HAEMOSTASIS
is recognised as one of the primary causes of hypercoagulability. It is formed immediately after vessel damage in a complicated series of intricate reactions in which plasma proteins, blood platelets and the vessel wall participate. Tissue factor (TF) initiates a series of interactions between the clotting factors of plasma, leading to the formation of prothrombinase; the latter rapidly converts prothrombin into thrombin.10
Fully automated assay Thrombin generation assays have been around since 1953 and the pioneering work of Oxford scientists Macfarlane and Biggs who first devised a thrombin generation test using a fibrinogen solution.11
In comparison, routine coagulation tests such as PT and APTT reflect only the beginning of the coagulation cascade. These measure clotting time only at the point of clot formation, when less than 10% of total thrombin has been generated by blood-clotting proteins. While they are helpful for predicting general bleeding risk, they provide little insight into the risk of hypercoagulability or the overall haemostatic status of the patient, so essential in major surgery and trauma. However, the pioneer of current TG testing for the routine laboratory
Pseudomyxoma peritonei is an extremely rare, slowly progressive tumour, that affects around two people per million of all ages
started with Professor Olaf Hemker, who developed the original, calibrated semi- automated thrombogram (CAT) assay in 2003. This was based on the continuous measurement of TG through its action on a fluorogenic substrate.12
The use of a calibrator was a step
forward, enabling the amount and activity of the generated thrombin to be measured more accurately. For the first time, it was therefore possible to distinguish normal conditions from hypo- and hypercoagulable states. The involvement of fluorescence in the CAT assay enabled measurement to take place in a cellular milieu such as platelet-rich plasma.
Explaining the challenge, Professor Hemker said: “It took a while before we
realised that the difficult part was not getting a signal out of clotting plasma but getting thrombin concentrations out of the signal. Finally, after some 15 years we have a method that could be used beyond the limited circle of specialised laboratories.” However, although numerous data
were published demonstrating its value, its time-consuming, manual aspects, alongside its potential for pre-analytical variability, as well as lack of standardisation or official validated cut-offs, have severely limited its use in clinical practice. This changed with the arrival of Stago’s ST Genesia, the first fully automated TG analyser for clinical use. As Dr Stanford added: “While I valued the ability to be able to measure thrombin generation, using the CAT was more labour-intensive. Being able to move from running a semi-automated assay to one that is fully automated, with a higher throughput and standardised results was essential for a high-pressure setting like pseudomyxoma peritonei surgery.”
Reproducibility and standardisation
The fully automated ST Genesia combines pre-analytics, diagnostic validation, standardisation and automation. It includes a set of reagents
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