T. Matsuo et al., Characteristics of heparin-induced platelet aggregates in chronic hemodialysis with long-term heparin use, HAEMOSTASIS, 30(5), 2000, pp. 249-257
This study investigated the usefulness of a new platelet aggregometer with
a laser-scattering method for detection of heparin-induced small platelet a
ggregates in chronic hemodialysis patients. Using this device, small platel
et aggregates (particle size 9-25 mum) were detectable, but these aggregate
s could not be detected using a conventional light transmittance aggregomet
er. The laser-scattering intensity of the small aggregates was increased wi
th an increasing dosage of heparin as agonist. These aggregates were disagg
regated by heparin neutralization with protamine sulfate. Induction of smal
l platelet aggregates by heparin was inhibited by preincubation with nafamo
stat mesilate, a synthetic protease inhibitor, and cilostazol, a platelet p
hosphodiesterase inhibitor, but not by the therapeutic doses of aspirin or
argatroban, a selective thrombin inhibitor. The dialysis patients with long
term heparin use could be divided into two groups: responders to heparin, w
ho formed small aggregates with a scattering intensity over 0.51 x 10(5) V
after addition of 0.5 IU/ml of heparin obtained from normal platelet-rich p
lasma without inductor, and nonresponders, who showed an intensity under 0.
51 x 10(5) V. The rate of heparin responders among dialysis patients was si
gnificantly higher than the rate among normal subjects. Heparin-induced sma
ll aggregates were detected in 13 (36.1%) of 36 normal subjects with no his
tory of heparin infusion and in 37 (62.7%) of 59 dialysis patients who rece
ived heparin anticoagulation during each dialysis session. Dialysis patient
s with coronary heart disease did not have a significantly higher rate of h
eparin responders than patients without complications. There was no signifi
cant difference in the positivity rate between cases complicated by diabete
s and those without diabetes. In patients who had more than 2 episodes of t
hrombotic occlusions of an arteriovenous fistula, the rate of responders an
d the enhancement of scattering intensity of smalt aggregates by heparin we
re significantly increased compared with these in patients without occlusio
ns during the preceding 2 years. Moreover, dialysis patients with a positiv
e heparin response showed a marked increase in scattering intensity of smal
l aggregates after heparin infusion in each dialysis session. Determination
of the response to heparin prior to heparin use in dialysis patients with
repeated thromboembolic com plication may be useful in choosing anticoagula
nt regimens. Copyright (C) 2001 S. Karger AG, Basel.