Near-patient testing for coagulopathy after cardiac surgery{dagger}

R. R. Johi1, M. H. Cross1 and S. D. Hansbro2

1 Department of Anaesthesia and 2 Department of Clinical Perfusion, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK

Corresponding author. E-mail: michael.cross@leedsth.nhs.uk
{dagger}This article is accompanied by Editorial I.

Accepted for publication: September 9, 2002


    Abstract
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Background. We assessed the accuracy and precision of a new near-patient testing system (Hemochron® Response) by measuring prothrombin time and activated partial thromboplastin time (PT and APTT) in 50 patients undergoing cardiac surgery using cardiopulmonary bypass and comparing the results with laboratory assays.

Methods. Blood samples were taken at the beginning of surgery and the PT and APTT was measured both in the laboratory and by the Hemochron® Response. The tests were repeated 30 min after reversal of heparin with protamine.

Results. Before bypass, the bias for PT was only +0.34, with small 95% limits of agreement. Making the same measurements after bypass, the Hemochron® Response under-read and the bias was –3.27, with an increase of the 95% limits of agreement. With the APTT, the bias and the 95% limits of agreement were greater before bypass, and became even wider after bypass.

Conclusions. We found good agreement in the PT and clinically acceptable levels of agreement in the APTT during the pre-bypass period. After bypass, bias became greater for both PT and APTT and the limits of agreement could be clinically unacceptable.

Br J Anaesth 2003; 90: 499–501

Keywords: complications, coagulopathy; heart, cardiopulmonary bypass; measurement techniques, coagulation; surgery, cardiovascular


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Excessive bleeding after cardiac surgery is a common problem with many causes. Although inadequate haemostasis may be a cause, abnormal coagulation after bypass can also contribute to the problem. Traditionally, the activated clotting time (ACT) is used to assess heparin reversal, and laboratory testing of the prothrombin time (PT) and the activated partial thromboplastin time (APTT) is used to guide therapy. The time to obtain laboratory reports of PT and APTT is often longer than clinicians would wish, and delayed information can lead to non-specific management of postoperative bleeding after cardiac surgery. This can be life threatening, costly and wastes valuable resources.1 Near-patient testing (NPT) of coagulation provides results rapidly and allows early decisions about the appropriate use of blood products when postoperative bleeding occurs.

We compared the results from a new NPT system (Hemochron® Response Whole Blood Coagulation System, International Technidyne Corporation Limited, Margate, Kent, UK) with laboratory results in samples from patients undergoing cardiac surgery using cardiopulmonary bypass. The equipment used to measure PT and APTT is also used to measure the ACT during the intraoperative period, and is therefore widely available in many cardiac operating theatres.


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
After obtaining local ethics committee approval and informed written consent, 50 patients undergoing coronary artery or valve surgery using cardiopulmonary bypass were studied. Patients receiving treatment with oral anticoagulants or heparin were excluded. The conduct of anaesthesia was not restricted by the study. Intraoperatively, aprotinin was given depending upon the surgeon’s preference.

The samples were taken by a single observer to standardize the technique and minimize sampling errors. After aspirating 8 ml from an arterial cannula (to clear the dead space), another 8 ml of blood was aspirated for the study. Exactly 2 ml of blood was transferred into each of the PT and APTT assay tubes (as described by the manufacturer). The tubes were vigorously shaken to achieve even mixing of blood and activation of the reagent before placing in the machine. Simultaneously, 1.4 ml of citrated blood was sent to the laboratory as a control. The tests were performed at two times; before systemic anticoagulation with heparin; and 30 min after reversal of heparin with protamine.

The Hemochron® Response measures PT, APTT, ACT and also estimates the international normalized ratio. Glass tubes containing a specific activator for PT and APTT and a small magnet are partially filled with blood and placed in the machine. The activating agent used in the PT tube is rabbit brain thromboplastin and in the APTT tube is kaolin and platelet factor substitute. Two magnetic detectors located in the test well continuously monitor the precise position of the magnet. When a specific displacement of the magnet occurs, the time between the beginning of the test and this clot end-point is displayed as the coagulation time for fresh whole blood. The plasma PT and APTT are subsequently calculated from the whole blood clotting value and displayed immediately.

In the laboratory, PT was measured using Instrumentation Laboratory (IL) PT-fibrinogen recombinant reagent and the ACL thousand series coagulation analyser. PT-fibrinogen recombinant reagent is a mixture of recombinant rabbit tissue thromboplastin, synthetic phospholipid and calcium ions. The ACL analyser determines the coagulation time by monitoring turbidity during coagulation. IL APTT reagent is a mixture of micronized silica and bovine brain cephalin. A mixture of plasma and APTT reagent is incubated for 5 min before being recalcified with a volume of calcium chloride. The coagulation time is determined by the ACL coagulometer in the same way as the PT using a combination of centrifugal and nephelometric analysis. Bias analysis, according to Bland and Altman,2 was used to test the agreement between the results.


