CARDIAC TESTING SERVICES

I am pleased to announce several changes to MDS Metro’s Cardiac Testing Services. Firstly, Dr. Arthur Dodek is joining us as a consultant to the cardiac service. Dr. Dodek trained in Internal Medicine and Cardiology at Royal Victoria Hospital, McGill, University of Washington Hospitals, and University of Oregon. He is a Clinical Professor in Medicine/Cardiology at UBC and recently finished a long term as Director of the Cardiac Catheterization Laboratory at St. Paul’s Hospital. He has written over ninety medical articles and is Co-ordinator of Continuing Medical Education courses for UBC and St. Paul’s Hospitals. He is a member of the Council of the College of Physicians and Surgeons of BC. His role at MDS Metro will include professional direction in the areas of quality assurance, continuing education and enhancement of testing. He will be our liaison with the medical community for this service. 

Secondly, we have made modifications to our computer system that will allow you to specify your personal preference for a reading physician for ECG and Holter tracings. If you have more than one office location, your preference will apply to all locations. Note that we have arrangements with specialists in all regions to interpret undesignated tracings and will continue to refer work to them unless you notify us otherwise. All cardiac work on pediatric (16 years and under) will continue to be referred to a Pediatric Cardiologist. 

If you wish to specify a reading physician, please fill out the attached form and return by fax or mail by August 1st, 2001.

Dr. Debbie Griswold
Vice President
Medical Affairs

FEATURE ARTICLE: NEUTROPENIA

Neutropenia is a common finding encountered in clinical practice. Normal absolute neutrophil counts (ANC) vary with age. For example, the normal ANC range for a term infant is 2.0 – 20.0 X 10⁹. On the other hand, the normal range in an adult is 2.0 – 7.5 X 10⁹/L. Race also influences the normal ANC range with individuals of African origin tending to have a lower limit of normal (i.e. 1.2 X 10⁹/L). This difference is of no health consequence.

In patients with severe neutropenia (<0.5 X 10⁹/L), there is an increased risk of acquiring life-threatening pyogenic infections. The duration and rapidity of the onset of neutropenia also correlate with the risk of serious bacterial infection. Individuals with neutrophil counts of 1.0 to 1.8 X 10⁹/L are at little risk.

Neutrophils are produced by maturation of myeloid stem cells in the bone marrow. Impaired production, peripheral destruction and an abnormal distribution of neutrophils can cause neutropenia. Examples of impaired production include suppression of stem cells by drugs or malignancy (e.g. leukemia, lymphoma and metastatic solid tumors), megaloblastosis and large granular lymphocytosis (a clonal T cell lymphoproliferative disorder). Peripheral destruction of neutrophils can result from severe infection, immune destruction and hypersplenism. The mechanism of neutropenia due to redistribution of neutrophils from the circulating to the marginated pool is of particular interest. It usually follows activation of endothelial cells by cytokines (e.g. interleukin-1 and tumor necrosis factor) that increase the adhesiveness of endothelial cells to circulating neutrophils. Malignancy and infection are two conditions in which cytokines are activated.

There are many classifications of the causes of neutropenia. In general, neutropenia can be classified as being due to either production defects or peripheral destruction (Table 1 & 2). Infection and drug-induced neutropenia are seen most commonly. Viral infection is the most frequent cause of infection-induced neutropenia. However, bacterial infection with sepsis may also result in severe neutropenia, and is due to depletion of the marrow neutrophil reserve pool.

Mechanisms of drug-induced neutropenia include idiosyncratic reactions, direct marrow toxicity and immune processes. Neutropenia usually begins approximately 7 to 14 days after initial exposure to the drug or immediately after re-exposure. The duration of drug-induced neutropenia varies greatly, ranging from only a few days to months or years. The drugs most commonly implicated are phenothiazines, sulphonamides, antithyroids, anticonvulsants and H2 blockers.

Autoimmune neutropenia due to IgG or IgM antibodies is also fairly common and may be seen in rheumatoid arthritis, systemic lupus erythematosus, autoimmune hemolytic anemia, and various connective tissue diseases.

Management of neutropenia differs according to the degree of neutropenia, rapidity of onset and the underlying disease. Removal of the causative agent is obviously the key factor in managing drug-induced neutropenia. It is important to exclude a primary bone marrow disorder such as myelodysplasia, leukemia or lymphoma in patients suffering from unexplained neutropenia - especially if it is associated with other abnormal blood counts, or clinical findings of lymphadenopathy or organomegaly. Further assessment by bone marrow examination may be indicated.

Management of other types of neutropenia depends on their severity. When neutropenia is an expected consequence of chemotherapy, prophylactic antibiotics may be given. Patients who have fever and severe neutropenia must be assumed to be infected and the source of infection must be sought. Since antibiotics are less effective without neutrophils, intensive antimicrobial therapy is often warranted.

Patients diagnosed with chronic benign neutropenia with no evidence of bacterial infections require no specific therapy. This is especially common in young children. However, patients with severe neutropenia and bacterial infection may benefit from administration of subcutaneous granulocyte colony-stimulating factor (G-CSF). Finally, corticosteroid therapy may be helpful in treating autoimmune neutropenia in patients suffering from diseases such as systemic lupus erythematosus.

