Consensus Guidelines: Preface
The International Consensus Group for Hematology Review is pleased to publish the attached guideline:
Suggested Criteria for Action Following Automated CBC and WBC Differential Analysis
Berend Houwen MD, PhD the founder of ISLH, who passed away recently, recognized the long-standing need for generally accepted guidelines (“rules”) which could be applied to criteria for review of CBC and differential results from automated hematology analyzers and he addressed it in a visionary manner. He invited twenty experts to a meeting to discuss the issues and agree upon the most appropriate criteria. Beckman Coulter Inc. generously provided an educational grant to fund this meeting and to provide financial assistance for the development of guidelines. Dr. Houwen gathered together hematology laboratorians who represented six countries and seventeen laboratories that were foremost in the use of review criteria. The laboratories included those servicing tertiary care hospitals, oncology hospitals, community hospitals, childrens’ hospitals, and doctors’ offices. For almost three full days, each parameter of the CBC was discussed in depth and consensus was reached regarding rules for the situations which should trigger a review of automated cell counter results potentially leading to further testing or blood smear review.
Each laboratory agreed to test these rules in their own facilities. Approximately 1000 samples were to be collected and tested according to a detailed protocol at each site. These samples were to represent the lab’s usual testing population. Of those 1000 samples, 200 were to be “repeat” samples in order to test the Delta Rules. A manual blood smear review of all samples was also to be performed, with a manual differential when indicated. Fifteen laboratories responded, providing results from a total of 13,298 patient samples for data analysis.
The Steering Committee for the International Consensus Group discussed extensively what constituted a positive finding on a peripheral smear. Once again, consensus was reached by agreement of the participating laboratories. The samples were then analyzed and truth tables established according to these criteria.
At the recommendation of Dr. Berend Houwen, the International Consensus Group for Hematology Review is placing the Consensus Rules in the public domain in the hopes that our experience may enhance your own laboratory rules for review of automated analyzer results. The information on this website includes the rules for review, definitions of delta terms, definitions of what constituted a positive smear finding in this study, a consensus rules results “truth table”, contact information for steering committee members, and a list of participating hospitals and laboratories. We thank each of the participating laboratories for taking the time to help determine the rules for this study, collecting and providing the data, reviewing the data analysis for their individual laboratories, and reviewing the attached material prior to publication on this website.
This material will be submitted in expanded form for journal publication within the next few months. Journal reference information will be posted on this website as soon as available.
We encourage laboratorians to explore the application of these rules in their own laboratories and to share their findings with the Consensus Group. Before activating any or all of these rules in your labs for clinical purposes, the Consensus Group strongly advocates testing of each rule in your own setting to verify the results with your patient population. If anyone would like to perform a formal study similar to that performed by the consensus participating laboratories, please contact a member of the steering committee for protocol information and guidance.
The International Hematology Consensus Group would like to extend their appreciation to Beckman Coulter, Inc. for their unrestricted educational grant which allowed our group to come together to formulate and to test these rules. These rules are dedicated to the memory of Dr. Berend Houwen: it was his foresight that recognized the need for these rules; it was his vision that an international consensus group was the best means to address the need; it was his initiative that formed the group and; and it was his leadership and wisdom that guided the group in it’s work.
Sincerely,
The Steering Committee
International Consensus Group
Consensus Guidelines: Delta Definitions
Delta checks: Delta checks operate to reduce hematological testing by recognizing previously detected validated abnormalities.
Delta limits: The delta limit for a particular test is the amount by which the most recent automated analyzer test result may differ from a previous test result before triggering smear review or some other action to validate the analyzer result. Delta limits should be established for each laboratory by taking into account physiological considerations as well as the characteristics of the automated analyzer used in that laboratory.
Delta pass and delta fail: Delta pass occurs when the result of the most recent automated analyzer test does not differ by more than the delta limit from the result of the previous test. Delta fail is when the result of the most recent test differs by more than the predefined delta limit from the previous test result.
Positive delta and negative delta: Positive delta occurs when the result of the most recent test differs in a positive direction from the result of the previous test i.e. it is larger, irrespective of whether the delta limit has been exceeded. Negative delta is when the result of the most recent test differs in a negative direction from the result of the previous test i.e. it is smaller.
Actions related to delta checks: The International Consensus Group did not set delta limits, leaving those to the individual laboraotory. However the group did suggest specific actions for situations where delta limits set by the individual laboratory are exceeded.
Consensus Guidelines: Positive Smear Findings
Below is the listing of criteria used to determine a positive smear finding for the study of suggested criteria for action following automated CBC and WBC differential analysis.
