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The blood bank at the VA Boston Healthcare system extended the use of 2 laboratory robots (Aethon, Pittsburgh, PA) for laboratory specimen pickup, transport, and delivery of blood products using a combination of 3 proven technologies. First, the adoption of a single universal cooler system for the transport of red blood cells and fresh frozen plasma (FFP) with electronic temperature monitoring/recording. Second, programmable robots capable of navigating throughout the hospital. Finally, the development of an interactive consult/order robot request form. Using a synthesis of these 3 technologies, the blood bank has reduced the need to use scarce human labor resources for transport of blood products within our facility, thus freeing up staff from this time consuming activity. We suggest that our experience be used as a paradigm for other facilities in their efforts to develop an integrated, electronic, and robotic system for the transport and delivery of blood products. Figure 1 Thermal Wizard Red Shield cooler. Figure 2 Validator, lucite blood product carrier, and gel blocks within cooler. Prior to acquiring the laboratory robots, the blood bank at the VA Boston Healthcare System adopted a single cooler system for storage and transport of red blood cells; this cooler system has enabled the blood bank to store red cells between 1°C and 6°C for up to 24 hours and provided an electronic temperature monitoring system with the ability to monitor internal cooler temperatures. The blood bank also developed an interactive electronic tracking and documenting process to fulfill the requirements of regulatory agencies for the traceability of blood products.1 In this report, we present our experience with developing our process for transport of blood products using a combination of 2 unique technologies: a single, unique cooler system and a commercially available robot. Additionally we describe a computerized process for tracking and documentation of blood products …

Cardiac troponin I (cTnI) and T (cTnT) are highly sensitive and specific biochemical markers for myocardial necrosis and are generally not elevated in cases other than acute myocardial infarction (AMI) and acute coronary syndrome (ACS). However, if the patient’s clinical picture for AMI or ACS do not match an elevated troponin result, the laboratory should suspect a false positive troponin value caused by analytical interferences with this assay. These analytic interferences include fibrin clots, microparticles in sample, hetereophile and human anti-animal antibodies, rheumatoid factor, interference by bilirubin, hemolysis, lipemia, elevated alkaline phosphatase activity, macro immunocomplex formation, and analyzer malfunction. In general, analytical interferences resulting in false positive troponin results are associated with a specific manufacturer’s troponin assay and are not encountered in all troponin assays. This review discusses steps which the laboratory should consider taking in the investigation of suspected analytical interference with the troponin assay. Awareness of the possibility of a false positive troponin result may assist the physician in the management of the patient without AMI or ACS and may spare the patient additional diagnostic procedures especially if the troponin result is not consistent with these diagnoses. A false positive troponin result is a reminder that although troponin plays an important role in the diagnosis of AMI and ACS , it should not be the only criterion for establishing these diagnoses.

1. What is this patient’s most striking laboratory result? 2. Why was there a concern about the possibility of an anaphylactic transfusion reaction in this patient? 3. What methods are commonly used for measuring IgA concentration? 4. What is the definition of IgA deficiency? 5. What illnesses are most often associated with IgA deficiency? 6. What is the prevalence of IgA deficiency in the blood donor population? 7. What is the significance of the detection of anti-IgA antibodies in patients with IgA deficiency? 8. What stimulates the production of anti-IgA antibodies? 9. What is the frequency of anaphylactic transfusion reactions and associated mortality in IgA-deficient patients? 10. How should patients with IgA deficiency and/or a previous history of anaphylactic transfusion reaction be managed?

