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At least 253 records · Page 14Linked to original sources
PubMed2005

Low frequency of elevated prothrombin times in patients with lupus anticoagulants when using a recombinant thromboplastin reagent: implications for dosing and monitoring of oral anticoagulant therapy.

Many patients with lupus anticoagulants (LA) are treated with oral anticoagulation and monitored using the international normalised ratio (INR) derived from the prothrombin time (PT). Recent reports have produced conflicting conclusions about the extent to which LA interferes with PT determination. The degree of anticoagulation may be overestimated in a patient whose LA affects the PT. A number of reports conclude that specific thromboplastin reagents containing recombinant tissue factor are sensitive to the presence of LAs and should not be used to monitor oral anticoagulant therapy in these patients. These studies were performed on orally anticoagulated patients. The present retrospective study on 400 patients with LAs who were not receiving therapeutic anticoagulation was performed to ascertain the frequency of prolonged PT in these patients when using Innovin recombinant thromboplastin. Only 17 (4.3%) out of 400 had prolonged PT in the presence of LA. As this is a low prevalence, and not all patients with LAs will require anticoagulant therapy, it is concluded that baseline INR determination should be used to highlight the need to monitor individual patients with LA-insensitive reagents. As the use of moderate-intensity oral anticoagulation for patients with LAs and previous thrombosis is receiving wider acceptance, an informed approach to anticoagulant monitoring will reduce the possibility of under-anticoagulating patients receiving this therapy.

Administration, Oral↗
PubMed1983

Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure.

The introduction of the activated partial thromboplastin time (APTT) as a screening test has resulted in increased recognition of circulating anticoagulants. The most frequently encountered inhibitor is the lupus-type anticoagulant. However, criteria for differentiation of this inhibitor are not well-established. We evaluated the ability of two procedures, tissue thromboplastin inhibition (TTI) and a new platelet neutralization procedure (PNP), to differentiate between various types of coagulation inhibitors. The TTI, widely used for the diagnosis of lupus anticoagulants, proved to be nonspecific. The PNP specifically separated lupus-type inhibitors from Factor VIII, X, and V inhibitors. The PNP may be a useful test for the diagnosis of lupus anticoagulants.

Blood Coagulation↗
PubMed2004

6,7-Dihydroxy-3-phenylcoumarin inhibits thromboplastin induced disseminated intravascular coagulation.

6,7-Dihydroxy-3-phenylcoumarin (DHPC) was tested to determine whether it had any effect on vitamin K inhibition, by investigating the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level and platelet count. The anticoagulant and antithrombotic effects of DHPC were compared with those of warfarin by conducting a 4 h acute trial on thromboplastin-induced disseminated intravascular coagulation (DIC), investigating various haemostatic and antioxidant system parameters and performing a haemogram. Of most significance was that in the 5-d DHPC trial on healthy controls, PT, APTT, fibrinogen, platelet count remained within normal levels. In the 4-h DIC trial, both DHPC (0.025 mg/kg, i.v.) and warfarin (0.25 mg/kg, i.v.) significantly inhibited DIC, by reducing the PT, APTT, and fibrin degradation products and increasing fibrinogen levels and platelet count. In the DIC drug groups, lipid peroxidation significantly increased only in the warfarin group and glutathione significantly increased only in the DHPC group. However leucocyte count was significantly higher in the DHPC than the warfarin group. Further investigation is required for why DHPC is effective on the parameters investigated, at doses one-tenth of those of warfarin.

Animals↗
PubMed2002

Reference ranges of the dilute tissue thromboplastin inhibition and dilute Russell's viper venom tests revisited.

