Coagulation | Recent advances hold great promise

Coagulation advances through innovative techniques and AI promise precision in diagnostics and treatment, ensuring personalized patient care.

Coagulation has come a long way since Huang Ti, the Chinese emperor, first described the length of bleeding time around 3000 years ago. It was in the year 1628, when William Harvey scientifically proved blood circula-tion, and in 1905 the phenomenon of coagulation was first put forward by the German scientist Paul Morawitz.

From these early observations of coagulation, modern science has ushered in a new era of breakthroughs in coagulation testing and treatment.

Some of the new developments in coagulation testing are groundbreaking advancements. Firstly, there have been significant improvements in the accuracy and efficiency of coagulation testing methods. Traditional tests, such as the prothrombin time (PT) and activated partial thromboplastin time (aPTT), have been the go-to for diagnosing coagulation disorders. However, newer technologies, like chromogenic assays and genetic testing, have taken center stage.

Coagulation analyzers
The growing prevalence of coagulation disorders has fueled a surge in demand for rapid and dependable diagnostic testing. This trend, coupled with continuous technological advancements, particularly the development of advanced coagulation analyzers, boasting enhanced accuracy and efficiency, is poised to drive substantial growth and innovation in the market. Furthermore, the expanding applications of coagulation analyzers in research institutes and veterinary clinics underscore their versatility and relevance across various domains. Moreover, the introduction of new and innovative blood coagulation testing devices is anticipated to further bolster market demand. As the number of surgical procedures and blood transfusions continues to rise, the need for efficient coagulation testing devices is expected to escalate accordingly, reflecting the critical role they play in ensuring patient safety and optimal clinical outcomes.

Emerging therapeutic approaches
MIT engineers have developed a two-component system, funded by the US Army Research Office and the Department of Defense, designed to aid in the formation of blood clots at sites of internal injury. Consisting of a nanoparticle and a polymer, the system mimics the body’s natural clotting mechanisms, offering a potential solution for managing severe internal injuries until patients can reach a hospital. Testing in mice showed its effectiveness in stopping bleeding, with the two-component system outperforming previous hemostatic nanoparticles.

Research is being done for testing in larger animal models and integrating portable imaging devices for rapid identification of bleeding sites. This represents a significant advancement in coagulation management, addressing the critical need to manage internal bleeding but further studies are needed to ensure its safety and efficacy before potential clinical implementation.

Nanotechnological tool
Blood clotting disorders, characterized by either excessive bleeding or unwanted blood clot formation, are significant contributors to global mortality. However, current methods for monitoring clot formation in human whole-blood ex vivo have limitations. In response, a new magnetic coagulometry platform has been developed, leveraging the sensitivity of the out-of-phase component of alternating current (AC) magnetic susceptibility (X”) to changes in the mobility and agglomeration of magnetic nanoparticles during blood clot formation.

By labeling human whole-blood with magnetic nanoparticles, this platform demonstrates that the dynamics of blood clot formation correlate with a decrease in the out-of-phase component X” over time, reflecting the activation of coagulation. Rapid immobilization and compaction of nanoparticles upon coagulation contribute to this decrease. Interestingly, the system shows sensitivity to the effects of various anticoagulant drugs, including direct oral anticoagulation (DOAC) drugs, which are not efficiently monitored by current clinical tests, such as prothrombin time (PT) and partial thromboplastin time (PTT).

The proposed magnetic coagulometry method combines AC magnetic susceptometry with purpose-designed iron oxide nanoparticles (IONPs) to monitor blood coagulation in whole human blood ex vivo. By labeling freshly donated human blood with these nanoparticles, the effects of antithrombotic drugs can be assessed by measuring the out-of-phase component of AC magnetic susceptibility.

This innovative approach gives new possibilities for whole-blood coagulation testing and addresses current limitations in existing methods, potentially enhancing diagnostic efficiency and clinical outcomes in the management of blood clotting disorders.

