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[Comparison of a sensitive rabbit brain thromboplastin and a human placenta thromboplastin for thromboplastin time determination].

Prothrombin times were measured in 120 orally anticoagulated patients and 122 patients not orally anticoagulated using two different commercial thromboplastin reagents, a rabbit brain thromboplastin (CRB-Thromboplastin, Roche) and a human placenta thromboplastin (Thromborel S, Behring). A good correlation (r = 0.93, slope = 1.089, intercept = 0.014) was found between the International Normalized Ratio (INR) values of the anticoagulated plasmas obtained with both thromboplastins. Defining five degrees of intensity of anticoagulation (between INR less than or equal to 2.0 to INR greater than or equal to 5.1) the intensity of treatment was judged concordantly with both thromboplastins in 67% of the patients and as differing by one degree in 32%. In only one out of 120 patients was a larger discrepancy of INR values found. - A good correlation (r = 0.93) was also found between the prothrombin times expressed as Quick percentage values as assessed with both thromboplastins in 122 patients not orally anticoagulated. In 82 cases a "normal" prothrombin time (Quick greater than or equal to 70%) and in 33 cases a "subnormal/diminished" percentage value (Quick less than 70%) was obtained with both thromboplastins. In only 7 out of 122 plasma samples was the Quick percentage normal with one and subnormal with the other reagent. - The good conformity of the INR values measured with two thromboplastins of differing species but similar sensitivity (International Sensitivity Index [ISI] = 1.14 for CRB-Thromboplastin, and = 1.10 for Thromborel S) supports the recommendation by the World Health Organization that the intensity of oral anticoagulation be expressed in terms of INR. Whether INRs obtained with thromboplastins of largely differing ISIs show sufficient conformity will need to be assessed by further prospective studies.

Animals↗

[Variability of INR due to thromboplastin. Comparison of two recombinant thromboplastins and one rabbit thromboplastin].

We have compared the INR obtained with three different thromboplastin reagents: one rabbit and two recombinant tissue factor thromboplastins using the same coagulometer. A preliminary study has shown that freezing of plasmas at -80 degrees centigrade causes a 6% increase in INR. We did this experiment on 57 plasma samples from patients receiving oral anticoagulant therapy, none of them receiving heparin. Results show that global prothrombin activity expressed in percentage is significantly lower with recombinant tissue factors than with rabbit thromboplastin. ISI of one of the two recombinant thromboplastins did not seem to be appropriate to our coagulometer highpointing the variability of INR due to the coagulation analyzer. This underlines the necessity for each laboratory to assess the ISI value provided by the manufacturer according to its working conditions. This study suggests that the results of prothrombin time should be exclusively expressed in INR for patients treated with oral anticoagulants.

Animals↗

[Determination of thromboplastin time with a new standardized thromboplastin from human placenta: results of a cooperative study].

In five centres a new sensitive standardized thromboplastin from human placenta (Thromborel S) for determination of prothrombin time (PT) was evaluated on plasmas from healthy subjects, from patients on oral anticoagulant therapy and from patients with different diseases, especially of the liver. The standardization of the human placenta thromboplastin (HPT) for prothrombin time determination was performed by comparison with a lot of the Reference Preparation British Comparative Thromboplastin (BCT). The obtained International Sensitivity Index (ISI) for 14 differents lots of the new thromboplastin varied between 1.04 and 1.29 (mean value: 1.16). The reagent is highly sensitive to the factors of the extrinsic coagulation pathway and is not affected by heparin at least up to 0.6 IU/ml. From the comparison with the British Comparative Thromboplastin lot No. 235, a therapeutical range for the stable phase of the oral anticoagulation of 2.4-4.0 prothrombin ratio or 15-27% of normal, respectively, was obtained. Comparison of prothrombin time determination using the Human Placental Thromboplastin and the British Comparative Thromboplastin lot No. 235 in 330 patients on oral anticoagulation showed good correlations either in "percent normal" or in prothrombin ratio.

Anticoagulants↗

Thromboplastin Bilbao: reproducibility and sensitivity of a Spanish thromboplastin.

