Clinical Chemistry AACC Online Job Center
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 47: 858-866, 2001;
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ambrose, T. M.
Right arrow Articles by Luchtman-Jones, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ambrose, T. M.
Right arrow Articles by Luchtman-Jones, L.
Related Collections
Right arrow Pediatric Clinical Chemistry
Right arrow Hemostasis and Thrombosis
(Clinical Chemistry. 2001;47:858-866.)
© 2001 American Association for Clinical Chemistry, Inc.

Articles

Evaluation of the TAS Analyzer and the Low-Range Heparin Management Test in Patients Undergoing Extracorporeal Membrane Oxygenation

Theresa M. Ambrose1,1, Curtis A. Parvin1, Eric Mendeloff2 and Lori Luchtman-Jones3a

Washington University School of Medicine, Departments of
1 Pathology Box 8118,
2 Cardiothoracic Surgery Box 8234, and
3 Pediatrics Box 8116, 660 South Euclid Ave., St. Louis, MO 63110.

aAuthor for correspondence. Fax 314-454-2780; e-mail LUCHTMAN{at}pcfnotes1.wustl.edu.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: The new Low-Range Heparin Management Test (LHMT), a method for point-of-care testing (POCT) of heparinization, has been designed to function at the low to moderate heparin concentrations typically found in patients undergoing extracorporeal membrane oxygenation (ECMO). In this study, the new method is compared with two POCT methods and a laboratory-based anti-Xa assay.

Methods: We obtained 760 whole blood samples from 13 patients undergoing ECMO. All samples were tested immediately by the LHMT, the Activated Clotting Time (ACT) test, and its low-range counterpart (ACT-LR). Aliquots from the same blood draw were frozen for later anti-Xa analysis using the Diagnostica Stago method on the Roche Cobas Fara-II.

Results: The precision was best for duplicate citrated LHMT samples (CV = 3.1%). LHMT clotting times (overall median, 162 s) were typically shorter than ACT or ACT-LR times (247 and 235 s, respectively). The relationship between the LHMT and the other POCT methods differed significantly from patient to patient (P <0.0001), and a meaningful single relationship between the methods could not be obtained. The overall correlation coefficient between clotting time values and actual heparin concentrations was <=0.48 for each of the instruments tested, although time plots of each analyzer’s data suggested that they detected heparin dosage changes within single patients.

Conclusions: The performance of the LHMT on the TAS Analyzer is equivalent to that of currently commercially available POCT methods. The lack of agreement between absolute clotting time values and heparin concentrations suggests the need for reexamination of current ECMO patient management strategy.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Since 1975, more than 11 000 critically ill infants have been treated using extracorporeal membrane oxygenation (ECMO)2 (1). A modified form of heart-lung bypass, ECMO provides temporary cardiopulmonary support when conventional modes of therapy have failed (2). ECMO patients are systemically heparinized to minimize activation of the clotting system as their blood circulates through the ECMO circuit. Because such critically ill patients have multiple risk factors for hemorrhage and thrombosis (2)(3)(4), frequent monitoring of the extent of heparinization is performed throughout the ECMO procedure. Although the College of American Pathologists has issued specific recommendations regarding the monitoring of unfractionated heparin therapy in patients with thromboembolic disorders and multiple clinical trials have clearly established the target therapeutic heparin concentrations for these patients at ~0.2–0.4 kIU/L (5)(6), comparable information for ECMO patients is not yet available.

Several types of tests are available for monitoring systemic heparinization. The activated partial thromboplastin time, routinely performed in most laboratories, evaluates the activity of several coagulation factors affected by heparin. Although the thrombin clotting time is widely available, it is used infrequently for the purposes of monitoring heparin. Because critically ill patients have multiple risk factors for coagulopathies, both tests yield nonspecific qualitative results. A more specific evaluation involves measuring heparin in blood by quantifying its inhibition of coagulation factor Xa (3). The anti-Xa assay performs well at the lower heparin concentrations typically found in ECMO patients (0.05–0.70 kIU/L), but it is performed infrequently in a limited number of laboratories.