A 63-year-old white man with a history of schizophrenia plus polysubstance and alcohol abuse was seen by his primary care physician during a routine visit, at which time he was found to have a serum sodium concentration of 113 mmol/L. The patient was contacted by phone and advised to return to Urgent Care for assessment, but he did not respond until 7 days later, at which time his serum sodium concentration was 106 mmol/L. He reported that he felt fine the day before but that he started feeling very lethargic that morning and had trouble “keeping his eyes open.” The patient was noted to be somnolent and confused. Table 1 summarizes the patient's laboratory data on admission. View this table: Table 1. Patient's laboratory results at time of admission. The patient admitted to having drunk one-half to 1 bottle of beer on the day of admission—only beer and no more than 2 beers. He later admitted, however, to a higher beer consumption of up to 12 bottles a day. He did not recall whether he had breakfast on the morning of admission, and his nutritional history was inconsistent. His severe hyponatremia and history of excessive consumption of beer, a poor source of sodium and protein, coupled with his poor intake of food was consistent with the diagnosis of beer potomania. The patient was treated with 500 mL of normal saline (300 Osm/L). The patient's serum sodium value increased to 116 mmol/L but then increased rapidly to 126 mmol/L over a 12-h period. The rapid overcorrection of sodium (10 mmol/L in the first 12 h) increased the risk of osmotic demyelination because complications have been noted if the serum sodium change is >0.55 mmol · L−1 · h−1 (>10 mmol/L in 24 h and >18 mmol/L in 48 h). The goal of the management of hyponatremia should be a sodium increase …

Humoral hypercalcemia of malignancy (HHM) is the cause of hypercalcemia in the majority of patients with hypercalcemia and cancer. Parathyroid hormone-related protein (PTH-RP) has been identified as the circulating factor that mediates HHM. An N-terminal and a C-terminal PTH-RP are clinically useful assays for screening patients for HHM, and both assays are elevated in such patients. C-terminal PTH-RP depends on glomerular filtration and accumulates in patients with renal failure without malignancy, resulting in falsely-elevated levels, whereas N-terminal PTH-RP is low or undetectable in such patients. We present a case of a patient with renal failure and hypercalcemia who did not have an obvious malignancy and who presented with an elevated C-terminal PTH-RP level and a normal N-terminal PTH-RP. In patients with renal failure and hypercalcemia without cancer, C-terminal PTH-RP may be falsely elevated, especially if the eGFR is

Acute profound thrombocytopenia may be associated with the administration of eptifibatide, a glycoprotein antagonist. A case report of a 61-year-old male is presented. The reported incidence of acute profound thrombocytopenia associated with eptifibatide is 0.1% to 1.0% and usually occurs within 24 hours following therapy. However, cases of profound thrombocytopenia have been reported to occur within 1 to 4 hours following infusion. Platelet counts should be monitored in patients receiving eptifibatide at least within 24 hours and preferably within 2 to 4 hours after administration. Submitted 5.8.06 | Revisions Received 6.28.06 | Accepted 7.17.06

A critical limit protocol requiring that all point of care glucose meter readings22.2 mmol/L (400 mg/dL) and2.2 mmol/L (40 mg/dL) be immediately confirmed by the laboratory was assessed. A total of 193 (2%) of 9,523 glucose meter determinations (63 patients) were22.2 or2.2 mmol/L. One hundred twenty-two (63%) of critically high and low glucose readings were followed up, and 71 (37%) results were not. Seventy-seven percent (55 of 71) of results without follow up were in patients with multiple glucose meter/central lab comparisons, suggesting that users may have thought it unnecessary to confirm such results. Split sample quality control specimens showed good correlation (r = 0.927) between glucose meter and central lab results, whereas correlation for follow-up glucose results was poorer (r = 0.793), perhaps reflecting time delay in obtaining a lab sample. For follow-up results, only 18% of high/low critical limit glucose meter readings were confirmed by drawing a lab specimen within 10 minutes. Fifty-eight percent were in 17 patients with multiple previous glucose meter readings, suggesting that users may have though it less urgent to confirm a sequence of such results. Eleven follow-up results (9%) showed a50% discordance between glucose meter/central lab with three (27%) glucose meter errors, emphasizing the need to confirm critically high/low glucose meter results to avoid potential errors. The critical limit protocol now requires that only the initial critically high/low glucose meter reading be confirmed by the lab and that these patients now be followed with lab values until glucose levels are between 5.6-16.7 mmol/L (100-300 mg/dL) before the glucose meter can again be used.

