Although unfractionated heparin is the most commonly used anticoagulant for hemodialysis and has been associated with bleeding episodes, a more devastating complication that can occur is heparin-induced thrombocytopenia (HIT). It is believed that HIT type II is much more dangerous than type I, because HIT type II is associated with thromboembolic complications whereas there are no such complications in HIT type I. However, increased clot formation in the extracorporeal circuit during hemodialysis with unfractionated heparin is sometimes experienced by not only patients with HIT type II but also those with HIT type I. Three patients with HIT type I are presented who suffered from clot formation during hemodialysis, and in whom 81 mg of aspirin and/or cessation of heparin was prescribed. All three patients had received recombinant human erythropoietin (rHuEpo). Both heparin and rHuEpo induce enhanced platelet aggregation; therefore, it is possible that even HIT type I patients may suffer clot formation in the extracorporeal circuit due to platelet activation via the synergistic effects of unfractionated heparin and rHuEpo.