Caldwell and colleagues emphasize the important clinical point that chronic liver disease must be carefully considered as a possible cause of unexplained thrombocytopenia. Because idiopathic thrombocytopenic purpura can be diagnosed only by excluding other causes of thrombocytopenia [1], exclusion of chronic liver disease is essential. This has been emphasized in more comprehensive reviews on the condition.

The initial goal of the practice guideline on idiopathic thrombocytopenic purpura developed by the American Society of Hematology [1] was to evaluate the strength of the evidence supporting the value of diagnostic procedures and treatments. Evidence is lacking; thus, recommendations were based on an explicit method of measuring opinion of the American Society of Hematology panel. On the basis of opinion, the panel recommended that tests for platelet-associated IgG (the test used in the study by Kajiwara and colleagues [2] cited by Caldwell and coworkers) is unnecessary and inappropriate in the evaluation of patients suspected of having idiopathic thrombocytopenic purpura, in whom the history, physical examination, and complete blood counts with examination of the blood smear do not suggest another cause for the thrombocytopenia [1]. In normal persons, as well as in patients with chronic liver disease or other disorders, platelet-associated IgG is a platelet -granule protein acquired by pinocytosis of plasma [3]. High levels of platelet-associated IgG do not imply an immunologic pathogenesis [3]. Furthermore, the panel recommended that tests for antigen-specific antiplatelet antibodies are unnecessary but may be appropriate [1]. These tests may be more specific for antiplatelet antibodies, but they are not standardized, have a wide range of sensitivity and specificity among research laboratories [4], and do not discriminate idiopathic thrombocytopenic purpura from nonimmune thrombocytopenias, such as gestational thrombocytopenia [5].

Thus, the diagnosis of idiopathic thrombocytopenic purpura remains clinical. All other possible causes of thrombocytopenia, especially common and potentially subtle disorders such as chronic liver disease, must be excluded by a careful evaluation.