Two widely used and well-established enzyme tests used to detect diseases of the liver, heart, skeletal muscle, brain, and kidney are elevations in the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). We hypothesized that the frequency of low ALT would greatly exceed the frequency of low AST in a population with a high prevalence of alcoholic liver disease. During 1 year, the frequency of low AST and ALT activity (

The causes for low serum alkaline phosphatase (ALP) activity (reference range 30-115 U/L) in a large Veterans Medical Center were reviewed. Of 69,864 ALP determinations made over a 4-year period, 130 were low (< 30 U/L, 0.19%), representing 88 individual patients. Of these, 83 (primarily men, 96%) patients' charts were reviewed and classified into two groups, those with and those without conditions previously reported to be associated with decreased serum ALP activity: 47% had conditions associated with low ALP activity, the most frequent being cardiac surgery and cardiopulmonary bypass (26.5%), malnutrition (12.0%), magnesium deficiency (4.8%), hypothyroidism (2.4%), and severe anemia (1.2%); 53% of patients did not have clinical conditions previously associated with low ALP activity. No case of clinically apparent hypophosphatasia, for which low ALP activity is the defining characteristic, was found in this population of veterans. A low serum ALP may be of significance in other patient populations such as children, where it is associated with achondroplasia and cretinism, or in postmenopausal women with osteoporosis taking estrogen replacement therapy. In the predominantly adult male population in this study, low ALP activity was rare; it was seen most frequently in cardiac surgery patients postoperatively, a clinical condition heretofore not commonly associated with low serum ALP activity.

The frequency and prevalence of hypomagnesemia (less than 0.72 mmol/L) in two divisions of a consolidated medical center with two distinct patient populations, acute and chronic, was studied. In the acute care patient population, the frequency and prevalence of hypomagnesemia was 41.4% (222 of 536 determinations) and 26.1% (92 of 353 patients) compared to a frequency of 12.5% (50 of 399 determinations) and prevalence of 3.5% (9 of 258 patients) in the chronic care population. Although the two divisions have similar numbers of hospital discharges, the acute care facility handles acute medical and all surgical cases, whereas the chronic care facility handles primarily psychiatric cases. In the acute care facility, the most common diagnoses associated with hypomagnesemia were coronary artery disease, malignancy, coronary artery bypass surgery, chronic obstructive pulmonary disease and alcoholism, whereas in the chronic care facility, alcoholism, liver disease, and carcinoma were the most frequent diagnoses associated with hypomagnesemia. The frequency and prevalence of hypomagnesemia in a patient population depends on the type of patient population studied and is significantly greater in the acute care compared to the chronic care patient population.

The Veterans Affairs (VA) Boston Healthcare System, Boston, MA, instituted a protocol limiting the number of B-type natriuretic peptide (BNP) assays to 1 per hospitalization or outpatient visit and requiring approval of the cardiology service for more than 1 because of a 3-fold monthly increase in BNP testing. Effectiveness of this protocol was assessed by studying BNP utilization for 6-month periods before and after institution of the protocol. Before: 1,886 assays in 752 patients; mean BNP assays per patient, 2.5; direct reagent cost, $33, 948; 1 BNP assay in 57.3% (431) of patients; 321 patients with multiple and 204 patients with serial BNP requests. After: 782 assays (-58.5%) in 593 patients (-21.1%); mean BNP assays per patient, 1.3 (-48.0%); direct reagent cost, $14,076 (-58.5%); 1 BNP assay in 81.1% (481) of patients; 112 patients with multiple and 24 patients with serial BNP requests (-88.2%). The emergency department was the source of BNP assays in 15.4% of requests before compared with 58.1% after introduction of the protocol. The protocol with slight modifications has been adopted by other VA medical centers in New England and may serve as a model for other medical facilities seeking to control BNP utilization.

