Characteristics of heparin-induced platelet aggregates in chronic hemodialysis with long-term heparin use.

This study investigated the usefulness of a new platelet aggregometer with a laser-scattering method for detection of heparin-induced small platelet aggregates in chronic hemodialysis patients. Using this device, small platelet aggregates (particle size 9--25 microm) were detectable, but these aggregates could not be detected using a conventional light transmittance aggregometer. The laser-scattering intensity of the small aggregates was increased with an increasing dosage of heparin as agonist. These aggregates were disaggregated by heparin neutralization with protamine sulfate. Induction of small platelet aggregates by heparin was inhibited by preincubation with nafamostat mesilate, a synthetic protease inhibitor, and cilostazol, a platelet phosphodiesterase 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, who 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 plasma without inductor, and nonresponders, who showed an intensity under 0.51 x 10(5) V. The rate of heparin responders among dialysis patients was significantly higher than the rate among normal subjects. Heparin-induced small aggregates were detected in 13 (36.1%) of 36 normal subjects with no history of heparin infusion and in 37 (62.7%) of 59 dialysis patients who received heparin anticoagulation during each dialysis session. Dialysis patients with coronary heart disease did not have a significantly higher rate of heparin responders than patients without complications. There was no significant difference in the positivity rate between cases complicated by diabetes and those without diabetes. In patients who had more than 2 episodes of thrombotic occlusions of an arteriovenous fistula, the rate of responders and the enhancement of scattering intensity of small aggregates by heparin were significantly increased compared with these in patients without occlusions during the preceding 2 years. Moreover, dialysis patients with a positive heparin response showed a marked increase in scattering intensity of small aggregates after heparin infusion in each dialysis session. Determination of the response to heparin prior to heparin use in dialysis patients with repeated thromboembolic complication may be useful in choosing anticoagulant regimens.