Bedside testing of whole blood specimens offers the advantages of immediate access to results and smaller sample volumes. The Activated Clotting Time (ACT) test was developed for bedside monitoring of systemic heparin therapy during procedures such as cardiopulmonary bypass and hemodialysis. However, its use in both adult and pediatric patient populations has been complicated by the variability between different analyzers (5)(7)(8)(9)(10) and the lack of a linear relationship between ACT values and heparin concentration (5)(9)(11)(12). Nonetheless, it is the preferred test for monitoring the systemic heparinization of ECMO patients (8), and a survey of active ECMO centers revealed that it most often performed on the Hemochron analyzer (13). The current ECMO patient management strategy involves adjustment of heparin dosage to maintain whole blood ACTs within a particular target range. The Heparin Management Test (HMT) test card for use on the TAS Analyzer provides an alternative point-of-care system for heparin monitoring (14), but the accuracies of both the ACT and the HMT are limited at heparin concentrations <1 kIU/L (15). Recently, two point-of-care testing (POCT) methods have been developed for use at the low to moderate heparin concentrations typical for ECMO patients: the Low-Range ACT (ACT-LR) for use on the Hemochron Jr. instrument and the Low-Range Heparin Management Test (LHMT) for use with the TAS Analyzer.

The LHMT consists of a single-use test card containing dried clotting reagents and paramagnetic iron oxide particles. The test is performed by placing the LHMT card into the TAS Analyzer and adding a drop of whole blood (citrated or noncitrated). When the test is initiated, a magnetic field is applied, and the motion of the iron oxide particles is monitored optically. The test stops when the sample clots, immobilizing the particles, and the time is reported in seconds (16). Because of its appropriate linear range, convenience, and small sample requirements, the LHMT may offer particular advantages over the currently used ACT method for monitoring heparin therapy in ECMO patients. Although preliminary data have demonstrated good correlations between the LHMT and the ACT in anti-Xa in cardiac surgery patients (17), the LHMT test card has not yet been evaluated in ECMO patients, who typically are maintained at lower heparin concentrations.

The purpose of this study was to evaluate the LHMT on the TAS Analyzer in patients undergoing ECMO. The LHMT was compared with the POCT method currently used to guide clinical decision making (the ACT), with a laboratory-based reference method (heparin quantification via anti-Xa assay), and with another test designed for bedside heparin monitoring at low to moderate concentrations (ACT-LR).


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
materials
LHMT cards, control materials, and the TAS Analyzers were provided by Cardiovascular Diagnostics, Inc. (Raleigh, NC). The TAS Analyzer currently is marketed by Bayer (Tarrytown, NY) as the Rapid Point Coag. ACT tubes and control materials, for use on the Hemochron Model 401, as well as ACT-LR cuvettes for use on the Hemochron Jr. Signature were obtained from International Technidyne Corporation. All bedside testing was performed according to the manufacturer’s instructions provided in the instrument operator’s manual and the reagent package inserts. During active study periods, quality-control (QC) testing was performed on each device at least once per shift. Both normal and abnormal controls were run for the TAS and the Hemochron. An electronic QC device was used to ensure the performance of the Hemochron Jr. All analyzers remained within their established QC specifications for the duration of the study.

The quantitative determination of unfractionated heparin concentrations in plasma was performed by measuring anti-Xa activity in patient plasma samples using the Stachrom Heparin reagent set (Diagnostica-Stago) on the Cobas-Fara II Analyzer (Roche Diagnostics).

subjects
All patients undergoing ECMO and receiving unfractionated heparin in the Pediatric Intensive Care Unit at St. Louis Children’s Hospital between November 1, 1999, and February 15, 2000, were included in this study. Patient characteristics are given in Table 1 . Patients were managed according to the standard institutional ECMO protocol (see Table 2 ). Only results from one POCT instrument, the Hemochron Jr., were used for clinical decision making. Study sampling and testing (see below) was begun within 3–6 h of the initial heparin bolus. This study was approved by the Institutional Review Board of the Human Studies Committee at Washington University School of Medicine; the need to obtain informed consent was waived.


