ABSTRACT
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.
Subject(s)
Blood Platelet Disorders , Platelet Aggregation , Anti-Inflammatory Agents, Non-Steroidal , Aspirin/pharmacology , Blood Platelet Disorders/diagnosis , Clopidogrel/pharmacology , Humans , Pilot Projects , Platelet Function Tests/methodsSubject(s)
Bacterial Infections , Endocarditis, Bacterial , Endocarditis , Gram-Positive Bacterial Infections , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/diagnosis , Enterococcus , Enterococcus faecalis , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/diagnosis , Humans , Liver Cirrhosis/complicationsSubject(s)
Leukemia, Myeloid, Acute/complications , Wolman Disease/complications , Adult , Bone Marrow/pathology , Female , Humans , Karyotype , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Point Mutation , Wolman Disease/diagnosis , Wolman Disease/genetics , Wolman Disease/pathology , Wolman DiseaseABSTRACT
Somatic malignant transformation of germ cell tumours is a well-described but poorly understood phenomenon. It is characterized by differentiation of pluripotent teratoma cells into somatic tumour cells. Following malignant transformation, the most common histologies are sarcomas and primitive neuroectodermal tumours; however, other subtypes have been recognized including melanoma, leukaemia, and renal cell carcinoma. We report a case of a 38-year-old male who had recently completed treatment for a mediastinal germ cell tumour with teratomatous components. He presented several months after completion of chemotherapy with metastatic lesions in his spine and liver accompanied with severe pancytopenia. He was subsequently diagnosed with acute megakaryoblastic leukaemia (AMKL), and a biopsy of a liver lesion was consistent with metastatic melanoma. This case illustrates the simultaneous development of 2 rare malignant entities: mediastinal germ cell tumour-associated AMKL and somatic malignant transformation to melanoma. It also highlights the importance of close surveillance to detect these metastatic sequelae and the emerging role of tumour sequencing to establish targetable pathways.