1. Morphology
a. RBC morphology at either 2+ / Moderate or greater. The only exception is Malaria, where any finding will be considered a positive finding.
b. PLT morphology (giant platelets) at either 2+ / Moderate or greater.
c. Platelet Clumps at > rare / occasional
d. Dohle bodies at either 2+ / Moderate or greater
e. Toxic granulation at either 2+ / Moderate or greater
f. Vacuoles at either 2+ / Moderate or greater
2. Abnormal Cell Types
a. Blast > 1
b. Meta >2
c. Myelo / Promyelocyte > 1
d. Atypical Lymphs > 5
e. NRBC > 1
f. Plasma Cells > 1
Consensus Guidelines: Rules
|
Rule #
|
Parameter
|
Primary
|
and/or
|
Secondary
|
and/or
|
Tertiary
|
and/or
|
fourth
|
Action 1
|
Action 2
|
Action 3
|
|
1
|
Neonate | First sample | Slide Review | ||||||||
|
2
|
WBC, RBC, HGB, PLT, Retics | Exceeds linearity | Dilute sample and rerun | ||||||||
|
3
|
WBC, PLT | Lower than Lab verified instrument linearity | Follow lab SOP | |
|||||||
|
4
|
WBC, RBC, HGB, PLT | Vote Out | Check sample for clot | Rerun sample | If persists, perform alternate counting method | ||||||
|
5
|
WBC | <4.0 OR > 30.0 | and | first time | Slide Review | ||||||
|
6
|
WBC | <4.0 OR > 30.0 | and | delta failed | and | within 3 days | Slide Review | ||||
|
7
|
PLT | <100 OR >1000 | and | first time | |
|
|
|
Slide Review | |
|
|
8
|
PLT | Any value | and | Delta Check Fail | Slide Review | ||||||
|
9
|
HGB | <7g/dl or > 2g/dl above upper reference range for age and sex | and | first time | |
|
Slide Review | Verify sample integrity if indicated | |||
|
10
|
MCV | <75fl or > 105fl (Adult) | and | first time | and | specimen is < 24 hours old | Slide Review | ||||
|
11
|
MCV | >105 fl | and | adult | and | specimen is >24 hrs old | Slide Review for macrocytic associated changes | Request fresh sample if NO macrocytic associated changes seen | Report with comment if fresh sample is not available | ||
|
12
|
MCV | Any value | and | delta fails | and | specimen is <24 hours old | Verify sample integrity/identity | ||||
|
13
|
MCHC | >=2 units above upper limit of reference range | Check for lipemia, hemolysis, RBC agglutination, spherocytes. | ||||||||
|
14
|
MCHC | <30 | and | normal/high MCV | Investigate possible IV contamination or other sample specific cause. | ||||||
|
15
|
RDW | >22 | and | first time | Slide Review | ||||||
|
DIFFERENTIAL
|
|||||||||||
|
16
|
No diff or incomplete diff | Manual Diff and Slide Review | |||||||||
|
17
|
Neut # | <1.0 or > 20.0 | and | first time | Slide Review | ||||||
|
18
|
Lymph # | >5.0 (adult) or >7.0 (<12 yrs old) | and | first time | Slide Review | ||||||
|
19
|
Mono # | >1.5 (Adult) or >3.0 (<12 yrs old) | and | first time | Slide Review | ||||||
|
20
|
Eos # | >2.0 | and | first time | Slide Review | ||||||
|
21
|
Baso # | >0.5 | and | first time | Slide Review | ||||||
|
22
|
NRBC # | any value | and | first time | Slide Review | ||||||
|
|
RETICS | |
|
|
|
|
|
|
|
|
|
|
23
|
Retic Absolute # | >0.100 | and | first time | Slide Review | ||||||
|
SUSPECT FLAGS
|
|||||||||||
|
24
|
Suspect flag (except ImmG/Band) | Flag + | and | first time | and | adult | Slide Review | ||||
|
25
|
Suspect flag | Flag + | and | first time | and | child | Slide Review | ||||
|
26
|
WBC unreliability Flag | Flag + | any | Check sample integrity and rerun sample | If persists, review instrument output | Slide review with manual diff if indicated | |||||
|
27
|
RBC fragment | Flag + | any | Slide Review | |||||||
|
28
|
Dimorphic RBC | Flag + | and | first time | Slide Review | ||||||
|
29
|
Lyse resistant RBC | Flag + | any | Review WBC histogram/cytogram | Validate by lab SOP (consider incorrect retic count) | eg. Review smear for abnormal RBC morphology | |||||
|
30
|
PLT clump flag | any count | Check sample for clots | Slide review (PLT estimate) | If clumps persist, follow lab SOP | ||||||
|
31
|
Platelet Flags | PLT & MPV flags except plt clumps | Slide Review | ||||||||
|
32
|