View this table:
[in this window]
[in a new window]
  		Table 1. Patient characteristics: age and indication for ECMO.


View this table:
[in this window]
[in a new window]
  		Table 2. Selected criteria from ECMO protocol at St. Louis Children’s Hospital.

sample testing
ECMO patients routinely have blood drawn for various laboratory tests as part of their standard clinical care (see Table 2Up ). Excess blood from these scheduled draws was tested in parallel using the various POCT methods. All bedside testing was performed in duplicate immediately after whole blood sample collection. Because of limited sample stability, two of each analyzer were used to avoid testing delays because clotting begins immediately in whole blood samples. For all POCT analyses, blood was dropped from the original plastic collection syringe directly onto the analyzer. At designated intervals, the remaining blood was used to fill a standard 1.8-mL blue-top tube containing 32 g/L sodium citrate to maintain a blood:anticoagulant ratio of 9:1. After thorough mixing, blood was withdrawn from this tube with a syringe and used to perform the citrated LHMT tests. Aliquots of blood from this same tube were centrifuged to prepare platelet-poor plasma (using two 15-min spins at 3000g) and frozen for later anti-Xa analysis. Processing took place within 30 min of collection.

statistical analysis
Calculations involving patient results were performed using the mean of the duplicate instrument readings. Data from a patient on aprotinin were excluded from the overall analysis (see Discussion below). Because the distribution of the data was skewed, the median clotting times were determined for the various instruments and compared using the Mann–Whitney rank-sum test. Duplicate sample precision was calculated by taking the difference between the two readings, expressing this value as a percentage of the mean of the two readings, and then taking the mean of all percentage values thus obtained. Day-to-day precision was estimated by calculating the CV of repeated measurements of control material. When the linear regression methods recommended by the NCCLS guidelines (18) were inadequate to describe the data, curve fits were calculated using the robust regression method (19). Analysis of covariance (ANCOVA) was also performed using Stata (Stata Press). All other statistical analyses were carried out with Sigma Stat (Jandel Corporation) or Microsoft Excel (Microsoft Corporation).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
precision
The day-to-day precision of the TAS Analyzer was superior to that of the Hemochron analyzer, with a CV of 3.9% (n = 125) compared with a CV of 8.4% (n = 45). Because electronic QC was used with the Hemochron Jr., the readings never varied. The duplicate sample precision was similar for all bedside tests evaluated. The citrated LHMT test had the lowest average difference of 3.1% (n = 206), followed by the ACT-LR with 3.5% (n = 577), the ACT with 4.1% (n = 638), and the whole-blood LHMT with 4.6% (n = 621).

accuracy
Comparison of LHMT with other POCT methods.
Table 3 lists the median clotting times obtained using the various POCT methods. The clotting times obtained using the TAS Analyzer with either citrated or noncitrated whole blood were significantly shorter than those obtained using either the Hemochron or the Hemochron Jr.; these differences were statistically significant (P <0.001; see Table 4 ). Because regression techniques were inadequate to describe the overall relationship among the various POCT methods, a meaningful single estimate of overall bias between the instruments could not be obtained. Instead, ANCOVA analysis revealed that the relationship between each instrument pair varied significantly from patient to patient (P <0.0001; see Figs. 1 and 2 ). It can be seen from Table 4 that correlations between the various instruments were weak even for individual patients.


View this table:
[in this window]
[in a new window]
  		Table 3. Median clotting times obtained using the various POCTs.


View this table:
[in this window]
[in a new window]
  		Table 4. Correlation coefficients for POCT clotting times vs clotting times obtained by a different POCT method.



