Aerobic exercise improves postprandial inflammatory and hemostatic markers after a high-fat meal: a randomized crossover study.

Exercise intensity modulates postprandial lipemia. However, its effect on hemostatic and pro- and anti-inflammatory markers in the postprandial state is still unknown. Eleven young males performed a 2-day trial on different conditions: (i) REST: rest for 45 min; (ii) MIE: moderate-intensity exercise; and (iii) HIE: heavy-intensity exercise. Experimental conditions were performed in the evening. On the following morning, blood samples were taken in the fasted state (0 h) and at 1, 3, and 5 h after the consumption of a high-fat meal (HFM). Interleukin-10 (IL-10) levels were higher in the HIE vs. MIE trial at 0 and 1 h (p < 0.033) and IL-10 incremental area under the curve (iAUC) was greater in the MIE (p = 0.027) and HIE (p = 0.045) trials vs. REST. Lower levels of anti-coagulation factor VII (FVII) were observed at 1 h in the MIE condition vs. REST (p = 0.043). In comparison with REST, MIE improved hemostatic (FVII) and anti-inflammatory markers (IL-10 iAUC) whereas HIE enhanced IL-10 in the postprandial state. Regardless of the exercise intensity, aerobic exercise mitigates the deleterious consequences of an HFM. Novelty: Prior aerobic exercise at moderate-intensity attenuates next day's postprandial FVII and IL-10 levels whereas exercise performed at heavy-intensity increases IL-10 levels. Moderate-intensity exercise may be more beneficial to improve hemostatic (FVII) and anti-inflammatory (IL-10) responses while heavy-intensity exercise may improve anti-inflammatory (IL-10) levels only.

The relationship between coagulation disorders and the risk of bleeding in cirrhotic patients.

INTRODUCTION AND OBJECTIVES: For long, bleeding in cirrhotic patients has been associated with acquired coagulation disorders. The aim of our study was to investigate the impact of acquired coagulation disorders on bleeding risk in cirrhotic patients. MATERIALS AND METHODS: Blood samples were collected from 51 cirrhotic patients with (H+) or without (H-) bleeding events and 50 controls matched by age and sex. Thrombin generation was assessed as endogenous thrombin potential (ETP). Hemostatic balance was assessed by means of ratios of pro- to anticoagulant factors and by ETP ratio with/without protein C (PC) activator (ETP ratio). RESULTS: Bleeding events occurred in 9 patients (17.6%). Compared with controls, VIII/anticoagulant factors, VII/PC and XII/PC were significantly higher in (H+) patients. No significant difference as regards all ratios across patient groups was detected. ETP ratio was significantly higher in (H+) patients than in controls (p=0.017). However, there was no significant difference between patient groups as regards ETP ratio. CONCLUSION: Hemostatic balance is shifted toward a hypercoagulability state even in cirrhotic patients who experienced bleeding. These findings provide evidence against traditional concept of hemostasis-related bleeding tendency in cirrhotic patients.

Human Cells as Platform to Produce Gamma-Carboxylated Proteins.

The gamma-carboxylated proteins belong to a family of proteins that depend on vitamin K for normal biosynthesis. The major representative gamma-carboxylated proteins are the coagulation system proteins, for example, factor VII, factor IX, factor X, prothrombin, and proteins C, S, and Z. These molecules have harbored posttranslational modifications, such as glycosylation and gamma-carboxylation, and for this reason they need to be produced in mammalian cell lines. Human cells lines have emerged as the most promising alternative to the production of gamma-carboxylated proteins. In this chapter, the methods to generate human cells as a platform to produce gamma-carboxylated proteins, for example the coagulation factors VII and IX, are presented. From the cell line modification up to the vitamin K adaptation of the produced cells is described in the protocols presented in this chapter.

Tissue factor-dependent pathway in severe preeclampsia revisited: a Brazilian cohort study.

Previously we investigated the tissue factor (TF)-dependent coagulation pathway and key haemostatic cofactors in white women with preeclampsia (P-EC) and suggested that plasma factor VII (FVII) levels can differentiate women with P-EC from healthy nonpregnant women or normal pregnant women, at the same trimester, with high sensitivity, specificity, positive and negative predictive values. Here we re-examine the TF-dependent pathway in a large cohort of Brazilian women. A total of 240 women were studied. These included healthy nonpregnant women (n = 79), normotensive pregnant women (n = 80) and women with severe P-EC (n = 81). Commercially available enzyme-linked immunosorbent assays were used to measure plasma FVII, activated factor VII (FVIIa), TF and tissue factor pathway inhibitor (TFPI). All study participants were matched for age. Pregnant women (with/without P-EC) were matched for gestational age and parity. Plasma levels of FVII, FVIIa and TFPI were significantly increased in women with severe P-EC compared with healthy nonpregnant women (P < 0.01) or normotensive pregnant women (P < 0.01). FVIIa was also higher in normotensive pregnant women compared with nonpregnant women (P < 0.01). However, no such significant trends were observed for plasma TF levels (P = 0.074). In conclusion, circulating FVII, FVIIa and TFPI were significantly elevated in women with severe P-EC in the absence of comparable changes in plasma TF levels. The present work is in agreement with our previous report on FVII levels in white women with P-EC. Thus, this lends further support to the notion that plasma FVII levels are potentially valuable diagnostic marker for P-EC, irrespective of ethnicity.

Assessing the coagulation factor levels, inherited thrombophilia, and ABO blood group on the risk for venous thrombosis among Brazilians.