Prothrombin time (PT) is the control test for oral anticoagulant therapy as well as the screening test for defects of the extrinsic pathway of coagulation. Its responsiveness to decreased extrinsic clotting factors depends on the source and type of tissue factor thromboplastin extract. In 1994, a rabbit brain thromboplastin - Thromboplastin Bilbao (TBi) - was introduced as a replacement for a human brain preparation used since 1983, with the aim of establishing a national standard. The purpose of this study was to check the reproducibility, the inter-assay/intra-assay accuracy and the stability of this reagent under temperature changes and over time. A method modified from Frei et al. [World Health Organisation Regional Publications, Eastern Mediterranean Series, Alexandria, 1995] was used for the preparation of thromboplastin extract. Thirty-five batches of human TBi were prepared from 1983 to 1988, while from 1993 to 1999 13 batches of rabbit TBi were produced. The inter-assay reproducibility of rabbit TBi exhibited a coefficient of variation (CV) of 1.07-1.57% for normal plasma and of 1.25-2.56% for anticoagulated plasma. The intra-assay CV was 0.06-1.30% for normal plasma and 1.23-2.66% for anticoagulated plasma. The stability of the reagent to temperature changes and time was also estimated, with similar results for the two thromboplastins. As a result of the Oral Anticoagulant Treatment Quality Assessment Scheme in the Basque Country, an in-house rabbit thromboplastin with good sensitivity and reproducibility was developed.

Animals↗

Experimental gram-negative peritonitis: decreased thromboplastin activity in organs with a simultaneous rise of thromboplastin in blood monocytes and peritoneal macrophages.

Thromboplastin values in blood monocytes, peritoneal macrophages, and in tissue samples from lung, aortic wall, liver, spleen, pancreas, kidney, jejunum, and colon were determined at 4, 10, and 16 h after induction of acute peritonitis (cecal perforation) or sham operation in rats. A maximum 35-fold and 100-fold rise of values was respectively demonstrated in monocytes and peritoneal macrophages in septic animals as compared to controls. This monocyte-macrophage-derived thromboplastin is probably central to the activation of blood coagulation and fibrin depositions/adhesion formation in septic peritonitis. A simultaneous and significant fall in thromboplastin content of standardized specimens from lung, aortic wall, liver, spleen, pancreas, and jejunum was observed in rats with peritonitis. This could reflect mobilization of thromboplastin in favor of the infectious focus. No significant changes were detected in tissue from kidney, whereas samples from the colon of septic animals showed a consistent increase as compared to controls.

Animals↗

The calibration of the second primary international reference preparation for thromboplastin (thromboplastin, human, plain, coded BCT/253).

An international collaborative exercise has been undertaken to calibrate a replacement for the first WHO primary international reference preparation (IRP) for thromboplastin. The replacement preparation is a lyophilised batch of British Comparative Thromboplastin (BCT/253, human plain) for use in the Quick prothrombin time test. Seventeen centres participated. The experimental design, calibration model and statistical analysis were based on the recommended WHO procedure. As a result of this calibration exercise an International Sensitivity Index (ISI) of 1.1 has been assigned to the preparation by WHO and it has been officially recognised as the second primary IRP for thromboplastin. The calibration of BCT/253 is an essential link in a new hierarchical structure for the standardisation of the prothrombin time. The aim is to provide a uniform international system of reporting prothrombin time results using International Normalised Ratios (INR) derived from the ISI of individual thromboplastins.

Humans↗

[Lyophilized plasmas for the control of thromboplastin time values and calibration of thromboplastins].

The paper deals with the production of normal and pathological plasmas for the calibration of thromboplastin. Calibration is performed according to WHO principles. We compared single charges of thromboplastin (Sevac, CSSR, human brain) with each other and a selected reference charge with British thromboplastin. Lyophilised reference plasmas produced (20-50 healthy blood donors) and plasmas taken from patients treated with coumarin derivates (single and mixtures) could replace their fresh equivalents which was confirmed by testing 4 different batches. The stability of these plasmas (for a time of at least 12 months) was proved by repeated checks. These plasmas also served as controls in other laboratories in Czechoslovakia.

