change was not different from the casein group. There was no effect of soy on soluble fibrin (a marker of fibrin production), plasminogen activator inhibitor-1 (a marker of fibrinolytic inhibitory potential), D-dimer (a marker of fibrin turnover), or von Willebrand factor (a marker of endothelial damage). In conclusion, the results of the current study do not support biologically significant estrogenic effects of soy/phytoestrogens on coagulation, fibrinolysis, or endothelial function.


Assuntos
Glycine max , Hemostasia , Fitoestrógenos/farmacologia , Pós-Menopausa/sangue , Idoso , Dieta , Feminino , Humanos , Isoflavonas/urina , Lipídeos/sangue , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Precursores de Proteínas/análise , Protrombina/análise , Fator de von Willebrand/análise
13.
Blood ; 104(9): 2682-9, 2004 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-15231565

RESUMO

Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 microg-500 microg) of vitamin K(1) supplements (K(1)) taken daily for 7 days. The threshold K(1) dose causing a statistically significant lowering of the INR was 150 microg/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 microg/day. Circulating undercarboxylated osteocalcin did not decrease until 300 microg K(1)/day compared with 100 microg K(1)/day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic gamma-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that short-term variability in intake of K(1) is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 microg/day of vitamin K(1) do not significantly interfere with oral anticoagulant therapy.


Assuntos
Anticoagulantes/uso terapêutico , Vitamina K/farmacologia , Adulto , Anticoagulantes/administração & dosagem , Disponibilidade Biológica , Brassica , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Antagonismo de Drogas , Estabilidade de Medicamentos , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Osteocalcina/sangue , Protrombina/análise , Spinacia oleracea , Vitamina K/administração & dosagem
14.
Clin Lab Haematol ; 25(6): 397-404, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14641145

RESUMO

Vitamin K deficiency is a known cause of coagulopathy in hospitalized patients, but the extent of the problem has not been well assessed. This noninterventional, prospective observational study of 35 adults was undertaken in the intensive care unit (ICU) and examined the incidence of and the methods for diagnosing vitamin K deficiency. Measurements of prothrombin time, Echis time and plasma concentrations of under-carboxylated prothrombin (proteins induced in vitamin K absence or antagonism, PIVKA-II), vitamin K1 and ferritin were made during the 48 h after admission to the unit and repeated if coagulopathy developed later. Plasma vitamin K1 was low in 15 admissions (43%), in 11 cases of patients with coagulopathy and in four cases without coagulopathy. PIVKA-II was present in 12 cases (34%), of whom four had low vitamin K1 levels. All of the eight patients with raised PIVKA-II but normal vitamin K concentration were hyperferritinaemic. We conclude that low plasma vitamin K levels, suggestive of low tissue stores, are common in intensive care patients with or without coagulopathy. As 34% of patients had a raised PIVKA-II, this suggests that vitamin K stores may be insufficient to maintain full gamma-carboxylation of prothrombin and emphasize the need to anticipate vitamin K deficiency in the ICU setting by appropriate supplementation.


Assuntos
Biomarcadores/análise , Testes de Coagulação Sanguínea , Unidades de Terapia Intensiva , Precursores de Proteínas/análise , Protrombina/análise , Vitamina K 1/sangue , Deficiência de Vitamina K/epidemiologia , Adolescente , Adulto , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/epidemiologia , Feminino , Ferritinas/análise , Ferritinas/sangue , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Processamento de Proteína Pós-Traducional , Venenos de Víboras/farmacologia , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/diagnóstico
15.
Thromb Res ; 108(4): 209-13, 2002 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-12617983

RESUMO

INTRODUCTION: Prothrombin can associate with rat chylomicrons in vitro. This enhances a platelet factor Xa mediated prothrombin activation when the chylomicron-prothrombin complex is exposed to platelets. Vitamin K-dependent pro- and anti-coagulation proteins are associated with TG-rich lipoproteins obtained from human plasma. In the present study, we examined the effects of saturated and unsaturated fat meals on the association of prothrombin and protein S with TG-rich lipoproteins in vivo. MATERIALS AND METHODS: Human EDTA plasma was separated from normal subjects after overnight fasting and 2.5 h after ingestion of either a saturated fat meal (butter and cream) or an unsaturated fat meal (soybean oil) containing 54-80 g fat (60.2 E%). The prothrombin and protein S in delipidated lipoproteins were determined by SDS-PAGE combined with Western blotting. RESULTS: Both prothrombin and protein S associated with TG-rich lipoproteins in fasting and in postprandial samples. The levels of prothrombin and protein S in postprandial TG-rich lipoproteins, especially after ingestion of a saturated fat meal, were higher than those in fasting TG-rich lipoproteins. CONCLUSIONS: The levels of both prothrombin and protein S in TG-rich lipoproteins in plasma increased after a single fat meal. This association is more pronounced after saturated fat meals and one may hypothesize that it can be linked to atherogenic properties of TG-rich lipoproteins.


