Although heparin-dependent antibodies (HDAs) typically manifest with thrombocytopenia as in heparin-induced thrombocytopenia (HIT), they may also manifest with preserved platelet counts. We describe a 35-year-old woman who developed severe thrombotic complications due to heparinization and unrecognized HDAs. She had received subcutaneous heparin as prophylaxis for deep vein thrombosis during a 5-day hospitalization for postpartum cardiomyopathy. Five days after discharge (day 1), she developed bilateral lower extremity arterial thrombi and underwent heparinization and successful lower extremity thrombectomies. A pulmonary embolus and hepatic and renal infarcts were then found. On days 2-6, the patient experienced a myocardial infarction, ischemic cerebrovascular accident, recurrent lower extremity arterial thrombus, and splenic infarct. On day 7, blood obtained on day 4 was found to be strongly positive for HDAs. In the interim, the patient had been transitioned to warfarin. Her platelet counts were never less than 75% of baseline and were consistently above 200 x 10(3)/mm(3). Hypercoagulability studies were negative. The patient's score on the Naranjo adverse drug reaction probability scale indicated that the relationship between this adverse reaction and heparin was probable. An extensive MEDLINE search located 22 other reports of patients who developed HDAs, sometimes associated with thrombosis, but whose platelet counts did not decrease. As with our patient, many of these case reports described clinicians who overlooked thrombosis due to HDAs because the patients did not have HIT. Clinicians should be cognizant of this possibility and consider a diagnosis of HDAs in patients with ongoing thrombosis who are receiving heparin therapy. It is strongly recommended that heparin be substituted with another anticoagulant in such cases until the presence of HDAs can be definitively ruled out.