Monitoring the new antithrombotic drugs.
Today there is a diverse group of anticoagulant and antithrombotic drugs available that includes warfarin derivatives, heparin, low-molecular-weight heparins, thrombin inhibitors, factor Xa inhibitors, and various antiplatelet agents. Many of these new drugs do not alter measurable blood coagulation parameters, yet they are effective antithrombotic agents through their actions on vascular endothelial cells and proteins. Thus, these new agents do not affect the traditional clot-based prothrombin time/International Normalized Ratio (PT/INR) and activated partial thromboplastin time (aPTT) tests, and monitoring and standardization require the development of new methods. In addition to clot-based assays, chromogenic assays, enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), flow cytometry, and other techniques have been used to monitor these new drugs. On the other hand, some of the new antithrombotic drugs do affect the PT, aPTT, and activated clotting time (ACT); however, they behave differently from the warfarin derivatives and heparin. The traditionally used relationship of target time to clot values and INR to clinical effect cannot necessarily be transferred to the new drugs. Unfortunately, monitoring is not as simple as it was for warfarin and heparin. Although the new antithrombotic drugs have been approved for clinical use, assay systems for monitoring most of them are still in development or have not been clinically validated. This applies to each of the clinical settings targeted for prophylaxis, treatment, or interventional procedures (i.e., high- and low-dosing regimens typically require different monitoring methods). In addition to basic monitoring, other issues such as sensitivity of the drug to different laboratory monitoring reagents and instrumentation, drug combination monitoring, and patient-related factors that contribute to the variability of the results still need to be addressed.
Walenga
Jeanine M
JM
Department of Thoracic and Cardiovascular Surgery, Loyola University Chicago, Maywood, Illinois, USA. jwaleng@lumc.edu
Hoppensteadt
Debra A
DA
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods*; D004730:Endothelium, Vascular / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005434:Flow Cytometry / Q000379:methods; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods; D008954:Models, Biological; D010314:Partial Thromboplastin Time / Q000379:methods; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011517:Prothrombin Time / Q000379:methods; D012680:Sensitivity and Specificity; D013925:Thromboplastin / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology
D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D006493:Heparin; D013925:Thromboplastin