Assuntos
Gorduras na Dieta/administração & dosagem , Lipoproteínas/sangue , Proteína S/análise , Protrombina/análise , Óleo de Soja/administração & dosagem , Triglicerídeos/sangue , Adulto , Western Blotting , Eletroforese em Gel de Poliacrilamida , Jejum/sangue , Feminino , Humanos , Lipídeos/sangue , Lipoproteínas/química , Masculino , Período Pós-Prandial/fisiologia
16.
Thromb Haemost ; 86(3): 909-13, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11583326

RESUMO

We compare the relative activities of surface-bound and fluid-phase thrombin and their inhibition by heparin and Intimatan, a novel heparin cofactor II (HCII) agonist. In vitro, we compared the observed amidolytic activities of fluid-phase and surface-bound thrombin with the expected activities based upon 125I-specific activity. In vivo, we compared the inhibitory effects of heparin and Intimatan on thrombin activity bound to injured vessel walls. In vitro, the correlations between observed and expected activities of fluid-phase and surface-bound thrombin, were: r = 0.9974, p < 0.001; and r = 0.9678, p < 0.001; respectively. In vivo, injured vessel wall surface-bound thrombin activity persisted for > 24 h. This activity was not inhibited by heparin, but was inhibited by Intimatan, p < 0.001. We conclude that surface-bound thrombin is as active as fluid-phase thrombin and remains protected from inhibition by heparin, thereby contributing to vessel wall thrombogenicity following injury. In contrast, surface-bound thrombin is inhibited by Intimatan, thereby effectively decreasing vessel wall thrombogenicity following injury in vivo.


Assuntos
Anticoagulantes/farmacologia , Testes de Coagulação Sanguínea , Dermatan Sulfato/análogos & derivados , Dermatan Sulfato/farmacologia , Cofator II da Heparina/farmacologia , Trombina/antagonistas & inibidores , Trombose/etiologia , Animais , Lesões das Artérias Carótidas/sangue , Membrana Celular/química , Avaliação Pré-Clínica de Medicamentos , Endotélio Vascular/química , Endotélio Vascular/efeitos dos fármacos , Feminino , Cofator II da Heparina/agonistas , Humanos , Masculino , Tempo de Tromboplastina Parcial , Protrombina/análise , Coelhos
17.
Scand J Clin Lab Invest ; 61(5): 349-56, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11569481

RESUMO

OBJECTIVE: We studied the effect of a diet supplementation with fish oil in insulin-dependent diabetic patients with nephropathy in order to evaluate whether abnormal transcapillary escape rate of albumin and procoagulant activity in these patients could be modified. METHODS: A double-blind, randomized, controlled study was carried out at a tertiary referral centre. The subjects were 29 insulin-dependent diabetic patients with nephropathy. One year of fish oil supplementation (4.6 g n-3 fatty acids/day) was compared with placebo (olive oil). The main outcome measures were N-3 fatty acid proportions of platelet lipids, transcapillary escape rate of albumin, prothrombin fragment 1 + 2, thrombin-antithrombin complexes, markers of fibrinolysis, fibrinogen, factor VII antigen and activity, thrombomodulin, von Willebrand factor, platelet factor 4 and beta-thromboglobulin. These were measured every 6 months. RESULTS: Neither transcapillary escape rate of albumin (7.4 (median) (5.0-9.8) (range) % vs. 7.0 (4.6-10.6) %) nor prothrombin fragment 1 + 2 (0.97 (0.72-2.40) nmol/L vs. 1.01 (0.59-3.11) nmol/L) changed after 12 months of fish oil supplementation. CONCLUSION: Increased transcapillary escape rate of albumin and activity could not be modified during diet supplementation with fish oil in insulin-dependent diabetic patients with nephropathy.


