title: Evidence of activation of the protein C pathway during acute vascular damage induced by Mediterranean spotted fever.
abstract: Mediterranean spotted fever (MSF) is a rickettsiosis that induces widespread microvascular injury. To obtain quantitative information on the in vivo activation and inactivation of the protein C system during the acute phase of endothelial damage, several components of the protein C pathway were studied in 28 MSF patients. Upon admission (day 1), patients showed clear evidence of endothelial damage as reflected by the significant decrease in the ratio VIII:C/vWF:Ag (0.36 +/- 0.14, mean +/- SD) compared with normals (0.98 +/- 0.14), and clinical and laboratory signs of hemostatic alterations such as decreased platelet count, positive fibrinogen/fibrin degradation products, and increased thrombin:antithrombin-III complex levels. Antigenic protein C (72% +/- 18%) and protein C inhibitor (PCI) (41% +/- 20%) were significantly decreased (P less than .001). Complexes of activated protein C (APC) with PCI or with alpha 1-antitrypsin (alpha 1AT) and of plasma kallikrein with PCI (KK:PCI) were measured using sandwich enzyme-linked immunosorbent assays. APC:alpha 1AT complex levels were increased in patients at day 1 (27 +/- 13 ng/mL) compared with controls (7 +/- 2 ng/mL), and APC:PCI and KK:PCI complexes, which were not detectable in any of the controls, were present in 57% and 75% of the 28 MSF patients, with mean levels of 11 +/- 5 and 46 +/- 16 ng/mL, respectively. After remission of the disease (day 30), a trend toward normal values in the majority of the parameters studied was found. This study shows that, in the course of endothelial injury, MSF patients experience a generalized activation of the protein C pathway, resulting in consumption of protein C and PCI, and in the appearance of APC:inhibitor complexes. Moreover, these data provide the evidence that KK:PCI circulating complexes occur in vivo.
authors.affiliation: Department of Medicine, School of Medicine, Murcia, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Vicente
authors.forename: F
authors.initials: F
authors.lastname: España
authors.forename: D
authors.initials: D
authors.lastname: Tabernero
authors.forename: A
authors.initials: A
authors.lastname: Estellés
authors.forename: J
authors.initials: J
authors.lastname: Aznar
authors.forename: S
authors.initials: S
authors.lastname: Hendl
authors.forename: J H
authors.initials: JH
authors.lastname: Griffin
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000032:analysis*; D001798:Blood Proteins / Q000032:analysis; D001907:Boutonneuse Fever / Q000097:blood*; D005169:Factor VIII / Q000032:analysis; D006801:Humans; D008875:Middle Aged; D010976:Platelet Count; D011486:Protein C / Q000378:metabolism*; D018046:Protein C Inhibitor; D012016:Reference Values; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D001779:Blood Coagulation Factors; D001798:Blood Proteins; D011486:Protein C; D018046:Protein C Inhibitor; D014841:von Willebrand Factor; D005169:Factor VIII