1. What is it? Why do we need it POC?
Coagulation Testing
What is it?
Why do we need it POC?
Marcia L. Zucker, Ph.D.
Director of Clinical Research
ITC Educational Services, Edison, NJ

2. Coagulation Testing
Monitoring hemostasis
Bleeding Clotting

3. Coagulation Testing Monitoring therapy Heparin Coumadin Thrombolytics
Intrinsic Pathway
Extrinsic Pathway
Common Pathway
CLOT
Heparin Coumadin
Monitor with
ACT / aPTT
Monitor with PT
Thrombolytics
TT / Fibrinogen

4. Coagulation is Complex
Platelet Adhesion
shape change
release
3 sec
10 sec
5 min
ADP release
Platelet
Aggregation
Coagulation
Fibrin formation

5. Coagulation is Complex

6. Common(?) Coagulation Tests
Laboratory
PT..
aPTT
TT..
Fib.
Anti Xa
Anti IIa
Factor Assays
Point of Care
ACT
Celite®
Kaolin
Glass beads
Silica
thromboplastin

7. Differences in test methods
Standard Laboratory
Platelet Poor Plasma
Sodium Citrate Anticoagulant
1:9 Dilution
Variable Preanalytical Delay
Point of Care
Whole Blood
No Added Anticoagulant
No Dilution
No Preanalytical Delay

8. POC Coagulation Analyzers
HEMOCHRON 401 / 801 / Response
HEMOCHRON Jr. Signature
ProTime
Medtronic HMS / HemoTec ACT II
CoaguChek / CoaguChek Pro DM
Bayer RapidPoint
i-STAT
Others

9. POC Coag Analyzers Differ
Test methodology
Sample size and application
Sample measurement
Clot detection method
Enzyme detection method
Reagent composition
Results

10. Clinical Applications
Operating Room
Cardiac Surgery
Interventional Cardiology and Radiology
Critical Care
Satellite Sites
Dialysis
ECMO
Emergency Room
Anticoagulation Clinic

11. Activated Clotting Time
Extrinsic Pathway
Intrinsic Pathway
ACT
Common Pathway
CLOT

12. What do we use an ACT for? Maintain Balance Heparin
Bleeding Thrombosis
Heparin
Rapid Anticoagulant Effect
Individual sensitivities vary significantly
Potency differences
Source: Bovine or Porcine
Lot to Lot variability
Rapidly Reversible with Protamine

13. Why are there so many different ACTs?

14. Monitoring - ACT Benefits Industry Standard Since 1970s
Recommended as primary method in AmSECT guidelines (perfusion)
Easy to run

15. Monitoring - ACT Disadvantages Each system yields different numbers
High sensitivity to hypothermia and hemodilution (with exceptions)
Little or no correlation to heparin level
especially true for pediatric patients

16. Heparinized ACT - CPB
Data from Huffman, et.al AmSECT meeting 17

17. Monitoring in CPB - ACT
Data from clinical evaluation, on file, ITC

18. Pharmaceutical Intervention
Amicar or Tranexamic Acid
No effect on standard celite ACT
Continued debate on efficacy
Multiple reports
Reduction in post-operative blood loss
Reduced transfusion requirements

19. Pharmaceutical Intervention
Aprotinin
Significant elevation of celite ACT
Two dosing regimens
Full Hammersmith
2 x 106 KIU loading dose; 2 x 106 KIU pump prime; x 106 KIU/hr infusion
Half Hammersmith
1 x 106 KIU loading dose; 1 x 106 KIU pump prime; x 106 KIU/hr infusion

20. ACT Monitoring-Aprotinin Treatment
Celite ACT
Not recommended
Still used with target times of >750 seconds
Kaolin ACT
Unaffected by moderate doses of aprotinin
Used with target times of > 480 seconds
ACT+
Unaffected by ALL doses of aprotinin
Used with target times of > 400 seconds

21. ACT Monitoring -Aprotinin Treatment
Data from clinical evaluation, on file, ITC

22. Alternative Monitoring - Aprotinin
HiTT - High Dose Thrombin Time
Adapted from Huyzen, et. al. J.CardioThorac. Vasc. Anesth. 8:153, 1994

23. Alternative Monitoring - Aprotinin
Adapted from Huyzen, et. al. J.CardioThorac.Vasc.Anesth. 8:153, 1994

24. Thrombin Time TT Intrinsic Pathway Extrinsic Pathway Common Pathway
CLOT

25. Other POC Coag in the OR aPTT / PT Fibrinogen Dosing Assays
Pre- and post-procedural screening
Fibrinogen
Dosing Assays
Customize heparin and protamine for each patient
HEMOCHRON HRT / PRT
Hepcon HMS
RapidPoint

26. Other POC Coag in the OR Heparin neutralization verification
Ensure complete removal of circulating heparin
aPTT
PDA-O - ACT based
TT / HNTT - Thrombin Time based
heparinase ACT

27. Outcome studies - POC in OR
Reduced Blood Loss/Transfusion
Use of HRT and PRT (RxDx System)
Jobes, D. et. al., J.Thorac.Cardiovasc.Surg.
Reduced Cost
Resulting from POC Assays
RxDx combined with TT / HNTT
Jobes, D. et. al., Am Soc Anesth Mtg.

