No 105 January 2010

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							                     LAB CONNECTIONS                                                                     January 2010
                                                                                                         Issue # 105


IN THIS ISSUE: The hematology division of the HRLMP provides two articles. The first describes the
indications for testing in thrombophilia patients, and the second gives an update on the CELLAVISION
implementation.


WHAT’S NEW? Follow the links to learn...
1. Why HRLMP has discontinued including electrophoresis scans in reports (ctrl + clik                HELPFUL
   to follow link)                                                                                   WEBLINKS
2. What is the appropriate protocol for testing for infectious diarrhea? (ctrl + clik to follow      For information on
   link)                                                                                             the Hamilton
3. When an APTT test is indicated (ctrl + clik to follow link)                                       Regional Laboratory
4. Changes to ordering practices for some hematology tests (ctrl + clik to follow link)              Medicine Program,
                          Thrombophilia Testing in Inpatients                                        visit:
                                                                                                     http://www.hrlmp.ca
  Thrombophilia (thrombo [thrombus] – philia [loving]), are biochemical
  predispositions to thrombosis, that can be hereditary or acquired. Hereditary
  thrombophilias include: Factor V Leiden (4% prevalence in Caucasians and < 1%
  in Africans), the G20210A prothrombin gene mutation (2% prevalence), protein C                  YOUR FEEDBACK
  deficiency (0.3% prevalence), protein S deficiency (0.3% prevalence), and                       IS VALUED!
  antithrombin deficiency (0.04% prevalence). (1-4) Among acquired
  thrombophilias, antiphospholipid antibodies are the most important type and                     Editorial Board:
  these are generally subcategorized as non-specific inhibitors (NSI; previously
                                                                                                  Chemistry: Dr. V. Grey
  termed “lupus anticoagulant”; <1% of the population) and anticardiolipin                        Microbiology: Dr. C. Main
  antibodies (5% population).(5)                                                                  Pathology: Dr. J. Jansen
                                                                                                  Genetics: Dr. J. Waye
  Risks Associated with Thrombophilia: Hereditary thrombophilias and                              Hematology: Dr. M.
                                                                                                  Crowther
  antiphospholipid antibodies are important risk factors for a first episode of
  venous thromboembolism (Relative Risk:           Factor V Leiden, 5; G20210A                    Editorial Office:
  prothrombin gene, 2.5; Protein C or S deficiency, 10; antithrombin deficiency, 40;
  non-specific inhibitor, 10; anticardiolipin antibody, 2). However, they are                     Dr. Vijay Laxmi Grey,
                                                                                                  Editor
  generally not important risk factors for arterial thrombosis. Thrombophilia is
                                                                                                  E-mail: grey@hhsc.ca
  also associated with some pregnancy complications.                                              Charlotte Baker, Editorial
                                                                                                  Assistant
  Value of Thrombophilia Testing: While testing for thrombophilia has provided                    E-mail: bakerch@hhsc.ca
  insights on common and rare predisposing factors for thrombosis, the value of
                                                                                                  Your feedback and
  testing individual patients (for hereditary thrombophilias or antiphospholipid
                                                                                                  suggestions are most
  antibodies) has been questioned and how the findings should influence the
                                                                                                  welcome!

                                                                                     /cont’d...
                                                     -2-

management of patients with thrombosis is uncertain and controversial. For example, the results of
thrombophilia tests have little influence on decisions about how long to treat patients with venous
thrombosis.(6)     Although thrombophilia may increase the risk of post-operative venous
thromboembolism, knowing whether or not a patient has thrombophilia does not usually influence
decisions about use of primary prophylaxis and, therefore, testing is not needed before surgery.(7)

Another factor that adds to the complexity of whether or not patients with thromboembolism should be
tested for thrombophilia is that testing at the time of acute thrombosis and other illnesses can result in
false-positive test results.(1; 2) This is particularly a problem for measurement of protein S, protein C and
antithrombin, and for non-specific inhibitors (approximately 5% of hospitalized patients test positive for
non-specific inhibitors). In addition, current or recent anticoagulant therapy may cause false-positive
thrombophilia tests results, particularly for protein C, protein S and antithrombin and non-specific
inhibitors. For these reasons, testing for hereditary thrombophilias and antiphospholipid antibodies
should not be done for in-patients, other than in exceptional circumstances (e.g. suspected neonatal
“purpura fulminans”). Decisions about thrombophilia testing are best made in a specialist outpatient
clinic, when thrombosis is no longer acute and when appropriate counseling is available.

