Further complexities in diagnosing acquired thrombocytopenia: unexpected parallels between antibody-mediated delayed thrombocytopenia with abciximab and heparin induced thrombocytopenia.

674 Acute thrombocytopenias are common clinical problems of diverse etiologies and paradoxically, some of the most dramatic forms are iatrogenic in nature (1). For example, drugs that are given to patients to treat or prevent arterial or venous thrombosis (such as heparin, abciximab, and other agents that block the platelet integrin receptor αIIbβ3) can cause immune reactions that lead to life-threatening situations (1-8). The specific drug implicated as the cause of an individual patient’s thrombocytopenia is an important issue to sort out, and this is commonly done by evaluating the clinical scenario and excluding potential causes (1, 3). Laboratory tests have provided information about the causes and mechanisms of drug-induced thrombocytopenia (1, 3). However, the results of such tests, even if available, are typically reported long after clinical decisions are made about probable and potential causes and appropriate therapies. Thrombocytopenia due to agents that block platelet αIIbβ3 integrin-ligand interactions has increased, subsequent to an increased use of these drugs for arterial thrombotic states, including acute coronary syndromes and arterial revascularization procedures (2, 4-8). In some patients, anti-αIIbβ3 therapy with abciximab is associated with acute thrombocytopenia, within hours of therapy, or pseudothrombocytopenia that does not need treatment (6-8). The more rapid thrombocytopenia after abciximab therapy has often been used to distinguish this entity from heparin-induced thrombocytopenia (HIT), which characteristically presents later, 5-10 days after heparin exposure (3, 6-8). However, there are now two reports, including the paper by Nurden and coworkers in this issue of Thrombosis and Haemostasis (see pages 820-828), illustrating that antibody-mediated thrombocytopenia complicating abciximab therapy can also present as a delayed, rather than an immediate fall in the platelet count (7, 8). The similar timing of delayed abciximab-related thrombocytopenia and HIT appears to represent emergence of antibodies from primary immunization in individuals exposed to these anticoagulants (3, 7, 8). The similarity in timing poses new and difficult challenges for clinicians relying on the clinical picture, and in particular the timing of the drop in the platelet count, to determine the most probable cause. This is an even greater problem when one considers that patients who receive anti-αIIbβ3 therapy are also commonly exposed to heparin. The study by Nurden and coworkers in this issue of Thrombosis and Haemostasis is important for several reasons. First, it reports a detailed analysis of the antibodies in a group of patients who developed delayed thrombocytopenia after therapy with abciximab, that demonstrates the characteristics of the antibodies generated, including their specificity for abciximab (7). It also illustrated that the association of these antibodies with delayed thrombocytopenia could not be attributed to HIT. Perhaps one of the most interesting and potentially important observations made by these investigators was the demonstration that three of their patients with delayed abciximab-associated thrombocytopenia had developed antibodies that induced platelet activation and aggregation in vitro, in a manner that required the anFurther complexities in diagnosing acquired thrombocytopenia: unexpected parallels between antibody-mediated delayed thrombocytopenia with abciximab and heparin induced thrombocytopenia