View larger version (49K):
[in this window]
[in a new window]
  		Figure 1. LHMT clotting times vs ACT clotting times for nine representative ECMO patients, along with robust regression curves.



View larger version (49K):
[in this window]
[in a new window]
  		Figure 2. LHMT clotting times vs ACT-LR clotting times for nine representative ECMO patients, along with robust regression curves.

Comparison of POCT methods with a laboratory-based heparin assay.
The correlations between clotting time values and actual heparin concentrations as determined by the anti-Xa assay were poor for each of the tests evaluated. Although the overall correlation coefficients were statistically significant (P <0.00001; see Table 5 ), an individual clotting time value is not predictive of the anti-Xa activity of the sample (see Fig. 3 ).


View this table:
[in this window]
[in a new window]
  		Table 5. Correlation coefficients for POCT clotting times vs plasma heparin concentration as determined via anti-Xa assay.



View larger version (36K):
[in this window]
[in a new window]
  		Figure 3. Clotting times vs plasma heparin concentration as determined by anti-Xa assay for the various POCT methods.

Effect of aprotinin.
It was observed that coadministration of the drug aprotinin to a study patient (patient 2) prolonged clotting times on each of the analyzers, although heparin concentrations remained below 0.66 kIU/L (measured by the anti-Xa assay). Aprotinin, an antifibrinolytic drug, often is administered during cardiac procedures and previously has been shown to potentiate the effects of heparin and further prolong the clotting times in cardiac surgery patients (14)(20)(21). Because the increase in clotting times for patient 2 (see Table 2Up ) was found to be statistically significant (P <0.001), the data from this patient were not included in the overall analysis.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Clotting times obtained with the LHMT did not correlate well with those obtained using other POCT methods or with laboratory-based heparin measurements. The results of this study serve to demonstrate the tremendous variations in coagulation measurements that can be expected in the ECMO patient population. Studies involving cardiac bypass patients have demonstrated that factors such as hemodilution, hypothermia, coagulopathy, platelet activation, and hypercoagulability affect the relationship between heparin dosage, resulting plasma concentration, and clotting times (7)(9)(10)(12). The situation is even more complex in pediatric patients who may have immature coagulation systems (3). In addition, heparin pharmacokinetics, which are age dependent (22), are poorly understood in newborns and children (3). In this study, certain variables that can affect the clotting times, such as hematocrit and platelet count, were tightly controlled according to the institutional ECMO protocol. Additionally, the frequent blood transfusions administered to ECMO patients preclude consideration of coagulation factor deficiencies generally found in newborns. Nevertheless, as in other studies of this kind, it was not possible to control all of the factors involved, and wide variations in coagulation measures were observed.

This study demonstrated significant differences in the clotting time results obtained by different instruments. Indeed, several previous studies have demonstrated that activated clotting time values are known to be very method dependent (5)(7)(8)(9)(10). Although this fact can be partially attributed to analytical factors such as differences in coagulation activators, reagents, detection technologies, and individual operator variability, it is clear that physiological factors also play a role. Indeed, the findings of this study have demonstrated not only that the results on one POCT method do not correlate well with results on other POCT methods, but also that the relationship among the various POCT methods varies significantly from one patient to another. The ANCOVA results suggest that the unknown and uncontrolled physiological variability in the response of the patients to heparinization has a greater impact on the relationship than a controllable analytical factor.

