Laboratory Testing

Challenges and Strategies for
Implementing an Interpretative
Hemostasis Service
Kandice Kottke-Marchant, MD, PhD
Chair, Pathology & Laboratory Medicine Institute
Cleveland Clinic
Cleveland, OH, USA

Laboratory Testing
Test
Result
Factory?
OR
Diagnostic
Information
Service?

Healthcare Reform
• Value-based delivery system
• Value = Quality or Benefit / Cost
• Laboratory Testing IS good value now
- Benefit (70% of medical decisions based
on testing)
- Cost (Lab testing only 2% CMS charges)

Laboratory Testing
Progression
Patient
Visit
Dr Orders
Test
Sample
Collected
When is a Pathologist’s
Consultation Helpful?
Test
Result
Available
Dr
Interprets
Test
Dr
Treats
Patient
Pre-Pre-Analytic
Analytic Phase
(Test Performed)
Post-Post-Analytic
Pre-Analytic
Laposata M. Clin Chem Lab Med 2007;45:712
Post-Analytic

Rapidly Increasing Medical
Knowledge
• 20,000+ medical journals
• DRG’s thousands
• Test menu
- Cleveland Clinic 2600 tests
• Number of drugs increasing
• McGlynn study
- 6712 adults in 12 metropolitan areas
Increasing
Interpretation
complexity
- Evaluated 439 indicators of quality care
- 54.9% subjects received recommended
care
- Only 61.7% received correct laboratory
tests Mcglynn EA, et al. N Eng J Med 2003; 348:2635

Unique Issues with Hemostasis
Testing
• Test selection
• Population-based reference range
• Sample collection issues (hemolysis, fill
volume, correct anticoagulant)
• Interfering drugs (heparin, DTI, anti-Xa)
• Sample transport – time, temperature
• Sample processing – delays, centrifuge,
aliquot
• Storage – freezing, thawing
• Testing – best methodology,
functional/antigen assay

Laboratory Value Focus
Patient
Visit
Dr Orders
Test
Sample
Collected
Current Value
Focus:
Pre-analytic errors
(labeling, lost sample,
incorrect collection)
Efficient test
performance
(Lean and Six Sigma)
Correct reporting
Test
Result
Available
Dr
Interprets
Test
Dr
Treats
Patient
Pre-Pre-Analytic
Analytic Phase
(Test Performed)
Post-Post-Analytic
Pre-Analytic
Laposata M. Clin Chem Lab Med 2007;45:712
Post-Analytic

New Laboratory Value Focus
Patient
Visit
Dr Orders
Test
Sample
Collected
Future Quality
Focus:
Pre-pre analytic errors
(order the correct
test)
Post-post analytic
errors
(Test interpretation)
Test
Result
Available
Dr
Interprets
Test
Dr
Treats
Patient
Pre-Pre-Analytic
Analytic Phase
(Test Performed)
Post-Post-Analytic
Pre-Analytic
Laposata M. Clin Chem Lab Med 2007;45:712
Post-Analytic

What Does Increased Value Look
Like on the Hemostasis Service?
• Beyond result and reference range
• Identify High Hct – False h PT, APTT
• Identify preanalytic issues – short draw,
clotted sample, hemolyzed
• Identify interfering drugs – heparin, DTI
• Use algorithms to diagnose bleeding
disorders and thrombophilia risk
• Interpret results with clinical and
medication history

Evaluation of an Elevated APTT
Order Repeat APTT
Analyze
Results
Order More
Testing
Results: Bleeding
Risk (YES/NO)
+/- Therapy
Perform Testing
Perform Testing
Surgery

What are the Elements of an
Interpretive Hemostasis Service?
• “Goal-oriented” test ordering
• Package or battery of initial tests
• Additional testing based on an algorithm
• Assesses interfering drugs, alternate
reasons for test abnormalities, clinical
history, summarizes results
• Reports an interpretation of results,
indicating cause and significance of the
coagulation abnormality

Why Offer an Interpretive
Hemostasis Service?
• Evaluate coagulation abnormalities more
efficiently
• Streamline testing type and cost
• Decrease sample volume
• More rapid results
• Exclude interfering drugs
• Provides physician with an interpretation
and estimation of bleeding risk or
recommendation for therapy

How does it work?
Order Elevated APTT
Panel
Perform Initial
Testing
(PT, APTT, Mixing)
Additional
Tests
Are Added
per
Algorithm
Freeze
Aliquots
-80 o C
Tabulate
Pertinent
Clinical
Data and
Medication
History
Pathologist
And Resident
Review All Cases
3 times per day
Develop Interpretive
Report
(Discuss with Physician)
Results: Bleeding
Risk (YES/NO)
+/- Therapy
Surgery

