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Prediction of vitamin K response using the Echis time and Echis-prothrombin time ratio.

Echis carinatus venom contains proteases capable of activating both normal and descarboxy prothrombin. We showed this venom (Sigma) principally activates prothrombin with almost no factor X activation. Echis time in combination with prothrombin time can predict vitamin K responsiveness since the Echis time is usually normal in the presence of descarboxy prothrombin associated with vitamin K deficiency. 38 patients with abnormal routine prothrombin times (PT) had both coagulant and immunogenic factor II assays along with Echis times done before and after vitamin K. Of 22 patients responding to vitamin K, based on correction of PT, 21 had normal initial Echis times and of 16 not responding, 11 had abnormal Echis times, giving a sensitivity of 95.4% and specificity of 68.8% for vitamin K responsiveness. 90% of patients with a PT/Echis time ratio less than 1.3 and a prolonged Echis time did not correct their PTs with vitamin K therapy. The 5 non-responders with normal Echis times all showed normal initial coagulant and antigenic prothrombin, but 3 had low F V and/or F VII.

Blood Coagulation Disorders↗

Aprotinin prolongs whole blood activated partial thromboplastin time but not whole blood prothrombin time in patients undergoing cardiac surgery.

Aprotinin is being used increasingly to limit cardiopulmonary bypass (CPB)-induced coagulation derangements. Since whole blood prothrombin time (PT) and activated partial thromboplastin time (APTT) assays are beneficial in the treatment of bleeding after CPB, we studied the potential effect of aprotinin on these whole blood assays. Blood specimens from 151 cardiac surgical patients were obtained in two phases: prior to heparin administration, before CPB, and subsequent to heparin neutralization after CPB. After collection, blood specimens were divided into two aliquots and mixed with either normal saline (NS) or aprotinin (A, 200 or 400 Kallikrein inhibiting units (KIU)/mL). Whole blood specimens were used to measure whole blood PT and APTT using CoaguChek Plus instruments. Whole blood PT results were similar between normal saline. (NS)- and aprotinin-spiked specimens before CPB (A, 12.9 +/- 1.5s; NS, 12.8 +/- 1.5s; P = 0.76) and after CPB (A, 17.5 +/- 2.4s; NS, 17.7 +/- 2.4s; P = 0.58). In contrast, whole blood APTT results were prolonged in aprotinin-spiked specimens prior to CPB (A, 63.3 +/- 32.2s; NS, 38.6 +/- 16.3s; P < 0.0001) and after CPB (A, 65.9 +/- 23.7s; NS, 45.7 +/- 14.4s; P < 0.0001). A dose-dependent prolongation of whole blood APTT by aprotinin was demonstrated by a greater mean difference in APTT (P = 0.0001) between specimens spiked with NS or 200 KIU (17.5 +/- 12.2s) vs 400 KIU (27.8 +/- 21.5s) of aprotinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of a new chromogenic substrate assay for the measurement of the prothrombin time.

The chromogenic prothrombin time assay Nycotest Chrom was evaluated and compared with another chromogenic assay (Chromoquick) and with the well-known coagulometric Thrombotest. The intra-assay variation of the test was satisfying both in the normal range (CV = 3.6%) and in the therapeutical range of oral anticoagulation (CV = 3.5%). These values were somewhat higher than those of the Chromoquick test (1.3% and 1.1%) and those of the Thrombotest (2.3% and 2.5%). The inter-assay variation coefficient amounted to 3.3% in the normal range and in the therapeutical oral anticoagulation range to 4.4%. The respective values for the Chromoquick test were somewhat lower (2.2% and 3.9%), those of the Thrombotest in the normal range were also lower (2.1%), and in the therapeutical range they were much higher (9.2%). The coefficients of correlation of the Nycotest Chrom test in the therapeutical range were highest when comparing them with those for the Chromoquick test (r = 0.97; p < 0.0001) and somewhat lower in comparison with the Thrombotest (r = 0.95; p < 0.0001). The results of the three methods paralleled also in the starting phase of oral anticoagulation treatment. Storage at 4 degrees C and at 25 degrees C showed good stability of the Nycotest Chrom reagent for up to 24h. We conclude that the Nycotest Chrom assay is well suited for the measurement with a centrifugal fast analyser, which is attractive on behalf of the usually large series of request for prothrombin time measurements when monitoring oral anticoagulation therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Warfarin therapy. The effect of heparin on prothrombin times.

Sharp decreases in the prothrombin time after discontinuing heparin have been reported in patients undergoing oral anticoagulant therapy. Twenty-five patients receiving continuous intravenously administered heparin and orally or intravenously administered warfarin were studied. All patients had prothrombin times greater than 1.40 times control, and activated partial thromboplastin times 1.5 to three times control before discontinuing heparin therapy. Prothrombin times on the heparin infusion and four to six hours after it was discontinued were compared. The mean change in the prothrombin time was -1.60 s with a range of +0.8 to -5.5 s. Eight (32%) of 25 patients had a decrease of greater than 2 s. The decrease in prothrombin time correlated poorly with heparin dose or activated partial thromboplastin time in patients taking heparin. Since the change in prothrombin time is unpredictable, a repeated prothrombin time is recommended after stopping heparin therapy prior to discharging a patient.

