COAGULATION BIOMARKER


Hypercoagulability and cancer: a thrombin generation analyser role


Results of a recent clinical study using a fully automated, standardised thrombin generation analyser have shown that it is possible to identify breast cancer patients who are at high risk of disease recurrence.


with thrombosis the second leading cause of death after the disease itself.2,3 Breast cancer is the most common malignant disease worldwide, with women facing a three- to four-fold increased risk of VTE compared to those of the same age without the disease.4


A diagnosis of cancer increases the risk of venous thromboembolism (VTE) for all patients, accounting for up to 20% of cases,1


Cancer-associated


hypercoagulability is also linked to a greater chance of early disease recurrence (E-DR).5


Survival too is reduced,6 even


when prognosis would otherwise be relatively good.


One imperative for clinical research has been to find more-accurate prognostic cancer biomarkers, especially for high-risk patients. A recent prospective study charts significant progress in E-DR by validating


the role of thrombin generation (TG), and its measurement, when using the fully automated, standardised TG analyser, Stago’s ST Genesia.7,8


The Stago analyser has enabled the study


to confirm the significance of endogenous thrombin potential (ETP) as a potential biomarker for use during chemotherapy, supporting its inclusion in a diagnostic model to predict E-DR. Furthermore, clinicians have been able to devise a risk assessment score assigning patients to one of three categories, with likely outcome benefits for high-risk patients.


Automated continuous TG measurement


The original Calibrated Automated Thrombogram (CAT) assay was developed by Professor Hemker in 2003 and is based


on the continuous measurement of TG through its action on a fluorogenic substrate. As thrombin has been known to have multiple roles in the regulation of the coagulation cascade, it was already recognised that measurement of TG might aid in predicting E-DR. The CAT assay made it possible to distinguish normal conditions from hypo- and hypercoagulable states. However, this is only available as a partially automated assay and risks pre-analytical variability. The time- consuming, manual aspects, alongside a lack of standardisation and no official validated cut-offs, have severely limited its use in clinical practice (Table 1). Thrombin generation assays have been


around since 1953 following the pioneering work of the Oxford scientists Macfarlane and Biggs, who first devised a thrombin generation test using a fibrinogen solution. Routine coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (APTT) reflect only the beginning of the coagulation cascade. They measure clotting time only at the point a fibrin clot is formed, when less than 10% of total


Table 1. The same parameters and their results run using both a CAT system and ST Genesia. The STG-Ref Plasma is useful for improving laboratory-to-laboratory assay reproducibility and standardisation.


CAT system PPP-reagent LOW Normalised CV (%) Lag time (min)


Time to peak (min) ETP (nM.min)


Peak height (nM) Velocity index (nM.min) ETP: endogenous thrombin potential WWW.PATHOLOGYINPRACTICE.COM APRIL 2021 22


External Ref Plasma from Stago 8 7


10 17 27


3.6 9.0


1167 108 20


ST-Genesia STG-BleedScreen


Robust mean Normalised CV (%) (n=34)


STG-Ref Plasma 3.1 3.7 3.2 6.3


11.4


Robust mean (n=10)


2.44 5.86 774 94.1


38.02


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