2009 lap audioconference series simple tests, tough problems patient …€¦ · patient care and...

Simple Tests, Tough Problems Patient Care and Laboratory

Inspection in Coagulation

John D. Olson, MD, PhD, FCAP

January 21, 2009

2009 LAP Audioconference Series

Objectives: After participating in this session, you will be able to: to describe patient care and accreditation issues regarding: • ProTime/INR

• ISI, Sensitivity, Critical Values • Calculation Verification

• Monitor Heparin Therapy • aPTT and Reagent Sensitivity • Heparin Assay

• D-Dimer Assay • Type and Magnitude of Units • Threshold for exclusion of VTE

Accreditation The College of American Pathologists (CAP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. CME Category 1 The College of American Pathologists designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit TM. Physicians should only claim credit commensurate with the extent of their participation in the activity. CE (Continuing Education for non-physicians) The CAP designates this educational activity for a maximum of 1 credit/hour of continuing education. Each participant should only claim those credits/hours he/she actually spent in the activity. ASCP Statement This activity is acceptable to meet the continuing education requirements for the ASCP Board of Registry Certification Maintenance Program. California and Florida Statement This activity is approved for continuing education credit in the states of California and Florida.

Laboratory Accreditation Program AudioconferenceSimple Tests, Tough Problems: Patient Care and Laboratory Inspection in CoagulationJohn D. Olson, MD, PhD, FCAP

January 21, 2009

© 2009 College of American Pathologists 1

Every patient deserves the Gold Standard.

John D. Olson, M.D., Ph.D.

Professor, Department of Pathology UTHSCSA

Director of Clinical LaboratoriesUniversity Health System

Voice: 210 567 6650Email: [email protected]

Relevant Financial Interests -NONE

Off Label Usage - NONE

Every number is a life.

www.cap.org

Simple Tests, Tough ProblemsPatient Care and Accreditation in the Coagulation Laboratory

©2009 College of American Pathologists. All rights reserved.

3Every patient deserves the Gold Standard.

Following today’s presentation you will be able to describe patient care and accreditation issues related to:• ProTime/INR

ISI, Sensitivity, Critical ValuesCalculation Verification

• Monitor Heparin TherapyaPTT and Reagent SensitivityHeparin Assay

• D-Dimer AssayType and Magnitude of UnitsThreshold for exclusion of VTE


January 21, 2009




Report SummaryDade-Behring BCS

Specimen CG2-15pResult 19.1Mean 19.24SD 0.45n 72SDI -0.31

Upper Limit 20.2Lower Limit 18.1

PT

2004 CG2-C 15% = 2.88 sec. = 6.4 sd






January 21, 2009




Errors Calculating the INRApr 2002No. (%)

Jan 2003No. (%)

TotalNo. (%)

Labs Submitting

1843 1970 3813

Total Errors 182 183 365

Random Errors 105 (57.7) 103 (56.3) 208 (57.0)

Calc. Errors 77 (42.3) 80 (43.7) 157 (43.0)

Calc. Errors Total

4.2%77/1843

4.0%80/1970

4.1%157/3813

7





HEM.23220: For PT, is there documentation that the ISI is appropriate to the particular PT reagent and instrumentation used?

Can calibrators be used to set the ISI within the laboratory for a specific method?

HEM.23360: Is the appropriate geometric mean of the PT reference interval used in the INR calculation?

Laboratory Accreditation Program AudioconferenceSimple Tests, Tough Problems: Patient Care and Laboratory Inspection in CoagulationJohn D. Olson, MD, PhPhD, FCAP

January 21, 2009




• HEM.23290: Is the calculation of the INR appropriately adjusted for every new lot of PT reagent, changes in types of reagent, or change in instrumentation?

• HEM.23430: Are there checks of patient reports for correct INR calculations, patient values, and reference ranges under the following circumstances?Change in lot or type of PT reagentChange in instrumentEstablishment of new PT reference rangeChange in INR calculationAt defined intervals, in the absence of the above changes



INR Calculation Summary



HEM.23100: Are documented criteria established for immediate notification of a physician or other clinical personnel responsible for patient care when results of certain tests exceed critical limits important for prompt patient management decisions?


