Next Generation Sequencing of Human Platelet Antigens for Routine Clinical Investigations and Donor Screening.

Human platelet antigen (HPA) genotyping is performed in a number of clinical scenarios, including characterization of immune-mediated thrombocytopenia and provision of HPA-matched platelets. Current gold-standard methods for HPA genotyping utilize single nucleotide variant (SNV) based approaches. This review aims to ascertain if next generation sequencing (NGS) has reasonable grounds to replace SNV-based genotyping for HPA systems. A systematic review was conducted following a comprehensive literature search in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies were subjected to screening based on a defined set of inclusion/exclusion criteria. Study quality, characteristics and results were extracted and a meta-analysis was performed to assess the concordance of HPA genotyping results between NGS and the SNV-based comparators for HPA-1,-2,-3,-4,-5,-15. In total, 3374 potentially eligible articles were identified, only 6 of which were included in the meta-analysis. The pooled proportion agreement for the overall concordance of the 6 included studies was shown to be 0.998, 95%CI [0.995, 0.999], P < .001. The discrepancies between HPA genotypes obtained by the two platforms were due to allele dropout in real-time PCR, thus discordant results were in favor of NGS over SNV-based comparators. Currently available platforms for NGS are not without their limitations, including high upfront and ongoing costs, data management and storage, accurate variant calling and availability of appropriately trained staff. Despite the high level of concordance between NGS and current gold-standard methods, these significant challenges mean that NGS is currently not viable as a stand-alone technique for HPA typing.

The usefulness of a predictive instrument to reduce inappropriate admissions to the coronary care unit.

A mathematical instrument was developed to supplement the diagnostic information available to physicians in the emergency room to improve physicians' diagnostic accuracy in managing patients with acute ischemic heart disease and thereby reduce inappropriate coronary care unit admissions. The instrument was empirically derived and is based on nine clinical, historical, and electrocardiographic predictive variables. Probabilities of acute ischemic heart disease generated by the instrument were given to the house staff in an emergency room during alternate months. Comparison of the control months (455 patients) with the experimental months (401 patients) showed the following: The overall diagnostic accuracy increased from 83% to 91% (P less than 0.005), the overdiagnostic accuracy increased from 51% to 33% (P less than 0.01), and the admission rate to the coronary care unit fell from 26% to 14% (P less than 0.001), while the inappropriate discharge rate from the emergency room did not change, 3% versus 3% (not significant).