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Blood Res 2022; 57(S1):

Published online April 30, 2022

https://doi.org/10.5045/br.2022.2022048

© The Korean Society of Hematology

Advances in laboratory assessment of thrombosis and hemostasis

Jaewoo Song

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea

Correspondence to : Jaewoo Song, M.D., Ph.D.
Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
E-mail: labdx@yuhs.ac

Received: February 23, 2022; Revised: April 19, 2022; Accepted: April 21, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Technologies in laboratory diagnostics are changing fast with progress in understanding and therapy of diseases. Unfortunately, new analyzers are often needed to be installed in a clinical laboratory to implement such techniques. The demand for new hardware is a bottleneck in improving the diagnostic services for many facilities with limited resources. In this regard, hemostasis laboratories take a slightly different position. Because many in vitro diagnostic tests target the functional aspects of hemostasis, further meaningful information can be obtained from the same analyzers as in current use. Automated coagulometers are good candidates for such further utilization. Clot waveform analysis is a leading example. Behind the simple values reported as clotting time, clotting curves exist that represent the process of fibrin clot formation. Clot waveform analysis examines the clotting curves and derives new parameters other than clotting times. The clot waveform parameters are now in active use in assessing the hemostatic potential of hemorrhagic patients. Clinical application of coagulometers can also be widened by modifying the reagent formulation. For example, the chromogenic factor VIII assay with bovine source reagent compositions has recently been introduced for hemophilia A patients on emicizumab prophylaxis. Also, new immunoturbidimetric functional assays for von Willebrand factor have been developed recently. Thus, new clinically relevant information can be mined from the automated coagulometers that are based on old technology.

Keywords Laboratory technology, Hemostasis, Coagulation, Assay

Article

Review Article

Blood Res 2022; 57(S1): S93-S100

Published online April 30, 2022 https://doi.org/10.5045/br.2022.2022048

Copyright © The Korean Society of Hematology.

Advances in laboratory assessment of thrombosis and hemostasis

Jaewoo Song

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea

Correspondence to:Jaewoo Song, M.D., Ph.D.
Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
E-mail: labdx@yuhs.ac

Received: February 23, 2022; Revised: April 19, 2022; Accepted: April 21, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Technologies in laboratory diagnostics are changing fast with progress in understanding and therapy of diseases. Unfortunately, new analyzers are often needed to be installed in a clinical laboratory to implement such techniques. The demand for new hardware is a bottleneck in improving the diagnostic services for many facilities with limited resources. In this regard, hemostasis laboratories take a slightly different position. Because many in vitro diagnostic tests target the functional aspects of hemostasis, further meaningful information can be obtained from the same analyzers as in current use. Automated coagulometers are good candidates for such further utilization. Clot waveform analysis is a leading example. Behind the simple values reported as clotting time, clotting curves exist that represent the process of fibrin clot formation. Clot waveform analysis examines the clotting curves and derives new parameters other than clotting times. The clot waveform parameters are now in active use in assessing the hemostatic potential of hemorrhagic patients. Clinical application of coagulometers can also be widened by modifying the reagent formulation. For example, the chromogenic factor VIII assay with bovine source reagent compositions has recently been introduced for hemophilia A patients on emicizumab prophylaxis. Also, new immunoturbidimetric functional assays for von Willebrand factor have been developed recently. Thus, new clinically relevant information can be mined from the automated coagulometers that are based on old technology.

Keywords: Laboratory technology, Hemostasis, Coagulation, Assay

Fig 1.

Figure 1.Clotting curve shapes determine the clotting times (prothrombin times here), but not vice versa. The slopes and amplitudes of the clotting curves differ significantly and imply variable coagulation potential. However, the clotting times (prothrombin times here) are the same for all six test samples.
Blood Research 2022; 57: S93-S100https://doi.org/10.5045/br.2022.2022048

Fig 2.

Figure 2.The clotting curve can be differentiated by a numerical method, and the 1st and 2nd derivative curves can be drawn. If the light transmission is read (turbidimetry) for clot detection, the 1st and the 2nd derivative peaks are directed downward (A). Conversely, if scattered light is read (nephelometry), the 1st and the 2nd derivative peaks are directed upward (B).
Blood Research 2022; 57: S93-S100https://doi.org/10.5045/br.2022.2022048

Fig 3.

Figure 3.The clotting time and the CWA parameters present different aspects of a clotting reaction. The clotting curve parameters were collected from randomly selected blood samples referred for PT and APTT. The CWA parameters (|min1| and |min2|) and the clotting times (PT and APTT) were obtained from each plasma sample and dot-plotted on |min1| vs. PT (A), |min2| vs. PT (B), |min1| vs. APTT (C), and |min2| vs. APTT (D) planes. It is apparent by a simple visual ex-amination that both PT and APTT are poorly correlated with |min1| or |min2|. Samples with the same PT or APTT demonstrated a wide range of |min1| or |min2| values.
Blood Research 2022; 57: S93-S100https://doi.org/10.5045/br.2022.2022048

Fig 4.

Figure 4.PT and APTT are technically defined as the time needed for the clotting velocity and acceleration to reach the maximum after adding each reagent to plasma. Thus, PT is the time point of the min1 and APTT of the min2.
Blood Research 2022; 57: S93-S100https://doi.org/10.5045/br.2022.2022048

Fig 5.

Figure 5.VWF:RCO can be automated by replacing platelets of the original VWF:RCO with microparticles. In the method developed by Werfen, ristocetin primed plasma VWF binds glycocalicin. The bound glycocalicin molecules can be detected by anti-glycocalicin-coated microparticles (A). Alternatively, the glycocalicin with a GOF mutation of platelet type VWD can be used without ristocetin, as for the reagent from Siemens (B).
Blood Research 2022; 57: S93-S100https://doi.org/10.5045/br.2022.2022048
Blood Res
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