Wondfo Academy

At the conclusion of the landmark ISTH2024 conference, the echoes of innovation in thrombosis and hematology continue to resonate. The event showcased cutting-edge technology that is redefining the diagnostics and treatment of blood disorders, offering a glimpse into a future where precision and efficiency in patient care are paramount.

Activated Partial Thromboplastin Time (APTT) is a crucial diagnostic test widely used to evaluate the coagulation pathways, particularly the intrinsic and common pathways. It plays a pivotal role in diagnosing various bleeding and thrombotic disorders, monitoring anticoagulant therapy, and identifying potential coagulation factor deficiencies.

Impact of Haemolysis on APTT
Haemolysis, the rupture of red blood cells, can significantly interfere with APTT results, leading to inaccurate clotting times. This interference arises from the release of cellular components, such as tissue factor (TF) and platelet factor 4 (PF4), which activate the coagulation cascade.
A study investigating the impact of haemolysis on APTT compared haemolysed samples (HLS) with non-haemolysed samples (NHLS) from the same patients [1]. The results indicated that haemolysis caused clinically significant differences in APTT and one-stage clotting assays (OSCA). Elevated PF4 levels were observed in HLS, confirming in vitro platelet activation. However, the study found no statistically significant differences in factor VIIa (FVIIa) concentrations. These findings underscore the importance of rejecting haemolysed samples for accurate APTT and OSCA results.

APTT in Anticoagulation Therapy Development
Venous thromboembolism, comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant cause of morbidity and mortality worldwide. Traditional anticoagulant therapies, while effective, pose a risk of bleeding complications. Recent advancements have explored targeted anticoagulation strategies, such as antibody-drug conjugates (ADCs).
One innovative application of APTT is demonstrated in the development of a novel antibody-drug conjugate (ADC) for targeted anticoagulation therapy. An ADC combining a highly specific anti-fibrin antibody with the direct thrombin inhibitor, hirudin, was developed to concentrate within fibrin-rich thrombi, thus requiring a lower systemic concentration to achieve effective anticoagulation. Among the five ADC molecules tested, ADC-hir10 showed a significant anticoagulant effect, reaching 65% of the efficacy of an equivalent dose of hirudin in the APTT assay[2]. This result underscores the potential of APTT as a reliable method for screening and evaluating new anticoagulant agents by measuring their ability to prolong clotting times and comparing their effectiveness to established anticoagulants.

APTT and Clot Waveform Analysis (CWA) in Acquired Haemophilia A (AHA)
Acquired haemophilia A is a rare but severe bleeding disorder characterized by the presence of autoantibodies against factor VIII (FVIII). Traditional APTT testing, while useful, may not fully capture the complexity of the disorder.
Clot waveform analysis (CWA) is a recently developed global coagulation assessment, based on the continuous observation of changes in light transmittance, absorbance, or light scattering that occurs as fibrin formed in a plasma sample during routine clotting tests such as APTT and prothrombin time (PT) [3]. The CWA derivative curves displayed abnormal patterns, such as shouldering and biphasic shapes, which correlated with the clinical course of the disease [4]. These atypical curves normalized with treatment and reappeared upon relapse, highlighting their potential utility in monitoring disease progression and treatment response. In conclusion, CWA will enhance the diagnostic capability of APTT by analyzing the dynamic changes in clot formation.

Conclusion
The research presented at ISTH 2024 highlights the critical role of APTT in modern hematology and underscores the importance of continued innovation and rigorous evaluation in the field. As we refine these diagnostic and therapeutic approaches, the potential for improved patient care and outcomes in thrombotic and bleeding disorders becomes increasingly attainable.

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Thrombus Testing
Novel thrombosis biomarker —— TAT . PIC . TM . t-PAIC . FDP . D-Dimer (CLIA) performed on FC-2100 & Accre8

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Thromboelastography —— TLT-101

Coagulation tests —— OCG-102

Reference

[1] https://isth2024.eventscribe.net/fsPopup.asp?PresentationID=1433079&mode=presInfo

[2] https://isth2024.eventscribe.net/fsPopup.asp?efp=R0tKSkNBT0ExNjMzNg&PresentationID=1432527&rnd=0.7634202&mode=presInfo

[3] Nogami, Keiji. “Clot Waveform Analysis for Monitoring Hemostasis.” Seminars in thrombosis and hemostasis vol. 49,6 (2023): 592-599. doi:10.1055/s-0042-1756706

[4] https://isth2024.eventscribe.net/fsPopup.asp?PresentationID=1432112&mode=presInfo

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