1. Performance evaluation: Hemochron Junior and i stat ACT devices during CPB
Nabeel Razzaq

2. Why Anticoagulate?
Allows the safe conduct of any form of extracorporeal circulation
Prevent
Activation of Coagulation Cascade - foreign bypass circuit
Clots into the patient - Multiple organ dysfunction
Clots in circuit can trigger DIC
Clot off the oxy and cease extracorporeal support
Death
Electron microscope blood clot and fibrin on oxygenator

3. The need for checking
Monitoring is essential
Speed of clotting effected by- Temperature, Heamodilution, Thrombocytopenia, Coagulopathies, Heparin resistance, Kidney function
POC - Quick and reproducible test needed in this TH environment
Heparin- Most common anticoagulant for CPB / ACT
Reliability is essential for any POC ACT device

4. Background
Currently most machines already out there have a mechanical endpoint
Medtronic: HMS, Act plus - Plunger speed
Helena: Magnet rotation
Hemochron: Fluid movement
(Abbott POC: istat- Amperometric Electroactive Endpoint)
Research already out there
(Ojito et al 2012) 400 data points none above ACT 250
(Lewandrowski et al 2011) 242 data points cardiac surgery range
(Schussler et al 2003) 128 data points
(Paniccia et al 2003) et al 168 samples

5. Our Study International Multi-Centre Study Papworth Hospital Basel
Cape Town
This is the Preliminary data- 171 Patients, 2071 data points to date
400 patients with 5000 data points now had been completed (Very Similar trends)

6. Hemochron Detection mechanism- Mechanical endpoint
Point of detection
Hemochron
Detection mechanism- Mechanical endpoint
0.5ml/ Waste removed / uses 15 microliters out of 50
Sample warmed / clot formation activated by Kaolin or Celite
The sample is moved back and forth through the test channel
Clot detection mechanism
Flow is measured through the narrowing of channel by a series of LED optical detectors When flow reaches below predetermined rate set by Hemochron- thus proposing a fibrin clot, the test stops
Papworth range- > 400 seconds for bypass

7. Electrochemical sensor
Abbott- istat
Detection mechanism - Electrochemical- Amperometric endpoint
Cartridge contains a Thrombin substrate that has an amide linkage which mimics the amide linkage in fibrinogen which thrombin cleaves
Substrate: H-D-phenylalanyl-pipecolyl-arginine-p-amino-p methoxydiphenylamine Structure: Phenylalanine - Pipecolic acid - Arginine -- NH - C6H4 - NH - C6H4 -OCH3
2 drops of blood into cartridge, close flap and insert into machine- warms/mixes
Thrombin cleaves amide bond at carboxy- terminus of arginine in this compound- as it would in fibrinogen

8. Abbott- istat
Electrochemical sensor
Thrombin - Substrate reaction produces the electrochemically inert tripeptide Phenylalanyl - Pipecolyl – Arginine and the electroactive compound: NH3+ - C6H4 - NH - C6H4 - OCH3
Detected amperometrically by the electrochemical sensors as the compound produces an electrical current which stops the test
Test measured in seconds
Istat calibrates itself each cycle/ database management/less blood needed
Can use for Arterial Blood Gases too
Electronic checks and calibration each cycle voltage current test

9. Method Whole blood used from the same syringe used for all 4 tests
All standard Bypass Cases- In house surgery/ same day admissions.
Whole blood used from the same syringe used for all 4 tests
Duplicate ACTS 2 istats, 2 Hemochrons
Standard Protocol and times
TF1- Baseline
TF2- After heparin (300iu/kg)
TF3-TF6- On bypass (every 30 mins)
TF7- Post protamine
Data recorded in database

