Red Cell Filterability and Erythrocyte Membrane Microviscosity

The Journal of International Medical Research 1990; 18: 161 - 163
Red Cell Filterability and
Erythrocyte Membrane
Microviscosity During
Ticlopidine Treatment
G. Caimi, R. Lo Presti, A. Serra, G. Francavilla,
A. Catania and A. Sarno
Institute of Clinical Medicine and Cardiovascular
Diseases, University ofPalermo, Palermo, Italy
The effects of 10 days' treatment with 500 mg/day ticlopidine on the
filterability of red blood cells in suspension and on the microviscosity
of the red blood cell membrane was evaluated in 11 patients with
vascular atherosclerosis. The results show ticlopidine to be effective in
influencing the rheological measures of red cell filterability and
membrane microviscosity: filterability was increased and microviscosity was decreased. Ticlopidine also decreased the extent of fluorescence polarization. These results are discussed regarding possible
mechanisms of action of ticlopidine.
KEY WORDS: Ticlopidine; vascular atherosclerosis; erythrocytes; filterability; membrane
viscosity; fluorescence polarization.
INTRODUCTION
T
here have been several reports on
the effect of ticlopidine on blood
rheology.' This effect is only partially due
to its action on platelets and ticlopidine, in
fact, also seems to act on whole blood
filterability.' - 5 plasma viscosity':" and the
fibrinogen concentration.v' The influence
Received for publication: 20 February 1989;
accepted 17 November 1989.
Address for correspondence: Professor Oregario
Cairni, Via Leonardo da Vinci 52, 90145 Palermo,
Italy.
of ticlopidine on blood rheology during
ischaemic exercise has also been studied?
and it has been found to increase the ATP
content of red blood cells."
Almost all previous reports on the influence of ticlopidine on whole blood filtration,? - 5 evaluated according to the Reid
and Dormandy method," can be attributed
to the platelet anti-aggregating mechanism
and not to a specific action on erythrocyte
rheology. This latter consideration, associated with observations on the effect of
ticlopidine on the membrane of red blood
cells using spin label resonance," stimulated the present investigation on microvis-
© Copyright 1990 by Cambridge Medical Publications Ltd
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161
G. Caimi, R. Lo Presti, A. Serra et al.
Table 1
Haemorheological measures (mean ± SD) before and after 10 days'
ticlopidine treatment in patients with vascular atherosclerosis
Rheological
measure
Before treatment
10 days'
treatment
Filterability
index
0.52 ± 0.11
0.75 ± 0.13"
Fluorescence
polarization
0.289 ± 0.010
0.273 ± O.OO6b
3.28 ± 0.32
2.92 ± 0.16 b
Microviscosity
'P < 0.01 versus before treatment
"P < 0.02 versus before treatment.
cosity of the erythrocyte membrane and
behaviour of the filtration of suspended
red cells during ticlopidine treatment.
PATIENTS AND METHODS
Patients
This study included 11 patients (six men
and five women) aged (mean ± SD) 63.5
± 9.47 years with vascular atherosclerosis.
None of the patients was diabetic, as ascertained by the oral glucose tolerance test,
and none was hypertensive or dyslipidaemic. Patients with chronic renal failure
were also excluded.
Treatment
After a washout period of 3 weeks, all the
patients were treated with ticlopidine
(Tiklid® ) for 10 days.
Evaluation
On days 0 and 10 of treatment rheological
measures were made on fasting venous
blood for filterability index and membrane
microviscosity. The filterability index was
obtained by filtering red blood cells sus-
pended (5%) in autologous prefiltered
plasma, according to the method of Dodds
et al:" For evaluation of membrane microviscosity, ghosts were prepared according
to the method of Dodge, containing 1,6diphenyl-l,3,5-hexatriene, and microviscosity, in agreement with the Perrin equation,12.13 was calculated from the amount
of fluorescence polarization which was
measured using a Perkin-Elmer LS5 spectrophotofluorimeter.
Statistical analysis
The results were expressed as means ± SD
and were evaluated using Student's t-test
for paired data.
RESULTS
Although treatment was only continued for
the relatively short period of 10 days a
significant (P < 0.01) increase in the filterability index occurred compared with
before the treatment. In addition, the erythrocyte membrance microviscosity and the
amount of fluorescence polarization significantly (P < 0.02) decreased (Table 1).
DISCUSSION
Tiklid" is a registered tradename of Midy
Sanofi, Italy.
There are two conclusions to emerge from
the results of this study. The first concerns
162
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Ticlopidine in vascular atherosclerosis
the filtration of suspended red blood cells.
Since the method used was able to remove
platelets and protein precipitates, it is
likely that the increase in the filterability
index reflects an improvement in red blood
cell deformability. Although previously
published studies indicate that ticlopidine
influences the haemorheological properties,' - 7 the data obtained from this study
indicate a different interpretation of its
action.
The second conclusion concerns data
obtained from the fluorescence polarization technique which shows a reduction
in erythrocyte membrane microviscosity,
attributable to the known effect of ticlopidine in red blood cell membrane expansion." This effect seems to depend on lipid
-lipid and cholesterol- phospholipid bond
variations and appears to be common to all
substances which, like ticlopidine, are
amphiphiles."
In view of these results, rather than the
evaluation of individual phospholipids,
which are the principal components of the
red cell membrane, future studies will be
addressed towards the mechanisms behind
the reduction in red blood cell microviscosity. This is of immense theoretical interest and has major therapeutic implications.
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