What are the Elements?
• Defined order sets
• Algorithm for reflex testing; MEC approval
• Freeze plasma in individual aliquots; track
• Pathologist/hematologist with coagulation
expertise (residents)
• Clinical and medication history; EMR
• Established interpretations for algorithm
• Mechanism for reporting text reports
• Close communication with clinicians

Algorithm for a Prolonged aPTT
“Remove” Heparin
Hepadsorb
Hepzyme
Polybrene
Recheck aPTT
Recheck TT or anti-Xa
NL
STOP
+
Normal PT
Prolonged aPTT
?Heparin
Do TT or anti-Xa
Negative
Do Incubated
1:1 Mixing
Study
Check Hct
If Hct >55%, draw
With adjusted citrate
& repeat aPTT
CAUTION:
NL anti-Xa and Abn TT
Indicates Direct Thrombin
Inhibitor (DTI Drug)
Cannot “neutralize”
Will affect mixing studies,
Factor assays.
STOP Analysis

Algorithm for a Prolonged aPTT
Incubated Mixing Study
1:1 Mix+
Immediate
Acting
Inhibitor
(Probable
Lupus
Anticoagulant)
Lupus
Anticoagulant
Testing
1:1 Mix+
Delayed
Acting
Inhibitor
(Probable
Factor
Inhibitor)
Factor Assays
(VIII, IX, XI, XII)
Titer Inhibitor - Bethesda Assay
1:1 Mix
Negative
(Probable
Factor
Deficiency)
Factor Assays
(VIII, IX, XI, XII)

Algorithm for a Prolonged aPTT
1:1 Mix Negative
(Probable Factor Deficiency)
Factor Assays
(VIII, IX, XI, XII)
Only
FVIII
Low
Only
FIX
Low
FXI or
FXII
Low
More than
One Factor
Low
DO: Ristocetin
Cofactor & VWF
Hemophilia A (M)
Carrier State (F)
OR
Von Willebrand
DO: II,VII,X
Hemophilia B (M)
Carrier State (F)
Vit K Deficiency
OR
Warfarin Rx
FXI Deficiency
FXII Deficiency
OR
Carrier States
DO: D-dimer
Fibrinogen
DIC
OR
Hepatic

Developing the Interpretive
Report
• Use of “Coded Comments”
• 150 comments that encompass all decision
points of the aPTT algorithm; 757 total codes
• These codes can be pieced together to render a
patient-specific interpretation
• Codes entered into interpretive Middleware –
translated as text in report - LIS to EMR
(reported with lab results)
• Offers flexibility and consistency in reporting

APTT Incubated Mixing Study:
Interpretive Middleware

APTT Incubated Mixing Study:
Interpretive Middleware

Benefits of Interpretive
Middleware
• Allows standard workflow of interpretations
• Readily displays prior lab results; LIS interface
• Highlights abnormal results
• Standardizes coded comments (757 Codes)
• Allows algorithmic approach to interpretation
• Allows residents to enter preliminary comments
• Allows formatting and customization of
comments
• Standard codes can be edited; Use of free text
• Expedites signout – Rapid interface to EMR
- no need for tech entry of comments

Issues with Interpretive
Middleware
• Workflow complexity
• Not a part of LIS
• Need for IT support
• Results have to be validated in LIS to
appear in Middleware
• Does not connect with billing system
• Down time procedure needed (manual)

What other laboratory tests can
this be applied to?
• Other bleeding disorders: von Willebrand
disease
• Thrombophilia and Lupus Anticoagulant
• Molecular Coagulation Tests
• Platelet Function Tests and Aggregation
• Anemia
• Monoclonal Protein Analysis
• Hemoglobinopathies
• Toxicology
• Thyroid disease
• Liver function testing
• hyperlipidemia

Hypercoagulation Testing Algorithm
Add
2GPI
Ab
YES
Follow Fibrinogen
algorithm
(Reptilase, TT,
Imm Fib)
Follow VIII,
Fibrinogen,
CRP algorithm
Follow Protein
C algorithm
Follow Protein
S algorithm
Follow APC-R
algorithm
(Factor V
Leiden may be
performed)
ACA IgG
or IgM >20?
Decreased?
One or more
Elevated?
Decreased?
Decreased?
Decreased?
NO
PT
APTT
STACLOT
Anticardiolipin Ab
Fibrinogen
Factor VIII
CRP
Protein C Functional
Protein S Functional
Antithrombin Functional
APC Resistance
Prothrombin G20210A
Plasma Homocysteine
Abnormal?
YES
Do Heparin
Anti-Xa Assay

Hypercoagulation Panel
Interpretive Middleware

Hypercoagulation Panel
Interpretive Middleware

Roll-Out of Interpretive
Service
Date Panel Complexity Avg #/Mo
June 2011 TEG Low 195
August 2011 Asp/Clo, PFA-100 Low 250
April 2012 Platelet Agg; HIT Med 40
April 2012 VWF Panel High 64
June 2012 Lupus AC Panels High 244
June 2012
Mixing studies, Elevated
PT / aPTT panels
High 80
June 2012 Hypercoagulation Panels Very High 249
March 2013 Molecular Coagulation High 400
Dedicated IT analyst; 350+ emails; weekly meetings
Training for 10 coag techs, residents, 4 staff

