TROPONIN IN ACUTE CORONARY SYNDROMES (ACS) 

As a result of improved sensitivity and tissue specificity, cardiac Tn is now recommended as the preferred marker for diagnosis of myocardial injury.  If the timing of myocardial events is unclear, CKMB may be useful to clarify if the event is recent (within 48 hours), or to assess for re-infarction.

The troponins are a group of structural proteins involved in the regulation of skeletal and cardiac muscle contraction.  There are three troponin components, each with a specific function:  troponin I (TnI) inhibits actin and myosin interaction; troponin C (TnC) binds calcium; and troponin T (TnT) fixes TnI and TnC to the tropomyosin-actin filament.


               

Cardiac TnI and TnT are distinct from their skeletal muscle counterparts and have been recognized for over a decade as sensitive and specific serum markers of myocardial injury.  Two decision levels are useful for interpretation of cardiac Tn: minimal elevation suggests myocardial injury, and a higher value is suggestive of injury to the extent that it qualifies as acute myocardial infarction (AMI) as defined by the WHO.  Among patients with chest pain and unstable angina, elevated Tn above the health-related reference interval identifies a subgroup at increased short-term (30 days) risk of adverse cardiac events.  Prognosis is related in part to the degree of increase.  With AMI, TnI begins to rise relatively early after the onset of chest pain (4 – 12 hours), peaks at 15 to 25 hours, and remains elevated for 4-7 days.  Depending on the size of the infarct and the rate of reperfusion, peak concentrations up to 50 mg/L have been reported.  Appropriate patient triage requires correlation with clinical findings:  repeat testing within 24 hours may be indicated to monitor trend or in patients with high clinical probability and negative or low abnormal results, especially if the specimen was obtained within 6 hours of the onset of chest pain.  Tn is particularly useful in patients with equivocal ECG changes and for risk stratification in unstable angina.

Cardiac Tn may also be elevated with non-ischemic causes of myocardial injury, including myocarditis, mechanical/traumatic cardiac injury, or myocardial toxins (e.g. doxorubicin).

Due to differences in Tn assays, results must be interpreted in the context of the reported reference range and results obtained from different assays may not be used interchangeably.  Different ranges will be reported in different locations by MDS depending upon the local method.  The following ranges apply to TnI results from MDS Metro Laboratory Services (Bayer Centaur methodology) in the lower mainland area:

For questions or discussion, phone:

Dr. David Aitken or Dr. Margaret Kelly 1-800-431-7206
Dr. Michael McNeely 1-800-297-7747 (Vancouver Island)

References:

Jaffe AS, et al, It’s Time to Change to a Troponin Standard, Circulation 2000; 102: 1216-1220.
Ganong WF, Review of Medical Physiology 1997; (diagrammatic representation) p 62.

MACROPROLACTIN

Our endocrine laboratory is now able to detect the presence of macroprolactin. This entity consists of an immunoglobulin molecule bound to a prolactin molecule. In this form it is relatively resistant to degradation and rises to high levels in serum.  In some series, up to 25% of hyperprolactinemias have been attributed to this phenomenon.  In our experience the number is lower. Macroprolactin is almost always without clinical significance and the entity should be ruled out in any patient with hyperprolactinemia. Recall that other causes of prolactin elevation are: pregnancy and lactation, prolactin secreting pituitary adenoma, other tumours of the pituitary and stalk, non-functional tumors of the hypothalamus (craniopharyngioma, germinoma), cranial irradiation, drugs (fluphenazine, haloperidol, metoclopramide, domperidone, imipramine, amitriptyline, methyldopa, opiates, estrogens, cimetidine), renal disease, surgical stress, exercise, sexual intercourse, hypoglycemia, post epileptic siezure, breast stimulation, chest lesions, primary hypothyroidism, liver cirrhosis, and spinal cord disease. 

Reference:

Jeske W, Zgliczynski W, Zdunowski P. Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method. J Clin Endocrinol Metab. 2002 Apr;87(4):1909-10;

HETEROPHILE ANTIBODIES – A CAUSE OF FALSE POSITIVE RESULTS

We remind clinicians about the ever-present possibility of false positive results in immunoassays due to heterophile antibodies in a patient’s serum that may react with the testing reagents.  This phenomenon is said to occur in about 0.5% of patients and although this is a relatively small number it may have serious consequences if not recognized. A recent paper from our lab in conjunction with several Victoria clinicians discusses a case of false PSA and HIV elevation due to an antibody that reacts against mouse IgG.

Reference:

McAuley I, Steinhoff G, McNeely M, Blood P. “Incorrect biochemistry complicates prostate cancer management.” Can J Urology 2002; 9(2): 1496-1497.

PARATHYROID HORMONE

MDS Metro has introduced two advances in Parathyroid Hormone measurement.

