The Reevaluation of Thrombin Time Using a Clot Waveform Analysis.

Hideo Wada,Yuhuko Ichikawa,Motomu Shimaoka,Katsuya Shiraki,Minoru Ezaki,Yoshiki Yamashita,Hideto Shimpo,Takeshi Matsumoto

doi:10.3390/jcm10214840

Hideo Wada, Yuhuko Ichikawa + Show 6 more

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https://doi.org/10.3390/jcm10214840

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Abstract

Object: Although thrombin burst has attracted attention as a physiological coagulation mechanism, clinical evidence from a routine assay for it is scarce. This mechanism was therefore evaluated by a clot waveform analysis (CWA) to assess the thrombin time (TT). Material and Methods: The TT with a low concentration of thrombin was evaluated using a CWA. We evaluated the CWA-TT of plasma deficient in various clotting factors, calibration plasma, platelet-poor plasma (PPP), and platelet-rich plasma (PRP) obtained from healthy volunteers, patients with thrombocytopenia, and patients with malignant disease. Results: Although the TT-CWA of calibration plasma was able to be evaluated with 0.01 IU/mL of thrombin, that of FVIII-deficient plasma could not be evaluated. The peak time of CWA-TT was significantly longer, and the peak height significantly lower, in various deficient plasma, especially in FVIII-deficient plasma compared to calibration plasma. The second peak of the first derivative (1st DP-2) was detected in PPP from healthy volunteers, and was shorter and higher in PRP than in PPP. The 1st DP-2 was not detected in PPP from patients with thrombocytopenia, and the 1st DP-2 in PRP was significantly lower in patients with thrombocytopenia and significantly higher in patients with malignant disease than in healthy volunteers. Conclusion: The CWA-TT became abnormal in plasma deficient in various clotting factors, and was significantly affected by platelets, suggesting that the CWA-TT may be a useful test for hemostatic abnormalities.

Highlights

It is well known that thrombin directly activates fibrinogen to generate fibrin formation [1]
Thrombin activates many coagulation factors in the upper stream, such as clotting factor XI (FXI), FVIII, Factor X, and Factor V, resulting in thrombin generation to enhance coagulation reaction, a process known as thrombin burst [2,3]
The clot waveform analysis (CWA)-thrombin time (TT) in plasma deficient of various clotting factors showed prolonged peak time, and decreased peak height. These findings suggest that various clotting factors are required for the coagulation system involving thrombin burst induced by a small amount of thrombin [4,14]

Summary

Introduction

It is well known that thrombin directly activates fibrinogen to generate fibrin formation [1]. Thrombin activates many coagulation factors in the upper stream, such as clotting factor XI (FXI), FVIII, Factor X, and Factor V, resulting in thrombin generation to enhance coagulation reaction, a process known as thrombin burst [2,3]. The thrombin time (TT) is generally used to detect abnormalities of fibrinogen, such as dysfibrinogenemia [4,5], disseminated intravascular coagulation (DIC) [6], and liver dysfunction [7]. The TT is used to measure fibrinogen concentrations [8]. Thrombin burst has generally been evaluated by thromboelastography (TEG) [10] and the thrombin generation test (TGT) [11,12]

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