Plasma coagulation factor VII activity and its corrlates in healthy men

Objective: The aim of this study was to investigate the plasma coagulation factor VII activity and its correlates in healthy Australian men.
Design: Cross-sectional study.
Setting: Free living subjects.
Subjects: A total of 139 healthy Australian males aged 20–55 y with widely varying intakes of individual fatty acids.
Outcome measures: The concentration of phospholipid fatty acids and the parameters of biochemistry were analysed by standard methods. Citrated plasma factor VII activity was measured by using the ACL 200 system with commercially available kits.
Results: In the stepwise multiple regression, controlled for age, body mass index and dietary groups, the two most important variables of factor VII activity were selected in the forward entry model with R2¼0.474 and Po0.0001 from 19 independent variables, which were significantly correlated with plasma factor VII activity in age-adjusted bivariate analysis where significance was considered at Po0.01. Plasma factor VII activity was strongly negatively correlated with prothrombin time (PT) (Std. Coeff. -0.550), and significantly positively correlated with plasma phospholipid (PL) stearic acid (Std. Coeff. 0.285).
Conclusions: Increased factor VII activity was associated with shortening of PT. All types of fatty-acid concentrations of PLs were
significantly positively correlated with factor VII activity; however, stearic acid was more potent than other fatty acids in healthy Australian men.
Sponsorship: Meat Research Corporation of Australia.

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome—disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet–collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.

Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group—P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did—P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)—82.5 vs 50%, P<0.05.

These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.

Impact on hemostatic parameters of interrupting sitting with intermittent activity

Introduction: Excessive sitting has been associated with an elevated risk of vascular conditions, particularly venous thrombosis. Interrupting sitting time with intermittent physical activity can reduce venous stasis; however, impacts on other aspects of thrombogenesis are less understood. Purpose: To examine the effects of interrupting sitting time on blood coagulation and blood volume parameters in sedentary, middle-age, overweight/obese adults (11 men and 8 women; age = 53.8 T 4.9 yr, body mass index = 31.2 T 4.1 kgImj2; mean T SD). Methods: The randomized three-period, three-treatment acute crossover trial consisted of uninterrupted sitting and sitting interrupted by 2-min bouts of either light- or moderate-intensity treadmill walking every 20 min. In each trial condition, blood samples were collected at baseline before the consumption of a standardized meal (j2 h) and postintervention (5 h). Results: Plasma fibrinogen increased from baseline with uninterrupted sitting (0.24 gILj1, 95% confidence interval = 0.13–0.34, P G 0.001). Lightintensity but not moderate-intensity activity breaks attenuated the increase by 0.17 gILj1 (95% confidence interval = 0.01–0.32, P G 0.05). There were no between-condition differences in prothrombin time, activated partial thromboplastin time, von Willebrand
factor, D-dimer, or platelet count. Uninterrupted sitting reduced plasma volume and increased hematocrit, hemoglobin, and red blood cell count; effects attenuated by both light- and moderate-intensity breaks (P G 0.05). White blood cell count increased with uninterrupted sitting and further increased with moderate-intensity breaks. Mean platelet volume increased with moderate-intensity but not lightintensity breaks or uninterrupted sitting. Conclusion: Uninterrupted sitting increased fibrinogen and reduced plasma volume, with associated increases in hemoglobin and hematocrit. Activity breaks attenuated these responses, indicative of an ameliorating influence on the procoagulant effects of uninterrupted sitting.

Effects of long-term head-down-tilt bed rest and different training regimes on the coagulation system of healthy men

Immobility plus preexisting chronic disease or acute trauma can activate the coagulation system, thus increasing the risk for thromboembolic events. The effects of long-term bed-rest immobility and microgravity on the coagulation system of healthy persons (e.g., during crewed Mars missions) have not yet been studied. The main objective of the second Berlin BedRest Study (BBR2-2) "Coagulation Part" was to investigate adaptations of the hemostatic system during long-term bed rest (60 days) under simulated microgravity (6° head-down-tilt [6°HDT]) and after mobilization in three different volunteer groups (randomly assigned to CTR= inactive control group; RE= resistive exercise only group; and RVE= resistive exercise with whole-body vibration group). In 24 males (aged 21-45 years), before, during, and after long-term bed rest, key parameters of coagulation were measured from venous blood samples: D-dimer (DD), thrombin-antithrombin III complex (TAT), and prothrombin fragment F1 + 2 (PT-F1 + 2). Additionally, modified rotational thrombelastometry (ROTEM (®) ) analysis was performed. Times of exploratory analyses were as follows: baseline data collection 2 days before bed rest (BDC-2); eight different days of 6°HDT bed rest (HDT1-HDT60), and two different days after reambulation (R + 3 and R + 6). We found significant changes in DD, TAT, and PT-F1 + 2 over the total time course, but no consistent effect of physical interventions (RE, RVE) on these parameters. Notably, no parameter reached levels indicative of intravascular thrombin formation. All ROTEM® parameters remained within the normal range and no pathological traces were found. Sixty days of 6°HDT bed rest are not associated with pronounced activation of the coagulation system indicative of intravascular thrombus formation in healthy volunteers independent of the training type during the bed rest.