TISSUE-SPECIFIC EXPRESSION OF FUNCTIONAL PLATELET FACTOR-XI IS INDEPENDENT OF PLASMA FACTOR-XI EXPRESSION

Platelet factor XI is an alternatively spliced product of the factor X I gene expressed specifically within megakaryocytes and platelets as a n approximately 1.9-kb mRMA transcript (compared with similar to 2.1 k b in liver cells) lacking exon V. Flow cytometry with an affinity-puri fied factor XI antibody, with PAC1 antibody (to the GPIIb/IIIa complex on activated platelets), and with S12 antibody (to P-selectin, an alp ha-granule membrane protein expressed on the platelet surface during s ecretion) on platelets activated with ADP, thrombin, thrombin receptor peptide (SFLLRN amide), or collagen at various concentrations exposed platelet factor XI and PAC1 antibody binding in parallel. Unactivated platelets expressed approximately 40% of total platelet factor XI but no PAC1 binding sites. Enhanced membrane exposure of platelet factor XI is independent of alpha-granule secretion, because ADP and collagen exposed platelet factor XI but no S12 binding sites, Platelets from f our patients with plasma factor XI deficiency (<0.04 U/mL) had normal constitutive and activation-dependent expression of platelet factor XI , Well-washed platelets from normal and from factor XI-deficient donor s incubated with low concentrations of thrombin (0.05 to 0.1 U/mL) cor rected the clotting defect observed with factor XI-deficient plasma. T hus, functionally active platelet factor XI is differentially expresse d on platelet membranes in a tissue-specific manner both constitutivel y and in a concentration-dependent fashion by various agonists in the absence of detectable plasma factor XI. (C) 1998 by The American Socie ty of Hematology.