Scientific Calendar April 2024

Standard coagulation tests, such as activated partial prothrombin time (APTT), prothrombin time (PT) or fibrinogen (Fbg), are conventionally used to assess the patient's coagulation function based on clotting time. Prolonged clotting time alone does not, in most cases, allow conclusions to be drawn about the patient's underlying medical condition without further tests. Rapid diagnosis is often vital for patients in the emergency department or intensive care unit. Thus, it is important to use all available tools for obtaining a timely diagnosis in an efficient and targeted manner. With the clot waveform analysis (CWA) of the Sysmex CS- and CN-Series analysers, the user can record and evaluate not only the clotting time and the transmission curve of the reaction but also track its derivatives, providing information on the acceleration and deceleration of coagulation. This enables full tracing of the patient's clotting process and can serve as an initial indicator of a variety of clinical conditions [1].

The result of the measurement can be evaluated based on the shape of the reaction curve and its derivatives. The calculated parameters maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2), together with their corresponding timings Tmin1, Tmin2 and Tmax2, can also be used in the evaluation [2, 3]. Figure 1 shows an example of an APTT normal waveform on a Sysmex analyser. Trace A corresponds to the clot waveform generated using the intensity of the transmitted light. Trace B is the first derivative of the transmitted light intensity (dT/dt), which reflects the velocity of the coagulation reaction, and trace C is the second derivative of the transmitted light data (d2T/dt2), which reflects the acceleration of the reaction.[4]

This function has great potency and provides many possibilities in diagnostics and in monitoring the therapy of various diseases such as DIC, factor deficiencies, VTE and other clinical conditions.

One notable example of pathologies in which CWA has a clinical application is haemophilia A.

Several researchers have observed that the clot waveform analysis patterns based on APTT in haemophilia A patients differ from those in healthy individuals. In samples obtained from individuals diagnosed with haemophilia, the clotting time was markedly prolonged, accompanied by a significant slowing of the slope of the waveform compared to donor plasma. Accordingly, the values for min1 and min2 were significantly lower compared to the results in healthy patients [3,5].

The severity of haemophilia A depends on the plasma levels of factor VIII; less than 1% are classified as severe, 1-5% as moderate and 5-40% as mild haemophilia. Severe haemophilia is manifested by frequent spontaneous haemorrhages in joints and muscles, resulting in haemophilic arthropathy [6]. The values of CWA parameters, especially min2, diminish in correlation with the clinical severity of haemophilia A. This observation suggests their potential utility as discriminators between clinically severe and non-severe cases and helps with the assessment of clotting function for some haemophilia A patients whose factor level is not corresponding to the clinical severity [5,7].

The following illustration (Fig.2) give examples of how CWA patterns can look in patients with severe haemophilia A compared to healthy donors.