This study also found that the correlation between clotting times (as measured by the LHMT, ACT, or ACT-LR) and actual heparin concentrations (measured by the anti-Xa reference method) is poor. In vitro studies, performed by adding known amounts of heparin to fresh blood samples, have yielded some information about the relationship between clotting times and heparin concentrations. Andrews et al. (7) found that the Hemochron ACT gave a linear relationship with heparin concentrations of 0–5 kIU/L, whereas Despotis et al. (20) found linear correlations at heparin concentrations of 0–0.8 kIU/L. Results obtained using the HMT test on the TAS Analyzer have a log-linear relationship with heparin concentrations of 0–5 kIU/L (14). Although these in vitro studies suggest a predictable relationship between clotting time values and heparin concentrations, the physiological situation encountered in actual testing situations is vastly more complex. Indeed, extremely weak correlations between clotting times and heparin concentrations were obtained in studies using actual ex vivo samples from cardiac patients (9)(11)(12)(21) and ECMO patients (8). Fig. 3Up and Table 5Up emphasize the scatter observed in measurements of samples from ECMO patients. These results demonstrate that a clotting time value obtained using any of these POCT methods cannot be used to predict the actual heparin concentration.

Despite their limitations, any of the POCT devices investigated in this study can be used to monitor clotting time trends and response to changes in heparin dosage for individual patients. Fig. 4 shows the response of the various POCT analyzers to changes in heparin dosage for two ECMO patients. Although an individual measurement gives no predictive information about heparin concentration, it is obvious that the analyzers can be used in a serial fashion to follow clotting time trends. The current management strategy involves adjusting the heparin dosage to keep the clotting times within a particular range of values, typically 200–240 s (on the Hemochron instrument), although the target range can vary from patient to patient depending on the perceived risk of bleeding and would be different if another POCT device were used. The duplicate sample precision obtained in this study demonstrated a CV of 3–5% for the various instruments, corresponding to an ~10–15 s variability in the clotting times. If the instruments are used in a serial fashion and measurements that are close to the decision point are repeated, any of these analyzers is suitable for monitoring changes in heparin dosage in ECMO patients.



View larger version (33K):
[in this window]
[in a new window]
  		Figure 4. Serial response of individual POCT methods for two ECMO patients [patient 6 (top) and patient 8 (bottom)].

Arrows denote increases or decreases in heparin dosage. •, ACT; {blacktriangleup}, ACT-LR; {blacksquare}, LHMT; {diamond}, citrated LHMT.

To further validate this suggested approach, or to define a better one, new heparin management strategies could be explored using an evidence-based medicine approach. In such a pilot study, patients would be randomized to various treatment groups in which all measurements and decisions would be made using only one heparin monitoring method. This method could consist of either hourly clotting time measurements using a point-of-care assay as described in this study, or less frequent heparin concentration measurements using anti-Xa concentrations or a protamine titration method. The effects of other variables, including activated protein C, could also be incorporated into the decision-making process. In addition to overall survival, outcomes examined could include rethrombosis and excessive bleeding. Specific criteria could be developed to define these endpoints, including variables such as time to appearance of the first clot in the ECMO pump or number of units of packed red blood cells required. Such a study evaluating the effects of various heparin monitoring methods relative to clinical outcome would be of interest to the ECMO community.

Although none of the instruments displayed a clear advantage in terms of analytical performance characteristics, they did vary somewhat in terms of ease of use. With the TAS Analyzer, testing starts automatically upon addition of the blood drop to the sample card, whereas the Hemochron and the Hemochron Jr. require various degrees of manipulation for test initiation. Compared with the Hemochron devices, the TAS Analyzer has a more sophisticated user interface, which leads to longer test set-up times but improved data handling capabilities, including patient identification and sample memory. Additionally, the TAS (30 µL) and the Hemochron Jr. (50 µL) require much smaller sample volumes than the Hemochron (400 µL), an important point of consideration for a pediatric patient population.

In conclusion, study results demonstrate that the overall performance of the LHMT on the TAS Analyzer is equivalent to that of currently commercially available POCT devices. The point-of-care coagulation monitors investigated in this study can be used to follow trends in the clotting time and changes in heparin dosage. Different target clotting time ranges would need to be chosen for each specific test and analyzer, and serial measurements should be monitored instead of individual clotting time values. The lack of agreement between absolute clotting time values and heparin concentrations determined by anti-Xa assay suggests the need for reexamination of the ECMO patient management strategy, perhaps in a multicenter pilot study using an evidence-based medicine approach.