SUGGESTED READINGS

1.  Stock W, Hoffman R. White blood cells 1: non-malignant disorders. Lancet 2000; 355: 1351-1357.

2.  Lee: Wintrobe's Clinical Hematology, 10th ed. Lippincott Williams & Wilkins, 1999

TABLE 1 – Production Defects    

DISORDERS	MECHANISM
Cancer chemotherapy or radiation	Suppression of myeloid cell production (other cell lines often affected)
Myelodysplasia, leukemia and other primary hematologic neoplasms	Marrow replacement and/or ineffective granulopoiesis
Metastatic disease, such as lymphoma and solid tumors	Bone marrow replacement
Aplastic anemia	Immune inhibition of granulpoiesis, typically with suppression of erythropoiesis and megakaryocytes
Pure white cell aplasia	Selective impairment of granulopoiesis
Drug-induced neutropenia	Direct bone marrow suppression or antibody and complement-mediated damage to precursor cells
Large granular lymphocytosis/leukemia	Suppression of granulopoiesis by clonal T cell proliferation
Malnutrition (marasmus, anorexia nervosa), B12 and folate deficiency	Ineffective granulopoiesis
Chronic benign neutropenia of infancy and childhood	Antineutrophil antibodies are commonly detected, suggesting an immune mechanism
Chronic benign familial neutropenia	Hereditary (autosomal dominant)
Cyclic neutropenia	Hereditary (autosomal dominant) defect in the stem cell regulatory mechanism. Neutropenia recurs every 15-35 days.
Schwachman syndrome (neutropenia with metaphyseal dysplasia and pancreatic insufficiency)	Hereditary (autosomal recessive)
Kostmann’s syndrome (Severe infantile agranulocytosis with eosinophilia and monocytosis)	Hereditary (autosomal recessive)

DISORDERS	MECHANISM
Infection	Decreased production, redistribution and destruction of neutrophils.
Immune neutropenia	Immune destruction, e.g. associated with autoimmune disorders, isoimmune disorders (e.g. maternal IgG antibodies directed against antigens on fetal neutrophils), some drug reactions
Hypersplenism	Reticuloendothelial sequestration
Felty’s syndrome	Autoimmune destruction of neutrophils

  

CRITICAL AND PHONE VALUES

Critical and phone levels for some chemistry tests have been changed as a result of the British Columbia Association of Laboratory Physicians’ (BCALP) initiative to standardize critical levels throughout the province. Following completion and final implementation of the BCALP consensus document, a small number of additional changes are anticipated for other tests not addressed at this time. For any questions concerning critical or phone levels in chemistry, please contact:

Dr. Margaret Kelly  1-800-431-7206, ext 4426  604-412-4426 
Dr. David Aitken  1-800-431-7206, ext 4412  604-412-4412 
Dr. Michael McNeely  1-800-304-4011  250-881-3109 

Every effort is made to notify the physician of critical test results.  Your cooperation in leaving an on-call, after-hours number on the answering machine, or in providing the laboratory with home, cell, or pager numbers to be used for this purpose is greatly appreciated.

WEB WORLD

Have you visited the MDS Metro web site at www.mdsmetro.com? If not, you may be interested in a number of features designed for patients that may assist you in your practice. When you hit the Home Page, click the “Patients and Consumers” area. Then on the left hand side you will see links to:

Patient Instruction Cards Instructions for any of our tests that require special patient preparation.

Medical Conditions A listing of 30 medical disorders that employ lab testing with information on what tests are used and why.

Test Information A listing of 180 lab tests with a brief description (like a dictionary). In many cases a link is provided to additional information. 

If you want to know more about Special Tests that are offered through the MDS Specialty Diagnostics service you can go to www.mdscollaborate.com. 

If you have a medical question or a comment about our services you are always encouraged to phone one of our 12 medical staff members. However, if email is preferred, simply send a message to ASKDOC .

HEMOCHROMATOSIS GENE MUTATION 

On May 22, 2001 MDS Metro implemented Hemochromatosis Gene Mutation testing at our Burnaby Reference Laboratory. To facilitate the testing process, we have developed a specific requisition form to be used when ordering the Hemochromatosis Gene Mutation test. A sample is at the end of this newsletter. (You will need Adobe Acrobat to view this file.) To order additional copies, please use the Clinic and Physician Supply Requisition.

If you have any questions, please contact:   

Dr. Annette Poon  604-412-4523 
Dr. Martin Wood  250-881-3109 
Dr, Suseela Reddy  604-412-4483 
Dr. Richard Yu  604-412-4451 

 
 
Interpreting Physician for ECG and Holter Tracings
Ordering Physician

Name: __________________________________________________     

Billing # ____________________

My preference for interpreting physician is:

Name: _______________________________________________

Address: ______________________________________________

Please return by August 1 by fax or mail

Fax:      (604) 412-4512

Mail:    Cardiac Resource
           MDS Metro Laboratory Services
           3680 Gilmore Way
           Burnaby, BC V5G 4V8