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Beavers C, Kern W, Blick K. Isolated acute thrombocytopenia in a 21-year-old caucasian male. Lab Med. June 2009;40(6):337-339.Bromberg MB. Immune thrombocytopenic purpura, the changing therapeutic landscape. N Engl J Med. 2006; 355:1643-1645. Glassy EF. ed. Color Atlas of Hematology. Northfield, IL: College of American Pathologists; 1998.Kwon JY, Shin JC, Lee JW. Predictor of idiopathic thrombocytopenic purpura in pregnant women presenting with thrombocytopenia. Int J Gynacol Obstet. 2007;85-88. Taghizadeh, M. An update on immune-mediated thrombocytopenia. Lab Med. 2008;39(1):51-54.Tarr PI, Gordon CA, Chandler WE. Shiga like toxin producing Escherichia coli and hemolytic uremic syndrome. Lancet. 2005;365:1073-86.Woelke C , Eichler P. Washington G, etal. Post transfusion purpura in a patient with HPA-1a and GP1a/11a antibodies. Transfus Med 2006;16:69-72. Wyrick-Glatzel J.Thrombotic thrombocytopenic purpura and ADAMTS-13: New insights into pathogenesis, diagnosis and therapy. Lab Med. 2004;35(12):733-737.

The laboratory findings in this case represent classic findings seen in beta thalassemia minor including: erythrocytosis, decreased hemoglobin, normal hematocrit, normal RDW, and the presence of codocytes (target cells). This patient does have a mild anemia, but some patients with beta thalassemia minor have no anemia. Hemoglobin electrophoresis confirms this diagnosis, showing an increased Hb A2 level and decreased Hb A.In addition, the slightly increased iron and slightly decreased TIBC contradict a suspicion of iron deficiency. These chemistry results are typical for beta thalassemia, even though the red blood cells are microcytic and hypochromic.

Cardiac markers are measured for diagnosis and monitoring of cardiac disease, most often an AMI or other myocardial injury. They are also used to diagnose CHF. Newer cardiac markers give information on risk of future cardiac disease, further cardiac disease, and assist in predicting the response of heart disease to treatments. Cardiac markers are especially helpful in situations of a suspected AMI where the patient's electrocardiogram (ECG) does not present the typical pattern associated with an AMI.

There is very little difference in information gained from either assaying cTnI or cTnT. It has been reported in chronic renal failure that cTnT may be elevated with no myocardial injury. Since there is very little difference between results of either marker for diagnosis in ACS patients, a clinical laboratory needs to offer only one marker. cTnT measurement is offered by only one diagnostic company while currently more than ten diagnostic companies provide measurement methods for cTnI.

CK-MB assays used in cardiac damage diagnosis are mass immunoassay measurements. CK-MB is also present in skeletal muscle; therefore, skeletal muscle injury can also cause CK-MB elevation. CK-MB normal value for an adult: < 5.0 ng/mL

Cardiac troponins are the preferred marker. CK-MB (specified as mass measurement) is an acceptable alternative when cardiac troponins are not available. The 2007 ESC/ACC/AHA guidelines recommend use of cardiac markers to detect myocardial necrosis in the following manner: Elevations of cTnI or cTnT over decision limit on one occasion in the first 24 hours after chest pain. Elevations of CK-MB (specified as mass measurement) over decision limit on two successive samples or one sample that is two times the upper limit of normal during the first hours following chest pain. The CK-MB levels should exhibit a rising or falling pattern to be diagnostic. If the CK-MB levels do not fall, it is likely not an AMI.Healthcare facilities and cardiology staff develop their own criteria for AMI diagnosis and treatment based on these guidelines. Many facilities assay both cardiac troponin and CK-MB biomarkers and may request serial troponin levels to find two elevations similar to guidelines for CK-MB.