Summary:
 Hereditary thrombophilias and antiphospholipid antibodies are important in the development of
  venous thrombosis, but the role of testing for these abnormalities in the management of patients is
  uncertain. As a result, routine testing of patients with thrombosis is not recommended.
 Testing for many thrombophilias in hospitalized patients is discouraged unless there is an unusual
  clinical situation, such as neonatal purpura fulminans.
 In general, the decision to test patients for thrombophilia should be made in a specialist outpatient
  clinic.

References:

 1. Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V et al. Inherited
     Thrombophilia: Part 1. Thromb Haemost 1996; 76 (5):651-62.
 2. Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V et al. Inherited
     Thrombophilia: Part 2. Thromb Haemost 1996; 76 (6):824-34.
 3. Kearon C, Crowther M, Hirsh J. Management of patients with hereditary hypercoagulable disorders.
     Annu.Rev.Med. 2000; 51:169-85.
 4. Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis: a
     qualitative overview and proposed classification system. Ann Intern Med 2003; 138(2):128-34.
 5. Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a
     systematic review. JAMA 2006; 295(9):1050-7.
 6. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob G, Comerota AJ. Antithrombotic Therapy for
     Venous Thromboembolic Disease. ACCP Evidence-Based Clinical Practice Guidelines (Eight
     Editions). Chest 2008; 133:454S-545S.
 7. Arnold DM, Anderson J, Kearon C. Preoperative risk assessment for bleeding and thromboembolism.
     Br Med J 2009; 339:b2299.

Karen Moffatt, ART, FCSMLS (D), Clive Kearon, MB, MRCPI, FRCPC, PhD,
Mark Crowther, MD, MSc FRCPC, Catherine Hayward, MD, PhD, FRCPC,
Hematology Service, Hamilton Regional Laboratory Medicine Program
                                                                                                    /cont’d...
                                              -3-

                         Cellavision - Automating the Differential

In May 2009, the Hamilton Regional Laboratory Medicine Program introduced instrumentation
that helps to take the guess work out of the manual peripheral blood cell differential.
Cellavision instruments automate the manual differential of peripheral blood, body fluid
smears and provides functionality for digital slides.

The HRLMP purchased five Cellavision DM96 units. Units are located at the McMaster
University Medical Centre, Henderson General Hospital, Hamilton General Hospital and at
both St. Joseph's Healthcare campuses.

The HRLMP chose the Cellavision DM96 due to its ability to perform automatic preliminary
differential counts on peripheral blood and body fluid smears. The analyzer pre-classifies the
white blood cells, pre-characterizes parts of the red morphology and provides functionality for
platelet estimation. Preliminary results are verified by a medical technologist experienced in
morphology and are then released to the clinician.

The benefits associated with this technology include:
1. Increased speed of routine laboratory work
2. Increased efficiency
3. More standardized differential results
4. Long-term storage of cell images and results
5. Improved teaching ability
6. Enhanced ability to perform competency testing

We have already experienced some of these improvements. We have seen technologist
productivity increase, standardization of reporting, major consolidation of expertise, improved
turn-around-times (TAT) and improved consultative ability. The average TATs at the Hamilton
General Hospital are down from 6h to 3h and, more significantly, the variance has been reduced
substantially as the longest time to reporting of a differential has been reduced from 15.5 h to
5.5 h. Another important improvement is the increased sensitivity of Cellavision for detecting
malignant cells.

Although we have had some major success with the introduction of the Cellavision technology,
there continues to be challenges. For example, specific challenges have been identified in the
neonatal and pediatric populations. These include:
1. The effect of high hemoglobin values on the slide preparations
2. Platelet clumps often seen with finger poke or micro capillary procurement.

                                                                                       /cont’d...
                                              -4-

We are confident that through a troubleshooting partnership with Cellavision, Beckman Coulter
and Becton Dickinson, we will minimize these challenges and complete the strategic goal of full
consolidation of our morphological and differential workload to the Special Hematology
Laboratory located at the Henderson General Hospital. This consolidation will provide a
centralized location of expertise for Hamilton and regional hospitals.

Dr. Mark Crowther, Medical Director, Hamilton Regional Laboratory Medicine Program
Director, Hematology Service
Duane Boychuk, Director, Laboratory Services
Teresa Difrancesco, Manager, Special Hematology and Transfusion Medicine

						
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