Etscheid and colleagues have further addressed the dual role of FSAP in hemostasis and fibrinolysis. With refined methods they compared the activities of FSAP wild-type  (FSAP-wt) vs. FSAP variant Marburg I  (FSAP-MI).

pro-uPA was found to be cleaved much more efficiently and at lower concentrations than FVII, indicating a preference of FSAP for the fibrinolytic system. Purified FSAP -MI activated FVII much less effficient than FSAP-wt. This was confirmed with FSAP from plasma of 5 individuals homozygous for the FSAP -MI allele. Pro-uPA was only weakly processed by FSAP from homozygous Marburg I carriers.

However, the central finding was on Factor VIII (FVIII) processing: FSAP-wt caused inactivation of FVIII, whereas FSAP-MI caused activation.

The authors conclude that the hypothesis of a haemostatic imbalance and increased athero-thrombotic risk in Marburg I-carriers due to reduced uPA but unchanged FVII activation capacity needs a revision and should take into consideration circulating FVIII levels.

Title:
The Marburg I polymorphism (G534E) of Factor VII activating protease (FSAP) prevents FVII activation, but contributes to thromboembolic risk due to FVIII activation.

Authors and Source:
M Etscheid, L Muhl, D Pons, KT Preissner, W Ruf, W Jukema, SM Kanse
Poster presentation ISTH 2009: OC-TH-110