28. Outcome studies - POC in OR
Reduced Complication Rates
TT /HNTT
Re-Exploration for Bleeding Reduced from 2.5% to 1.1%
Re-Exploration for Coagulopathy Reduced from 1.0% to 0.0%
Jobes, et.al. 1997, NACB Presentation, Phila.

29. Clinical Applications
Operating Room
Cardiac Surgery
Interventional Cardiology and Radiology
Critical Care
Satellite Sites
Dialysis
ECMO
Emergency Room
Anticoagulation Clinic

30. Procedures Diagnostic Interventional Catheterization Electrophysiology
locate and map vessel blockage(s)
determine need for interventional procedures
Electrophysiology
Interventional
Balloon angioplasty
Arthrectomy (roto-rooter)

31. Diagnostic – Low dose heparin
Catheterization and Electrophysiology
unit bolus dose
frequently not monitored
if monitored –
ACT
aPTT

32. Interventional – Moderate dose
Angioplasty and Arthrectomy
10,000 unit bolus dose or
mg/kg
target ACT seconds
unless platelet inhibitors used
200 – 300 in presence of ReoPro

33. Why use platelet inhibitors?

34. Angioplasty promotes aggregation

36. Platelet Inhibitors ReoPro Integrelin Aggrastat elevates ACTs
target time = 250 sec with ReoPro
determined using FTCA510 tube
Integrelin
No reported effects on ACT
Aggrastat

37. Clinical Applications
Operating Room
Cardiac Surgery
Interventional Cardiology and Radiology
Critical Care
Satellite Sites
Dialysis
ECMO
Emergency Room
Anticoagulation Clinic

38. ACT or aPTT Determine when to pull the femoral sheath
Premature sheath pull can lead to bleeding.
Delayed removal can increase time in CCU.
Target set at each site.
ACT targets range from 150 – 220 seconds
aPTT targets range from 40 – 70 seconds

39. ACT or aPTT Monitor heparin therapy
Target times determined by each facility
APTT outcome study
Reduce time to result (112 vs <5 minute)
Reduce time to stabilization
Reduce dose adjustments
Reduce length of stay
By using POC aPTT instead of lab
Poster at AACC 2000 – Staikos, et.al.

40. What did it say? Mean time to lab result = 112 min
Mean time to POC result <5 min
Fewer dose adjustments needed in POC group to reach therapeutic level
Shorter time required to reach therapeutic level in POC group
Fewer dose changes in POC group

41. Activated Partial Thromboplastin Time
Extrinsic Pathway
Intrinsic Pathway
APTT
Common Pathway
CLOT

42. Activated Partial Thromboplastin Time
NOT a PTT
PTT is the predecessor of the aPTT
Not used anymore
Laboratory or Point of Care
High APTT values
the presence of heparin
underlying coagulopathy
Monitor heparin / coumadin® cross-over

43. Heparin versus Warfarin

44. Prothrombin Time PT Intrinsic Pathway Extrinsic Pathway Common Pathway
CLOT

45. Prothrombin Time Monitor warfarin therapy
Monitor heparin/warfarin crossover
Target times are set by
International Normalized Ratio (INR)
ISI = international Sensitivity Index
INR target ranges are specified by patient populations
prophylactic therapy for DVT: INR=
artificial heart valve: INR=

46. Will POC Results Match the Lab?
NO!
(Probably Not)
but it WILL Correlate

47. Correlate Does Not Mean Match

48. Coag is NOT Chemistry

49. Compare for your site.
Same System / Multiple Sites

50. Are differences important?
Sometimes no - aPTT C

51. Sometimes VERY - aPTT SP

52. Lot to Lot Reproducibility

53. Clinical Applications
Operating Room
Cardiac Surgery
Interventional Cardiology and Radiology
Critical Care
Satellite Sites
Dialysis
ECMO
Emergency Room
Anticoagulation Clinic

54. Dialysis / ECMO ACT (or nothing in dialysis)
Majority use P214 glass activated ACT
Some use ACT-LR; HemoTec
Better Control of Anticoagulation Leads to Increased Dialyzer Reuse
Potential for Long Term Cost Savings
No Compromise in Dialysis Efficacy (Kt/V)
Ouseph, R. et.al. Am J Kidney Dis 35:89-94; 2000

55. Emergency Room ACT; aPTT; PT; Fibrinogen
Immediate Identification of Coagulopathies
Optimization of Critical Decision Pathways
ACT Allows Early Detection of Traumatic Coagulopathy
Allows Early Treatment Decisions
Aids Damage Control Decisions
Aucar, J. et.al SW Surgeons Congress
Optimize Staffing During Off Hours

56. Anticoagulation Clinics
Results Available While Patient is Present
Improved Anticoagulation Management
Improved Standard of Care
Staff Efficiency
Immediate Retesting (if needed)
Fingerstick Sampling
Same System for Clinic and Home Bound Patients
Standardized ISI / PT normal
Test System Specific

