[Thromboplastin time, INR reporting and recommendations for anticoagulant therapy].
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We describe a test for LA based on the specific APTT behaviour of LA plasmas when the incubation time with the APTT reagent is increased from 1 to 20 min. "1-10 APTT" test was defined as the difference (s) between results of the APTT performed with 1 and the one performed with 10 min incubation. A test value > 11 s (upper normal limit determined on 134 normal plasmas) was considered positive for a LA. The test distinguished all the LA patients studied (n = 40) from patients with factor VIIIc inhibitors, patients receiving heparin or warfarin therapy and also patients with congenital factor deficiencies, except those with prekallikrein and factor XII deficiencies. The test detected LA in warfarin (n = 3) and in heparin (n = 2) LA anticoagulated patients. Among 195 patients referred for LA screening, the test detected LA in 5 patients with normal standard APTT. This simple test, using a single reagent for screening and confirmatory procedures is sensitive and fairly specific for LA when combined with mixing studies. However, since the test was defined using one APTT reagent, the performances of other reagents have to be assessed.
Hirudin prolongs the APTT when added to normal plasma and the extent of prolongation depends on the type of reagent used. The aim of this study was to compare the dose-response curves of 10 widely used APTT reagents for linearity and parallelism. On each of 10 working days a normal pooled plasma was mixed with increasing amounts of recombinant hirudin (HBW023) ranging from 0 to 5 micrograms/ml and tested for APTT by photo optical coagulometer. Within each working day, clotting times were measured in duplicate and the order of testing with each reagent was changed every day. Results were expressed as ratios of clotting times with hirudin to clotting times without hirudin, and the values plotted against the hirudin concentration on a log-log scale. The dose-response curves for all reagents were linear over 0.3-1.2 micrograms/ml. The reagent-related slopes ranged from 0.225 +/- 0.003 to 0.303 +/- 0.003 (mean +/- SE) and were significantly different. Precision studies indicated that the least sensitive reagent was also the least precise. These findings indicate that the clotting time values obtained for patients treated with hirudin will vary depending on the APTT reagent used.
The factor VIII:C-sensitivity of the aPTT in dogs was investigated for 2 different, commercially available reagents. For this purpose, 45 plasmas with a decreased factor VIII:C-activity, which were collected from haemophilic dogs (n = 10) at variable points of time of a substitution therapy were used. Moreover, by the stepwise addition of a canine factor VIII:C-deficient plasma to a reference pool plasma it was examined whether factor VIII:C-sensitivity could be increased by prediluting the plasma. By use of both reagents all 45 pathological plasmas (factor VIII:C-activity: 1.5-58%, reference values: 63-144%) showed a prolonged aPTT in relation to the respective reference values. The aPTT correlated well with a pathologically decreased factor VIII:C-activity. In conclusion, the aPTT measured with commercially available reagents according to the manufacturers' instruction is a well suited screening test for haemophilia A and monitoring of its therapy in dogs. Predilution of the dog plasma used in the test does not lead to a distinct of the sensitivity. On the contrary, a high dilution leads to a decrease of sensitivity.
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The present investigation examined if the aPTT shows sufficient sensitivity for single factor activities also in cats when measured with the test optimized for humans using a commercial reagent. Comparative measurements were done with different modifications of the aPTT (sample predilution, addition of fibrinogen). Measurements of the aPTT using different methods and the activity of the coagulation factors II, V, X, VIII, IX, XI, and XII were performed in 42 healthy cats in order to determine the reference ranges. The same measurements were done on 21 cat plasmas where at least one of the coagulation factors was diminished in relation to the corresponding reference range. The conventional aPTT reflected the decrease in coagulation factor activity in each of the 21 plasmas by prolongation above the reference range (14.6-24.4 s). The test thus possesses high sensitivity and is a suitable screening test also for the cat. In contrast, in tests with sample predilution the sensitivity was lower (3-4 false negative results). This was probably caused by the distinct increase of the range of the reference values.
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