A patient with congestive heart failure (CHF) may exhibit signs and symptoms that are nonspecific; among these are edema, hypertension, shortness of breath, and weakness. Until recently the diagnosis of CHF was difficult, lengthy, and often concluded by ruling out other conditions. B-type natriuretic peptide (BNP) and/or the N-terminal fragment, NT-proBNP, are now routinely measured to diagnose CHF. ProBNP is the precursor of BNP. It is released from the left ventricle myocardium in response to mechanical stretch. This stretch is described as an increase in ventricular wall tension because of pressure and volume overload that occurs in CHF. ProBNP is then enzymatically cleaved to produce BNP and NT-ProBNP. BNP is the active hormone composed of 32 amino acids. The N-terminal fragment is a larger chain of 76 amino acids; this fragment is inactive. Studies indicate that NT-proBNP has the same clinical utility as BNP.Besides diagnosing CHF, the levels of BNP and NT-ProBNP correlate to the severity of the heart disease, assist in detection of CHF where patients are asymptomatic, and differentiate patients whose pulmonary disease presents with symptoms similar to CHF.

Arneson W, Brickell J, eds.Clinical Chemistry: A Laboratory Perspective. Philadelphia: FA Davis; 2007.Burtis CA, Ashwoood ER, Burns DE, eds. Tietz Fundamentals of Clinical Chemistry. 6th ed. St. Louis, MO: Elsevier Saunders; 2008.Carreiro-Lewandowski E. Update on cardiac markers. Lab Med. 2006;37:597-605.D'Amore PJ. Evolution of C-reactive protein as a cardiac risk factor. Lab Med. 2005;36:234-238.Dotsenko O, Chackathayil J, Lip GY. Cardiac biomarkers:myths, facts and future horizons. Expert Review of Molecular Diagnostics. 2007;7:693-697.Foley, K. BNP: a novel biomarker. Advance for Medical Laboratory Professionals. August 25, 2008:9.Kaplan LA, Pesce AJ, Kazmierczak SC, eds. Clinical Chemistry Theory, Analysis, Correlation. St. Louis, MO: Mosby Elsevier Science; 2007. McDowell J. Reviewing the evidence for BNP, NT-proBNP testing. Clin Lab News. 2006;32:1, 3, 5.Rollins G. cTn and MI - what's the diagnosis? Clin Lab News. 2009;35:1, 3-4.Rollins, G. The BNP debate. Clin Lab News. 2009;35:1,3-4.Schreiber D, Miller SM. Use of cardiac markers in the emergency department. eMedicine. Updated July 2009. Available at: http://emedicine.medscape.com/article/811905-print. Accessed August 5, 2009. Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Circulation 2007;116:2634-2653.

Examination of CSF provides vital information which aids in the diagnosis of a wide variety of disorders: benign disordersmeningitisencephalitisbrain abscesssubarachnoid hemorrhagecerebral infract vs. intracerebral hemorrhagemultiple sclerosisGuillian-Barre's syndromespinal cord tumormalignant disordersleukemia CNS involvementmalignant tumors of the brain or spinal cordmetastasis of malignant tumors

The nitrites portion of the reagent strip provides a rapid screening test for the presence of gram-negative bacteria that are often responsible for urinary tract infections. Although urine cultures are still needed to confirm the diagnosis and monitor any urinary tract or kidney infection, the need for a culture may not be obvious because in some cases of early bladder infection, the symptoms may be vague or the patient may be asymptomatic. Diagnosis and treatment of cystitis (bladder infection) is important because if left untreated it may result in kidney damage, impairment of renal function, hypertension and/or septicemia.

A screening test for bilirubin in the urine is included in most urine dipsticks and may be present when liver disease or damage is suspected. Bilirubinuria can be detected before other clinical symptoms such as jaundice are present or recognizable. The detection of small quantities is very important in early diagnosis of obstructive and hepatic jaundice. This test is also useful in the differential diagnosis of obstructive jaundice (positive for bilirubinuria) vs. hemolytic jaundice (negative for bilirubinuria).