Potential impact of POC testing
Point-of-care (POC) testing is rapidly emerging as the gold standard in hemostatic management, driven by an increasing demand for rapid and accurate tests, coupled with advancements in technology. The expansion of POC hemostatic tests has significantly broadened the spectrum of available tests and increased the number of tests performed, offering a vital tool in the management of coagulation disorders.

Viscoelastic POC techniques, grounded in thromboelastography, offer valuable insights into clot formation dynamics, solidity, and stability over time. These tests are particularly advantageous in acute scenarios, such as trauma-induced coagulopathy, transfusion management, and intra- and postoperative bleeding.

One notable advantage is the ability to directly detect hyperfibrinolysis, a capability lacking in conventional coagulation tests. Moreover, viscoelastic tests utilize whole-blood samples, resembling in vivo hemostasis more closely than conventional laboratory tests.

Despite these advantages, further development is warranted, particularly in enhancing the accuracy and sensitivity of tests through advances in sensor technology. Challenges, such as the cost of reagents and complexity of use in some healthcare settings, underscore the need for ongoing refinement.

Platelet Function Tests (PFTs) are pivotal for assessing platelets function in hemostasis. While light transmission aggregometry has long been the gold standard, its cumbersome protocol has led to the development of several POC devices. These devices assess platelet aggregation response to specific agonists, such as ADP, collagen, and thrombin.

However, current clinically available POC PFTs have limitations, often relying on specific agonist-induced platelet aggregation, using citrate-anticoagulated blood under static conditions. Physiological factors, such as high flow, shear, and locally-generated thrombin are often overlooked. To better reflect physiological processes, POC tests should assess non-anticoagulated blood at high shear, capturing the dynamics of thrombus formation, platelet reactivity, thrombus stability, and endogenous thrombolysis rates.

Transformative potential of AI in coagulation
The transformative potential of artificial intelligence (AI) in coagulation management is substantial and promises to revolutionize patient care. With AI algorithms continually advancing, their application in coagulation presents numerous benefits. AI’s ability to analyze vast datasets rapidly, predict patterns, and identify patient-specific trends can significantly enhance diagnostic accuracy and treatment outcomes.

One notable application of AI in coagulation is its role in optimizing the management of anticoagulant therapies, such as warfarin and direct oral anticoagulants (DOACs). Through machine learning techniques, AI can predict suboptimal anticoagulation control, identify patients at risk of adverse events, and recommend personalized treatment strategies.

Additionally, AI-powered mobile applications enable real-time monitoring of medication adherence in stroke patients on DOACs, improving patient compliance and reducing the risk of stroke or bleeding.

Furthermore, AI-driven tools like AICute offer clinicians a rapid and accurate assessment of stroke risk, associated with heart disease, facilitating timely interventions and enhancing patient outcomes.

In the diagnosis of complex conditions like antiphospholipid syndrome (APS), AI-based neural networks demonstrate high sensitivity and specificity, enabling precise identification of affected individuals from healthy subjects.

Embracing AI technologies in coagulation testing and therapy monitoring represents a significant step forward in advancing healthcare delivery and enhancing patient well-being.

In recent times, novel oral anticoagulants (NOACs) have emerged as an alternative to the traditionally used Vitamin K oral antagonists (VKA) like warfarin for the treatment of atrial fibrillation (AF). NOACs that have a fixed dosing regimen with less monitoring required are more effective with a lower risk of bleeding complications, and have more predictable pharmacokinetics and pharmacodynamics compared to warfarin.

This integration of AI with NOAC therapy holds promise for optimizing anticoagulation control and improving patient outcomes.

Outlook
The innovative techniques emerging in coagulation management, coupled with the transformative potential of AI, herald a new era of precision and efficiency in healthcare. These advancements promise not only improved diagnostic accuracy and treatment outcomes but also personalized care plans tailored to individual patient needs.