Adult↗

Warfarin anticoagulation: difficulties in interpretation of the prothrombin time.

Studies of the prothrombin time in normals and patients receiving warfarin therapy revealed a marked shortening of the prothrombin time when the blood was collected in any type of collection tube other than a polypropylene tube. This shortening of the prothrombin time in patients receiving coumadin therapy was time and temperature dependent. This in-vitro shortening of the prothrombin time could lead to serious clinical errors involving dosage of warfarin derivatives to be administered to patients.

Anticoagulants↗

Statistical comparison of the fibrometer and the Electra 600 for prothrombin time determination.

Determinations of prothrombin time with the semiautomatic fibrometer and with a more automated machine (Electra 600) were compared in regard to reproducibility, accuracy, and speed. Prothrombin times determined for replicate samples with the two machines showed a correlation coefficient of 0.98, but the Electra 600 sensed the clot 0.5 seconds before the fibrometer. The overall coefficients of variation for multiple tests in the normal therapeutic and elevated ranges of prothrombin time were 3.5% for the fibrometer and 2.0% for the Electra 600. The average technician working time was 60% shorter with the fully automated machine than with fibrometer. It is concluded that the automated machine was more accurate and more rapid in determining prothrombin time.

Automation↗

Prothrombin time in retinitis pigmentosa.

The prothrombin time was recorded for 87 primary retinitis pigmentosa (RP) patients belonging to three different clinical categories. All categories showed prothrombin time higher than normal. There was no correlation between the age of onset and the prothrombin time, nor between duration of disease and the prothrombin time. The high prothrombin time in patients with RP suggests that further study of prothrombin time and related factors may help in better understanding of the pathogenesis of RP.

Adolescent↗

The use of pooled patient plasma as an abnormal prothrombin time control.

Five abnormal prothrombin time pooled patient plasma samples and seven commercially prepared abnormal prothrombin time control plasmas were compared. A fibrometer was used to run prothrombin time tests from 8 to 51 days on individual aliquots of the pooled patient plasmas and individual vials of the commercial products. Pooled patient plasmas exhibited greater reproducibility with generally lower coefficients of variation than did the commercial products, with the added advantage that they reflected the patient population more directly. Almost all samples displayed a significant rise in mean clotting times during the testing period. However, the reasons for this rise are not entirely clear.

Analysis of Variance↗

International standardization of laboratory control of oral anticoagulant therapy: a survey of thromboplastin reagents used for prothrombin time testing.

The prothrombin time (PT) test is the primary measurement in the laboratory control of oral anticoagulant treatment. The traditional expression of PT test results, either as percentage prothrombin activity or PT ratio, is inadequate for international communication and comparison because the values depend on the nature of the thromboplastin test system used. The WHO recommended universal scale of reporting PT results is based on calibration of local thromboplastin systems against an international reference preparation. This scale is the International Normalized Ratio (INR). Application of the INR scale in clinical practice should be encouraged by External Quality Assessment (EQA) schemes, which improve its precision. Many physicians are insufficiently aware of the different sensitivities of rabbit thromboplastins, which result in different anticoagulation intensities being employed in different clinics. Improvement in the situation can only be achieved by continuous education. The more widespread use of the INR scale should facilitate international comparison of anticoagulation results and eventually consensus on optimal target values. The introduction of the INR to countries not already using it, particularly the USA, should be strongly encouraged by all physicians with an interest in anticoagulation and especially those undertaking the long-term management of patients with prosthetic heart valves.

Animals↗

Proficiency testing and standardization of prothrombin time: effect of thromboplastin, instrumentation, and plasma.

Prothrombin times accumulated from ten different proficiency testing surveys were analyzed in terms of a linear additive model described by Evatt et al (Clin Lab Haemat 1981; 3:331-342). Different types of lyophilized plasma samples were used, i.e., plasmas artificially depleted of coagulation factors by adsorption to aluminum hydroxide, and pooled plasmas of patients receiving coumarin drugs. For each plasma sample, both instruments and thromboplastins had a highly significant effect on the prothrombin time. For most instruments and thromboplastins, a good correlation was found between instrument effect or thromboplastin effect and the mean prothrombin time if various artificially depleted plasma samples from a single manufacturer were used. Artificially depleted plasmas from a second manufacturer gave different relationships between estimated effects and mean prothrombin time. Relationships based on lyophilized pooled patient plasmas were different from those of artificially depleted plasmas from either manufacturer. The potential use of the additive linear model for standardization of the prothrombin time in monitoring oral anticoagulant therapy is discussed. Additional studies are required to establish the suitability of this model to define a universal scale for prothrombin times of fresh plasma samples of anticoagulated patients. If suitable, the model can be linked to the International Normalized Ratio proposed by the World Health Organization.

Analysis of Variance↗