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PubMedDate not supplied

Influence of fibrinogen degradation products on thrombin time, activated partial thromboplastin time and prothrombin time of canine plasma.

To investigate how thrombin time, activated partial thromboplastin time (APTT) and prothrombin time are influenced by fibrinogen degradation products (FDP), different concentrations (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8 and 1.0 mg/ml) of the purified FDP X, Y, D and E were added to the plasma of healthy dogs. If fragment Y was added to the plasma a considerable inhibitory effect could be demonstrated for all three test systems. A significant prolongation (p < 0.05) was found for concentrations of > or =0.1 mg/ml (thrombin time, APTT) and > or =0.2 mg/ml (prothrombin time). With FDP Y concentrations from >0.185 mg/ml (prothrombin time) to >0.24 mg/ml (APTT) coagulation time was prolonged beyond the respective reference range. As regards the other fragments, a comparable inhibitory effect could only be shown for fragment X added to the thrombin time test system. This effect can most probably be explained by the competition of the FDP X and fibrinogen for the fibrinogen binding sites of thrombin, rather than by a fibrin polymerization disorder. The results demonstrate that for plasma with normal fibrinogen concentration the group tests are only prolonged beyond the reference range at FDP concentrations very rarely found in spontaneous hyperfibrinolysis.

Animals↗
PubMedDate not supplied

Measurement of a newly developed thrombomodulin addition activated partial thromboplastin time assay in patients with deep venous thrombosis.

We developed a simple assay using rabbit thrombomodulin (TM) based on an activated partial thromboplastin time method, which detected the response to TM in plasma coagulation. We call it thrombomodulin addition clotting time (TACT). The anticoagulant response to TM was calculated by dividing the clotting time with TM by the clotting time with buffer solution. Results were expressed as TACT ratio, which indicates the degree of inhibition of plasma clotting by TM. Using this assay, we measured the TACT ratio in 80 patients with deep-vein thrombosis (DVT) and in 126 controls matched to the patients according to age and sex. A significant difference in the TACT ratio was observed between patients with DVT (mean 1.874) and controls (mean 1.956) (p < 0.001). Twenty- three patients (29%) had TACT ratios below the 10th percentile (1.757) of distribution of control subjects (odds ratio: 3.5; 95% confidence interval (CI): 1.7-7.2). After excluding subjects with a deficiency of protein C, protein S and antithrombin III, we found an odds ratio for DVT of 3.4 (95% CI: 1.6-7.2). These data suggest that natural anticoagulant deficiencies do not influence the TACT ratio, and our case-control study may show that the plasma of patients with DVT has a low response to TM.

Adolescent↗
PubMed2001

Effect of heparin on activated partial thromboplastin time in patients undergoing gynecologic or obstetric surgery.

The exaggerated prolongation of the activated partial thromboplastin time (APTT) by heparin prophylaxis for postoperative thromboembolism may cause bleeding complications. We examined the effects of various doses of unfractionated heparin on the APTT in patients who underwent a gynecologic or obstetric operation. A total of 68 patients who underwent a gynecologic operation (n = 47) or a cesarean section (n = 21) with risk factors for thromboembolism received a continuous intravenous infusion of unfractionated heparin (110-285 IU/kg/day) after surgery until the patient was mobilized the next day. A group of 61 postoperative patients who did not receive heparin served as controls. The APTT was measured in these 129 patients preoperatively and on postoperative day 1. A clinical deep vein thrombosis occurred in only 1 patient, who was in the control group. No bleeding complications occurred in any patient. The percent change in the APTT was significantly correlated with the dose of heparin administered (p < 0.001). Compared with the control group, the mean APTT was not prolonged in the patients who received heparin at 110-149 IU/kg/day. It was prolonged significantly in the patients who received heparin at greater than 150 IU/kg/day. An exaggerated prolongation of the APTT, defined as an APTT greater than 150% of the preoperative value, was found in 0 of 32 patients in the 110-149 IU/kg/day group, 1 of 28 patients (3.6%) in the 150-199 IU/kg/day group and 2 of 8 patients (25%) in the 200-285 IU/kg/day group. The continuous postoperative administration of intravenous heparin at less than 200 IU/kg/day does not result in an exaggerated prolongation of the APTT.

Adult↗
PubMedDate not supplied

Abnormally short activated partial thromboplastin times are related to elevated plasma levels of TAT, F1+2, D-dimer and FVIII:C.