The prototype history for this organism is either a still birth or a neonate with death ensuing within 2 or 3 days post-partem due to high fever, sepsis, and respiratory distress. The mother usually experienced a flu-like illness late in the third trimester of pregnancy, characterized by low-grade fever, myalgias, malaise and backache. In this case, biopsy material of brain tissue obtained at autopsy was submitted to the pathology laboratory for tissue diagnosis and fluid from the pia-arachnoid was sent to the microbiology laboratory for culture.

For the diagnosis of lupus anticoagulant, the International Society on Thrombosis and Hemostasis has set a protocol of diagnostic criteria that should be met. This includes the following requirements: The patient sample must show abnormal phospholipid-dependent reactions in the coagulation lab. The patient sample must show inhibition of clotting after the mixing study test has been performed. The patient sample must be proven to have an inhibitor and not a factor deficiency. The patient must have a definitive phospholipid-dependent antibody and not a specific factor inhibitor.

After review of the results, it is apparent that this patient has a factor deficiency. The initial PT test was prolonged, while the aPTT test was not. With this in mind, the laboratorian can narrow the possible factors that may be deficient in order to decide which additional studies may need to be performed to confirm the diagnosis.

This course will primarily focus on recommendations made by the American Diabetes Association (ADA) that are related to the diagnosis and monitoring of diabetes. The ADA states on its website, "Our mission is to prevent and cure diabetes and to improve the lives of all people affected by diabetes."*Other important agencies and studies referred to in this course are: International Diabetes Federation (IDF): An alliance of 200 diabetes associations; acts as a global advocate for individuals with diabetes. World Health Organization (WHO): An arm of the United Nations; provides programs for prevention, treatment, and care of those with diabetes worldwide. Diabetes Control and Complications Trial (DCCT): A major clinical study 1983-1993; proved the correlation between control of glucose blood level and lowered onset and severity of the complications of diabetes. *Reference: American Diabetes Association. Available at: http://www.diabetes.org/about-us/. Accessed April 14, 2010.

In 1997, the ADA recommended significant changes in the diagnosis of diabetes. The poorly reproducible oral glucose tolerance test (OGTT) was replaced with easier to use and more patient-friendly diagnostic criteria. An elevated fasting plasma glucose (FPG) was the preferred test to document hyperglycemia according to the 1997 ADA Clinical Practice Recommendations. An elevated casual plasma glucose with symptoms of diabetes and 2-hour plasma glucose after an ingestion of 75 grams of dissolved glucose were also used for diagnosis. In 2010, the ADA affirmed the decision of an international expert committee’s recommendation to use the HbA1c test to diagnose diabetes with a threshold > 6.5%Any one of the four criteria can be used. The hyperglycemia should be demonstrated a second time by any of the four criteria unless the glucose level is significantly high and diabetes is unquestionable. See Table 1 for diagnostic criteria and cut-off ranges.These criteria, the following categories, and classification of diabetes are used and reviewed regularly by ADA, WHO, and IDF.

Review Case A, Case B, and Case C by clicking on each one. Which of these patients do you think would be diagnosed with diabetes according to the criteria for diagnosis? Proceed to the next page to provide your response.

The ADA guidelines include recommendations for screening for diabetes. It is recommended to screen asymptomatic persons for diabetes or their risk of diabetes. Screening is recommended for all individuals age 45 years and older; a negative screen should be repeated every three years. Screening is essential for individuals who are overweight, defined as a body mass index (BMI) > 25 kg/m2. The ADA also recommends earlier screening for many individuals. Among these are individuals who are overweight and have additional risk factors. Additional risk factors include: Physical inactivity Family history of diabetes A member of a high-risk ethnic group Women who have had a large birth weight baby or gestational diabetes diagnosis should have earlier screening. Also included for earlier screening are individuals who are hypertensive or have lipidemia, vascular disease, or other clinical conditions associated with insulin resistance. Individuals who in previous testing had impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or HbA1C in the range of 5.7-6.5% should be screened for diabetes regularly.

Serum, plasma, and whole blood glucose levels are among the most common laboratory assays. Due to self-monitoring of blood glucose (SMBG), blood glucose is also the most common assay performed by patients themselves or their caretakers. Fasting, timed, and casual serum or plasma specimens are run in hospital laboratories for screening, diagnosis, and monitoring of patients.

