title: Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease.
abstract: We developed a simple assay for the measurement of tissue factor procoagulant activity (TF PCA) in whole blood samples that avoids the need for mononuclear cell isolation. This method combines convenience of sample collection and processing with a high degree of sensitivity and specificity for TF. Using this method, we have determined that TF PCA is detectable in whole blood samples from normal individuals, which is itself a novel observation. Essentially all PCA could be shown to be localized in the mononuclear cell fraction of blood. Compared with controls, whole blood TF levels were significantly (P < .000001) elevated in patients with sickle cell disease (SCD), regardless of the subtype of hemoglobinopathy (SS or SC disease). No significant difference in TF PCA was observed between patients in pain crisis compared with those in steady-state disease. Because TF functions as cofactor in the proteolytic conversion of FVII to FVIIa in vitro, it was expected that an increase in circulating TF PCA would lead to an increased in vivo generation of FVIIa. On the contrary, FVIIa levels were actually decreased in the plasma of patients with SCD. Plasma TF pathway inhibitor (TFPI) antigen levels were normal in SCD patients, suggesting that accelerated clearance of FVIIa by the TFPI pathway was not responsible for the reduced FVIIa levels. We propose that elevated levels of circulating TF PCA may play an important role in triggering the activation of coagulation known to occur in patients with SCD. Because TF is the principal cellular ligand for FVIIa, it is possible that increased binding to TF accounts for the diminished plasma FVIIa levels.
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA. keyxx001@tc.umn.edu
authors.forename: N S
authors.initials: NS
authors.lastname: Key
authors.forename: A
authors.initials: A
authors.lastname: Slungaard
authors.forename: L
authors.initials: L
authors.lastname: Dandelet
authors.forename: S C
authors.initials: SC
authors.lastname: Nelson
authors.forename: C
authors.initials: C
authors.lastname: Moertel
authors.forename: L A
authors.initials: LA
authors.lastname: Styles
authors.forename: F A
authors.initials: FA
authors.lastname: Kuypers
authors.forename: R R
authors.initials: RR
authors.lastname: Bach
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015942:Factor VIIa / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D015942:Factor VIIa