Evidence for a Relationship between High Fibrinogen Levels and Decreased Thrombin Activity in vivo in Elderly Subjects

Marongiu, Francesco; Mamusa, Angela Maria; Dessalvi, Paolo; Mameli, G.; Cambuli, A.B.; Sorano, G.G.; Conti, Maria; Farci, P; Balestrieri, A

doi:10.1159/000215897

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…In our study, though both FVIIc and D-dimer levels were higher in the elderly subjects than in the younger control group, high FVIIc levels were not correlated with an increase of D-dimer levels. Our results indicate that high FVIIc levels in the elderly do not necessarily lead directly to fibrin formation, as has been recently described for elevated fibrinogen levels in healthy elderly individuals (14).…”

Section: Itsupporting

confidence: 84%

Factor VII Hyperactivity in the Elderly

1991

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SummaryTo investigate the age-related increase in coagulation factor VII (FVII) and its significance in the elderly, we measured FVII coagulation activity (FVIIc), FVII antigen (FVIIag), and D-dimer levels in 150 normal subjects ranging in age from 60 to 98 years. We also measured blood lipid fractions and serum cholinesterase activity (ChE), os an indicator of hepatic protein synthesis. FVIIc (141 ± 36%), FVIIag(136 ± 28%), and D-dimer (0.150 ± 0.372 αd/ml) levels were significantly higher in the elderly than in younger controls (p <0.01). Both FVIIc and FVIIag levels were significantly higher in elderly women than in elderly men (p <0.01). FVIIc levels significantly correlated with FVIIag levels, but not with D-dimer levels. FVIIag was more closely correlated with ChE levels in both sexes (men: r = 0.425, womenr r = 0.365, p <0.001) than with the lipid fractions. When the elderly subjects were divided into atherosclerotic and nonatherosclerotic groups, both FVIIc (p <0.01) and FVIIag (p <0.05) levels were higher in the former group. Moreover, the FVIIc/FVIIag ratio and ChE levels were higher in both the elderly men and women with atherosclerosis. These results suggest that in elderly subjects, especially with atherosclerosis, hepatic FVII synthesis and the activation of FVII zymogen are both accelerated.

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Section: Itsupporting

confidence: 84%

Factor VII Hyperactivity in the Elderly

1991

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“…Also, the strong dependence of anticoagulation on [F°] illustrated in Figure 2 is somewhat surprising given that fibrinogen already is in at least a ten-fold excess over thrombin in most practical clinical situations. For example, fibrinogen concentrations vary from about 5 M in preterm human infants, 26 10 M in normal adult humans, 27 15 M in geriatric humans 28 and adult swine, 23 to 44 M for porcine infants (piglets)! 29 Thus, it can be anticipated that practical use of thrombin-binding anticoagulants may require some level of customization for use in human and veterinarian blood applications.…”

Section: Implications For Thrombin-binding Anticoagulants In Blood Comentioning

confidence: 99%

Contact activation of the plasma coagulation cascade. III. Biophysical aspects of thrombin-binding anticoagulants

Vogler

Nadeau

Graper

1998

J. Biomed. Mater. Res.

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A biophysical model linking fibrin polymerization kinetics (following release from a thrombin-fibrinogen complex), coagulation time, and competitive inhibition of thrombin illustrates the utility of thrombin-binding ligands as anticoagulants in blood collection applications. The resulting mathematical relationship connecting fibrinogen, ligand, and thrombin concentrations was tested against experimentally observed anticoagulation of whole, platelet-poor porcine plasma induced by short, single-stranded DNA oligonucleotides originally found to bind thrombin by screening combinatorial libraries. The thrombin-fibrinogen dissociation constant Ks served as the single adjustable parameter in a least-squares fitting of the model to experimental anticoagulation data. Best-fit Ks values corroborated microM values measured in plasma-free systems, and application of the model to a ligand challenge to the intrinsic pathway of plasma coagulation corroborated nM endogenous thrombin concentrations measured in porcine blood activated by endotoxin insult in vivo. The model fit to data suggests that only about 20% conversion of blood fibrinogen to fibrin is required to coagulate (gel) porcine plasma. This prediction is consistent with the common clinical laboratory observation of latent fibrin formation in "serum" separated from blood before fibrinogen is fully converted to fibrin. It was concluded that the thrombin-binding anticoagulation model was a reasonable simulation of the situation in which an initial bolus of either exogenous or endogenous thrombin is rapidly partitioned between fibrinogen-bound and ligand-bound forms with little or no additional free thrombin created over time.

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