    Comment
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Rapid evaluation of a coagulopathy following cardiac surgery is important if a rational approach to treatment is to be taken. Amongst the various tests of coagulation, thrombelastography is becoming widely accepted as being useful in this context. It is sensitive to heparin, allowing easy detection of residual heparin, and can diagnose coagulopathy. It can distinguish between coagulopathy caused by a platelet defect or a clotting factor defect.3 However, the need for precise operation of the equipment can limit its use in the operating room and many centres therefore continue to use ACT to confirm heparin reversal, and laboratory tests (platelet count, PT and APTT) to detect coagulopathy. A combination of these results can then be used in an algorithm to direct treatment of postoperative bleeding.1 Bedside monitors of coagulation in the intensive care unit have been assessed before.411 Although there is no strict definition of acceptable accuracy or precision for these monitors, an accuracy of ±10% and a precision of ±25% has become accepted.8 A direct comparison of this study with others is difficult because of differences in statistical methods and the patient population, but most studies suggest that the agreement with the laboratory result is good for the PT, but much less acceptable for the APTT. Lack of standardization of APTT reagents or transport time may be important in this respect. The results for both the PT and APTT for tests before bypass are similar to other studies and many clinicians would consider the agreement clinically acceptable. After cardiopulmonary bypass, the bias becomes greater and, although this in itself is not a problem, the worsening of the limits of agreement (much beyond the 25% limit for clinical acceptability) may make the clinician unhappy to use this monitor to measure the PT, or more especially the APTT. The reason for this change in agreement is not clear, but the transport time and the APTT reagent differences should not be relevant to this. The Hemochron® Response results are probably affected by haemodilution or platelet function, neither of which is important for the plasma-based laboratory tests.

The Hemochron® Response gives APTT and PT results rapidly following cardiac surgery but the accuracy and precision of the results means that the monitor is unsuitable for assessment of coagulopathy following cardiac surgery.


View this table:
[in this window]
[in a new window]
 
Table 1 Bias and precision comparing Hemochron® Response and ACL analyser
 

    References
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
1 Despotis GJ, Santoro SA, Spitznagel E, et al. Prospective evaluation and clinical utility of on-site monitoring of coagulation in patients undergoing cardiac operation. J Thorac Cardiovasc Surg 1994; 107: 271–9[Abstract/Free Full Text]

2 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1: 307–10[ISI][Medline]

3 Shore-Lesserson L, Manspeizer HE, DePerio M, et al. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999; 88: 312–19[Abstract/Free Full Text]

4 Lucas FV, Duncan A, Jay R, et al. A novel whole blood capillary technique for measuring the prothrombin time. Am J Clin Pathol 1987; 88: 442–6[ISI][Medline]

5 Ansell J, Tiarks C, Hirsh J, Mcgehee W, Adler D, Weibert R. Measurement of the activated partial thromboplastin time from a capillary (finger stick) sample of whole blood. Am J Clin Pathol 1991; 95: 222–7[ISI][Medline]

6 O’Neil AI, McAllister C, Corke CF, Parkin JD. A comparison of five devices for the bedside monitoring of heparin therapy. Anaesth Intensive Care 1991; 19: 592–6[ISI][Medline]

7 Hirsch J, Wendt T, Kuhly P, Schaffartzik W. Point-of-care testing measurement of coagulation. Anaesthesia 2001; 56: 760–3[CrossRef][ISI][Medline]

8 Reich DL, Yanakakis MJ, Vela-Cantos FP, DePerio M, Jacobs E. Comparison of bedside coagulation monitoring tests with standard laboratory tests in patients after cardiac surgery. Anesth Analg 1993; 77: 673–9[Abstract]

9 McCurdy SA, White RH. Accuracy and precision of a portable anticoagulation monitor in a clinical setting. Arch Intern Med 1992; 152: 589–92[Abstract]

10 Samama CHM, Quezada R, Riou B, et al. Intraoperative measurement of activated partial thromboplastin time and prothrombin time with a new compact monitor. Acta Anesth Scand 1994; 38: 232–7[ISI][Medline]

11 Boldt J, Walz G, Triem, Suttner S, Kumle B. Point-of-care (POC) measurement after cardiac surgery. Intensive Care Med 1998; 24: 1187–93[CrossRef][ISI][Medline]