January 21, 2009




ProTime Sensitivity

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

0 50 100 150

% Factor VII

INR

Upper limit of thereference interval



CG2 –C, 2000: Critical Value for INR(n=604)

Critical Value: INR # (%) of Laboratories

5.0 166 (27.5)

4.0 96 (15.9)

6.0 74 (12.3)

4.5 49 (8.1)

3.5 38 (6.3)



Value x sd n sdi min max score

CG1 – A 2006: aPTT


January 21, 2009




CG1-A 2006: Trinity AMAX aPTT

Specimen CG1-13

Lab Result 106

Mean 90.1

n 16

sd 11.2

SDI 1.4

Lower Limit 76

Upper Limit 106

Graded Unacceptable – 15% Limit=104



020

4060

80100

120

0 0.1 0.2 0.3 0.4 0.5Heparin (U/mL)

aPTT

(sec

onds

)

aPTT Reagent Sensitivity to Heparin



Heparin (U/mL)

Heparin Dose Response (Heparin Assay)

aPTT

(Sec

onds

)

0

20

40

60

80

100

120

140

160

180

0 0.2 0.4 0.6 0.8 1


January 21, 2009




Reagent 1Reagent 2

Response of the aPTT to Heparin:Comparison of Two Reagents

0

50

100

150

200

250

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9Heparin (u/mL )

aP

TT(s

eco

nds)





Cum Sum of Reagent Mean Differences

Data Set Mean Old LotSec (Reag #)

Mean New LotSec (Reag #)

DifferenceOld - New Sec

Cum SumDifference Sec

1

2

3

4

78.6(1)

61.5(2)

71.9(3)

62.8(4)

73.9(2)

59.5(3)

72.3(4)

60.3(5)

-4.7

-2.0

+0.4

-2.5

-4.7

-6.7

-6.3

-8.8

4 62.8(4) 68.4(5) +5.6 -0.7


January 21, 2009




Heparin Assay• Growth in the use of the Heparin

Assay109 Laboratories reporting in 1997315 Laboratories reporting in 2007

• Interesting dilemma regarding monitoring unfractionated heparin.



HEM.23575: Are recommendations available to clinicians concerning which laboratory tests to use for monitoring heparin, low molecular weight heparin, direct thrombin inhibitors (e.g., lepirudin, bivalirudin, argatroban) and/or oral anticoagulant therapy, and the therapeutic range for the tests?




January 21, 2009




Origin of Units Used to ReportD-Dimer

DD

D-Dimer Units (D-DU)≈185kDa

Fibrinogen Equivalent Units (FEU)≈370kDa

ED D



Variation in Reporting D-Dimer

Method Number CV (%)1 159 26.22 25 35.03 13 9.84 164 26.85 145 40.76 168 30.67 45 34.98 16 29.89 13 17.3

Mean Result Ranges:1556 to 4371 nG/mLCG2-A; 2004



Reporting the D-Dimer• D-Dimer Units (D-DU)• Fibrinogen Equivalent Units (FEU)

1 nG/mL D-DU = 2 nG/mL FEUIf one is clinically using a threshold developed for FEU units but the assay is generating D-DU, patients may be falsely considered at low risk for VTE


January 21, 2009




Supplemental Questions: Regarding D-Dimer

• Eight Questions Submitted regarding:

Units of Measurment– Conversion of Units

Use in Exclusion of VTE– Threshold Used for

Exclusion



D-Dimer Supplement• Total Participants - 4857 of whom 2232 report

D-Dimer• Total Surveys Returned - 2018 (42% of Total;

90% of those reporting the D-Dimer)• Using D-Dimer to Exclude VTE - 1506 (75%)

Using a Quantitative Assay - 1460Using a Semi-Quant Assay - 29Using a Whole Blood Assay - 17

• Number that Convert Units - 386 (19%)



Reporting Patterns: Method 1Type of units Units Reported Number

D-Dimer nG/mL 35FEU nG/mL 24

D-Dimer µG/L 1FEU µG/L 3

D-Dimer µG/mL 48*FEU µG/mL 338

D-Dimer mG/L 0FEU mG/L 0

Other 13Don’t Know 4

Total 466

Change Result Units

109 (23%)

Number Reporting a VTE Exclusion Threshold above Recommended: 47 (10%)


January 21, 2009




Reporting Patterns: Method 2Type of units Units Reported Number



D-Dimer µG/mL 2FEU µG/mL 2

D-Dimer mG/L 156*FEU mG/L 147


Total 343

Change Result Units

81 (24%)


31



Reporting: All Methods; Exclude VTEType of units Units Reported Number



D-Dimer µG/mL 39FEU µG/mL 336

D-Dimer mG/L 125FEU mG/L 143


Total 1506

Change Result Units

Report: 324 (22%)

Instrument 227LIS 148Both 55Neither 4


Actual: 511 (34%)



Summary• Among all methods for reporting the quantitative D-

Dimer, there is wide variation in the units reported.• Some laboratories may be using inappropriate

methods for excluding VTE.• As many as one third or more of laboratories using

quantitative assays for exclusion of VTE report using a threshold above that recommended by the manufacturer or reported in the literature.

• Many laboratories are unclear about which type of units they are reporting.

• Many patients may be erroneously excluded from VTE because of inappropriate thresholds.


