Performance of Prothrombin-Proconvertin Time as a Monitoring Test of Oral Anticoagulation Therapy

Abstract

P e r f o r m a n c e o f P r o t h r o m b i n -P r o c o n v e r t i n T i m e a s a M o n i t o r i n g T e s t o f O r a l A n t i c o a g u l a t i o nT h e r a p y Oral anticoagulation therapy (OAT) with vitamin K antagonists (VKA) is most commonly monitored with the prothrombin clotting time (PT), which is sensitive to decreases in activity of any of the v i t a m i n K-dependent coagulation factors (F), II, VII, or X, as well as to decreases in fibrinogen or coagulation factor V (FV). 1 In the past, the PT was usually reported as a ratio of patient to control plasma clotting times (PT-ratio), but a system of international standardization was developed because of variability in clotting times obtained with different thromboplastins and variability in the methods of reporting the results. Accordingly, for the purpose of OAT control, PT results are now generally reported as international normalized ratios (INRs), 2 ' 3 ie, PT ratios are transformed to the ratio that would have been obtained if a standard reference thromboplastin preparation with an assigned international sensitivity index (ISI) of 1.0 had been used. 2,3When the PT is not done on fresh samples, a prolongation of the clotting time may occur from ex vivo factor V degradation (if plasma is stored at room temperature for more than 6 hours), whereas artifactual shortening may occur because of cold activation of FVII if plasma is stored at 4°C. 4 One way to circumvent these problems is to apply the prothrombin-proconvertin time (PP or P&P) on plasma kept at room temperature. The PP is a modified PT that is only sensitive to changes in FTJ, FVII, and FX because addition of adsorbed bovine plasma to the thromboplastin supplies the test mixture with optimal amounts of fibrinogen and FV for clot formation.5 When the PP is done on dilute patient plasma, it is also insensitive to direct anticoagulants, such as the lupus anticoagulant or heparin.6 ' 7 The PP results traditionally have been reported as the percentage of total coagulant activity of HI, FVII, and FX based on a dilution curve of normal plasma and not as clotting time ratios (or INR). This complicates the interpretation of anticoagulation intensity in relation to PT-based results and may be one reason for the decreasing use of the PP as a monitoring device. Also, although the PP is derived from the PT, clinical studies using the INR calculated directly from the PP are lacking. In clinical studies using the PP, conversions to INR have 672 Downloaded from https://academic.oup.

Warfarin anticoagulation intensity in specialist‐based and in computer‐assisted dosing practice

“…In a study conducted 14 years ago, we confirmed that (as shown by others for the PT‐based INR) the risk of major haemorrhage was highly dependent on the INR‐calculated based on the P&P test, i.e. one in 118 treatment years when the INR was <4.5 vs. one in every 73 treatment days when the INR was >6.0 (Haraldsson et al. , 1997).…”

“…The risk of bleeding increases markedly when the anticoagulation intensity is over 5.0 (European, 1995) or over 6.0 (Cannegieter et al. , 1995; Haraldsson et al. , 1997).…”

“…The clotting times were measured during both periods with the P&P test and the INR was calculated as previously described (Haraldsson et al. , 1997).…”

“…, 1997). In 1992, the P&P test was measured on 3.8% (0.129 m ) sodium‐citrated plasma using the Simplastin A ® (Organon Teknika, Durham, NC, USA) with manufacturer‐assigned thromboplastin international sensitivity index (ISI) of 1.1 for the optical instrument used (Cobas Fibro, Hoffman‐LaRoche, Basel, Switzerland; Haraldsson et al. , 1997).…”

“…, 1982; Kirkwood, 1983; Gogstad et al. , 1986; Haraldsson et al. , 1997; Horsti, 2002; Hillarp et al.…”