COAGULATION BIOMARKER
thrombin will have been generated by blood-clotting proteins. While they are helpful in predicting bleeding risk, they provide little insight into the risk of hypercoagulability or the overall haemostatic capacity of the patient.
Understanding thrombin generation Measuring thrombin generation over physiological timescales generates additional clinical information, providing insight into a patient’s global haemostatic status (Fig 1). It has a pivotal role in haemostasis and thrombosis, acting on various cells – in addition to platelets – and playing a role in inflammation. In addition, it inhibits fibrinolysis by activating thrombin-activatable fibrinolysis inhibitor (TAFI). Thrombin is formed in the body 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, which rapidly converts prothrombin into thrombin. Newly formed thrombin is slowly inactivated by the several antithrombins of plasma in a complex and highly regulated system. The ST Genesia is able to achieve a low coefficient of variation (CV) for
400 Velocity index Peak height 300
Area under curve = ETP 200
100 Start tail 0 0 Lag time 5 Time to peak 10 15 Time (min) Fig 1. Diagram showing typical curve depicting TG activation in plasma.
reproducibility and repeatability, and particular attention has been given to temperature control, which is important in accurate TG measurement. Significantly, the pre-analytical stage makes it possible to work directly on normal citrated platelet-poor plasma (PPP) samples, without the need for additives such as corn trypsin inhibitor.
In addition to the ST Genesia, Stago has developed a range of associated reagents: three triggers to explore
Breast cancer is the most common malignant disease worldwide, with women facing a three- to four-fold increased risk of venous thromboembolism
different aspects of haemostasis through TG − the STG-DrugScreen, STG- BleedScreen and STG-ThromboScreen, which includes an assessment of the effect of thrombomodulin. It also offers complete traceability and up to three quality control (QC) levels for genuine quality management, with a reference plasma included for normalising results.
Multicentre HYPERCAN study The efficacy of ST Genesia and TG has already been demonstrated in other diseases. However, this is the first independent study to validate their combined roles in helping to risk-assess patients at high risk of early breast cancer relapse and also to indicate underlying mechanisms of cancer-associated hypercoagulability.8
The investigation was part of the long- running HYPERcoagulation in CANcer (HYPERCAN) study, originally set up in 2012. This ongoing Italian multicentre study is investigating overall cancer- associated hypercoagulability as a predictor both of thrombosis and cancer outcomes.9 The group looked at a specific cohort of 522 high-risk breast cancer patients after they had recently undergone surgery and had been prioritised for adjuvant chemotherapy. Fifty-two healthy women acted as controls. Plasma samples were tested for protein C, free protein S, and TG on the ST Genesia, using the STG- ThromboScreen reagent with and without thrombomodulin (TM).
Stago’s fully automated, standardised ST Genesia thrombin generation analyser. 23
A calibration test was carried out each day of testing. It set three levels of QC (low, normal and high), with a reference plasma to normalise parameters of TG performed in the absence of TM. This reference plasma is included in the
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Thrombin (nM)
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