For routine PTH determinations we are now using the DPC Immulite 2000 analyzer. This is the same method employed by BC Biomedical Laboratories and St. Paul’s Hospital and is therefore a de facto standard for the province.

For special circumstances, on a private payment basis, MDS is now able to offer a highly specific assay system that measures only the complete PTH (1-84) molecule (Cyclase Activating PTH or CAP) and the amount of the major inhibiting metabolite (PTH (7-84) a.k.a. Cyclase Inhibiting PTH or CIP). A ratio of active to inactive (CAP/CIP) provides a numerical indication of overall PTH activity.

The history of PTH is characterized by a series of “new” assays, each of which has come closer to revealing the true activity of the parathyroid gland and the action of PTH on bone and kidney. Early RIAs measured a mixture of intact PTH and a variety of fragments with different half-lives and activities. In the mid-1980s, monoclonal antibody techniques allowed the development of 2nd generation assays that measured only PTH molecules having both N-terminal and C-terminal ends. These, so called, “intact” PTH assays eliminated interference from mid-molecule and C-terminal fragments but it would soon be realized that the prefix “intact” was a misnomer.

It has recently been shown that 2nd generation “intact” PTH assays measure the complete (and active) PTH (1-84) molecule as well as its 7-84 metabolite.  This metabolite is now known to be an inhibitor of PTH activity and its concentration is elevated in persons with chronic renal failure. Thus, current “intact” PTH assays significantly overestimate PTH activity.

A 3rd generation assay is now available that detects only the complete PTH (1-84) molecule (Cyclase Activating PTH or CAP).  By coupling this assay with a co-standardized 2nd generation measurement we can compute the amount of the major inhibiting metabolite (PTH (7-84) a.k.a. Cyclase Inhibiting PTH or CIP). A ratio of active to inactive (CAP/CIP) provides a numerical indication of overall PTH activity.

2nd Generation Assay	PTH (1-84)  +  PTH (7-84)
3rd Generation Assay	PTH (1-84)	CAP
	-----------------------------------
Difference	PTH (7-84)	CIP
Ratio	CAP/CIP

   
 

How to Order:

For the routine Immulite assay, there is no change. Simply order it like any other test. It is covered by MSP.

For the CAP/CIP ratio call the MDS Customer Care Centre at 1-866-MDS-TEST (1-866-637-8378) This is not covered by MSP. In circumstances where it is not covered, the price of the test may be reimbursed by a patent’s private insurance plan.

PATHNET

PathNET, an electronic reporting system for laboratory test results, is now being used by over 2,000 physicians.

PathNet is the first organization to become formally recognised by HealthNet BC as Lab Test Standard compliant. The PathNet Privacy Policy has recently been reviewed by the Privacy Commissioner for BC.

For more information about PathNET, call 1-899-728-4777 or visit www.pathnet.ca.

ATHENA

MDS recently signed an agreement with Athena Labs of Worcester, MA to offer over 100 rare and specialized neurological tests for peripheral nerve disorders, neurogenetic disorders, Alzheimer’s disease, paraneoplastic syndromes, movement disorders, and neuromuscular conditions.

Excellent medical information about Athena testing can be viewed at http://www.athenadiagnostics.com/index.asp

Arrangements for this testing may be made by calling 1-866-MDS-TEST (1-866-637-8378).

WEB SITE – REFERENCE RANGES

MDS Metro’s laboratory test reference ranges are now available on our web site.

Palm^TM downloadable versions are also available.

If you do download the reference values, please return to the site on a regular basis to refresh your data. Our reference ranges do change from time-to-time.

DISPLAY OF RESULTS PREVIOUSLY REPORTED IN ERROR

In the near future, whenever a result has been corrected, the previous result will now also appear on the hard copy patient report.  The *C* designation will continue to print next to the result that has been corrected.  The result that was previously reported in error will appear at the end of the report and will include the original reporting date.

MDS Metro is making this change to comply with accreditation requirements.

MDS TO MANAGE DUKE UNIVERSITY’S LABS

MDS has signed a multi-year agreement with Duke University Health System to manage its clinical laboratories and integrate the clinical laboratory services across the full Duke University health System. In addition, MDS and Duke will form a joint venture to provide outreach services in North Carolina. 

MDS METRO RAISES $50,000 FOR HOSPICE PROGRAMS

The Sixth Annual MDS Metro Tournament for Hospice was held on Thursday, May 30 at Quilchena Golf & Country Club in Richmond.

Thanks to the generous support of our donors, sponsors and players, we raised $50,000, which will be shared between St. James’ Cottage Hospice in Vancouver and St. Michael’s Centre Hospice in Burnaby.

We are very proud of the success of this tournament, which has become our signature fund-raising event. Since 1997, our golf tournaments have raised over $300,000 for hospice care in BC.