Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Continuous infusion heparin therapy was monitored in twenty-five patients with simultaneously performed activated partial thromboplastin times and activated clotting times. These data were then compared by means of the coefficient of correlation. Significant correlation is demonstrated between the APTT and ACT in 88 per cent of cases.
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PMID:Bedside monitoring of heparin therapy. 66 5

Org 10172 provided adequate anticoagulation for this patient. An excellent correlation between anti-factor Xa activity and ACT was observed at the doses used for CPB. If high-dose Org 10172 is used, these data suggest that it may be possible to circumvent the measurement of anti-factor Xa activity by using the ACT as an index of this heparinoid's anticoagulant effect. Because postoperative bleeding may be excessive, however, development of a method of reversal of Org 10172 is desirable. Although the optimal ACT, dose, plasma concentration, and means of reversal (e.g., protamine vs. heparinase) remains to be determined, heparinoids provide an alternate means of anticoagulation for CPB in patients unable to receive standard heparin.
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PMID:"Heparin-free" cardiopulmonary bypass: first reported use of heparinoid (Org 10172) to provide anticoagulation for cardiopulmonary bypass. 169 48

Several laboratory methods are available to measure the anticoagulant activity of recombinant hirudin (r-hirudin), a potent thrombin inhibitor. These assays include clot-based, amidolytic, immunologic and physicochemical techniques. Although r-hirudin, like heparin, is an effective anticoagulant, the mechanism of action of the two agents is different. Thus it is not surprising that the global tests, such as the prothrombin time (PT), partial thromboplastin time (APTT) and the Heptest (Haemachem, Inc., St. Louis, Mo., USA), do not show adequate responses to r-hirudin. In the range of 0.5-10.0 microgram/ml, where full anticoagulation is achieved, as determined by animal models of thrombosis, these assays show little to no prolongation of the time to clot. In order to find a more suitable assay system, modifications of the above assays were evaluated. The diluted APTT and diluted Heptest showed linear concentration-dependent responses to lower levels of r-hirudin with an enhanced sensitivity than that of the classical assays. On the other hand, the diluted thrombin time was too sensitive. Whole-blood clotting assays, ACT and thrombelastograph, effectively measured r-hirudin levels up to 25 micrograms/ml. The amidolytic anti-factor IIa assay, specific for evaluating direct thrombin inhibition, was very effective particularly when modified to decrease the sample:thrombin ratio. This assay may be useful in quality control since it is biochemically defined, and reagents are easily standardized. The relevance of the results of the anti-IIa assay to clinical conditions, however, remains to be determined. Thrombin generation assays have limited value in monitoring the anticoagulant effect of r-hirudin since the effect of thrombin inhibition by r-hirudin on coagulation feedback mechanisms, and thus the effect on thrombin generation, appears to be minimal. Immunologic methods such as ELISA and RIA are under development, but they may only be useful for the direct quantitation of absolute levels of r-hirudin and not for monitoring the clinical anticoagulant action. Furthermore, these assays are only sensitive to sub-microgram/ml levels. Therefore, thrombin-based clotting and amidolytic assays may at present be the best choice for evaluating the functional, clinical antithrombotic effects of r-hirudin.
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PMID:Laboratory assays for the evaluation of recombinant hirudin. 130 Oct 38

Various preparations of heparin from different manufacturers are commercially available. The influence of bovine lung heparin (BLH) and porcine mucosal heparin (PMH) on anticoagulation and heparin plasma concentration was investigated in four groups of 10 patients undergoing elective aortocoronary bypass grafting either after single dose or repetitive dose (after 60 minutes) of one of these heparin preparations. Heparin plasma concentration increased significantly after injection of heparin (BLH: minimum, 1.67 U/mL; maximum, 2.10 U/mL; PMH: minimum, 1.69 U/mL; maximum, 2.15 U/mL). Sixty minutes after the initial dose, heparin plasma levels were higher in the patients who received PMH. Supplemental heparin doses 60 minutes after the loading dose increased plasma heparin concentration only with porcine mucosal heparin. Elimination of heparin in the urine was not different among the groups. Fibrinogen and antithrombin III concentrations, as well as activated clotting time (ACT; always greater than 400 seconds) and partial thromboplastin time (PTT; always greater than 300 seconds), did not differ among the groups, indicating effective anticoagulation during the bypass period with both types of heparin. It can be concluded that sufficient anticoagulation can be achieved with either kind of heparin. PMH seems to be longer acting and a repeat dose in these patients seems to be necessary only if cardiopulmonary bypass lasts longer than 90 minutes.
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PMID:Does the preparation of heparin influence anticoagulation during cardiopulmonary bypass? 193 49