There remains some disagreement on the use of the oral glucose tolerance test (OGTT) in diabetes testing and diagnosis. Those that recommend using OGTT assert that the OGTT better detects diabetics who are at risk for developing complications associated with diabetes.The ADA discourages the use of the OGTT for at-risk individuals unless blood glucose and HbA1C concentrations remain below diagnostic ranges for diabetes but patient displays symptoms of diabetes. The OGTT is utilized to diagnose gestational diabetes. Those at risk for gestational diabetes are screened with FPG, casual, and sometimes a 50-g oral glucose load. Definitive diagnosis of gestational diabetes is made with a glucose challenge test of 100-g or 75-g glucose and timed blood glucose measurements (OGTT).

American Diabetes Association. Standards of medical care in diabetes - 2010. Diabetes Care; January 2010;33:S11-S61.American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. January 2010;33:S62-S69.Anderson SA, Cockayne S. Clinical Chemistry Concepts and Applications. Long Grove, Illinois: Waveland Press, Inc, 2003.Bell JR. The new glycohemoglobin standard. Clin Lab News, American Association of Clinical Chemistry; October 2008; 34:1, 3-4.Burtis CA, Ashwood ER, Burns DE, eds. Tietz Fundamentals of Clinical Chemistry, 6th ed. St. Louis: Saunders, an imprint of Elsevier, Inc, 2008.Charles MA. Diabetes and the laboratorian: Opportunities for a new role. MLO. May 2001, 16-24.Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia WHO 2006. World Health Publications. Available at http://www.who.int/topics/diabetes_mellitus/en/ Accessed 1/11/10.Estimated average glucose, eAG. Available at:http://professional.diabetes.org/glucosecalculator.aspxAccessed 1/11/10.Kaplan LA, Pesce AJ, eds. Clinical Chemistry Theory, Analysis, Correlation. St. Louis: Mosby Inc, an affiliate of Elsevier Inc, 2010.Rollin G. A new role for hemoglobin A1C. Clin Lab News, American Association for Clinical Chemistry. December 2008; 34:1, 3.

High resolution electrophoresis (HRE) is routine electrophoresis using a high voltage. Serum samples separated with HRE may yield approximately fifteen distinct protein bands. Other HRE applications are the separation of CSF proteins for the diagnosis of multiple sclerosis and light chains in urine for early detection of lymphoproliferative disorders such as multiple myeloma. Both of these specimen separations require more resolution of proteins than routine protein electrophoresis can provide. Increasing the voltage will increase heat generated. To prevent denaturation of proteins, drying out of gels and other system components, a cooling system is included in HRE instrumentation.

Molecular diagnostic techniques utilize CE extensively. Automation, microvolume sample, increased sensitivity, immediate detection, and the computerization provided by CE enhance the analysis of nucleic acids. A multiple fluorescence detection system available with CE is also valuable.CE analysis of short tandem repeat polymorphisms is used in forensics, parentage testing, bone marrow engraftment analysis and other identification assays. Other testing for diagnosis of genetic diseases, oncology studies and DNA sequencing frequently utilize CE. DNA sequencing uses CE for separation of nucleotides labeled with multiple colored fluorescence dyes; CE and these markers enable computerized determination of the nucleotide sequence of DNA segments.