   Acknowledgments
 
We wish to thank Cardiovascular Diagnostics, Incorporated for financing this study and providing the TAS Analyzers and LHMT test cards and control materials. We would also like to thank Julie Leumas, Pam Stallings, Stephanie Morrow, Anne Bisch, and all of the Pediatric Intensive Care Unit Nurses at St. Louis Children’s Hospital for their invaluable assistance with the study, as well as Mike Landt for critical reading of the manuscript.


   Footnotes
 
1 Current address: Roche Diagnostics Corporation, Laboratory Systems Division, 9115 Hague Rd., Bldg. A, Indianapolis, IN 46250-0457.

2 Nonstandard abbreviations: ECMO, extracorporeal membrane oxygenation; ACT, activated clotting time; HMT, Heparin Management Test; POCT, point-of-care testing; ACT-LR, low-range ACT; LHMT, low-range HMT; QC, quality control; and ANCOVA, analysis of covariance.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Hansell D. ECMO. The nursing monitor. Winston-Salem 1997 Wake Forest University Baptist Medical Center NC. .
  2. Bartlett RH, Roloff DW, Custer JR, Younger JG, Hirschl RB. Extracorporeal life support: the University of Michigan experience. JAMA 2000;283:904-908.[Abstract/Free Full Text]
  3. Andrew M, Monagle PT, Brooker L. Thromboembolic complications during Infancy and childhood 2000:448pp BC Decker, Inc Hamilton, Ontario, Canada. .
  4. DelaCruz T, Stewart D, Winston S, Weatherman KS, Phelps JL, Mendoza JC. Risk factors for intracranial hemorrhage in the extracorporeal membrane oxygenation patient. J Perinatol 1997;17:18-23.[Medline] [Order article via Infotrieve]
  5. Olson J, Arkin CF, Brandt JT, Cunnigham M, Giles A, Koepke JA, Witte DL. College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy: laboratory monitoring of unfractionated heparin therapy. Arch Pathol Lab Med 1998;122:782-798.[ISI][Medline] [Order article via Infotrieve]
  6. Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med 1993;119:104-109.[Abstract/Free Full Text]
  7. Andrew M, MacIntyre B, Williams W, Gruenwald C, Johnston M, Burrows F. Heparin therapy during cardiopulmonary bypass requires ongoing quality control. Thromb Haemost 1993;70:270-277.[ISI][Medline] [Order article via Infotrieve]
  8. Green TP, Isham-Schopf B, Steinhorn RH, Smith C, Irmiter RH. Whole blood activated clotting time in infants during extracorporeal membrane oxygenation. Crit Care Med 1990;18:494-498.[ISI][Medline] [Order article via Infotrieve]
  9. Martindale SJ, Shayevitz JR, D’Errico C. The activated coagulation time: suitability for monitoring heparin effect and neutralization during pediatric cardiac surgery. J Cardiothorac Vasc Anesth 1996;10:458-463.[ISI][Medline] [Order article via Infotrieve]
  10. Seay RE, Uden DL, Kriesmer PJ, Payne NR. Predictive performance of three methods of activated clotting time measurement in neonatal ECMO patients. ASAIO J 1993;39:39-42.[Medline] [Order article via Infotrieve]
  11. Despotis GJ, Summerfield AL, Joist JH, Goodnough LT, Santoro SA, Spitznagel E, et al. Comparison of activated coagulation time and whole blood heparin measurements with laboratory plasma anti-Xa heparin concentration in patients having cardiac operations. J Thorac Cardiovasc Surg 1994;108:1076-1082.[Abstract/Free Full Text]
  12. Esposito RA, Culliford AT, Colvin SB, Thomas SJ, Lackner H, Spencer FM. The role of the activated clotting time in heparin administration and neutralization for cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983;85:174-185.[Abstract]
  13. Graves DF, Chernin JM, Kurusz M, Zwischenberger JB. Anticoagulation practices during neonatal extracorporeal membrane oxygenation: survey results. Perfusion 1996;11:461-466.[Abstract/Free Full Text]
  14. Gibbs NM, Weightman WM, Thackray NM. Evaluation of the TAS coagulation analyzer for monitoring heparin effect in cardiac surgical patients. J Cardiothorac Vasc Anesth 1998;12:536-541.[ISI][Medline] [Order article via Infotrieve]
  15. Weightman WM, Clapin AOG, Michalopoulis N, Gibbs NM. Sensitivity and specificity of the Hemochron, Hemotec and APTT for the detection of low concentrations of heparin. Anaesth Intensive Care 1996;24:472-476.[ISI][Medline] [Order article via Infotrieve]
  16. Oberhardt BJ, Dermott SC, Taylor M, Alkadi ZY, Abruzzini AF, Gresalfi N. Dry reagent technology for rapid, convenient measurements of blood coagulation and fibrinolysis. Clin Chem 1991;37:520-526.[Abstract/Free Full Text]
  17. . Cardiovascular Diagnostics Corporation, Inc. LHMT Test Cards package insert 1999 Chiron Diagnostics Corporation Walpole, MA. .
  18. . National Committee for Clinical Laboratory Science. Method comparison and bias estimation using patient samples. NCCLS guideline EP9-A 1995 NCCLS Villanova, PA. .
  19. Li G. Robust regression. In: Hoaglin DC, Mosteller F, Tukey JW, eds. Exploring data tables, trends, and shapes. New York: John Wiley & Sons, 1985:281–340..
  20. Despotis GJ, Filos KS, Levine V, Alsoufiev A, Spitznagel E. Aprotinin prolongs activated and nonactivated whole blood clotting time and potentiates the effect of heparin in vitro. Anesth Analg 1996;82:1126-1131.[Abstract]
  21. Culliford A, Gitel S, Starr N. Lack of correlation between activated clotting time and plasma heparin during cardiopulmonary bypass. Ann Surg 1981;193:105-111.[ISI][Medline] [Order article via Infotrieve]
  22. Jick H, Sloane D, Borda JT, Shapiro S. Efficacy and toxicity of heparin in relation to age and sex. N Engl J Med 1968;270:284-286.