Reference ranges for two well-recognized tests for the lupus anticoagulant were determined utilizing 98 healthy subjects. The purpose of the study was to compare the reference ranges for the dilute tissue thromboplastin inhibition test on this group of healthy subjects calculated by parametric and nonparametric statistical methods, and to compare these results with results obtained on subsets of 20 and 40 randomly selected individuals from the group of 98. The same procedures were followed for the dilute Russell's viper venom test. Results were recorded in seconds of clotting times and in ratios (subject/mean of that set or subset). Statistical analysis revealed Gaussian distribution of the results in the large group as well as in each subset for both tests. The results showed more variation between sets of the dilute tissue thromboplastin inhibition test than of the dilute Russell's viper venom test. Nonparametrically calculated reference ranges were wider than those determined by a parametric method, especially if confidence intervals are provided for both reference ranges in the group of 94 controls or in a subset of 40 subjects. The nonparametric technique utilizes all data for the calculation of reference ranges of such sample sizes no matter how wide the results are spread. There was no significant difference between the reference ranges of subsets and the whole group (p > 0.05) calculated by both statistical techniques.

Adolescent↗
PubMed2002

[Effect of activators for activated partial thromboplastin time test on its results in the tube and automated test versions].

Effects of activators used in combination with partial thromboplastin (PT), manufactured by the Kirov Institute of Hematology and Blood Transfusion, on the results of the activated partial thromboplastin time (APTT) test and its sensitivity to heparin were studied. Kaolin manufactured in Russia and by Aldrich firm and silica from Sigma were used. The method was reproduced in tubes and on Organon Teknika photooptic coagulometers: semiautomatic Coag-A-Mate XM and automated Coag-A-Mate RA-4. The concentration and optical density of the activator affected the results of APTT test, which prompts the use of kits calibrated for the PT/activator combination but not separate reagents. Combination of PT manufactured by the Kirov Institute and suspension of Russian kaolin ensured high sensitivity of the method to heparin content in the plasma and good reproducibility of the method both in tubes and on Organon Teknika coagulometers: coefficient of variation of APTT in all variants of the tube test were no higher than 10% and in the automated variant 2.6-6.2%.

Autoanalysis↗
PubMed1996

The tissue thromboplastin inhibition test in the detection of lupus anticoagulants: importance of a correction factor eliminating the influence of fibrinogen level.

Tissue thromboplastin inhibition test (TTI) is a highly sensitive but poorly specific test used in the diagnosis of lupus anticoagulant (LA) which is usually requested for patient with inflammatory status. Therefore, we investigated the influence of fibrinogen level on TTI using Recombiplastin (Ortho), Neoplastine (Diagnostica Stago) and Thromborel S (Behring), in a group of 84 patients with fibrinogen levels ranging from 1.6 to 11.8 g/l. The highly significant (p < 0.0001) positive correlation observed between fibrinogen level and TTI with the 3 thromboplastins allowed the calculation of a new TTI value corrected for fibrinogen level named TTIfg. TTIfg was defined as TTI - ("S" x fibrinogen level) where "S" was the slope of the regression line defining TTI as a function of fibrinogen values. In the group studied, the low TTI specificity, respectively 64%, 67% and 75% with Recombiplastin, Neoplastine and Thromborel S, was greatly improved to respectively 95%, 93% and 95% when results were expressed as TTIfg. TTIfg remained as sensitive as TTI when evaluated in a group of 38 patients with previously diagnosed LA.

Fibrinogen↗
PubMed1998

Use of different thromboplastin reagents causes greater variability in international normalized ratio results than prolonged room temperature storage of specimens.

OBJECTIVE: To determine whether a 24-hour delay in testing affects international normalized ratio (INR) reproducibility as much as using alternative thromboplastin reagents. METHODS: Specimens from warfarin-treated patients were tested at 0 hours and again at 24 hours to determine the INR, each time using RecombiPlasTin, Innovin, and C-Plus thromboplastin reagents. RESULTS: There was no clinically significant difference in INRs when a specimen was tested with the same reagent at 0 and 24 hours. However, at 0 hours, the INRs were significantly higher when a specimen was tested using C-Plus and RecombiPlasTin as compared with the result with Innovin (both P < .0001). CONCLUSIONS: A specimen can be maintained at room temperature for 24 hours without a significant change in the INR. Changing the reagent, however, can result in statistically and clinically significant differences in the INR.

Anticoagulants↗
PubMed1985

Hydroxyeicosatetraenoic acids and other unsaturated fatty acids inhibit endotoxin-induced thromboplastin activity in human monocytes.

