We deserve no credit for the muddied waters of heparin-induced thrombocytopenia terminology. The concept of early, mild, nonimmune, clinically inconsequential heparin-induced thrombocytopenia was advanced years ago as heparin-induced thrombocytopenia type 1 (1). In fact, low platelet counts in some hospitalized patients may often be unrelated to heparin and may be due instead to infection, surgery, other drugs, and stresses. The recommendation to designate this as "heparin-associated thrombocytopenia" to distinguish it from serious heparin-induced thrombocytopenia (2) has not gained wide favor. Furthermore, separating heparin-induced thrombocytopenia from heparin-induced thrombocytopenia with thrombosis syndrome is artificial and misleading, since isolated heparin-induced thrombocytopenia presents an extreme risk for thrombotic complications (Rice L. Heparin-induced thrombocytopenia: myths and misconceptions that will get you into trouble. In preparation). In our paper, the term heparin-induced thrombocytopenia signified the serious, immune clinicopathologic syndrome. We usually refer descriptively to early thrombocytopenia that may or may not be heparin related, its import being that it can be confused with heparin-induced thrombocytopenia at the bedside or in clinical studies.

Dr. De Palma questioned the frequency of heparin-induced thrombocytopenia. Prospective studies finding frequencies of 3% to 5% have been reviewed and re-reviewed (3). The 26% reported by Bell and Royall (4) illustrates how nonimmune thrombocytopenia can contaminate results. Our paper's reference 2 found antibody to heparin-induced thrombocytopenia in 3.3% of orthopedic patients receiving subcutaneous unfractionated heparin prophylaxis (8 of 9 affected patients developed venous or arterial thromboembolism) (5). That study found no heparin-induced thrombocytopenia with low-molecular-weight heparin. However, others have observed heparin-induced thrombocytopenia with low-molecular-weight heparin in about 0.5% of patients (3), as in our patient 1. A similar frequency of heparin-induced thrombocytopenia has been caused by heparin leaching from coated pulmonary artery catheters (3, 6). Our group has highlighted the risks for heparin-induced thrombocytopenia from catheter flushes and even from an oral pentasaccharide glycosaminoglycan used for interstitial cystitis (7, 8).

Delayed-onset heparin-induced thrombocytopenia clearly explains some cases of a condition that has been ascribed to early "warfarin resistance" (see our patient 2). We are aware of delayed heparin-induced thrombocytopenia presenting at as late as 46 days. Disease-related factors beyond heparin must affect the risk for developing antibodies to heparin–platelet factor 4 or for the full-blown heparin-induced thrombocytopenia syndrome. For example, a high rate of positive results by enzyme-linked immunosorbent assay is seen after heart surgery in the absence of the clinical heparin-induced thrombocytopenia syndrome, but this is much less common in other clinical situations (9).