If a family history of thrombocytopenia is present, a careful work-up is warranted to prevent inappropriate therapies (poorly chosen medication or splenectomy) while it is essential to compile a record of clinical complications such as bone marrow failure, oncological disorders, sensorial hearing loss, renal failure or others. For some patients, significant bleeding may only arise after surgery or trauma and a sufficient challenge to the hemostatic system. Similar bleeding patterns are found in type 1 or 2 VWD and therefore some IPDs can be wrongly diagnosed as VWD. During initial screening, particularly important is measuring the platelet count

and the mean platelet volume; while a peripheral blood smear is recommended for Selleckchem LDK378 giant platelet syndromes as electronic counters see more may underestimate platelet numbers and size

[24,27]. Measuring the Ivy bleeding time is no longer standard practice and some replace it by the platelet function analyzer (PFA-100). Laboratory investigation of platelet aggregation, ATP secretion and quantification of platelet receptors by flow cytometry are standard procedures. Often requiring specialist help, immunofluorescence (e.g. distinctive patterns for myosin-IIA in leukocytes are typical of MYH9 disease) and electron microscopy are often useful as an aid to diagnosis; while evaluating platelet adhesion and spreading on protein surfaces is informative especially if accompanied by a study of signalling pathways (phosphorylations, western blotting) [7,11,13,24,25,28]. Finally, flow chambers

and computerized analysis of thrombus formation on protein-covered surfaces (e.g. Fg, VWF, collagen) under controlled flow, procedures often validated for platelets from genetically-modified mice, will fast become applicable to human pathology [29]. Platelets are easily obtainable and citrated MCE platelet-rich plasma is mostly used to study platelet function under basal and activated conditions [3,5]. Algorithmns are being developed to permit step-by-step detection of specific pathologies. Defects in platelet adhesion, aggregation, G protein signaling, secretion and platelet production can result from mutations in platelet-specific genes leading to isolated thrombocytopathy or thrombocytopenia for which the main clinical feature is bleeding (e.g. BSS, GT, P2Y12 deficiency and other diseases as reviewed in Molecular basis of platelet disorders). In contrast, when mutations occur in widely expressed genes, patients usually develop a broader clinical phenotype with bleeding accompanied by neuropathology, endocrine dysfunction, other hematological and/or metabolic problems. Therefore, clinical investigation and platelet research go hand-in-hand to improve knowledge of broad phenotype mendelian disorders [10,30].