Screening and confirmation testing for drugs of abuse in urine (DAU) represent areas for potential reduction of laboratory workload and attendant cost savings. Following a careful review of the dinical needs of the underlying veteran patient population served by 7 medical facilities in the Boston area, DAU test ordering frequencies, positive rates for several screening panels and the associated confirmation tests, DAU panel standardization, and confirmation testing only by request were introduced. These changes were all reviewed and approved by the clinician users of DAU testing at each institution before the changes were implemented. Before standardization of DAU screening panels, 59,835 DAU screening requests were done at a cost of $216,005; following standardization, there was 47% decrease in DAU screening utilization (27,876) and costs ($100,633). Before implementation of a DAU confirmation by request only policy, 5,331 confirmation tests were done at a cost of $111,502; after institution of the confirmation policy, there was 95% decrease in confirmation tests (5,080) and costs ($105,826). DAU panel standardization and DAU confirmation by request only have resulted in substantial reductions of laboratory workload and costs in a veterans population and may serve as a model for other patient populations with perhaps similar outcomes.

Lithium is widely used to treat bipolar affective disorders, but it has a narrow therapeutic window (0.6 to 1.2 mmol/L), and lithium toxicity often accompanies its use. This patient had acute, severe lithium intoxication (4.3 mmol/L) as a result of self-intoxication. He was successfully treated with hemodialysis, which

Two divergent laboratory approaches to the measurement of lactate dehydrogenase (LD) isoenzymes (LDIs) were evaluated. Abnormal values for total creatine kinase (CK), CK-MB, total LD, and LDIs were greater than 250 U/L, greater than or equal to 5% total CK, greater than 180 U/L, and LD1/LD2 ratio greater than 1.0, respectively. The first approach, measuring LDI on all requests regardless of total LD activity, showed the following results: 161 LDI specimens, 63 CK-MB + (LD1 greater than LD2, 6; LD1/LD2 normal, 57); 98 CK-MB - (LD1 greater than LD2, 5, LD1/LD2 normal, 93). Medical chart review of the 98 CK-MB negative specimens, representing 44 patients, showed that in seven patients with acute myocardial infarction (MI), none would have been missed clinically even if LDIs had not been done, and in only one case did LDIs play a confirmatory role in a patient who persistently had CK-MB-negative results but who had a strong clinical suspicion of MI. None of the 42 patient specimens with normal total LD activity had an LD1 greater than LD2. The second approach, measuring LDIs only if requested, only if total CK was abnormal, only if results for CK-MB were negative, and only if total LD was abnormal, showed the following results: 71 LDI specimens were not done (46 with normal total LD, 25 CK-MB + specimens). Medical chart review of the 71 LDIs not determined, representing 38 patients, showed that none of the 14 patients with the final diagnosis of MI would have been clinically missed, even if LDI had not been done, and in only one instance did LDIs confirm the clinical suspicion of MI in a patient with previously negative results for CK-MB. The LDI protocol represented by the second approach has been shown to be an effective means of identifying those occasional patients who require this confirmatory test, in whom the CK-MB results are negative but in whom there is a strong clinical suspicion of MI.

Two divergent laboratory approaches to the determination of direct bilirubin were assessed. The first approach, assaying direct bilirubin (DB) on all total bilirubin (TB) requests regardless of TB values, resulted in a true negative rate (normal TB level less than 1.0 mg/dL [less than 17 mumol/L], and DB level, less than 0.4 mg/dL [less than 6.8 mumol/L]) of 98.7% (984/997 specimens) and a low false negative (normal TB level, abnormal DB level) rate of 1.3% (13 of 997). The second approach, assaying DB on physician request and only if the TB level was greater than or equal to 1.0 mg/dL (1.7 mumol/L), resulted in a true negative rate (normal TB level, no liver disease) of 87.7% (150%) of 171 patients) and a relatively low false negative rate (normal TB level, liver disease) of 12.3% (21 of 171) patients. Medical chart review revealed that, with either approach, none of the patients with false negative results with hepatobiliary disease would have been missed clinically, even if the DB assay had not been done. It is possible to screen DB requests using a TB of 1.0 mg/dL (17 mumol/L) as a means to determine whether DB should be assayed.

