Excess soluble urokinase-type plasminogen activator receptor in the plasma of patients with paroxysmal nocturnal hemoglobinuria inhibits cell-associated fibrinolytic activity.

The plasma levels of soluble urokinase-type plasminogen activator receptor (uPAR; CD87) measured by enzyme-linked immunosorbent assay were higher in patients with paroxysmal nocturnal hemoglobinuria (PNH) (5.8 +/- 4.7 ng/ml, mean +/- S.D., n = 9) than in normal donors (2.0 +/- 0.8 ng/ml, mean +/- S.D., n = 15). The high level of soluble uPAR in PNH plasma competed with the membrane uPAR expressed by normal blood neutrophils for binding to urokinase-type plasminogen activator (uPA). We also found that uPA complexed with soluble uPAR was partly resistant to inactivation by plasminogen activator inhibitors in the plasma, although uPA was inactivated similarly by plasma containing high and low levels of uPAR. PNH-affected blood cells are deficient in urokinase-type PAR, a glycosyl-phosphatidylinositol (GPI)-anchored protein. The deficiency of uPAR on PNH-affected leukocytes and the increased soluble uPAR in the PNH plasma may synergistically contribute to the development of thrombosis in PNH by inhibiting the cell-associated fibrinolytic activity.