Guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists, Annex 6, TRS No 979

Overview

Oral anticoagulant drugs derived from 4-hydroxycoumarin (and sometimes from indandiones) are widely used in the treatment and prophylaxis of thrombotic disorders. Coumarin drugs inhibit the biosynthesis of vitamin K-dependent
coagulation factors by the liver. For each patient, the dose of these drugs must be adjusted periodically to ensure that an adequate, but not excessive, degree of anticoagulation is achieved. The adjustments are made on the basis of the results of the prothrombin-time or a similar test on the patient’s blood. The test, which requires reagents called thromboplastins, is controlled by the use of calibrated thromboplastins and plasmas. A procedure for the calibration of thromboplastins using a logarithmic plot of prothrombin times (PTs) has been developed (1) and was described in the report of the fortyeighth meeting of the WHO Expert Committee on Biological Standardization (2). 

The preparation, certification, and use of deep-frozen or lyophilized plasmas for ISI calibration and INR determination has been described as an important adjunct to fresh-plasma ISI calibration (21). The purpose of these Guidelines, which replace the Requirements published in the forty-eighth report of the WHO Expert Committee on Biological Standardization (2), now discontinued, is to take account of the above-mentioned observations and to describe in detail the technical methods currently in use. Modifications to the methodology may give comparable results, but must be validated against the methodology described in these Guidelines.