Abnormally short activated partial thromboplastin times (APTTs) are associated with an increased risk of thrombotic disorders. We have examined the status of coagulation activity in subjects with short APTTs. In addition, the presence of the thrombotic risk factors G1691A-factor V, G20210A-prothrombin gene mutation and factor VIII coagulant activity (FVIII:C) was determined. Plasma levels of TAT, F1+2, D-dimer and FVIII:C were markedly higher in subjects with short APTTs compared with subjects with normal APTTs. APTTs were inversely related to TAT, F1+2, D-dimer and FVIII:C levels. The prevalence of G1691A-factor V and G20210A-prothrombin gene mutation between the group with short APTTs and the control group was not significantly different. Hence, these gene polymorphisms do not contribute to the increased risk of thrombosis associated with short APTTs. In conclusion, short APTTs are indicative of marked coagulation activity and elevated FVIII:C levels. Elevated FVIII:C levels may play a pathogenic role in the increased risk of thrombosis associated with abnormally short APTTs.

3' Untranslated Regions↗
PubMed1984

Micro-activated partial thromboplastin time in diluted capillary blood.

A sensitive micromethod for estimating the activated partial thromboplastin time in diluted capillary blood with excellent reproducibility is presented, as are results of test conditions with regard to sampling, calcium concentration, osmolarity of the diluent and the influence of the packed cell volume.

Blood Coagulation Tests↗
PubMed1984

The role of complement in the induction of thromboplastin synthesis.

Complement appears to be an important system for cell activation in circulating blood. It is established that granulocytes may be stimulated through complement activation. In the present paper we propose also a central role of complement in the induction of thromboplastin synthesis in blood monocytes and endothelial cells.

Antigen-Antibody Reactions↗
PubMed1987

Use of a centrifugal analyzer for a chromogenic prothrombin time, a chromogenic activated partial thromboplastin time and a kinetic fibrinogen assay in a routine hospital laboratory.

A Cobas Bio centrifugal analyzer was used in a clinical laboratory for the performance of chromogenic clotting assays. Three commercially available photometric clotting tests--prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen--were compared with the traditional clotting assays during 3 months. No great discrepancies were found between the traditional assays and the new photometric assays. The chromogenic PT could replace the traditional thrombotest, PT and Normotest, because it was sensitive and accurate over a broad range of clotting factor activity. Furthermore the chromogenic PT could be used to discriminate between a decreased clotting activity due to vitamin K deficiency or to a decreased protein synthesis by the liver. A decreased protein synthesis was confirmed by measuring a decrease in the serum cholinesterase activity. The chromogenic aPTT could be used for the assay of heparin concentrations in the therapeutic range and turned out to be more sensitive for deficiencies of factor VIII and factor IX than a traditional clotting aPTT. We conclude that the accuracy and practicability of clotting assays are improved by the new assays without diminishing the clinical value of the results.

Blood Coagulation Tests↗
PubMed1989

Automated amidolytic method for evaluating the activated partial thromboplastin time compared with a conventional coagulation method.

We report studies of the validity and clinical application of a new amidolytic method for evaluating the activated partial thromboplastin time (APTT) compared with a conventional clotting method. The results with the two methods were well correlated for normal plasma and plasma from hemophilia patients. Congenital deficiencies of of the intrinsic coagulation pathway other than hypo- and dysfibrinogenemia detected by the amidolytic method agreed with those detected by the clotting APTT. The results with the two methods for plasma from patients under heparin treatment were statistically different, suggesting a lesser sensitivity of the amidolytic method to heparinization. The use of the amidolytic APTT reagent in combination with factor VIII and IX deficient plasma allowed the measurement of both factors. The results obtained with normal and hemophilic plasma were in agreement with those obtained with the one-stage clotting method in all except two occasions. Even though the amidolytic method demonstrated the presence of the lupus anticoagulant in the majority of tested samples of known lupus subjects, it was less sensitive to the abnormality than the clotting method.

Adult↗
PubMedDate not supplied

Influence of age, sex and ABO blood group on activated partial thromboplastin time.

To evaluate the influence of age, sex and ABO blood group on the activated partial thromboplastin time (APTT), we performed this test in 642 preoperative ambulant adult subjects. There was a significant negative correlation (R = 0.31, p < 0.001) between age and APTT. Sex and ABO blood group had a significant influence on APTT, with lower mean in females (30.9 s) and non-O subjects (30.7 s) than in males (31.6 s) and O subjects (32.0 s) (p = 0.015 and < 0.001, respectively). The largest difference between the upper cut-off values of APTT determined in patient subgroups defined on age, sex and ABO blood group is observed for non-O females over 40 years (36.9 s) and O males under 40 years (41.1 s). These results emphasize the laboratory's difficulties to define valid APTT normal range and thus to detect true mild coagulation disorders in preoperative asymptomatic patients.

ABO Blood-Group System↗
PubMedDate not supplied

Effect of dermatan sulphate on activated partial thromboplastin time determined with different reagents.

