Jean Amiral

Anticoagulant drugs have been used to prevent and treat thrombosis. However, they are associated with risk of hemorrhage. Therefore, prior to their clinical use, it is important to assess the risk of bleeding and thrombosis. In case of older anticoagulant drugs like heparin and warfarin, dose adjustment is required owing to narrow therapeutic ranges. The established monitoring methods for heparin and warfarin are activated partial thromboplastin time (APTT)/anti-Xa assay and prothrombin time – international normalized ratio (PT-INR), respectively. Since 2008, new generation anticoagulant drugs, called direct oral anticoagulants (DOACs), have been widely prescribed to prevent and treat several thromboembolic diseases. Although the use of DOACs without routine monitoring and frequent dose adjustment has been shown to be safe and effective, there may be clinical circumstances in specific patients when measurement of the anticoagulant effects of DOACs is required. Recently, anticoagulation therapy has received attention when treating patients with coronavirus disease 2019 (COVID-19). In this review, we discuss the mechanisms of anticoagulant drugs—heparin, warfarin, and DOACs and describe the methods used for the measurement of their effects. In addition, we discuss the latest findings on thrombosis mechanism in patients with COVID-19 with respect to biological chemistry.

Introduction: This review concerns biomarkers of blood activation and their measurement in plasma, as described in literature up to 2019, and from our personal experience. How their measurement can be informative and useful, for research studies or for diagnostic applications, is presented and discussed. Areas covered: Biochemistry and regulation of blood clotting cascade were elucidated these past decades. Understanding the various molecular mechanisms which initiate, amplify and propagate coagulation has allowed measuring biomarkers as early indicators of hemostasis activation. They present a high usefulness for detecting hemostasis and fibrinolysis abnormalities in the clinically silent period. Sophisticated technologies are necessary for their measurement, as biomarkers are present at very low concentrations (from 1.0 µg/ml). Expert opinion: Many analytes provide useful information for pathological evolution and disease severity, but only DDimer has entered routine applications. Limitations of biomarkers concern their short half-lives, their low plasma concentration, and their rapid variations. DDimer escapes these limitations and has become the biomarker of choice for ruling out DVT and PE and has increasing applications for adjusting anticoagulation or predicting diseases. Promising emerging biomarkers concern cell releasable proteins, extra-cellular vesicles, activated blood cells and cell aggregates, pathological metabolites and degradation products.