Human peripheral blood monocytes possessed increased thromboplastin activity when exposed to 10 micrograms/ml of bacterial endotoxin for 2 h. The effects of endotoxin were strongly inhibited by 10-20 microM of several unsaturated fatty acids: arachidonic, dihomo-gamma-linolenic, linoleic, linolenic and oleic acids. Two saturated fatty acids, arachidic and stearic acids, produced minimal inhibition at 20 microM. Three lipoxygenase-derived hydroxyfatty acids were also inhibitory, with IC50 values of 10 microM (5- and 12-hydroxyeicosatetraenoic acids) and 20 microM (15-hydroxyeicosatetraenoic acid). Leukotriene B4, 1 nM to 1 microM, was inactive. None of the fatty acids affected the ability of standard thromboplastin to shorten the clotting time of normal plasma or affected the activity of endotoxin as measured by a Limulus clotting assay.

Arachidonic Acid↗
PubMed1986

Inhibition of tissue thromboplastin-mediated blood coagulation.

Factors affecting the inhibition of tissue thromboplastin (TP)-mediated blood coagulation have been investigated. Human brain thromboplastin progressively loses procoagulant activity when incubated in the presence of defibrinated plasma and CaCl2. Inhibition is maximal at a CaCl2 concentration of 1.5 mM during incubation and involves the calcium dependent binding of a plasma component(s) to the TP-FVII complex, preventing the activation of FX. Chelation of calcium ions using EDTA releases active TP and FVII from the inhibited complex. No inhibition occurs during incubation of TP with Al (OH)3 adsorbed plasma and calcium ions unless a Factor VII concentrate (or purified FVII and FX) is also present. Incubation of TP with antithrombin III-deficient plasma and calcium ions also leads to inhibition. Moreover, purified AT III cannot substitute for adsorbed plasma in producing TP inhibition. The data are consistent with the presence in plasma of a potent AT III independent inhibitor of TP-mediated blood coagulation.

Blood Coagulation↗
PubMed1991

Extrinsic pathway inhibitor (EPI) and the post-heparin anticoagulant effect in tissue thromboplastin induced coagulation.

It is known that the anticoagulant effect of blood or plasma is greater when heparin is given in vivo than when added in similar heparin concentrations in vitro. In this study, we neutralized heparin in citrated blood with polybrene, and then triggered coagulation with dilute tissue thromboplastin (TTP) and CaCl2. The clotting time was longer and the release of fibrinopeptide A (FPA) was retarded in the post injection samples compared to samples spiked with heparin in vitro. We have earlier reported that the extrinsic pathway inhibitor (EPI) is released to the blood after heparin injection. This was demonstrated here also for LMW heparin Enoxaparine both after intravenous and subcutaneous administration. Polyclonal blocking antibodies to EPI were added to blood or plasma heparinized in vivo or in vitro, and the direct heparin effect was neutralized with polybrene. When TTP and CaCl2 now were added and clotting time and the release of FPA recorded, the postheparin effect was greatly reduced by the antibodies. Addition of EPI antibodies to post-heparin plasma samples from cancer patients caused a marked reduction in the thromboplastin clotting times. We conclude that the release of EPI to the blood contributes significantly to the anticoagulant effect of heparin ex vivo.

Antibodies↗
PubMed1998

Activated partial thromboplastin time is a predictive parameter for further miscarriages in cases of recurrent fetal loss.

