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 40âyears of age were recruited. Menaquinone-7 (MK-7) was administrated at 90âµg for 30âdays. 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 30âdays 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 terapêuticoRESUMO
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/análiseRESUMO
Multiple blood cell types and metabolic pathways involved in the modulation of platelet reactivity were investigated in streptozotocin-induced diabetic rats treated with garlic oil. Platelet counts of diabetic rats treated with garlic oil were significantly (P<0.01) reduced as compared to diabetic control rats. Garlic oil also increased the leucocyte counts of diabetic rats as compared to diabetic control rats. The significant (P<0.001) decreases by garlic oil of plasma concentration factors, V, VII, VIII: C, IX and X in diabetic rats may be interpreted to mean that there was a modulation of factor VII similar to that brought about by thrombin on factors V and VIII: C. This reversal of hypercoagulation through integrated biochemical reaction is suggestive of multicellular modulation of platelet reactivity, erythrocytes and neutrophils and the functional interactions between plasma coagulation factors and platelet cofactors.
Assuntos
Células Sanguíneas/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Plaquetas/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Alho , Óleos de Plantas/farmacologia , Animais , Proteínas de Artrópodes , Diabetes Mellitus Experimental/sangue , Precursores Enzimáticos/análise , Fator IX/análise , Fator V/análise , Fator VII/análise , Fator VIII/análise , Fator X/análise , Contagem de Leucócitos , Masculino , Contagem de Plaquetas , Ratos , Serina Endopeptidases/análiseRESUMO
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 farmacológicoRESUMO
BACKGROUND: This study was performed to assess the effect of poly-N-acetyl glucosamine fiber slurry on plasma clotting proteins, platelets, and red blood cells in the clotting of the blood. METHODS: Citrate phosphate dextrose whole blood was stored at 22degreesC for 48 hours to prepare platelet-poor plasma, platelet-rich plasma (PRP), and PRP plus red blood cells with hematocrit values of 20%, 35%, and 45% with and without an equal volume of poly-N-acetyl glucosamine fibers (1 mg/mL 0.9% NaCl). RESULTS: Thromboelastogram data show that poly-N-acetyl glucosamine fibers (p-GlcNAc) significantly reduced the R time in platelet-poor plasma, PRP, and PRP supplemented with red blood cells. Poly-N-acetyl glucosamine fibers increased, but not significantly, Annexin V and factor X binding to platelets, platelet microparticles, and red blood cell Annexin V binding. Poly-N-acetyl glucosamine fibers increased the production of thromboxane B2 by PRP. CONCLUSION: Poly-N-acetyl glucosamine slurry activates platelets.
Assuntos
Acetilglucosamina/farmacologia , Plaquetas/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hemostáticos/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Acetilglucosamina/química , Anexina A5/análise , Anexina A5/sangue , Anexina A5/efeitos dos fármacos , Fatores de Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/química , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/química , Fator X/análise , Fator X/efeitos dos fármacos , Fator X/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/efeitos dos fármacos , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/análise , Fibrinogênio/efeitos dos fármacos , Fibrinogênio/metabolismo , Hematócrito , Hemostáticos/química , Humanos , Selectina-P/análise , Selectina-P/sangue , Selectina-P/efeitos dos fármacos , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/efeitos dos fármacos , Testes de Função Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/análise , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/análise , Complexo Glicoproteico GPIb-IX de Plaquetas/efeitos dos fármacos , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Protrombina/efeitos dos fármacos , Tromboelastografia , Tromboxano B2/sangue , Fatores de TempoRESUMO
Oral anticoagulants achieve an antithrombotic effect only several days after initiation of treatment. A rapid decline of the vitamin-K dependent natural anticoagulants (proteins C and S) during this period might result in a prothrombic phase. We addressed this question by measuring the rates of decline of these proteins, as well as the vitamin K dependent procoagulants, in two groups of patients: A "high dose group" (n = 7), who received a single 40 mg dose of warfarin, and a "low dose group" (n = 20), who received daily individually adjusted doses. In the high dose group an early and marked decline of factor VII:C and protein C antigen was observed, while levels of the other vitamin K dependent factors were still relatively high. In the low dose group, all these proteins declined more gradually. Mean +/- SD of protein C antigen level at 46 hr was 56 +/- 12% in the low dose group, and only 44 +/- 6% (p less than 0.05) in the high dose group. We conclude that during the initiation of warfarin therapy there is a transient prothrombotic phase, which is less marked in patients given daily adjusted doses.