Global Assay Technology for RBDs
Laboratory assays for RBDs have gone high-tech, with the use of such measures as thromboelastography (TEG) and microfluidicsalso known as "lab-on-a-chip." Standard coagulation assays, including those most commonly used for RBDsthe 1-stage aPTT and PTdo not reflect overall in vivo biology and have other limitations specific to these disorders.17, 18
For instance, the aPTT and PT only provide information on the initial stage of clot formation. Although they do provide a specific biochemical diagnosis, results do not necessarily correlate with the clinical phenotypes of some RBDs.18
With FVII deficiency, only the PT is prolonged. Other tests are normal.19 With FX deficiency, there can be varying test results, depending on the source of thromboplastin used.19
The aPTT may miss a FXI defect, because the lower limit of the normal range is between 60 and 70 IU/dL. Finally, with FXIII deficiency, all standard coagulation assays provide normal results.19
TEG and microfluidics offer alternative approaches for monitoring RBDs. TEG provides a global picture of the coagulation process.20
First described in 1948, its use has increased recently in point-of-care management for perioperative bleeding in cardiac and liver transplantation. For inherited bleeding disorders, it is primarily
used for monitoring response to therapeutic interventions (eg, fibrinogen).20, 21
TEG provides information on clot formation rate, propagation kinetics, fibrin-platelet interaction, and clot firmness and fibrinolysis.20
To date, it has been used to understand the mechanism of action of whole blood clot formation, making it especially useful for investigating the RBDs.18
During standard TEG tracking, the dynamic changes occurring until maximum amplitude of clot formation are of special interest. By calculating the slope at each time point of the coagulation course, a velocity profile of clot formation is achieved (see Figure 1
Microfluidics, another alternative testing approach, has an application for the diagnosis of RBDs. In broad terms, it is the science concerned with the design and construction of microminiaturized devices containing chambers and tunnels through which fluids flow in a controlled manner.17
Small platforms provide the possibility to isolate, purify, manipulate, and transport particles, biomolecules, bacteriophages, cells, or organisms for a simplified, parallel analysis. The goal of this technology is to improve and extend the possibilities of bioassays, cell biology, and biomedical research. The miniaturization process allows for more accurate modeling of physiological situations.
With applications in drug discovery, cell biology, and tissue engineering, microfluidic systems in development can model biological environments and physically mimic biological tissues and organs.17
Its use in diagnosing RBDs is still in its nascency, and its efficacy remains to be seen.