Increased coagulation factor levels have been demonstrated to be a risk factor for venous thromboembolism in patients of Caucasian origin. Coagulation factors, hereditary thrombophilia, and ABO blood group were evaluated for venous thrombosis risk in a heterogeneous Brazilian population consisting of 122 women and 53 men, with a median age of 36 years (range 13-63), matched to a control group by age, sex, and ethnicity. Increased levels of factor VIII (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.6-6.0), von Willebrand factor (OR, 2.8; 95% CI, 1.4-5.4), non-O blood group (OR, 2.1; 95% CI, 1.3-3.4), and thrombophilia (OR, 3.4; 95% CI, 1.6-7.1) emerged as independent risk factors for venous thromboembolism. The interaction of high levels of factor IX and factor XI with other independent variables increased the potential for thrombosis synergistically. Therefore, the ability of identifying underlying thrombophilia risk factors in our population was enhanced by the inclusion of these factors in the prothrombotic laboratory workup.

Pediatric reference intervals for uncommon bleeding and thrombotic disorders.

This study provides pediatric reference intervals and median values for factors II, V, VII, X, fibrinogen, alpha-2-antiplasmin (AP), antithrombin (AT), plasminogen, protein C (PC), and protein S (PS) for children 7 to 17 years of age. All analytes exhibited at least some age dependence in late childhood and adolescence either when compared against adult values or when medians for children were regressed against age.

Distinctive effects of red wine and diet on haemostatic cardiovascular risk factors.

The aim of this study was to compare the effects of Mediterranean-type diet (MD), high-fat diet (HFD), and red wine supplementation on plasma concentration of emergent haemostatic cardiovascular risk factors (HCVRF) and on variables of primary haemostasis (bleeding time, plasma von Willebrand factor and platelet aggregation/secretion). In a controlled prospective intervention study, two groups (21 healthy males each) received either MD or HFD during 90 days. Between days 30-60, both diets were supplemented with 240 ml/ day of red wine. After adjusting by baseline values, MD was associated with: lower plasma fibrinogen (p =0.03), factor VIIc (p=0.034) and factor VIIIc (p=0.0057); higher levels of protein S (p=0.013); longer bleeding time (p=0.017); and marginal increases in platelet serotonin aggregation and secretion after stimulation with epinephrine. Red wine supplementation, in both diets, resulted in decreased plasma fibrinogen (p=0.001) and factor VIIc (p=0.05), and in increased t-PA (p=0.01) and PAI-1 (p=0.0003). The effects of wine on antithrombin III (p=0.01) were divergent: there was a decrease in the HFD group but it increased slightly in the MD group. No effects of diet or wine were detected in plasma protein C, C-reactive protein or von Willebrand factor. BT did not change significantly with wine supplementation. Wine intake resulted in a significant increase in ex vivo platelet aggregation and secretion after stimulation with collagen (1 and 2 microg/ml, p < or = 0.01). MD and moderate consumption of red wine have complementary, mostly beneficial effects on haemostatic CV risk factors. The longer BT in individuals on MD, obtained independently of red wine, denotes less interaction of platelets with the vascular wall, which could be beneficial from the point of view of CV risk.

Surgical restoration of portal flow corrects procoagulant and anticoagulant deficiencies associated with extrahepatic portal vein thrombosis.

Extrahepatic portal vein thrombosis (EHPVT) is associated with abnormal circulating procoagulants and anticoagulants. Eleven children with EHPVT and abnormal coagulation factors underwent a mesenterico-left portal vein bypass to restore portal flow. Coagulation factors had returned to normal by one year. The data suggest that portal venous flow is essential for maintaining normal coagulation.

[Effect of oral and intramuscular vitamin K on the factors II, VII, IX, X, and PIVKA II in the infant newborn under 60 days of age]. / Efecto de la vitamina K oral e intramuscular sobre los factores II, VII, IX, X y PIVKA II en el recién nacido hasta los 60 días de edad. Relación con la alimentación.

BACKGROUND: Neonates on exclusive breast feeding that do not receive vitamin K at birth are at higher risk hemorrhagic disease of the newborn. AIM: To compare the effect of oral or intramuscular administration of vitamin K1 (VK1), on clotting factors II, VII, IX, X and PIVKA II, in children until the 60 days of age with exclusive breast feeding or mixed feeding. PATIENTS AND METHODS: Forty healthy full term infants, distributed in two groups, A: 20 with mixed feeding (formula-feeding and breast-feeding) and B: 20 with exclusive breast feeding, were studied. Nine infants of each group received 1 mg of VK1 intramuscularly and eleven 2 mg VK orally 5 ml of cord blood was collected initially from each infant. Venous blood samples were taken on 15, 30 and 60 days of age. RESULTS: All factors increased in a progressive form reaching levels over 50% at 60 days of age, in both groups. PIVKA II decreased significantly during the study period (p < 0.01). Factor II increased more in children with mixed feeding that received intramuscular vitamin K, than in the rest of study groups. No other differences between groups were observed. No infant had an abnormal bleeding during the study period. CONCLUSIONS: Oral administration of vitamin K is as effective as the intramuscular route in the prevention of the hemorrhagic disease of the newborn.

Hiperatividade do fator VII no plasma de portadores de hepatopatia esquistossomótica / Hyperactivity of factor VII in the plasma of schistosomotic hepatopathy patients

Aproximadamente 15% dos indivíduos normais säo "ativadores" em relaçäo ao fator VII da coagulaçäo, isto é, em seu plasma, quando submetido ao frio, há uma ativaçäo "ex vivo" deste fator. Verificamos que cinco de 37 portadores de hepatopatia esquistossomótica (13,5%) eram "ativadores" do fator VII. Esse fato precisa ser considerado quando o fator VII for usado para avaliaçäo da capacidade hepatocelular de síntese protéica em portadores de hepatopatia esquistossomótica