Risk markers are first hypothesized and then tested. Once a potential marker is identified, concentrations of the serum marker are correlated with patient outcomes. Cardiovascular risk marker studies are typically either retrospective or prospective epidemiology studies. A retrospective study looks backwards at a patient population. For example, we identify (through a hospital database perhaps) patients who have had myocardial infarcts or some other adverse outcome as well as similar subjects without that outcome to use as controls. We then go back and find archived patient serum samples and relate the concentrations of our new risk marker with patient outcomes. Retrospective studies can only be performed if you have archived samples from the patient. Prospective studies look forward in time. For example, we first select a group of subjects and measure our new risk marker in these patients over time. After a few years, we see how the serum concentrations relate to the patient outcomes. Obviously, prospective studies take much longer to perform than retrospective studies. Whatever study model is used, when assessing the value of a cardiovascular risk marker, we must correlate serum concentrations with a specific outcome. The outcome is determined by the study authors. Outcomes could be things like myocardial infarction, stroke, a diagnosis of coronary artery disease, death, or any cardiovascular 'event.'Concentrations of risk markers are divided into tertiles, quatriles or quintiles. This simply means that the top 33%, top 25% or top 20% of the serum concentration values are compared to the bottom 33%, 25% or 20%. For example, risk marker studies will often compare the outcomes of patients with serum concentrations in the upper tertile (those in the top third) with those in the bottom tertile (those in the bottom third) to see if the top 33% had significantly worse outcomes; if so, the risk marker has clinical value.

Suspect a fracture if: The victim felt a bone snap or the injury was severe. The injured part is painful or tender. The injured part moves abnormally. There is a deformity or the opposite extremity looks different. There is swelling or bluish discoloration. When in doubt, treat the affected area as though there were a fracture.

The fibrinogen assay performed in the clinical laboratory is a quantitative measure of factor I. This assay is used to determine whether there is enough fibrinogen present to allow for normal clotting. It is performed in cases of an unexpected, prolonged bleeding event, or an unexpected abnormal PT and/or APTT. Additionally, it is also used to aid in the diagnosis of disseminated intravascular coagulation (DIC). A normal reference range is typically around 200-400 mg/dl. That range is significant because fibrinogen levels

Molecular based clinical diagnostic test methodologies differ according to the target of interest. For example, patients suspected of having different diseases will require the identification of different targets. These targets might be found in different cells of the body and may therefore require different specimens to provide the answers. Patient A suspected of having Disease 1-requires the identification of a target of missequenced DNA- might require specimen of whole blood Patient B suspected of having Disease 2-requires identification of a target of antibody production-methodology might require specimen of serum Using this specific approach of disease diagnosis based on unique target identification, tests can provide answers that are more rapid sensitive specific

Hereditary hemochromatosis (HH) is a disorder of iron regulation that results in excessive dietary iron absorption through the gastrointestinal tract. Over time, the resultant iron overload and its deposition in tissue may lead to widespread organ damage, a variety of chronic disorders, and even death. Although it is a genetic disorder, clinical symptoms most typically become apparent in middle aged adults. Iron overload occurs in a variety of hereditary and acquired forms, known as iron storage diseases. HH is the most common cause of inherited iron overload. (1) Due to lack of awareness, HH often goes undetected or unrecognized by health care providers. Early detection to prevent the serious complications associated with iron overload has important consequences for reducing morbidity and mortality. Laboratory tests that assess iron levels and molecular assays for genetic mutatations are essential for both its detection and diagnosis.

Hereditary hemochromatosis (HH) is frequently discovered only during management of associated illness or routine health evaluations. It has been estimated that only a small percentage of all affected persons are actually diagnosed. Individuals with HH may be symptomatic for several years prior to diagnosis and may have consulted multiple health care providers.Under-diagnosis of HH is thought to occur due to:• Lack of specificity of early signs and symptoms• Asymptomatic status of some patients until damage to organs and tissues has occurred• Confusion with liver disease due to other causes• Insufficient awareness and knowledge of HHEarly identification of persons with HH is essential to prevent serious and irreversible complications associated with severe iron overload. A classic triad of skin hyperpigmentation (bronzing), type 2 diabetes, and hepatic cirrhosis has long been recognized as evidence of advanced iron overload. However, persons with HH may present with a much wider variety of signs and symptoms, particularly if they are seen before significant iron accumulation has occurred. Age of presentation and disease severity are highly variable. A diagnosis of HH is based on laboratory evidence of iron overload, genetic mutations associated with HH, and presence of clinical signs and symptoms consistent with HH.(10)

The diagnosis of hereditary hemochromatosis (HH) is made through a combination of laboratory tests and medical evaluation of a patient's signs and symptoms. Iron overload is identified by tests that evaluate iron metabolism, while molecular assays are needed to document mutations in the HFE gene or others such as hepcidin, hemojuvelin, or transferrin receptor. Individuals with documented iron overload who exhibit signs and symptoms consistent with HH and who possess HFE or other mutations are considered to have HH. Other causes of secondary iron overload may need to be ruled out.An example of a testing algorithm is shown.