10. Results - Coefficient of variation
Device 1 (H)
Device 2 (IS) n
mean ACT sd
CV (%)
TF1
166
119
8.6
7.2
133
7.8
5.8
TF2
167
596
79.3
13.3
161
650
37.3
5.7
TF3
589
84.4
14.3
164
676
55.0
8.1
TF4
548
82.7
15.1
163
592
40.7
6.9
TF5
132
509
60.9
12.0
130
552
38.8
7.0
TF6 84
502
111.6
22.2 83
540
24.2
4.5
TF7
121
9.7
131
5.4
4.1
Total
1043
418
68.7
16.4
1028
459
34.9
7.6
Figure 1: Table showing Coefficients of variation, (which are a standardised measure of dispersion allowing direct comparison) CVs at varying time frames
CV% - The gold standard for comparing reliability = (SD/Mean)
Istat is more reliable overall CV% consistently <8.5%, Hemochron can be high as 22%
TF2-TF6, The danger zone- need reliability!
Reliability is better for both devices at TF1 (baseline) and TF7 (post protamine)
Also, Device 2 is systematically higher than Device 1

11. Results - Scatter diagram
Visual representation of the reliability.
The measurement of each device on x and y- if agree with one another would be on the straight line- H on left I on right.
More variation/dispersion/disagreement/less reliable on hemochron
This disagreement increases with increasing ACT values.
Each one of these represents a patient-the further away from the line to more unreliable they are- look how unreliable they are especially in the danger zone!
Figure 2: Scatter diagram of Hemochrons
Figure 3 : Scatter diagram of istat
Istat is the most reliable machine, more agreement
Each dot represents a patient, further away from the line is more unreliable >400- danger zone!
Disagreement increases with increasing ACT values
Visual representation of reliability
Intra device comparison- one on each axis
Straight line would indicate agreement between means

12. Results- Scatter diagram
1888 paired measurements in 171 patients
Hemochron on x axis / istat on y axis
Showing differences of means between devices
Straight line if no difference in means- High level of disagreement at higher ACT’s
Figure 4- Scatter showing means of both Hemochrons and istats against each other.

13. Bland- Altman Graph The Gold standard for comparing different devices
X axis represents- Y axis- (
The systematic bias- ie mean difference between devices is 9.2% meaning H 9.2% lower.
Dotted lines show 95% CI (LOA) very large! = Big difference.
The Gold standard for comparing different devices
X axis- The mean of the Hemochron and the istat
Y axis- (H-istat/average) as a % due to magnitude of difference increasing with increasing ACT
9.2% systematic bias- Hemochron reads lower than Istat
High 95% CI limits of agreement between devices- big disagreement

14. Clinical Impact
Current practice- do I need to give more heparin? Which is it 330/400/470???
Better to be safe?- Too much Heparin
More Heparin and Protamine – both have disadvantages
Heparin/Protamine complex- Type 1 immune reactions/Complement system
Both anticoagulants – too little or too much protamine more risk of bleeding
More transfusions
More time in hospital
Too little heparin/ protamine
Clots and dangers as mentioned previously

15. Conclusion
We found the Abbott Istat to be a more reliable device than the Hemochron when measuring ACTs on CPB using 2071 data points; in both non- anticoagulated patients and in fully heparinised patients
Reliability decreases in both devices as ACT increases
The istat and hemochron should not be used interchangeably to measure ACT due to their high levels of disagreement
Safe ranges for CPB would need to be adjusted when using istat to measure ACT

16. References
Lewandrowski EL, et al - Clinical evaluation of the i-STAT kaolin activated clotting time (ACT) test in different clinical settings in a large academic urban medical center: comparison with the Medtronic ACT Plus. Am J Clin Pathol May;135(5):741-8
Guzzetta NA, et al -. Correlations between activated clotting time values and heparin concentration measurements in young infants undergoing cardiopulmonary bypass. Anesth Analg Jul;111(1):173-9.
Ojito JW et al - Comparison of point-of-care activated clotting time systems utilized in a single pediatric institution. J Extra Corpor Technol Mar;44(1):15-20.
Paniccia R et al- Evaluation of a new point-of-care celite-activated clotting time analyzer in different clinical settings. The i- STAT celite-activated clotting time test. Anesthesiology Jul;99(1):54-9.
Chia et al Comparison of activated clotting times obtained using Hemochron and Medtronic analysers in patients receiving anti-thrombin therapy during cardiac catheterisation. Thromb Haemost Mar;101(3):
Spinler et al Anticoagulation monitoring part 2: Unfractionated heparin and low molecular-weight heparin. Ann Pharmacother Jul-Aug;39(7-8): Epub 2005 Jun 14.

17. Questions?
Thank you very much for listening