A published scoring system based on four performance characteristics of a laboratory test—sensitivity, specificity, and predictive value of a negative and a positive test—was evaluated to determine whether it could be applied to the problem of eliminating routine urine culture based on leukocyte esterase-nitrite (LE/N) dipstick urine findings. Equal weight was assigned to each of the four performance characteristics, and a scoring scale ofl 00 was used for simplicity. A positive urine culture was defined as more than 105 colony-forming units per milliliter. Urine studies from the medical literature were assigned, based on the published scoring system, into one of three categories: accept, more than 80; conditional accept, 70 to 80; and reject, less than 70. Agreement between the published scoring system and author (empirical) acceptability was good for urine studies with scores of greater than 80 or less than 70. Agreement for urine studies with scores between 70 and 80 was not good (∼40% disagreement), which lead us to designate this range as “equivocal.” The published scoring system used for assessing the feasibility of eliminating routine urine microscopy based on dipstick urine findings cannot be applied without modification to urine studies that assess the feasibility of eliminating routine urine culture based on LE/N dipstick findings. The following set of recommendations are proposed as a guide to provide a rational basis for accepting or rejecting LE/N screening for urine culture: accept if the score is more than 80; equivocal if the score is 70 to 80; accept if cost savings (reagent and technician time) is of primary importance, reject if sensitivity is unacceptably low; and reject if the score is less than 70.

One thousand consecutive urine specimens were studied to assess the sensitivity of a commercially available dipstick (Chemstrip 8, Boehringer Mannheim Corp., Indianapolis, IN) to predict the presence or absence of microscopic abnormalities. The Chemstrip 8 had a sensitivity of 78%, specificity of 54%, and a false negative rate of 38%. An additional 1,000 consecutive urine specimens were then studied using the Chemstrip 9, a reagent dipstick that includes the leukocyte esterase (LE) test. The Chemstrip 9 had a sensitivity of 82%, specificity of 42%, and a false negative rate of 36%. Chi-squared analysis revealed that the two dipsticks were not significantly different (chi 2 = 0.17, P greater than 0.5). Clinical review of patients with false negative results showed that approximately one-third to one-half of these patients had either spinal cord injury or genitourinary problems. Maximal potential savings in workload of approximately 10% were found if microscopic examinations were to be performed only on urine specimens with abnormal dipsticks. Our data suggest that in our patient population, we should not eliminate microscopic urine examination based on abnormal dipstick findings.

Over a five-month period, using data from patients in whom alkaline phosphatase (ALP) isoenzyme studies were requested routinely, we compared actual clinical diagnoses with the predicted diagnoses based on the results of electrophoretic separation of ALP isoenzymes on cellulose acetate before and after heat treatment and on elevated enzymatic activity of gamma glutamyl transferase (GGT) and alanine aminotransferase (ALT) activity. ALP isoenzymes were interpreted on a qualitative basis (presence or absence of liver, bone, or other isoenzyme) by individual clinical pathologists. Overall, the consistency of agreement in 61 patients was 66% for GGT, 51% for ALP isoenzymes, and 21% for ALT. In 44 patients with definite diagnoses, the sensitivity and specificity, respectively, of each laboratory test for patients with liver disease were 88 +/- 5.7% and 64 +/- 14.5% (ALP isoenzymes); 88 +/- 5.7% and 91 +/- 8.6% (GGT); and 6 +/- 4.1% and 91 +/- 8.6% (ALT). In patients with bone disease, the sensitivity and specificity of ALP isoenzymes was 75 +/- 10.8% and 86 +/- 6.6%, respectively. The results indicate that isoenzymes as currently performed need to be improved through standardization of the interpretation of ALP isoenzyme patterns to establish uniformity of comments.

