Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3397-3404
Factor XI Messenger RNA in Human Platelets
Danko Martincic,
Vladimir Kravtsov, and
David Gailani
From the Departments of Pediatrics, Pathology, and Medicine,
Vanderbilt University, Nashville, TN.
The bleeding diathesis associated with congenital deficiency of
factor XI (FXI) is variable and correlates poorly with standard coagulation assays. Platelets are reported to contain FXI activity that
may substitute for the plasma protein. The presence of this platelet
activity in some patients deficient in plasma FXI could partly explain
the variable bleeding associated with the deficiency state. Polyclonal
antibodies to plasma FXI recognize a 220 kD platelet membrane protein
distinct in structure from plasma FXI. The messenger RNA (mRNA) coding
for this protein has been postulated to be an alternatively spliced FXI
message lacking the fifth exon found in the liver (wild type) message.
We analyzed RNA from platelets, leukocytes, and bone marrow for FXI
mRNA by reverse transcription polymerase chain reaction (RT-PCR)
technology. Single FXI mRNA species were identified by RT-PCR in
platelet 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 mRNA was also identified in three leukemia
cell lines with megakaryocyte features (MEG-01, HEL 92.1.7, and
CHRF-288-11). The data show that platelets contain wild-type FXI mRNA.
FXI protein, therefore, may be present in platelets 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 antibodies is a
product of an alternatively spliced mRNA from the FXI gene.