Assuntos
Coagulação Sanguínea , Capilares/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Óleos de Peixe/administração & dosagem , Albumina Sérica/metabolismo , Antitrombina III/análise , Plaquetas/química , Método Duplo-Cego , Fator VII/análise , Fator VII/metabolismo , Ácidos Graxos Ômega-3/sangue , Fibrinogênio/análise , Fibrinólise , Hemoglobinas Glicadas/análise , Humanos , Radioisótopos do Iodo , Lipídeos/sangue , Azeite de Oliva , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Placebos , Óleos de Plantas/administração & dosagem , Fator Plaquetário 4/análise , Protrombina/análise , Soroalbumina Radioiodada , Trombomodulina/sangue , beta-Tromboglobulina/análise , Fator de von Willebrand/análise
18.
Poult Sci ; 80(5): 615-20, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11372711

RESUMO

In a preliminary experiment, the inclusion of vitamin K1 (K1) at a dietary level of 0.1 mg/kg was as effective as 1 or 2 mg/kg in reducing plasma prothrombin time (PT). To obtain an estimate of the dietary K1 requirement and to compare the biopotency of different vitamin K sources for poults, three additional experiments were conducted. In Experiment 1, an incomplete factorial arrangement of treatments was used in which five dietary concentrations of K1 (0, 0.1, 0.25, 0.5, or 2.0 mg/kg) were tested and two concentrations of neomycin (0 or 75 mg/L) in drinking water were used in conjunction with 0, 0.1, and 0.5 mg of K1/kg of diet. Thus, we used a total of eight treatments. Each treatment was given to two pens of poults, with eight poults per pen. Prothrombin time and prothrombin concentration (PC) in plasma were not influenced by inclusion of neomycin in drinking water. The K1 requirement was estimated, on the basis of PT and PC, to be 0.099 and 0.13 mg/kg, respectively, in Experiment 1. Dietary K1 concentrations tested in Experiment 2 were 0, 0.08, 0.31, or 0.44 mg/kg. A similar protocol to that of Experiment 1 was used in this experiment. The results of Experiment 2 indicated that the dietary K1 requirement was 0.079 mg, based on the influence of dietary K1 on PT. In Experiment 3, dietary treatments consisted of the equivalent of 0.22, 0.55, or 1.11 microM of menadione equivalent/kg from vitamin K1, menadione dimethypyrimidinol bisulfite (MPB) or menadione nicotinamide bisulfite (MNB), respectively, and a control without supplementation of any vitamin K source. The results of Experiment 3 showed that the biopotency of K1 was greater than that of MPB or MNB. The biopotencies of MPB and MNB were similar, although MNB was more potent in reducing plasma PT when supplemented at the level of 0.1 mg of menadione/kg. A nadir of PT and a plateau of PC were evident with a dietary supplementation of MPB or MNB at a level of 0.25 mg of menadione/kg. Results of this research show that the dietary K1 requirement of young turkeys is in the range of 0.079 to 0.13 mg/kg, and ingestion of neomycin did not affect estimates of the requirement. The biopotency of vitamin K1 in reducing plasma PT and increasing plasma PC was greater than that of MPB or MNB. The biopotency of MNB was greater than that of MPB when menadione supplementation was equivalent to 0.10 mg of K1/kg.


Assuntos
Neomicina/administração & dosagem , Niacinamida/análogos & derivados , Inibidores da Síntese de Proteínas/administração & dosagem , Perus/crescimento & desenvolvimento , Vitamina K 1/administração & dosagem , Vitamina K/análogos & derivados , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Disponibilidade Biológica , Galinhas , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Masculino , Neomicina/metabolismo , Necessidades Nutricionais , Inibidores da Síntese de Proteínas/metabolismo , Protrombina/análise , Tempo de Protrombina/veterinária , Perus/fisiologia , Vitamina K 1/análogos & derivados , Vitamina K 1/metabolismo , Vitamina K 3
19.
J Thorac Cardiovasc Surg ; 118(4): 610-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10504624