OBJECTIVE: To determine whether clinically routine clotting tests such as activated partial thromboplastin time (aPTT), prothrombin time (PT), or fibrinogen can be used to predict further miscarriages. DESIGN: Prospective study. SETTING: Nagoya City University Hospital, Nagoya, Japan. PATIENT(S): A total of 261 patients with a history of two consecutive first-trimester spontaneous abortions who had no antiphospholipid antibodies or other autoimmune diseases and no anatomic anomalies were examined for aPTT, PT, and fibrinogen before becoming pregnant again. INTERVENTION(S): Blood tests were performed before pregnancy. Patients then were followed up during subsequent pregnancy and their outcomes were compared with their previous blood test results. MAIN OUTCOME MEASURE(S): Activated partial thromboplastin time, PT, and fibrinogen were measured by coagulation time methods. RESULT(S): Fifty-eight of 261 patients (22.2%) had a subsequent miscarriage. Mean (+/-SD) values for preconception aPTT in individuals whose subsequent pregnancies ended in success and failure were 88.2%+/-23.4% and 99.3%+/-26.4%, respectively. The difference was statistically significant. Respective values were 106.8%+/-22.8% and 106.3%+/-21.4% for PT and 245+/-61.1 mg/dL and 259.1+/-57 mg/dL for fibrinogen. These findings were not significantly different. CONCLUSION(S): A shortened aPTT before conception is associated with further miscarriages in patients with a history of recurrent spontaneous abortions who have no antiphospholipid antibodies.

Abortion, Habitual↗
PubMed2002

Dilute prothrombin time-based lupus ratio test. Integrated LA testing with recombinant tissue thromboplastin.

The lupus ratio (LR) test is a normalized ratio of the clotting times obtained with low and high phospholipid (PL) concentrations, where the test plasma is mixed 1:1 with normal pooled plasma (NP). As an integrated, automated, and computer-assisted assay, this principle has been applied to the dilute activated partial thromboplastin time (dAPTT) and dilute Russell viper venom time (dRVVT) test systems. In this study, we used recombinant thromboplastin to develop an automated LR test based on the dilute prothrombin time (dPT). Using plasma samples from a selected group of patients (N=92) with a well-defined lupus anticoagulant (LA) status, the dPT-based LR test showed fair agreement with the dAPTT-based LR test (kappa=.60, P<.001) and good agreement with the dRVVT-based LR test (kappa=.78, P<.001) regarding the classification of plasmas as LA-negative or -positive. Most discordant plasmas were low positive. Correlation between dPT- and dRVVT-positive LRs was only moderate (r(s)=.51, P=.002), and correlation between dPT- and dAPTT-positive LRs was nonsignificant (r(s)=.23, P=.18). Using dilutions of pooled LA-positive plasma, the dAPTT-based LR test appeared to be the most sensitive of the three tests. This study confirms the general validity of the LR principle and shows that the dPT-based LR test yields reproducible results. The low coefficients of variation (CV) of the LR assays, combined with a fairly low correlation among the three tests, support the assumption of antibody heterogeneity of LA-positive plasmas and the desirability of performing more than one test.

Adult↗
PubMed1977

Stability studies on lyophilised reference thromboplastins for standardisation of prothrombin-times.

An international framework for anticoagulant control has been developed based on British Comparative Thomboplastin (B.C.T.) and the model provided by the British system for anticoagulant control. An alternative international system has been proposed, based on lymphilised thromboplastins prepared at the National Institute of Biological Standards and Control, London. Since 1969, stability studies on two of the N.I.B.S.& C. reagents, the primary material 67/40 and the secondary thromboplastin 69/223, have been in progress at the National (U.K.) Reference Laboratory for Anticoagulant Reagents and Control, Manchester. Both the proposed N.I.B.S.&C. reference preparations have deteriorated, while two lyophilised reagents prepared at the National (U.K.) Reference Laboratory have revealed no evidence of instability. In national and international standardisation reliance on B.C.T. should continue.

Anticoagulants↗
PubMed1997

[Combined hereditary deficiency in factors VII and X revealed by a prolonged partial thromboplastin time].

BACKGROUND: Congenital factors VII and X deficiency is rare. Association of both deficiencies is exceptional. CASE REPORT: A 3 year-old boy, born to consanguinous Moroccan parents, had a prolonged partial thromboplastin time discovered fortuitously. This finding led to the diagnosis of combined factors VII and X deficiency. His siblings had the same deficiencies. CONCLUSION: Profound deficiencies in factors VII and X are inherited following an autosomal-recessive mode. These deficiencies may be asymptomatic, only discovered by prolonged partial thromboplastin time. They may also be revealed by intracranial bleeding and other severe hemorrhages. Treatment consists of administration of factor VII or PPSB.

