Background: Clot waveform analysis (CWA) has been reported to extend the interpretation of clotting time measurement. To date, effect of coagulation factor deficiencies and that of pharmacological anticoagulation have been quantitatively assessed by decrease in peak values in successive derivatives of the clotting reaction curves. In addition, abnormal waveforms have been reported to appear in patients with coagulation disorders or on warfarin therapy.

Aims: To make comparison between deficiency of coagulation factors and pharmacological inhibition of activated coagulation factors using CWA.

Methods: The samples of coagulation factor deficiency were prepared by adding normal pooled plasma to each factor deficient plasma (i.e., factor II, V, VIII, IX, X, XI and XII). The samples of pharmacological inhibition were prepared by spiking normal plasma with various anticoagulants. APTT measurement and APTT-CWA were performed using various APTT reagents and automated blood coagulation analyzers, CS5100 and CN6000 (Sysmex).

Results: Abnormal waveforms in first derivative curves were observed more clearly with decreasing activity of each coagulation factor except for factor II. The abnormality exhibited two patterns, i.e., the steepness of the first derivative curve changed either before or after reaching the peak. APTT reagents seemingly affected such appearances. The abnormal waveforms were not observed in plasma spiked with any anticoagulants. The parameters of CWA, i.e., maximum velocity, maximum acceleration, and maximum deceleration, appeared to make a hyperbolic curve with upward convex to drop to zero, dependently on decreasing coagulation factors. This feature is distinct from features of plasma spiked with anticoagulants.

Conclusions: The abnormal waveforms were induced by impaired usage of substrates (i.e., coagulation factors) but not by impaired usage of enzymes (i.e., activated coagulation factors). The appearance of abnormal waveforms potentially distinguishes coagulation abnormalities. Thus, findings obtained through CWA would provide insights into coagulopathy and anticoagulation.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/comparison-between-coagulation-factor-deficiencies-versus-pharmacological-inhibition-of-activated-coagulation-factors-using-clot-waveform-analysis/