Blood Coagulation Tests↗

[Comparative multicenter study of a rabbit high-sensitivity thromboplastin and a recombinant thromboplastin with synthetic phospholipids].

PURPOSE: The purpose of the present study was to compare the results obtained with a human recombinant thromboplastin (Innovin, Baxter) (IN) and a high-sensitivity rabbit brain reagent (Thromboplastin IS, Baxter) (IS), on the performance of prothrombin time (PT) test and the functional assay of factors included in the extrinsic coagulation system, in order to establish possible differences on imprecision, diagnostic accuracy and sensitivity to the oral anticoagulant defect, between the two products. MATERIAL AND METHODS: Six Spanish hospital took part in the study. Plasma samples from 221 healthy subjects, 100 patients with severe liver disease, 27 with dysfibrinogenaemia, 10 with lupus anticoagulant and from 13 individuals propositus and their relatives with congenital deficiencies of the extrinsic coagulation pathway, and their relatives were studied; 188 patients stabilized on oral anticoagulant therapy and 82 on heparin therapy were also included. The in vitro effect of heparin was tested by addition of increasing amounts of heparin (0.3 to 10.0 IU/mL) to aliquots of normal plasma. RESULTS: Both in the intra-assay and in the inter-assay imprecision study, a better coefficient of variation was obtained with IN when the PT was performed on abnormal samples. Prothrombin time ratio from patients with liver disease had significantly higher values with IS. On the contrary, IN had a higher sensitivity in samples from patients with dysfibrinogenaemia or from those stabilized on oral anticoagulant therapy. In showed a very low sensitivity to heparin at concentrations corresponding to the therapeutic range. CONCLUSIONS: The results of this field study indicate that IN, compared with a high-sensitivity rabbit brain thromboplastin, is a suitable reagent for PT determination in normal subjects, patients with liver disease or with congenital deficiencies of clotting factors. It shows a higher sensitivity in cases of dysfibrinogenaemia and in patients on oral anticoagulant therapy. In addition, the recombinant reagent had better reproducibility when the PT was performed on abnormal samples, and it was hardly affected by heparin within the therapeutic range.

Afibrinogenemia↗

[Prothrombin time and thromboplastin time. On-site measurement of the prothrombin time and activated partial thromboplastin time of surgical patients with laser photometry].

UNLABELLED: Turnaround time for analysis of prothrombin time (PT) and activated partial thromboplastin time (APTT) by standard laboratory methods ranges between 40 min and several hours. The delay in obtaining the test results limits their clinical utility for treatment of perioperative coagulation disorders and adequate anti-coagulation therapy. In this study, we compared on-site coagulation testing (OCT) of whole blood, which takes about 3 min, with standard laboratory plasma coagulation tests by our institutional laboratory (LAB) to assess the accuracy of the OCT in a clinical setting (abdominal and postcardiac surgery). METHODS: PT of 62 patients with abdominal surgery was measured intra- and postoperatively using both LAB (KC 40, Thromborel S, Centeon) and OCT (CoaguChek Plus, Boehringer Mannheim) systems. APTT was determined by LAB-(KC 40, Pathromtin, Centeon) and OCT-methods in 53 patients who underwent cardiac surgery requiring cardiopulmonary bypass. RESULTS: Linear regression demonstrated a strong and significant (p = 0.0001) correlation of OCT- and LAB-determinations both for PT (r = 0.92) and APTT (r = 0.91). For PT testing, bias analyses showed an agreement between OCT- and LAB-International Normalized Ratio (INR) (bias = 0.24; relative error = 14.6%) that was considered clinically acceptable, with 95% of the INR-differences lying between -0,26 and +0,74 (mean +/- 2 SD). Although commercial APTT-reagents usually differ in their sensitivity to heparin, we also found an acceptable agreement between OCT- and LAB-APTT values (bias = 6.7 s +/- 22 s; mean +/- 2 SD; relative error = 12%). CONCLUSION: On-site coagulation monitoring provides a rapid, convenient, and accurate assessment of coagulation that can both guide specific anti-coagulation therapy and optimize therapy control of coagulation disorders after cardiac and abdominal operations. As a consequence, OCT offers a valuable tool to reduce the inappropriate use of fresh frozen plasma and to improve cost-effectiveness.