Five widely used activated partial thromboplastin time (APTT) reagents (Actin-FS, Actin-FSL, Hemolab Silimat, IL-Test APTT Ellagic Acid and Thrombofax Activated) were compared for their sensitivity and precision in measuring the effect of dermatan sulphate on blood coagulation. On each of 4 days, aliquots of the same normal human plasma pool were mixed with dermatan sulphate (MF701) at concentrations ranging from 10 to 100 micrograms/ml, and APTT was measured in duplicate with all reagents by a photo-optical coagulometer. The order of testing between and within reagents was changed every day. The relationship of APTT ratio to dermatan sulphate concentration was linear with all the reagents. There were statistically significant differences between reagents in their sensitivity to DS, as reflected by linear regression slopes. IL-Test was the most sensitive reagent. At dermatan sulphate concentrations of 20, 50, and 80 micrograms/ml APTT ratio ranged from 1.5 to 1.7, 1.9 to 2.3 and 2.3 to 2.9, respectively, according to the reagent. The lambda coefficient and coefficient of variation derived from regression analysis, both reflecting assay precision, ranged from 0.57 to 0.71 and from 4.6 to 5.1%, respectively, with all but the least precise reagent. The best sensitivity/precision balance was displayed by IL-Test. The APTT reagent should therefore be standardized, with special regard to sensitivity to DS, when testing the relationship of dermatan sulphate clinical effects to APTT response.

Blood Coagulation↗
PubMed2004

Transition from argatroban to oral anticoagulation with phenprocoumon or acenocoumarol: effects on prothrombin time, activated partial thromboplastin time, and Ecarin Clotting Time.

Treatment with the direct thrombin inhibitor argatroban (ARG) is often followed by vitamin K-antagonist treatment (VKA). Phenprocoumon (PC) and acenocoumarol (AC) are frequently used in Europe. The standard monitoring test for VKA, pro-thrombin time (PT), is prolonged by direct thrombin inhibitors. Therefore the International Normalized Ratio (INR) obtained during combined treatment does not reflect the true effect of the VKA. A similar interference of the VKA on the activated partial thromboplastin time (aPTT), a monitoring assay for direct thrombin inhibitors, can occur. In 39 healthy volunteers the effect of ARG alone or combined with PC or AC on PT, INR, aPTT, and Ecarin Clotting Time (ECT) was investigated. 6 groups each of 6-8 volunteers received a 5-hour infusion of either 1.0, 2.0 or 3.0 microg/kg/min ARG (days 1, 3, 4 and 5) before initiation of either PC or AC (day 1) and during continued VKA dosing (target INR 2-3). A linear relationship (INR(ARG+VKA) = intercept + slope * INR (VKA alone)) was observed between the INR measured "on" and "off" ARG. The slope depended on the argatroban dose and on the International Sensitivity Index (ISI) of the PT reagent, the steepest slope (i.e., the largest difference between INR (ARG+VKA) and INR (VKA alone)) was seen with the highest ARG dose and the PT reagent with an ISI of 2.13. There was a close correlation between plasma levels of ARG and aPTT or ECT. Under VKA the ARG-aPTT relationship indicated an increased sensitivity of the aPTT to ARG, VKA treatment had no effect on the prolongation of the ECT induced by argatroban. In conclusion, ARG at doses up to 2 microg/kg/min can be discontinued at an INR of 4.0 on combined therapy with VKA, as this would correspond to an INR between 2.2 and 3.7 for the VKA. If it is necessary to monitor ARG in the critical transition period, the ECT which is not influenced by VKA can be used as an alternative to the aPTT.

Acenocoumarol↗
PubMed1996

The mechanism of inhibition of factor III (thromboplastin) activity by apolipoprotein B-100. Protein-protein interactions.

Factor III (thromboplastin) activity is inhibited by apoB-100, but the mechanism of inhibition is unknown. By examining the effect of purified apoB-100 on factor III activity, we showed that apoB-100 can inhibit factor III via a different mechanism from that caused by the issue-factor pathway-inhibitor, which is mainly carried on the surface of lipoproteins. Although the presence of calcium ions and factors X and VII may enhance the rate of inhibition, they are not a prerequisite for the inhibition of factor III by apoB-100. In addition, by investigating the changes in the UV spectra of apoB-100 on interaction with factor III and factors X and VII and by assigning the shifts in absorption spectra to particular amino acids, we showed that these interactions involve negative and positive residues within these proteins. By following the rates of interactions between apoB-100 and either factors III, X, VII, a two-step mechanism for the inhibition process involving factors X and VII was postulated. In this mechanism, the primary interaction of apoB-100 with factor III is followed by a rate-limiting step that can be accelerated by the presence of either factor X or VII and leads to the inhibition of factor III. Furthermore, a computer-based analysis of the sequences of factor III revealed a possible binding site for apoB-100.

