Hereditary thrombocytopenias: the challenge of increasing frequency and differential diagnosis

Hereditary thrombocytopenias are often difficult to diagnose. Since most of them are rare diseases, their characteristics are less known by physicians who deal with adults. While pediatricians are accustomed to considering genetic diseases in the differential diagnosis of diseases affecting their young patients, clinicians who treat adults often overlook this possibility. Making a definitive diagnosis usually requires complex laboratory techniques. In addition, because this is a very dynamic field half of the patients have forms that have not yet been identified with new disease definitions being made every month with next-generation sequencing (NGS). These patients are often mistakenly diagnosed with immune thrombocytopenia, and, accordingly, they are at risk of receiving unnecessary immunosuppressive therapy. Misdiagnosis is widespread in patients whose low platelet count is discovered in adulthood because, in these cases, the hereditary origin of thrombocytopenia can be overlooked. The age of manifestation and the duration/chronicity of symptoms are crucial clinical features for identifying hereditary thrombocytopenia disorders. It is important to establish the correct diagnosis because it has recently been shown that some hereditary forms of thrombocytopenia predispose to other diseases such as leukemia, renal failure, and bone marrow failure; therefore, affected individuals should be kept under close surveillance and, when necessary, treated for concomitant diseases. This review aims to determine when to suspect and how to diagnose and manage inherited thrombocytopenias. It also intends to detail the less common kinds of isolated thrombocytopenias highlighting that not all isolated thrombocytopenias that emerge in adults are immune thrombocytopenia.