Correlates of plasma and platelet tissue factor pathway inhibitor, factor V, and Protein S

Abstract

SummaryBackgroundPlasma Tissue Factor Pathway Inhibitor (TFPI) circulates bound to factor V (fV) and Protein S (PS). Estrogen therapy decreases plasma TFPI and PS. TFPI, fV, and PS circulate within platelets, and are released upon activation to modulate thrombus formation.ObjectiveIdentify factors affecting the concentrations of plasma and platelet TFPI, fV, and PS.MethodsBlood samples were obtained from 435 healthy individuals. Plasma total TFPI, TFPIɑ, fV, and PS, and platelet TFPI, fV, and PS were quantified. Correlations between these protein concentrations and age, gender, race, and estrogen use were established.ResultsIn males, only plasma fV increased with age, while in females, all plasma analytes increased with age. Males had higher plasma total TFPI, TFPIα, and PS than females. The platelet proteins in either sex remained relatively stable with increasing age. Platelet TFPI and PS were comparable in both sexes, while platelet fV was higher in females. Estrogen use was associated with decreased plasma total TFPI and TFPIα, and platelet PS, but not with platelet TFPI concentration. Racial differences in plasma and platelet proteins were observed, some of which were larger than inter-individual differences observed within racial groups. TFPI, fV and PS concentrations correlated in plasma, while only fV and PS correlated in platelets.ConclusionsPlasma and platelet TFPI, fV and PS differ in their: (i) in vivo association; (ii) demographic correlates; and (iii) alteration by estrogen therapies. Therefore, the plasma and platelet pools of these proteins may modulate hemostasis and thrombosis via different biochemical pathways.

Measurement of plasma and platelet tissue factor pathway inhibitor, factor V and Protein S in people with haemophilia

“…As in the blood donor population, the strongest correlations observed in the haemophilia population were between plasma total TFPI and plasma TFPIα, and between platelet FV and platelet PS. There was also a weak correlation between plasma TFPIα and plasma FV.…”

“…Total TFPI and TFPIɑ‐specific bead‐based proximity assays were performed as previously described . Total PS and FV ELISAs (Enzyme Research Laboratories) were performed according to manufacturers’ instructions.…”

“…The initial model was reduced by removal of non‐significant terms (respecting the model hierarchy). Equations used to calculate adjusted values are as previously published . The correlation between the seven parameters was estimated by the restricted maximum‐likelihood method using the log‐transformed results.…”

“…The majority of plasma TFPI is C‐terminally truncated, bound to lipoproteins and has decreased anticoagulant activity compared with plasma TFPIα . Plasma TFPIα accounts for approximately 20% of total plasma TFPI and circulates bound to FV and/or PS . Approximately 10% of TFPI present in whole blood is concentrated within platelets .…”

“…We previously measured the plasma and platelet concentrations of TFPI, FV and PS in a cohort of 435 blood donors to gain a better understanding of how these factors correlate with each other and how they vary by demographic characteristics in a healthy population . This study revealed platelet TFPI correlates poorly with plasma TFPI, as well as with platelet FV and PS.…”