The major determinant of prognosis in cases of hereditary hemochromatosis (HH) is the degree of organ damage from iron overload at the point of diagnosis. The presence of liver cirrhosis reduces life expectancy. Damage that has occurred to tissues and organs is irreversible, but further damage can be halted with treatment. When there is no evidence of cirrhosis at time of diagnosis, life expectancy may be equal to that of persons without HH. With proper management of HH through treatment, affected individuals have good long-term outcomes. Hepatocellular carcinoma associated with cirrhosis, hepatic failure, and cardiac failure are the most common causes of death in persons with HH. Compared to the normal population, liver cancer is many times more prevalent as a cause of death in persons with HH. Cardiomyopathy, diabetes, and cirrhosis are all more common causes of death among persons with HH than among normal persons. The earlier HH is detected, before the onset of severe organ damage, the lower the risk of mortality.

Serum ferritin (SF) level reflects the amount of storage iron in tissues. An elevated SF combined with elevated TS implies primary iron overload. Patients with hereditary hemochromatosis (HH) generally show increases in SF as adults, but a normal SF does not rule out the diagnosis of the disease. Children and premenopausal females with HFE mutations may have had inadequate time to develop iron overload, but may do so later in life.SF alone is inadequate as the sole screening test for HH because it lacks the necessary sensitivity and specificity. SF is frequently elevated in persons with inflammation, cancer, or infection. SF is often ordered along with the serum iron and TIBC when iron overload is suspected. SF is also important is assessing the efficacy of treatment of HH.Upper limits of reference intervals for SF are 200 ng/mL for premenopausal women and 300 ng/mL for men and postmenopausal women. 40 ng/mL is a typical lower limit for the reference interval.SF is measured in serum using immunochemical methods such as enzyme-linked immunosorbent assay (ELISA), immunoradiometric assay, immunochemiluminescent assay, and immunofluorometry. SF tests are available as automated assays and in kit form.(2)

Human papillomavirus (HPV) is a frequently occurring viral sexually transmitted infection (STI). HPV infections often present with mild signs and symptoms or are asymptomatic, and do not always progress to a disease state. HPV infections are especially frequent in adolescents and young adults, between the ages of 15-24 years. About 20 million Americans are currently infected with HPV and there are several million new infections each year in the U.S. Since HPV infections are so common, the CDC believes that most sexually active adults are infected at some point during their lifetime. Though the majority of HPV infections are transient and do not result in serious disease, clinicians are concerned about the HPV infections that cause cervical and other anogenital carcinomas. Diagnosis and management of HPV has changed dramatically with the introduction of DNA methods for diagnosis of HPV infections and vaccines for the prevention of HPV infections. Understanding HPV characteristics and diagnostic testing is important for clinical laboratory scientists.

Requisitions must be designed to ensure that ordering physicians can choose tests that are medically necessary for their patients. Requisitions should contain reminders about Medicare rules of medical necessity and list the contents of panels and profiles. Requisitions must provide a place for the physician to include diagnosis (ICD9-CM) codes. Physicians should be encouraged to use only the requisitions supplied by the laboratory to order tests.

Local Medical Review Policies (LMRPs) are published by Medicare for some laboratory tests. They are usually developed for tests that can be used for screening or diagnosis of disease. LMRPs use CPT codes to identify the tests and ICD-9 codes to determine when coverage is allowed. If an LMRP test is ordered by a physician, an ICD-9 code that is included in the LMRP must be given to the laboratory or the Medicare program will not pay for the test. It is against the law for a laboratory to change or add an ICD-9 code submitted by a physician. A laboratory should not submit a claim for an LMRP test that is not accompanied by an acceptable ICD-9 code. The Balanced Budget Act of 1997 made it illegal for physicians to order LMRP tests and not supply an ICD-9CM code with the order.