Serum γ-glutamyl transpeptidase (GGT), leucine aminopeptidase, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase activities were assayed in controls and in patients with liver, pancreatic, or bone disease. GGT activity was above normal in all forms of liver disease studied (viral hepatitis, cirrhosis, cholecystitis, metastatic carcinoma to liver, pancreatic carcinoma, liver granuloma, and acute pancreatitis). GGT more sensitively indicated hepatic disease than did alkaline phosphatase, much more so than did leucine aminopeptidase. GGT was disproportionately more active in relation to the transaminases in cases of intraor extrahepatic biliary obstruction; the reverse was true in cases of viral hepatitis. GGT activity was normal in children, adolescents, and pregnant women, and in cases of bone disease and renal failure. Kinetic measurement of GGT activity offers a simple, sensitive, and direct means for distinguishing whether bone or liver is the source of increased serum alkaline phosphatase activity. Activity was highest in obstructive liver disease.

Glutathione, ascorbic acid and many commonly used antibiotics falsely elevate uric acid concentrations when measured with the Du Pont "aca," in which the copper-chelate method is used. L-Dopa interferes with both the copper-chelate method and the Technicon "SMA 12/60" phosphotungstate method. A new kinetic uricase method has been developed for use on the Du Pont aca. This kinetic uricase method has a coefficient of variation of 2.40% and gives values that are essentially identical to those obtained by a manual end-point uricase method.

A weighted scoring system based on the selection of four measures of the performance characteristics of a laboratory test--sensitivity, specificity, and false positive and false negative rates--was devised to provide a rationale basis for ranking and evaluating dipstick urine screening tests as a criterion for elimination of routine urine microscopic examination. Equal weight was assigned to each performance characteristic, and an arbitrarily chosen scoring scale of 100 was selected for simplicity. When a summation procedure was applied to urine studies available in the medical literature, three categories of author acceptability were found: accept: score greater than 80; conditional accept: score 70-80; reject: score less than 70. Studies incorporating leukocyte esterase (LE) were found to have the highest scores and the highest author acceptability, whereas studies lacking LE had the lowest scores and lowest author acceptability. This easy-to-use, weighted scoring system is proposed as a guide for deciding whether dipstick screening tests are acceptable as a way of eliminating routine microscopic examination.

A voluntary lipid-screening project to identify known coronary-risk factors, undertaken by a class of second-year medical students at SUNY, Downstate Medical Center, involved 164 students (128 male, 36 female). The mean levels of cholesterol were similar in men (202.1 mg/dl) and in women (206.5 mg/dl). Mean triglyceride and uric acid levels were significantly higher in men (93.6 and 5.6 mg/ld, respectively) than in women (72.0 and 4.2 ml/dl, respectively) (< 0.001, p < 0.001) whereas mean HDL-cholesterol was significantly higher in women (67.6 mg/dl compared with 49.7 mg/dl) (p < 0.001). Of 23 students (14%) who had cholesterol levels of 240 mg/dl or higher (mean: 260 mg/dl), only eight (35%) voluntarily dieted and sought medical advice. Studies one to eight months later showed that their cholesterol levels (initial mean: 264 mg/dl) had increased by a mean of 28% and their triglyceride levels (initial mean: 94 mg/dl) by a mean of 19%. Although knowledge of a single lipid abnormality—elevated chol...

The article by Ryder et al, "Serum Angiotensin Converting Enzyme Activity in Patients With Histoplasmosis" (p 1888), provides a good opportunity to discuss a common error in the clinical assessment of any proposed new diagnostic test. Such a test is often developed for the diagnosis of a specific disease. It is then found to show positive results in a high percentage of patients with the disease. Next, a control group, often consisting of a group of volunteers, healthy medical students, some blood donors, or a randomly selected group of laboratory technicians, is selected for testing. The results are found to be normal, or negative, in this control group; on that basis, the laboratory test is then claimed to be specific for the disease. Results of the clinical evaluation of this new laboratory test are published in a medical journal; there is a resultant flush of enthusiasm for the test. Clinicians