The rate of acute restenosis in patients after percutaneous transluminal coronary angioplasty (PTCA) is related to thrombotic complications triggered by the PTCA. This risk is reduced by anticoagulating the patients with heparin after the procedure. The anticoagulation state of patients receiving heparin therapy is routinely monitored with the activated partial thromboplastin time (APTT) test. In an effort to provide more timely results regarding the status of patients who are receiving heparin after PTCA, a study was conducted to see whether low-range activated clotting time measurement (LR ACT) performed at the bedside could provide information comparable to that from APTT values determined in the laboratory. The study showed that the LR ACT values were comparable to laboratory-generated APTT values (R2 = 0.68). The LR ACT data generated were superior to the APTT data in terms of timeliness and the wider range of heparin levels covered. Having these values available allowed the CCU staff to react rapidly to changes in the patient's coagulation status.
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PMID:Heparin monitoring in the coronary care unit after percutaneous transluminal coronary angioplasty. 234 Dec 65

Hemorrhagic disorders due to systemic heparinization are frequent during extracorporeal lung support (veno-venous extracorporeal membrane oxygenation: vv-ECMO). The development of heparin-coated systems has reduced the need for high-dose heparinization. Whereas the use of these heparin-coated membrane lungs and tubings has been described in former studies in adults, only few reports exist in children. This case report describes the application of a heparin-coated extracorporeal system for long-term vv-ECMO in a 13-month-old infant suffering from acute hypoxic respiratory failure after correction of tetralogy of Fallot. Only moderately elevated levels of activated clotting time (ACT, 120-160 s) and activated partial thromboplastin time (aPTT, 40-60 s) were necessary to avoid thrombotic events in the extracorporeal system. Thoracotomies were performed twice without bleeding complications by discontinuation of the systemic heparinization. We conclude that the use of heparin-coated membrane lungs in infants may improve the safety of extracorporeal lung support and permits surgical intervention without major risk of bleeding.
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PMID:Extracorporeal membrane oxygenation with heparin-coated systems in a 13-month-old infant with acute hypoxic respiratory failure after correction of tetralogy of Fallot. 760 51

Heparin anticoagulation during cardiovascular surgical procedures remains poorly investigated and understood. The objective of this investigation was to assess the effectiveness of three methods of heparin administration. Heparin sulfate (75 IU/kg) administered to patients undergoing aortoiliac surgery was randomised to one of three methods: Group I (n = 9) heparin was injected into a central venous line 5 minutes before infrarenal aortic clamping; Group II (n = 9) heparin was injected into the distal aneurysm immediately after infrarenal aortic clamping; and Group III (n = 8) heparin was injected into a central venous line immediately after infrarenal aortic clamping. Blood samples were analysed for anticoagulant activity from both the upper and lower extremities at 5, 15, 30, 60, and 120 minutes after heparin administration. Anticoagulation, as measured by aPTT, antifactor Xa levels, and ACT, was achieved in all three groups by 5 minutes, but initially with lower heparin activity (measured as antifactor Xa) in the upper extremity (Group II) and lower extremity (Group III), respectively. These differences were also evident in ACT and aPTT determinations. Intravenous heparin administration prior to aortic cross-clamping achieves excellent anticoagulation (anti-factor Xa approximately 1 U/ml) in both upper and lower extremities after 5 minutes. With regional administration, rapid heparin redistribution occurs, but it takes longer to achieve the same level of anticoagulation distant from the site of administration. Nevertheless, from a practical perspective the method of administration does not appear to have a great influence on the eventual achievement of adequate anticoagulation.
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PMID:Time-related anticoagulation after regional and systemic administration of heparin in patients undergoing aortoiliac surgery. 781 23