Immature granulocyte flag | Flag + | and | first time | Slide Review | ||||||
|
33
|
Immature granulocyte flag | Flag + | and | previous confirmed result | and | positive delta fail for WBC | Slide Review | ||||
|
34
|
Left shift flag | Flag + | Follow lab SOP | ||||||||
|
35
|
Atypical/Variant lymphs | Flag + | and | first time | Slide Review | ||||||
|
36
|
Atypical/Variant lymphs | Flag + | and | previous confirmed result | and | positive delta fail for WBC | Slide Review | ||||
|
37
|
Blast flag | Flag + | and | first time | Slide Review | ||||||
|
38
|
Blast flag | Flag + | and | previous confirmed result | and | delta pass or negative delta for WBC | and | within 3-7 days | Follow lab SOP | ||
|
39
|
Blast flag | Flag + | and | previous confirmed result | and | positive delta fail for WBC | Slide Review | ||||
|
40
|
NRBC flag | Flag + | Slide Review | If positive, enumerate NRBC count, correct WBC if appropriate | |||||||
|
41
|
Retics | Abnormal pattern | Look at instrument output | Repeat if aspiration problem | If persists, review slide | ||||||
Consensus Guidelines: Truth Table
Delta checks: Delta checks operate to reduce hematological testing by recognizing previously
| Number | Percentage |
|
| True Positive |
1483 | 11.20% |
| False Positive |
2476 | 18.60% |
| True Negative |
8953 | 67.30% |
| False Negative |
386 | 2.90% |
| Total number of samples |
13298 |
Consensus Guidelines: Participating Laboratories
| Last Name | First Name | Company/Institute | Country | Phone | |
| Barnes | Patrick | Barnes Jewish Hospital | US | 314-362-5048 | PWB0280 @bjc.org |
| Becker | Rhonda | University of California, Davis Medical Center | US | 916-734-3475 | rhonda.becker @ucdmc.ucdavis.edu |
| Fawcett | Terry | Biospecifix | Australia | 61-3-9890-8498 | auscorpmarketin @ozemail.com.au |
| Fernandes | Bernard | Mt Sinai Hospital, Dept. of Pathology & Lab Medicine | Canada | 416-586-4462 | bfernandes @mtsinai.on.ca |
| Houwen | Berend | Beckman Coulter, Inc. | |||
| Kemerer | Linda | Grant/Riverside Methodist Hospitals | US | 614-566-5686 | lkemerer @ohiohealth.com |
| Jamieson | Bette | The Children's Hospital, Dept. of Pathology | US | 303-861-6252 | jamieson.bette @tchden.org |
| Johnstone | Lynn | Health Alliance Laboratories | US | 513-585-1410 | JohnstlM @healthall.com |
| Machin | Samuel | University College Hospital, Dept. of Haematology | UK | (44)20 7380 9884 | samuel.machin @ucl.ac.uk |
| McFadden | Stefanie | Laboratory Consultant | US | 614-579-5999 | stefhem @aol.com |
| Ready | Kirk | Chinook Health Region, Corp. Office | Canada | 403-382-6093 | kready @mail.chr.ab.ca |
| Rosenfeld | David | Liverpool Hospital | Australia | (61) 2 98 28 51 67 | d.rosenfeld @unsw.edu.au |
| Simon | Ramon | Beckman Coulter Eurocenter S.A. | Switzerland | 41-22-994-08-08 | ramon.simon @beckman.com |
| Simson | Elkin | Mt Sinai Hospital | US | 212-659-8181 | elkin.simson @mssm.edu |
| Soppa | Vicky | Mayo Foundation, Hematopathology | US | 507-284-3198 | soppa.vicky @mayo.edu |
| Suter | Michael | OML Laboratories | US | 541-687-2134, x 8182 | msuter @omlabs.com |
| Villarubia | Jesus | Hospital Ramon y Cajal | Spain | 34 91 336 8224 | jvillarrubia.hrc @salud.madrid.org |
| Wall | Debbie | Dynacare Laboratories, Dynacare Northwest, Inc. | US | 206-215-3945 | dwall @dynacare.com |
| Walters | Jeri | Sinai Samaritan Medical Center, East Campus | US | 414-328-7920 | jeri.walters @aurora.org |
Consensus Guidelines: Steering Committee
For further information on the consensus rules, please contact any of the following Steering Committee Members
Elkin Simson
Mt Sinai Hospital
New York, NY US
Email: [email protected]
Phone: 212-659-8181
Stefanie McFadden
Laboratory Consultant
Columbus, OH US
Email: [email protected]
Phone: 614-579-5999
Patrick Barnes
Barnes Jewish Hospital
St Louis, MO US
Email: [email protected]
Phone: 314-362-5048
Samuel Machin
University College Hospital, Dept. of Haematology
London, UK
Email: [email protected]
Phone: (44)20 7380 9884