Blood Coagulation Factors↗
PubMed1981

Clearance of fibrin from glomeruli. Renal cortical fibrinolytic response after thromboplastin infusion in the rat.

1. The time sequence of glomerular fibrin deposition, renal cortical fibrinolytic response and thrombocytopenia after thromboplastin infusion in rats has been established. 2. Fibrin clearance is rapid and is associated with markedly increased cortical fibrinolytic activity. 3. Plasma fibrinolytic activity was unchanged. 4. Experiments in which the dose-response relationship between thromboplastin dose, fibrin deposition and fibrinolytic response was examined showed that fibrinolytic response increased with fibrin deposition in glomeruli. 5. The dose-response experiments also provided data which suggested that the method of measurement of cortical fibrinolytic activity in the presence of deposited fibrin measures excess rather than total plasminogen activator production.

Animals↗
PubMed1998

A comparison of artificially-depleted, lyophilized coumarin and fresh coumarin plasmas in thromboplastin calibration. European Concerted Action on Anticoagulation.

Artificially-depleted lyophilized plasmas and lyophilized coumarin plasmas were prepared and compared with fresh coumarin plasmas to assess their comparative reliability in local thromboplastin calibration using the manual prothrombin time (PT) technique. Their certified PT values were inserted in turn on the vertical axis in place of the PT obtained with fresh coumarin plasmas. PT results were obtained at eight ECAA national laboratories ('test centres') and inserted on the horizontal axis. The resulting thromboplastin calibration slopes were compared with conventional fresh coumarin plasma calibration slopes at the same 'test centres'. When 60 artificially-depleted plasmas were substituted for 60 fresh plasmas, the mean calibration slopes with the human plain International Reference Preparation (IRP) were 4.2% higher. For comparison with 20 lyophilized coumarins, three sets of 20 artificially-depleted plasmas were selected in sequential order from the 60. The lyophilized coumarin plasmas gave a mean deviation of 9.6% from the fresh plasma calibration slopes compared with values of 2.0%, 6.1% and 11.7% for the three sets of 20 depleted plasmas. Although both types of lyophilized plasma calibration slopes give measurable differences from conventional fresh plasmas, these may be regarded as acceptable in clinical terms.

Blood Coagulation Tests↗
PubMed2001

Prothrombin time inhibition detected with recombinant but not with conventional thromboplastins in two patients with high-titre IgM and moderate-titre IgA anticardiolipin antibodies.

We report two cases of high-titre IgM and moderate-titre IgA anticardiolipin antibodies (ACA) in whom prothrombin times (PT) derived using recombinant thromboplastins (rTP) were prolonged but were normal when measured with conventional thromboplastins. The anticoagulant nature of these antibodies cannot be categorized as the classical lupus type. We suggest that routine screening for the presence of antiphospholipid antibodies (APA) should be performed in patients who fall into this category.

Aged↗
PubMed1979

Activated partial thromboplastin time and minor coagulopathies.

Five commercially available activated partial thromboplastin time (APTT) test systems were compared with the kaolin partial thromboplastin time (KPTT) method to determine sensitivity in detecting minor coagulation defects. All reagent systems detected severe factor VIII-, IX-, and XI-deficient hemophilia. Homozygous states of factor XII deficiency, Fletcher factor deficiency, and high-molecular-weight kininogen deficiency (Fitzgerald trait) also showed abnormally long APTTs by all systems. Of 19 samples from patients with deficiencies of factors XII, VIII, IX, XI, and II ranging from 2.5 to 52%, eight had deficiencies that were not detected by reagent A (ellagic acid); two, by reagent B (ellagic acid); two, by reagent C (kaolin); one, by reagent D (silica); one, by the KPTT method. All deficiencies were detected by reagent E (celite). Heparin effect on plasma was less well detected by reagent A (ellagic acid) than with the other test systems. APTT test systems can vary greatly in their abilities to detect minor coagulation abnormalities.

Adult↗