January 21, 2009




Method used to determine Threshold for VTE exclusion

• Survey in 2006• Four questions regarding the

method used to determine the threshold for exclusion of VTE using the D-Dimer

• Surveys sent to 5600 laboratories• Responses from 4112 (73.4%)



Do you use the D-Dimer assay for the exclusion of VTE?

Response Number

Yes 2430

No 1255

Don’t Know 427

Total 4112



What method was used to determine the threshold?

Manufacturer 1322 (54%)Literature 249 (10%)

Local Data 520 (21%)Other 116 (5%)

Don’t Know 195 (8%)No data 28 (1%)

Total 2430


January 21, 2009




What number of cases was used to determine threshold?

< 50 136 (26%)50 – 100 167 (32%)

101 – 150 64 (12%)151 – 200 37 (7%)

> 200 42 (8%)Don’t Know 70 (13%)

No Data 4 (1%)Total 520



HEM.37915: If the laboratory reports D-Dimer assay results in units other than those recommended by the assay manufacturer, are the type of unit and magnitude of the D-Dimer result reported correctly?



HEM.37925: If a D-Dimer method is used in the evaluation of venous thromboembolism, has the method been validated for this purpose?


January 21, 2009




HEM.37930: If a D-Dimer test is used for exclusion of deep vein thrombosis and/or pulmonary embolism, does the laboratory report the cutoff value for exclusion of venous thromboembolism, as well as the reference range?

HEM.37935: If a D-Dimer test is not used for exclusion of deep vein thrombosis and/or pulmonary embolism, does the laboratory inform clinicians that the test should not be used to exclude deep vein thrombosis or pulmonary embolism?



References• Ansell J, et al. Pharmacology and Management of the Vitamin K Antgonists.

American College of Chest Physicians Evidence Based Clinical Practice Guidelines (ed. 8) Chest 2008;133:160s-198s.

• Critchfield GC, Bennett ST. The influence of the reference mean prothrombintime on the international normalized ratio. Am J Clin Pathol. 1994 Dec;102(6):806-11.

• Dempfle CE. D-dimer assays: The current status and new assay technologies. Thromb Res. 2005 Aug 30

• Fairweather RB, et al. College of American Pathologists Conference XXXI on laboratory monitoring of oral anticoagulant therapy. Arch Pathol Lab Med.1998;122:768-781.

• Goodacre S, et al. Variation in the diagnostic performance of D-dimer for suspected deep vein thrombosis. QJM. 2005 Jul;98(7):513-27. Epub 2005 Jun 13

• Hirsch J, et al. Parenteral Anticoagulants. American College of Chest Physicians Evidence Based Clinical Practice Guidelines (ed. 8) Chest 2008;133:141s-159s.

• NCCLS. One-stage prothrombin time (PT) test and activated partial thromboplastin time (aPTT) test; approved guideline H47-A. Wayne, PA: NCCLS, 1996.

• Olson JD, et al. 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.




References (cont.)• Olson J, et al. Use of the D-Dimer for Exclusion of VTE: Difficulties Uncovered

through the Proficiency Testing Program of the College of American Pathologists (CAP). J Thromb Hemostasis, Abstract, August 2005.

• Rosborough TK. Comparison of anti-factor Xa heparin activity and activated partial thromboplastin time in 2,773 plasma samples from unfractionated heparin-treated patients. Am J Clin Pathol. 1997;108:662-668.

• Smythe MA, et al. Different heparin lots. Does it matter? Arch Pathol Lab Med. 2001;125:1458-1462.

• Smythe MA, et al. Use of the activated partial thromboplastin time for heparin monitoring. Am J Clin Pathol. 2001;115:148-155.

• Spannagl M, Haverkate F, Reinauer H, Meijer P. The performance of quantitative D-dimer assays in laboratory routine. Blood Coagul Fibrinolysis. 2005 Sep;16(6):439-43.

• Wolf SJ, McCubbin TR, Feldhaus KM, et al. Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism. Ann Emerg Med. 2004 Nov;44(5):503-10.

• Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med. 2004 Apr 20;140(8):589-602.



January 21, 2009




Questions?



Technical Assistance

• http://www.cap.org

• Email: [email protected]

• 800-323-4040, ext. 6065



Past Audioconferences• Missed part/all of an audioconference?• Want to hear it again?• Want to tell a co-worker?• Virtual Library of Past Audioconferences

– Available 24/7 on www.cap.org 4 weeks post session (see Attachment A for steps on how to access post audioconferences).Laboratory Improvement and Accreditation tabPreparing to Inspect


January 21, 2009


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Attachment A: Steps to Access the Virtual Library of Past Audioconferences

2009 lap audioconference series simple tests, tough problems patient …€¦ · patient care and...

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