57. Anticoagulation Clinics
Potential for Self-Testing
High Risk Patients
Patients Who Travel Frequently
Home-Bound
Patients in Rural Areas Far from Clinic
Improved Outcomes Through More Frequent Testing

58. How to compare INR differences
Has the Hemostatic Balance been Upset?
Is the Clinical Response Different?

59. Patient Management 6.0 5.0 4.0 3.0 2.0 1.0 Target INR 3.0
Must change dose
Target INR 3.0
Range
Call Clinic
May change dose
Patient Management

60. What’s the catch?
Regulatory compliance
Connectivity

61. Regulatory compliance
Who sets the rules?
JCAHO
Joint Commission on Accreditation of Health Care Organizations
CAP
College of American Pathologists
FDA
Food and Drug Administration

62. CLIAC CLIA Committee CLIA - Clinical Laboratory Improvement Act
Define and interpret CLIA regulations
CLIA - Clinical Laboratory Improvement Act
Designed to ensure accuracy of results from clinical laboratories
Compliance required to pass
JCAHO and / or CAP inspections
CLIA defines regulations for each test
CDC / FDA complexity categories

63. CLIA Applies to ALL Testing Areas
Central Laboratory
Satellite Labs
Critical Care
Surgical Suite
Clinics
Bedside testing
Doctor’s office

64. CLIA Regulations for Coagulation
Central Laboratory can hold the CLIA license
Satellites can have independent licensure
Moderately Complex tests
Except - ProTime and Coaguchek are waived
Requires
Certified Laboratory Director
Record Keeping
Training
Quality Policy

65. Implementing POC coag requires:
RECORD KEEPING
Method Validation - accuracy
comparison to current standard
Linearity Assessment
Also used for ACT “calibration/ verification”
Is assay performance appropriate to clinical needs?
Does linear range span clinical range?
Training
competency evaluations at predetermined intervals

66. Routine Quality Control
Instrument Performance Verification
Electronic Quality Control with Numeric Output
Two levels per 8 hour shift
Assay Performance Verification
Wet QC as per Manufacturer’s Recommendation
Two levels for each box of reagent when opened

67. Connectivity Everyone wants it Multiple definitions
Almost no one is ready to implement
Multiple definitions
Download to computer
To LIS or to HIS or to both or to data management software
Real time or batch
QC data, patient data, or both

68. Short term solutions
Interim programs for data capture, QC compliance tracking
transfer to file format easily adaptable
Requires independent transfer protocol
e.g., ITC ReportMaker
Dedicated interface specific to one manufacturer’s instrumentation
e.g., Abbott; Lifescan
Manufacturer ensures system compatibility

69. Instrument manufacturer neutral interface
RALS-plus
Telcor
Manufacturer works with interface supplier to ensure compatibility
Interface supplier works with LIS / HIS supplier to ensure compatibility

70. Quick Script or Quick EDI
Telcor concept
Quick Serv (DM)
LIS/HIS
Quick Script or Quick EDI
Quick Linc
ITC
Dawning box
Data translation
Via hospital Ethernet OR
Cath lab
CCU

72. RALS plus concept RALS-Core System (RCS) RALS-IMS LIS HIS Glucose ICU
Results that meet user-defined criteria are transferred to the LIS for placement on the patient’s permanent medical record
HIS
RALS-ADT gathers demographic data
to enable patient verification
Test results are transferred
from a RALS-Plus Test Station
to the RALS-Plus Core System (RCS)
Glucose
ICU
RALS Dataport
Coagulation ER
RALS Plus Test Station
Urinalysis
9 West
RALS Remote Connect
Hospital Client PC
POCC’s can view, analyze, or edit results using the RALS-Plus IMS (Information
Management System)
RALS-IMS
RALS-Core System (RCS)
Located in the Hospital Data Center
Blood Gas

73. Long term Solutions POC Connectivity Industry Consortium
Accepted as NCCLS document POCT1-A
sections of the CIC specification approved by:
IEEE
HL7
Standardization of POC connectivity:
Messages
Protocols
Technologies

74. Why Bother with POC Coag?
Improved TAT - Turn Around Time
Defined from the Clinician, not Lab view
When is Turn Around Important
Emergency Room
ICU/CCU Dose Adjustments
Operating Room / Cath Lab
STAT Testing Turn Around

75. STAT Testing TAT
Fitch, et.al, J. Clin Monit & Comput :

76. Standardized Clinical Interpretation
Defined Assay Sensitivity
Requires Lot to Lot Reproducibility
Defined Reagent Variability
Identical Instrumentation and Reagents at All Testing Sites
Defined Critical Clinical Decision Points
No Change of Normal Ranges or Target Times Between Lots of Test Reagents or Testing Locations
NEED TWO COPIES OF THIS SLIDE

77. Why Bother with POC Coag?
Improved Clinical Outcome
Reduced LOS – Length of Stay
Improved, timely patient care