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Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function. We evaluated the Optimul assay at two centres in Australia, one regional and one tertiary metropolitan, to assess its feasibility as a screening test applicable to remote regional centres. Concentration-response curves were established from 45 healthy volunteers at the participating regional hospital and from 31 healthy volunteers at the tertiary institution. Optimul successfully detected anti-platelet effects in individuals taking aspirin (n=4), NSAID (n=2), clopidogrel (n=2) and dual therapy with aspirin and clopidogrel (n=1). When tested in parallel to LTA in individuals referred for the evaluation of abnormal bleeding symptoms there was overall a very good level of agreement between Optimul and LTA [Cohen's kappa (k2)=0.84], supporting its role as a useful screening tool in the assessment of platelet function. Optimul assay performance was quick and the methodology simple, requiring no specialised training or resources to be implemented at either the regional or metropolitan laboratory. Widespread implementation, particularly in regional laboratories within Australia where specialised platelet function testing is unavailable, has the potential to drastically improve the inequity of access to such services.

Germline mutations of runt-related transcription factor-1 (RUNX1) cause famil-ial platelet disorder with predisposition to myeloid malignancy (FPDMM), most commonly associated with thrombocytopenia and propensity to develop myeloid neoplasms. A key clinical question is which patients with a family history of thrombo-cytopenia should undergo genetic testing for RUNX1 mutations. Typically, molecular diagnosis by genetic sequencing is performed when the clinical phenotype is sug-gestive of this diagnosis; however, our understanding of the spectrum of associated features suggestive of this diagnosis continues to evolve. Herein, we report a case se-ries of 3 unrelated families with RU N X1-associated FPDMM and clinical phenotypes not typically reported with this condition. These cases expand our understanding of FPDMM and highlight the complexity of transcriptional regulation of hematopoiesis and its potentially diverse phenotypes. We describe our approach to diagnosis and management of these individuals and the importance of long-term surveillance in these cases.

Idiopathic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by relapsing/remitting thrombocytopenia. Bleeding complications are infrequent with platelet counts above 30x10(9)/L, and this level is commonly used as a threshold for treatment. The question of another/co-existent diagnosis or an alternate mechanism of platelet destruction arises when bleeding is experienced with platelet counts above this threshold. We report a case of anti-GPVI mediated ITP that was diagnosed following investigations performed to address this key clinical question. A patient with ITP experienced exaggerated bruising symptoms despite a platelet count of 91x10(9)/L. Platelet functional testing showed an isolated platelet defect of collagen-induced aggregation. Next generation sequencing excluded a pathogenic variant of GP6, and anti-GPVI antibodies that curtailed GPVI function were confirmed by extended platelet phenotyping. We propose that anti-GPVI mediated ITP may be under-recognized, and that inclusion of GPVI in antibody detection assays may improve their diagnostic utility and in turn, facilitate a better understanding of ITP pathophysiology and aid individualized treatment approaches.

Gene association with HLA suggests involvement of immune mediated mechanisms in the pathogenesis of Parkinson's disease (PD). Only a small number of studies have found differences between circulating leukocyte populations in PD patients compared to controls, with conflicting results. To clarify whether there is a circulating leukocyte PD phenotype, we assessed the numbers of T, B and natural killer cells, and monocytes and found a small reduction (15-25%) in CD4 + T and CD19 + B cells in PD. These findings suggest some compromise in immune cells in PD and have potential implications for immune function and the progression of PD.

Gene association with HLA suggests involvement of immune mediated mechanisms in the pathogenesis of Parkinson's disease (PD). Only a small number of studies have found differences between circulating leukocyte populations in PD patients compared to controls, with conflicting results. To clarify whether there is a circulating leukocyte PD phenotype, we assessed the numbers of T, B and natural killer cells, and monocytes and found a small reduction (15-25%) in CD4 + T and CD19 + B cells in PD. These findings suggest some compromise in immune cells in PD and have potential implications for immune function and the progression of PD.