Factor XI messenger RNA in human platelets

The bleeding diathesis associated with congenital deficiency of factor XI ( FXI) is variable and correlates poorly with standard coagulation assays. Pl atelets are reported to contain FXI activity that may substitute for the pl asma protein. The presence of this platelet activity in some patients defic ient in plasma FXI could partly explain the variable bleeding associated wi th the deficiency state, Polyclonal antibodies to plasma FXI recognize a 22 0 kD platelet membrane protein distinct in structure from plasma FXI. The m essenger RNA (mRNA) coding for this protein has been postulated to be an al ternatively spliced FXI message lacking the fifth exon found in the liver ( wild type) message. We analyzed RNA from platelets, leukocytes, and bone ma rrow for FXI mRNA by reverse transcription polymerase chain reaction (RT-PC R) technology. Single FXI mRNA species were identified by RT-PCR in platele t and bone marrow RNA, but not leukocyte RNA, that are the same size as the message from liver RNA. Sequencing of PCR products confirmed that the FXI mRNA species in platelets is identical to the one in liver. Wild-type FXI m RNA was also identified in three leukemia cell lines with megakaryocyte fea tures (MEG-01, HEL 92.1.7, and CHRF-288-11). The data show that platelets c ontain wild-type FXI mRNA. FXI protein,therefore, may-be present in platele ts and may be released during platelet activation. The data do not support the premise that the 220 kD platelet protein that cross-reacts with FXI ant ibodies is a product of an alternatively spliced mRNA from the FXI gene. (C ) 1999 by The American Society of Hematology.