Absorption↗
PubMed2000

Functional effects of the ABO locus polymorphism on plasma levels of von Willebrand factor, factor VIII, and activated partial thromboplastin time.

Lower levels of factor VIII and von Willebrand factor (vWF) have been reported in individuals with blood type O compared with individuals with other ABO blood types. However, this relationship has been demonstrated only by association studies and not by linkage studies. Also, it is not clear whether the ABO locus exerts a functional effect directly on these plasma factors or whether the ABO locus is in linkage disequilibrium with another locus that controls these factors. To distinguish between these 2 possibilities, we applied new statistical methods combining linkage and association tests in a pedigree-based sample. In contrast to most previous studies that used the ABO phenotypes, our study used the ABO genotypes, permitting us to distinguish AO from AA and BO from BB. Our results clearly showed significant linkage between the ABO locus and vWF antigen (P=0.00075). In addition, factor VIII coagulant activity and activated partial thromboplastin time showed suggestive linkage with the ABO locus (P=0.10 and P=0.13). All 3 plasma phenotypes showed significant differences between OO and non-OO genotypes. In addition, vWF antigen exhibited significant differences between O heterozygotes and non-OO homozygotes. This study is unique because it used a combined linkage and association test, which indicated that the ABO locus itself has a functional effect on these plasma phenotypes.

ABO Blood-Group System↗
PubMed2003

Relationship of activated partial thromboplastin time to coronary events and bleeding in patients with acute coronary syndromes who receive heparin.

BACKGROUND: Antithrombotic therapy with intravenous heparin in conjunction with aspirin reduces negative cardiovascular (CV) outcomes in patients with acute coronary syndromes. The need for a therapeutic range with the activated partial thromboplastin time (APTT) has not been validated in patients with arterial thrombosis who receive heparin. Therefore, it is unclear whether there is an association between recurrent CV events and low APTT values and between bleeding and high APTT values. METHODS AND RESULTS: We examined the relationship between the APTT and recurrent cardiovascular events and bleeding among 5058 patients with an acute coronary syndrome without ST elevation who received intravenous heparin in the OASIS-2 trial. The increase in relative risk of recurrent CV events was 1.54 (95% CI 1.10 to 2.15; P=0.01) among patients with APTT values <60 seconds compared with patients with APTT values > or =60 seconds. When patients had persistently subtherapeutic APTT values for more than 48 hours, the increase in relative risk of a recurrent CV event was 1.84 (95% CI 1.25 to 2.70). Higher APTT values were associated with bleeding; for every 10-second increase in the APTT, the probability of major bleeding was increased by 7% (95% CI 3% to 11%; P=0.0004). CONCLUSIONS: In patients with acute coronary syndromes without ST elevation who are treated with intravenous heparin, our findings justify regular APTT monitoring to minimize recurrent ischemic events and bleeding.

Acute Disease↗
PubMed1982

Indium-111-labeled platelets: effects of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time.

The goal of heparin therapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin therapy is unclear. To explore this relationship, we studied the effect of several heparin regimens on the accretion of indium-111-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5. Platelet accretion by venous thrombi occurs within narrow limits of heparin effect as reflected by the APTT.

Animals↗
PubMed1996

Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial.

BACKGROUND: Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. METHODS AND RESULTS: Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. CONCLUSIONS: Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.

Adult↗
PubMed1999

Automated heparin-delivery system to control activated partial thromboplastin time: evaluation in normal volunteers.

BACKGROUND: Unfractionated heparin is used widely; however, control of the level of anticoagulation remains its greatest problem, with fewer than 35% of patients having activated partial thromboplastin times (aPTTs) within a range of 55 to 85 seconds in recent trials. METHODS AND RESULTS: We developed and tested a prototype of an automated heparin control system (AutoHep) in which a computer-based titration algorithm adjusted the heparin infusion to reach a target aPTT. In 1 study, 12 healthy male subjects received an intravenous infusion of heparin with the rate determined by AutoHep and were randomized to receive an initial bolus or no bolus of heparin preceding the infusion. A second study evaluated the automated blood sampling system in 12 subjects. Of the 344 end-point aPTT measurements, 78% were within +/-10 seconds of the target (prespecified primary end point), and 89% were within a +/-15-second range. The time to achieve a target aPTT was 93 minutes without and 150 minutes with an initial heparin bolus. The total percentage of time within the target range +/-15 seconds was 46 of 48 hours (96%). The automatic blood sampling system successfully obtained 96% of all scheduled samples. CONCLUSIONS: These results suggest that the AutoHep system has the potential to significantly improve aPTT control of intravenous heparin compared with current clinical practice.

Adult↗