The standard high-range activated clotting time (sHR ACT) is used to monitor anticoagulation postangioplasty (PTCA), but may be unreliable. We assessed the accuracy of a new method we termed the ACT differential (ACT Diff), obtained by measuring the difference between an sHR ACT and a heparinase ACT from the same sample. Heparinase removes heparin from its sample and provides a current heparin-free baseline. For phase 1 of the study, the sHR ACT, ACT Diff, and laboratory APTT were measured in 250 samples from 75 PTCA patients. In 125 samples with an APTT prolonged but within measurement range, linear regression against the APTT was performed. The correlation coefficient was 0.74 for the ACT Diff and 0.24 for the sHR ACT. An ACT Diff of 15-25 sec was found to equal an APTT of 2.5-3.5 x control. In 50 samples with a normal activated partial thromboplastin time (APT), there was good differentiation by the ACT Diff of results from those adequately heparinized, with a value of 0.9 +/- 4.4 sec. The sHR ACT was 114 +/- 15.5 sec, and could not reliably distinguish between anticoagulated and nonanticoagulated samples. In 75 samples obtained with a high APTT (above measurement range), the ACT Diff was > 30 sec in 95% of samples, and again this allowed differentiation from therapeutic samples. The equivalent sHR ACT was 148 sec, and could not reliably distinguish between anticoagulated and overanticoagulated samples as the ACT Diff could. In phase 2, to examine the clinical usefulness of the ACT Diff, 286 patients were managed post-PTCA by starting heparin when ACT Diff fell to < 50 sec, maintaining ACT Diff at 15-25 sec during heparin infusions, and following cessation of heparin, by removing sheaths when the ACT Diff was < 7 sec. These patients were compared to a control group of 250 patients. Major bleeding (5% vs. 0.5%, P < 0.005) and minor bleeding (30% vs. 13%, P < 0.001) were significantly reduced in the group managed using the ACT Diff. The reduction in bleeding was thought to be due to the rapid availability of reliable results. Abrupt closure was low in both groups (0% with ACT Diff vs. 0.8%). No other thrombotic events occurred. Following phases 1 and 2, the ACT Diff replaced the APTT in all PTCA patients at this institution. In the 18 mo from July 1993, 1,104 patients were managed this way. Incidence of major bleeding (0.2%), transfusion requirement (0.1%), false anneurysm (0.6%), and abrupt closure during heparin infusion (0.1%) remained low. In conclusion, the ACT Diff is more accurate than an sHR ACT, and its clinical use in PTCA patients is associated with a very low incidence of complications from anticoagulation. Its routine use should be considered by units unable to obtain rapid APTT results.
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PMID:Activated clotting time differential is a superior method of monitoring anticoagulation following coronary angioplasty. 880 69

A new microsample coagulation analyzer (Hemochron Jr.) has recently been developed which performs a modified activated clotting time (ACT+) and an aPTT by using different reagents. The Hemochron Jr. measures the clotting time of a 5-microliter whole-blood sample by an optical detector and extrapolates the results to the activated clotting time (ACT+) or the plasma-activated partial thromboplastin time by using a validated regression analysis. We compared 124 simultaneous ACT+ and Hemochron ACTs, and 53 paired Hemochron Jr. aPTTs and hospital laboratory aPTTs, in 44 patients during coronary intervention. The Hemochron Jr. aPTT closely correlated with the lab aPTT (r = .79, P < .0001), and the test results were available much more rapidly than the lab aPTT (3.5 +/- 1.1 vs. 56.3 +/- 25.5 min, P = 0.0029). A comparison of duplicate ACT+ measurements did not identify a significant difference in the means (292 +/- 115 sec vs. 293 +/- 112 sec, P = 0.72). The ACT+ closely correlated with the Hemochron ACTs (r = .85, P < .0001). At baseline, the mean ACT+ (175 +/- 43 sec) exceeded the Hemochron ACT (144 +/- 36 sec) by 22% (P < .001). After heparin administration, the mean ACT+ (378 +/- 74 sec) exceeded the Hemochron ACT (332 +/- 65) by 12% (P < .001). The Hemochron Jr. provides a fast and reproducible methodology for measuring ACT and aPTT, using a small blood volume. Further studies are required to determine the optimal anticoagulation range when using the Hemochron Jr. during or after interventional procedures.
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PMID:Clinical evaluation of a microsample coagulation analyzer, and comparison with existing techniques. 887 58

Using the dog as an animal model, we developed an experimental preparation to compare hemodynamic and hematologic toxicity of anticoagulation reversal. Currently, protamine sulfate reversal of standard unfractionated heparin and low-molecular-weight heparin (LMWH) anticoagulation causes adverse side effects, including decreased systemic mean arterial pressure (MAP), decreased cardiac output (CO), decreased oxygen consumption (VO2), and thrombocytopenia. In addition, standard protamine is only marginally effective at reversing the factor Xa inhibition induced by LMWHs. We have produced protamine-like variant peptides to decrease the adverse responses attributed to standard protamine. The hemodynamic, hematologic, and coagulation effects of standard protamine and the protamine variant (+18RGD) were assessed after reversal of LMWH anticoagulation in anesthetized dogs. Flow probes and vascular catheters were surgically implanted for measurement of hemodynamic parameters including MAP, CO, VO2, and heart rate (HR). Hematologic studies (platelet and white blood cell counts) and coagulation studies (activated clotting time [ACT], activated partial thromboplastin time [aPTT], thrombin clotting time [TCT], antifactor Xa and antifactor IIa values) also were performed. The protamine variant +18RGD was less toxic, induced less thrombocytopenia, and was more effective in anticoagulation reversal than was standard protamine sulfate. Results of this study indicate that the dog may be a useful model for investigating important hemodynamic, hematologic, and coagulation parameters during reversal of LMWH anticoagulation by use of synthetic protamine variants.
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PMID:Comparison of the hemodynamic and hematologic toxicity of a protamine variant after reversal of low-molecular-weight heparin anticoagulation in a canine model. 915 Apr 94


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