Lavender top tubes are having an identity crisis these days. If there’s an order for hemoglobin A1c, does it belong in Chemistry or Hematology? The trend to integrate and automate testing platforms and to reduce blood draw volumes is dissolving the traditional lines among the types of assays typically done by specific clinical laboratory disciplines. Nowhere is this truer than in the consolidation of EDTA sample testing by performing A1c on an integrated hematology line. With such a system in place, a laboratory can perform more than 90 percent of assays requiring lavender top tubes and integrate testing and management of EDTA samples and data—hands-free.
The application of hemoglobin A1c
The American Diabetes Association (ADA) has long recommended hemoglobin A1c to monitor glycemic control in patients diagnosed with diabetes. Diagnosis of diabetes by the physician has been based on a patient’s plasma glucose concentration test, which includes the fasting plasma glucose (FPG) test, the two-hour plasma glucose test, and casual plasma glucose testing. Recently, an International Expert Committee added the A1c (threshold = 6.5 %) as another option for the physician to diagnose diabetes. The American Diabetes Association suggests screening a defined population of people with specific criteria for diabetes. (See “ADA recommendations,” below.) The Diabetes Control and Complications Trial (DCCT)1, a major clinical study, used A1c to follow more than 1,400 volunteers over a 10-year period and concluded that keeping blood glucose levels close to normal could delay the onset of associated complications related to eye, kidney, and nerve damage. The DCCT and the United Kingdom Prospective Diabetes Study (UKPDS) showed that A1c is the best long-term marker of diabetes control, leading to better outcomes for diabetic patients. The British study indicated that monitoring A1c reduced deaths, microvascular complications, and myocardial infarction by 21%, 37%, and 14%, respectively.2
Typically, A1c testing is the second highest test order on the EDTA tube, following the CBC. Why? In addition to the increased prevalence of diabetes (See “The diabetes burden,” below), patients with diabetes are at increased risk during unplanned hospital visits or surgery, due to the delicate metabolic balance between their insulin and its counter-regulatory hormones. Clinicians need to understand the patient’s diabetic status and ensure that he or she achieves optimum glycemic control prior to or during these events in order to maximize positive outcomes.3 Therefore, labs are realizing an increase in requests for faster A1c test results, especially during emergency department visits and pre-surgical evaluations.
Determinations of A1c on an automated hematology line use ion exchange HPLC, the reference methodology, to report results which allow the lab to see many interfering substances, including various hemoglobin variants. The determinations are anchored to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference method and are National Glycohemoglobin Standardization Program (NGSP)-certified and traceable to the DCCT trial. As with currently reported hematology parameters, methods are now well standardized and provide an index of overall glycemic exposure and risk for long-term complications.
Integrating hematology and A1c: one lab’s story
Regional Medical Laboratory, Inc., (RML) is located in Tulsa, OK. RML has two hematology automation lines that went live in April 2013. One is located at St. John Medical Center, and the other is located at a new RML reference laboratory. Both are interfaced through single data management software. The reference laboratory has an integrated hematology line with two integrated HPLC A1c testing analyzers. RML pathologist William Fitter, MD, reports that the physicians are pleased that chromatography is being used rather than point-of-care assays or immunoassays. “From the beginning, RML has done A1c using chromatography. We have always had the position that it was the reference method, the ideal method for looking at A1c.” RML’s current workload is 400-500 A1c tests/day.
Implementing an integrated hematology and A1c line solved a number of issues the laboratory needed to improve with regard to A1c testing: poor turnaround time, batch testing, manual chromatograph review of all results, and EDTA/A1c shared tube searches. Hematology supervisor Jennifer Starks, MT (ASCP), reports the hematology/A1c line has improved A1c turnaround time from 24 hours to four, enabled auto-verification and reporting of hematology and A1c testing, and provided hands-free operations for hematology and A1c testing. Pathologist Cindi Starkey, MD, reports that staff is autoverifying and reporting approximately 95 percent of samples.
Statistics recently released by the Centers for Disease Control and Prevention (CDC) reported that diabetes is the seventh-leading cause of death in the United States and costs $174 billion per year (direct and indirect costs). It affects 29.1 million people, or 9.3% of the U.S. population, and of these, eight million have not been diagnosed. Diabetes is also a major cause of heart disease, kidney failure, new cases of blindness, and stroke. Perhaps most alarming, an estimated 86 million Americans aged 20 years and older have pre-diabetes.5
The new hematology/A1c line has also allowed RML to improve staffing levels. Before the new system was introduced, two people were needed to run the hematology line and a third to do the A1c testing, and the third had to be qualified to do moderately complex testing. Now one laboratorian is able to run the line with the A1c’s and manage all the hematology equipment, including one slidemaker/stainer.
The hematology line tube sorter has played a key role in sample management. This “smart sorter” helps eliminate duplicate testing if the laboratory receives two purple top tubes on the same patient because an A1c was ordered and two tubes were inadvertently drawn. Samples requiring hematology and A1c analysis are first analyzed for hematology values and are then returned to the sorter, which redirects the sample to the A1c analyzer. Hematology samples that require attention are prioritized and sorted first. If hematology samples are normal and the A1c is abnormal, the sample is flagged and isolated for review.
According to Starks, “The tube sorter allowed us to eliminate an FTE. We used to review every tube that came off our line. Now we run between 800 and 1000 CBCs a day with only two people.”
The hematology component
Integrated hematology automation line with A1c testing has been available since 2008. This line incorporates sophisticated, rules-based sample and data process management software that enables laboratories to auto-validate 85 percent or more of their hematology and A1c testing results without manual intervention. These laboratory-specific rules reflect best practices and the laboratory’s unique workflow characteristics and provide the required standardization in the decision making and sample management.
Laboratory configurations that used to be characterized by individual islands of automation are now seeing those islands converge into single, dedicated sample-driven assemblies. For EDTA samples, more results can be reported from a single tube than ever before. Having the ability to make A1c results available 24/7 provides the physician with the flexibility to test patients to reduce this healthcare burden, while also obtaining a full battery of hematology results that can help reflect blood dyscrasias or the presence of diabetes complications.
- American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Suppl.1):S81-S90. http://diabetes.niddk.nih.gov/dm/pubs/control. Accessed August 20, 2014.
- Stratton IM, Adler A, Mattews D, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000; 321:405-412.
- Plodkowski R.A, Edelman S. Pre-surgical evaluation of diabetic patients. Clinical Diabetes. 2000;19.2(95).
- American Diabetes Association. Standards of medical care in diabetes-2010. Diabetes Care. 2010;33(1).
- Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and its Burden in the United States, 2014. Atlanta, GA: U.S. Department of Health and Human Services; 2014. http://www.cdc.gov/diabetes/index.htm. Accessed August 20, 2014.