Platelet coagulation factor XI_a-inhibitor, a form of Alzheimer amyloid precursor protein

An inhibitor of coagulation factor XI_a was purified from serum-free conditioned medium of HepG2 liver cells. Platelets stimulated with thrombin or calcium ionophore (A23187) secrete a protein functionally and immunologically identical to the inhibitor, implying a role for this inhibitor in hemostasis. Analysis of the amino-terminal amino acid sequence and immunologic reactivity showed the inhibitor to be a truncated form of the Alzheimer's amyloid precursor protein that contains a Kunitz-type serine protease inhibitor domain and at least a portion of the amyloid β protein. It inhibits factor XI_a and trypsin with a K₁ of 450 ± 50 pM and 20 ± 10 pM, respectively. Heparin (1 unit/ml) did not significantly effect inhibition of trypsin, but inhibition of XI_a was 15 times greater (K₁=25 ± 15 pM) in the presence of heparin.