Thomas B. Givens

Classification of factor deficiencies from coagulation assays using neural networks

Activated partial thromboplastin time (APTT) and prothrombin time (PT) assays are widely used to screen for coagulation disorders and to monitor administration of therapeutic drugs. The analysis of data from coagulation assays has traditionally concentrated on determination of clot times (for APTT and PT) and magnitude of signal change during coagulation (e.g. for PT-based fibrinogen quantitation). The purpose of this study was to determine if the diagnostic power of these assays could be increased by using neural networks to interpret multiple parameters from these assays. Error back-propagation neural networks were trained using multiple variables derived from APTT and PT optical data for 200 normal and abnormal patient specimens. These networks were used to: (1) classify samples as either deficient or non-deficient with respect to individual blood components; and (2) estimate the approximate concentration of specific coagulation factors. Results indicated that these networks could be successfully trained to identify specific factor deficiencies at less than 30% normal levels with good specificity and variable sensitivity, but that they estimated actual concentrations poorly in most cases. These results support possible applications for neural networks identifying specific coagulation abnormalities from non-specific APTT and PT assays using expanded data parameter sets.

PREDICTING THE PRESENCE OF PLASMA HEPARIN USING NEURAL NETWORKS TO ANALYZE COAGULATION SCREENING ASSAY OPTICAL PROFILES

A method for predicting the presence of heparin from coagulation screening assays is described and data are presented. This method incorporates the use of a multilayer perceptron trained through an error back-propagation algorithm in analyzing clotting optical data profiles. This method may lead to the identification of abnormalities from screening assays that might otherwise go undetected, or require additional testing to isolate.

A Novel Device for the Evaluation of Hemostatic Function in Critical Care Settings.

Major surgical procedures often result in significant intra- and postoperative bleeding. The ability to identify the cause of the bleeding has the potential to reduce the transfusion of blood products and improve patient care. We present a novel device, the Quantra Hemostasis Analyzer, which has been designed for automated, rapid, near-patient monitoring of hemostasis. The Quantra is based on Sonic Estimation of Elasticity via Resonance Sonorheometry, a proprietary technology that uses ultrasound to measure clot time and clot stiffness from changes in viscoelastic properties of whole blood during coagulation. We present results of internal validation and analytical performance testing of the technology and demonstrate the ability to characterize the key functional components of hemostasis.

Optimising assay sequence on automated coagulation instrumentation

An embedded knowledge-based system has been developed to determine the optimum sequence for assays performed on a random access coagulation analyser. This knowledge base is in the form of a set of rules describing penalties associated with certain sequences of assays. The optimisation of assay sequences increases throughput and reduces consumption of cleaning solutions and generation of waste. A flexible design also facilitates updates to the knowledge base as assays are modified and added in the future.

Improvements in accuracy and reproducibility of quantitative clotting factor assays by use of a novel approach for modeling reference curves

A method for creating a reference model in the quantitative assay of specific clotting factor activities is described. This method incorporates the use of a piecewise function with two component polynomials. This function allows more accurate representation of the global coagulation reaction, a sequential activation of multiple serine protease enzymes and cofactors, leading to improvements over traditional methods in range, accuracy, precision and robustness in reported activity levels. Clotting factor assay results using this method are compared with traditional and other candidate methods.