RESUMO

OBJECTIVE: Autotransfusion during and after cardiac surgery is widely performed, but its effects on coagulation, fibrinolysis, and inflammatory response have not been known in detail. METHODS: Hemostatic and inflammatory markers were extensively studied in 40 coronary artery bypass patients undergoing a consistent intraoperative and postoperative autotransfusion protocol. An identical autotransfusion protocol was applied to 4916 consecutive coronary patients and the overall clinical results were evaluated in this large patient population. RESULTS: The autologous blood pooled before bypass remained nearly inactivated after storage. A slight elevation of thrombin-antithrombin complex and prothrombin fragment 1.2, as well as plasmin/alpha(2)-antiplasmin complex was found in the content of the extracorporeal circuit after surgery, indicating thrombin formation and fibrinolytic activity. Also some increase of beta-thromboglobulin was present. In the mediastinal shed blood, complete coagulation, as evidenced by the absence of fibrinogen, had taken place and all parameters described above were extremely elevated. However, no thrombin activity was detected. As for the inflammatory response, moderately increased levels of complement activation products, terminal complement complex, and interleukin-6 traced in the extracorporeal circuit reached very high levels in mediastinal shed blood. Autotransfusion of the residual extracorporeal circuit blood and the mediastinal drainage was followed by elevation of most of these markers in circulating plasma. On the other hand, no correlating harmful effects were recorded in the study patients or in the consecutive 4916 patients. Coagulation disturbances were rare and allogeneic transfusions were required in fewer than 4% of all patients. CONCLUSIONS: The hemostatic and immunologic systems were moderately activated in the autologous blood remaining in the extracorporeal circuit, whereas the mediastinal shed blood was highly activated in all aspects. However, autotransfusion had no correlating clinical side-effects and the subsequent exposure to allogeneic blood products was minimal.


Assuntos
Antifibrinolíticos , Transfusão de Sangue Autóloga , Ponte de Artéria Coronária , Idoso , Antitrombina III/análise , Biomarcadores/sangue , Coagulação Sanguínea/fisiologia , Ponte Cardiopulmonar , Ativação do Complemento , Complexo de Ataque à Membrana do Sistema Complemento/análise , Drenagem , Feminino , Fibrinogênio/análise , Fibrinolisina/análise , Fibrinólise/fisiologia , Hemostasia/fisiologia , Humanos , Interleucina-6/sangue , Cuidados Intraoperatórios , Modelos Lineares , Masculino , Mediastino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Cuidados Pós-Operatórios , Protrombina/análise , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Trombina/biossíntese , alfa 2-Antiplasmina/análise , beta-Tromboglobulina/análise
20.
Blood ; 93(10): 3401-7, 1999 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-10233892

RESUMO

We measured the urinary excretion of Isoprostane F2alpha-III and Isoprostane-F2alpha-VI, two markers of in vivo lipid peroxidation, and the circulating levels of the prothrombin fragment F1+2, a marker of thrombin generation, in 18 antiphospholipid antibodies-positive patients, in 18 antiphospholipid antibodies-negative patients with systemic lupus erythematosus, and in 20 healthy subjects. Furthermore, 12 patients positive for antiphospholipid antibodies were treated with (n = 7) or without (n = 5) antioxidant vitamins (vitamin E at 900 IU/d and vitamin C at 2, 000 mg/d) for 4 weeks. Compared with antiphospholipid antibodies-negative patients, antiphospholipid antibodies-positive patients had higher urinary values of Isoprostane-F2alpha-III (P =. 0001), Isoprostane-F2alpha-VI (P =.006), and plasma levels of the prothrombin fragment F1+2 (P =.0001). In antiphospholipid-positive patients, F1+2 significantly correlated with Isoprostane-F2alpha-III (Rho =.56, P =.017) and Isoprostane-F2alpha-VI (Rho =.61, P =.008). After 4 weeks of supplementation with antioxidant vitamins, we found a significant decrease in F1+2 levels (P <.005) concomitantly with a significant reduction of both Isoprostane-F2alpha-III (P =.007) and Isoprostane-F2alpha-VI (P <.005). No change of these variables was observed in patients not receiving antioxidant treatment. This study suggests that lipid peroxidation might contribute to the activation of clotting system in patients positive for antiphospholipid antibodies.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Ácido Ascórbico/uso terapêutico , Fibrinogênio/metabolismo , Peroxidação de Lipídeos , Lúpus Eritematoso Sistêmico/sangue , Fragmentos de Peptídeos/análise , Precursores de Proteínas/análise , Protrombina/análise , Vitamina E/uso terapêutico , Adolescente , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Dinoprosta/análogos & derivados , Dinoprosta/urina , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/urina , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores de Tempo
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