Humans↗

The determinants of activated partial thromboplastin time, relation of activated partial thromboplastin time to clinical outcomes, and optimal dosing regimens for heparin treated patients with acute coronary syndromes: a review of GUSTO-IIb.

CONTEXT: Unfractionated heparin remains widely utilized in the treatment of acute coronary syndromes (ACS). However, limited data exist on optimal dosing and range of activated partial thromboplastin time (aPTT) in this setting. A large trial of thrombolysis for acute myocardial infarction has reported an association between longer aPTTs and adverse outcomes. OBJECTIVES: Estimate the optimal heparin-dosing regimen in achieving early therapeutic aPTTs (50 to 75 seconds) and determine the association of aPTT and death, reinfarction, and bleeding in population with ACS. DESIGN: Subgroup analysis within a randomized, controlled trial of 5861 patients given unfractionated heparin who had aPTTs at 6, 12, or 24 hours, with outcome analyses by weight categories. SETTING: In 373 hospitals in 13 countries from May 1994 to October 1995. PATIENTS: A total of 12142 patients admitted for ACS, stratified by the presence (n = 4131) or absence (n = 8011) of ST-segment elevation, and randomized to 72 hours of unfractionated heparin. RESULTS: In a simulated weight-adjusted model, based on retrospective grouping by weight, a simulated dose of 60-U/kg bolus and 12-U/kg/h infusion resulted in the highest proportion of therapeutic aPTTs. After adjustment for baseline variables, longer 12-hour aPTT was associated with the composite of 30-day death or reinfarction in patients not treated with thrombolytic therapy (odds ratio, 1.10; 95% CI, 1.00 to 1.22; P = 0.047). Longer aPTT at 6 hours was associated with increased moderate or severe bleeding for the entire cohort. There was also a significant, nonlinear correlation of the 12-hour aPTT with moderate or severe bleeding in thrombolysis-treated patients. CONCLUSIONS: For ACS patients who are treated with heparin, aPTT is highly associated with body weight. Longer aPTT within the first 12 hours is associated with adverse outcomes in ACS. Heparin dosing for ACS should be weight based.

Acute Disease↗

Failure to detect variant (CRM+) plasma thromboplastin antecedent (factor XI) molecules in hereditary plasma thromboplastin antecedent deficiency: a study of 125 patients of several ethnic backgrounds.

Plasma samples of 125 patients from 80 kindreds with hereditary plasma thromboplastin antecedent (PTA, factor XI) deficiency were tested by factor XI radioimmunoassay (RIA) and electroimmunoassay (EIA) in an attempt to detect variant molecules. Ninety-six patients (70 kindreds) were Jewish, and 29 (10 kindreds) were of other ethnic backgrounds, namely, Japanese, black American, Korean, Arab, Indian, and English. Seventy-eight patients were homozygotes, and 47 were heterozygotes. Both non-Jewish homozygotes and heterozygotes had lower factor XI activity than respective Jewish subjects. Twenty-eight homozygotes whose factor XI clotting activities (XI:C) were 1.5% to 13% had factor XI-related antigen (XI:RAG) levels less than 10% by EIA. In 72 homozygotes, including 22 patients who were also tested with EIA, XI:C was 2.9% +/- 3.0% (mean +/- SD) and XI:RAG tested by RIA, 2.9% +/- 3.0%. In 47 heterozygotes, XI:C and XI:RAG tested by RIA were 51.9% +/- 16.6% and 51.0% +/- 16.2%, respectively. Similar results were obtained when only unrelated patients (62 homozygotes and 27 heterozygotes) were analyzed. There was a highly significant correlation between XI:C and XI:RAG (RIA) in 38 homozygotes and 47 heterozygotes (r = 0.94, n = 85, P less than 0.001). Thus, we failed to identify functionally abnormal factor XI molecules (CRM+ variant) in these patients with hereditary factor XI deficiency.

Black People↗