The following articles in journals at HighWire Press have cited this article:


Home page
 Br J AnaesthHome page
B. Tremey, B. Szekely, S. Schlumberger, D. Francois, N. Liu, K. Sievert, and M. Fischler
Anticoagulation monitoring during vascular surgery: accuracy of the Hemochron(R) low range activated clotting time (ACT-LR)
Br. J. Anaesth., October 1, 2006; 97(4): 453 - 459.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
S. A Spinler, A. K Wittkowsky, E. A Nutescu, and M. A Smythe
Anticoagulation Monitoring Part 2: Unfractionated Heparin and Low-Molecular-Weight Heparin
Ann. Pharmacother., July 1, 2005; 39(7): 1275 - 1285.
[Abstract] [Full Text] [PDF]

Home page
 PerfusionHome page
D. Giavarina, M. Carta, A. Fabbri, J. Manfredi, E. Gasparotto, and G. Soffiati
Monitoring high-dose heparin levels by ACT and HMT during extracorporeal circulation: diagnostic accuracy of three compact monitors
Perfusion, January 1, 2002; 17(1): 23 - 26.
[Abstract] [PDF]

Home page
 Clin. Chem.Home page
M. Laposata
Point-of-Care Coagulation Testing: Stepping Gently Forward
Clin. Chem., May 1, 2001; 47(5): 801 - 802.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit an electronic Letter to
the Editor about this paper
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ambrose, T. M.
Right arrow Articles by Luchtman-Jones, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ambrose, T. M.
Right arrow Articles by Luchtman-Jones, L.
Related Collections
Right arrow Pediatric Clinical Chemistry
Right arrow Hemostasis and Thrombosis

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS