Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4856-4863
Hematopoietic Cells From 
-Spectrin-Deficient Mice Are Sufficient
to Induce Thrombotic Events in Hematopoietically Ablated Recipients
Nancy J. Wandersee,
John C. Lee,
Tamma M. Kaysser,
Roderick T. Bronson, and
Jane E. Barker
From The Jackson Laboratory, Bar Harbor, ME; the School of Medicine,
University of Connecticut, Farmington, CT; Motorola Corp, Schaumberg,
IL; and the Tufts University School of Veterinary Medicine, Boston, MA.
Thrombotic events are life-threatening complications of human
hemolytic anemias such as paroxysmal nocturnal hemoglobinuria, sickle
cell disease, and thalassemia. It is not clear whether these events are
solely influenced by aberrant hematopoietic cells or also involve
aberrant nonhematopoietic cells. Spherocytosis mutant
(Spna1sph/Spna1sph; for simplicity
referred to as sph/sph) mice develop a severe hemolytic anemia
postnatally due to deficiencies in 
-spectrin in erythroid and other
as yet incompletely defined nonerythroid tissues. Thrombotic lesions
occur in all adult sph/sph mice, thus providing a
hematopoietically stressed model in which to assess putative causes of
thrombus formation. To determine whether hematopoietic cells from
sph/sph mice are sufficient to initiate thrombi, bone marrow
from sph/sph or +/+ mice was transplanted into mice with no
hemolytic anemia. One set of recipients was lethally irradiated; the
other set was genetically stem cell deficient. All mice implanted with
sph/sph marrow, but not +/+ marrow, developed severe anemia and histopathology typical of sph/sph mice. Histological
analyses of marrow recipients showed that thrombi were present in the
recipients of sph/sph marrow, but not +/+ marrow. The
results indicate that the -spectrin-deficient hematopoietic cells
of sph/sph mice are the primary causative agents of the
thrombotic events.