Billing for the Interpretation
• Result is patient-specific
• Test results are correlated with clinical condition
• Diagnosis and/or recommendation
demonstrating clinical judgment is provided to
the physician
• The interpretation is signed by the pathologist
(MD, not resident)
• The result is filed in the patient’s medical record
MacMillan DH, et al. AJCP 2001;116 (Suppl 1):S129

Laboratory Interpretation Codes
• Code Description
• 86320-26 Immunoelectrophoresis, serum
• 86325-26 Immunoelectorphoresis, other fluids
• 86327-26 Immunoelectrophoresis, 2-dimensional
• 86334-26 Immunofixation eleectrophoresis
• 87162-26 Darkfield examination, any source
• 87207-26 Smear, primary source, for inclusion bodies/parasites
• 88371-26 protein analysis by Western blot, interpretation
• 88372-26 protein analysis by Western blot, with probe, interpretation
• 89060-26 Crystal identification by light microscopy
• 83020-26 hemoglobin, electrophoresis
• 83912-26 Nucleic acid probe
• 84165-26 protein, electrophoretic fraction and quantitation
• 84181-26 Western blot interpretation
• 86390-26
report
Fibrinolysis or coagulopathy screen interpretation and
• 85576-26 Platelet aggregation (in vitro), each agent
• 86255-26 Fluorescent antibody, screen, each antibody
• 86256-26 fluorescent antibody, titer, each antibody
• 83912-26 Molecular diagnostics, interpretation and report
• 80500 CP Consultation, limited
• 80502 CP Consultation; comprehensive

Impact of Hemostasis Diagnostic
Reports
Cleveland Clinic Survey 2010
• Impact Differential Dx 89.6%
• Shorten Time to Dx 73.3%
• Prevent Mis-diagnosis 89.3%
• Avoid Hospital Admission 26.3%
• Reduce Length of Stay 33.3%
N=113
Did the inte rp re ta tio ns le a d to the fo llo wing while ma king a
d ia g no sis?
120
100
80
60
40
Yes
No
20
0
Reduce the number of
laboratory tests required
Reduce the use of
procedures
Change in medications or
blood products
administered
K Kottke-Marchant, L Yerian, J Rogers

How he lp ful ha ve yo u fo und the fo llo wing co a g ula tio n p a ne ls in
imp ro ving yo ur o ve ra ll d ia g no stic p ro ce ss?
Platelet flow cytometry panel
Platelet aggregation panel
Elevated PT panel
Elevated PT/PTT panel
Elevated PTT panel
Von Willebrand panel
Hypercoagulation panel
Lupus anticoagulant panel
0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50
K Kottke-Marchant, L Yerian, J Rogers

How sa tisfie d a re yo u with the curre nt turna ro und time to re ce ive
the p a tho lo g y inte rp re ta tio n fo r he mo sta sis p a ne ls?
8
2
14
21
91%
Extremely satisfied
Satisfied
Not satisfied
Extremely dissatisfied
70
Not applicable
N=115
K Kottke-Marchant, L Yerian, J Rogers

Benefit of Interpretive
Middleware
• Analyzed TAT improvement with 100 cases, pre and
post implementation (TEG testing)
• The time between laboratory receipt and staff signout
• AMEDx reduced TAT for TEG, approximately 115
minutes.
Timing N TAT (Mean
+/- SD) min
Pre
Middleware
Post
Middleware
50 414 +/- 204 380
50 299 +/- 126 285
Median
(min)
P=0.0011
J. Rogers, MD

Quality Assessment in
Interpretive Reporting
• Large variability in acceptable
interpretations
• Misleading interpretations may be
worse than no interpretation at all
• Interpretations should follow
established testing guidelines
• Need for quality assessment in this
area: NASCOLA

Benefit of InterpretiveTesting
adding value to lab services
• Decision Support: Order the RIGHT test
and the right NEXT test
• Provide information on the clinical
implications of test result (diagnostic
interpretive service)
• Middleware may help standardize service,
but is associated with its own issues
• Survey clinicians to assess benefit of
service

Future Goals
• Serve as “gate keeper” – evaluate the
appropriateness of each order and consult with
clinicians to decrease inappropriate orders
- Thrombophilia panels in hospital ICU patients
- Lupus anticoagulant panels in patients on
heparin or DTI drugs
• Use IT solutions to improve access to clinical
information
- Input drug information at time of order
- Direct access to pharmacy IT
- EMR Display of combined lab, therapeutic data
(Hct/Transfusion, APTT/Heparin, warfarin/INR)