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Blood, 1 June 2002, Vol. 99, No. 11, pp. 3999-4005
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Microvascular abnormalities in sickle cell disease: a
computer-assisted intravital microscopy study
Anthony T. W. Cheung,
Peter
C. Y. Chen,
Edward C. Larkin,
Patricia L. Duong,
Sahana Ramanujam,
Fern Tablin, and
Ted Wun
From the Department of Medical Pathology, University of
California (UC) Davis School of Medicine, Davis, CA; Department of
Bioengineering, UC San Diego, La Jolla, CA; Department of Anatomy,
Physiology and Cell Biology, UC Davis School of Veterinary Medicine,
CA; Department of Internal Medicine (Hematology), UC Davis School of
Medicine, Sacramento, CA; and Veteran Administration Northern
California Health Systems, Rancho Cordova, CA.
The conjunctival microcirculation of 18 homozygous sickle cell
disease (SCD) patients during steady-state, painful crisis, and
postcrisis conditions was recorded on high-resolution videotapes using
intravital microscopy. Selected videotape sequences were subsequently
coded, frame-captured, studied, and blindly analyzed using
computer-assisted image analysis protocols. At steady-state (baseline),
all SCD patients exhibited some of the following morphometric abnormalities: abnormal vessel diameter, comma signs, blood
sludging, boxcar blood flow phenomenon, distended vessels, damaged
vessels, hemosiderin deposits, vessel tortuosity, and
microaneurysms. There was a decrease in vascularity
(diminished presence of conjunctival vessels) in SCD patients compared
with non-SCD controls, giving the bulbar conjunctiva a "blanched"
avascular appearance in most but not all SCD patients during
steady-state. Averaged steady-state red cell velocity in SCD patients
was slower than in non-SCD controls. During painful crisis, a further
decrease in vascularity (caused by flow stoppage in small vessels) and
a 36.7% ± 5.2% decrease in large vessel (mostly venular) diameter
resulted. In addition, the conjunctival red cell velocities either
slowed significantly (6.6% ± 13.1%; P < .01) or
were reduced to a trickle (unmeasurable) during crisis. The
microvascular changes observed during crisis were transient and
reverted to steady-state baseline after resolution of crisis. When
combined, intravital microscopy and computer-assisted image analysis
(computer-assisted intravital microscopy) represent the availability of
a noninvasive tool to quantify microvascular abnormalities in vascular
diseases, including sickle cell disease. The ability to identify and
relocate the same conjunctival vessels for longitudinal studies
uniquely underscores the applicability of this quantitative real-time technology.
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