Monitoring Coumadin-the original oral anticoagulant.

1. David L. McGlasson, MS, MLS(ASCP)CM[⇑][1] 1. 59th Clinical Research Division Laboratory Services, Wilford Hall Ambulatory Service Center, Lackland AFB, TX 1. Address for Correspondence- David L. McGlasson MS, MLS(ASCP)CM, Clinical Research Scientist, 59th Clinical Research Division Laboratory Services, Wilford Hall Ambulatory Service Center, Lackland AFB, TX 78236-9908, 210-292-6555, David.mcglasson{at}us.af.mil 1. Discuss the use of the prothrombin time (PT)/international normalized ratio (INR) for monitoring subjects on the oral anticoagulant Coumadin. 2. Be aware of the relevance of clinical and genetic data (CYP2C9, VKORC1) in predicting Coumadin dosing in subjects requiring different INR ranges. 3. Be knowledgeable of the chromogenic factor X (CFX) assay for monitoring Coumadin in subjects with lupus anticoagulants, transitioning subjects to Coumadin from direct thrombin inhibitors and for accurately following patients with elevated INRs. The prothrombin time (PT) has been the primary screening test for the laboratory evaluation of patients with an acquired or inherited coagulation factor deficiency of what was originally known as the extrinsic or common pathway of coagulation. It is used in conjunction with the international normalized ratio (INR) to monitor oral anticoagulant therapy (OAT) subjects on the oral anticoagulant, Coumadin.1 Tissue factor (TF) in vivo activates the coagulation cascade through the formation of the TF/FVIIa complex. The PT adds a TF/calcium mixture to citrated platelet-poor-plasma (PPP) in vitro to obtain the time for clot formation. There are many variables such as proper specimen collection, multiple reagent/instrument combinations and, most importantly, the sources of thromboplastin, usually rabbit and recombinant tissue factor, selected for the assay.1,2 The INR and Local INR Calibration The commercial thromboplastins vary widely in their sensitivities to Coumadin. Instrumentation differences (photo-optic or mechanical clot detection) may also play a clinically significant role in the performance of the PT/INR assay. With so many variables, providers treating subjects on OAT can be confused when comparing patient results from a number of laboratories using different reagent/instrument combinations. A facility that uses a high sensitivity thromboplastin will generate longer PT results than an assay that uses a low sensitivity thromboplastin. Therefore a subject on OAT may have a PT of 14 seconds with a low sensitivity reagent or 18 seconds with a more sensitive thromboplastin. Hence a subject monitored with insensitive thromboplastins would appear to require a higher dosage of Coumadin to… ABBREVIATIONS: CFX - chromogenic factor X; CLSI - Clinical and Laboratory Standards Institute; CYP2C9 - cytochrome P450; DTI - direct thrombin inhibitor; FII - coagulation factor II (prothrombin); FX - coagulation factor X; GMNPT - geometric mean normal prothrombin time; INR - international normalized ratio; IRP - international reference preparation; ISI - international sensitivity index; LA - lupus anticoagulant; OAT - oral anticoagulation therapy; PGX - pharmacogenetics; PST - patient self-testing; PT - prothrombin time; TTR - time in therapeutic range; VKORC1 - vitamin K epoxide reductase complex subunit 1; WHO - World Health Organization 1. Discuss the use of the prothrombin time (PT)/international normalized ratio (INR) for monitoring subjects on the oral anticoagulant Coumadin. 2. Be aware of the relevance of clinical and genetic data (CYP2C9, VKORC1) in predicting Coumadin dosing in subjects requiring different INR ranges. 3. Be knowledgeable of the chromogenic factor X (CFX) assay for monitoring Coumadin in subjects with lupus anticoagulants, transitioning subjects to Coumadin from direct thrombin inhibitors and for accurately following patients with elevated INRs. [1]: #corresp-1