It is important that billing department employees are clear and accurate when communicating with physician office personnel and patients. Never guess at the answer to a question; ask if you are unsure. Do not speculate or express personal opinions. When requesting diagnosis information from the physician office staff, be careful to not lead them to give a billable code. The code must come from the patient's medical record. Billing department employees must accurately state laboratory policies and procedures, or forward the call to a supervisor to avoid misstatements and misunderstandings.

Billing: Highest risk activity a laboratory has. All laboratory activities contribute to the billing process. Many of the risk areas included in this program are components of the billing function. Medical necessity: Medicare is only allowed, by law, to pay for tests that are reasonable and necessary for the diagnosis and treatment of disease. Medical necessity is an underlying principle of the Medicare program. Tests performed for screening or routine exams are not considered medically necessary by the Medicare program.

Requisitions must be designed to ensure that ordering physicians can choose tests that are medically necessary for their patients. Requisitions should contain reminders about Medicare rules of medical necessity and list the contents of panels and profiles. Requisitions must provide a place for the physician to include diagnosis (ICD9-CM) codes. Physicians should be encouraged to use only the requisitions supplied by the laboratory to order tests. Ambiguous or unclear test orders When the orders for a test are not absolutely clear, the laboratory must contact the ordering physician to clarify the orders before performing and billing for the test. The laboratory cannot guess at the order. The laboratory cannot perform and bill for tests that are not specifically ordered. The laboratory cannot change a physician order without contacting the physician. In any case where specimen integrity or patient care will be compromised by a delay in testing follow the policies the laboratory has established for such cases.

LMRPs (Local Medical Review Policies) are published by Medicare for some laboratory tests. They are usually developed for tests that can be used for screening or diagnosis of disease. LMRPs use CPT codes to identify the tests and ICD-9 codes to determine when coverage is allowed. If an LMRP test is ordered by a physician, an ICD-9 code that is included in the LMRP must be given to the laboratory or the Medicare program will not pay for the test. It is against the law for laboratory to change or add an ICD-9 code submitted by a physician. A laboratory should not submit a claim for an LMRP test that is not accompanied by an acceptable ICD-9 code. The Balanced Budget Act of 1997 made it illegal for physicians to order LMRP tests and not supply an ICD-9CM code with the order.

It is important that billing department employees are clear and accurate when communicating with physician office personnel and patients. Never guess at the answer to a question; ask if you are unsure. Do not speculate or express personal opinions. When requesting diagnosis information from the physician office staff be careful to not lead them to give a billable code: The code must come from the patient's medical record. There is an incentive program for patients to find and report fraud and abuse by health care providers, including laboratories, so: Billing department employees must accurately state laboratory policies and procedures, or forward the call to a supervisor to avoid misstatements and misunderstandings.

Several laboratory methods are currently available to aid in the detection of C. difficile including culture for toxigenic C. difficile (considered the “gold standard” for viable C. difficile detection), detection of Toxin A, B, or both, and molecular detection methods. These methods differ in their sensitivity and specificity and should always be used in conjunction with clinical considerations. To make the diagnosis, it is usually only necessary to submit 1-2 diarrheic (non-formed) stools per episode. Once positive for C. difficile by any laboratory method, there is no need for follow-up assays to make sure the organism or toxins are absent from the initial episode. If assays are performed for subsequent episodes, culture or tissue culture assay for Toxin B are probably most appropriate to avoid the possibility of detecting the initial antigen, toxin, or gene.

Laboratory specimens that are unlikely to cause disease and do not meet the criteria for category A or B substances are not subject to Division 6.2 regulations. Specimens for which the hazardous materials regulation (HMR) does not apply include human or animal samples (including, but not limited to, secreta, excreta, blood and its components, tissue and tissue fluids, and body parts) being transported for routine testing not related to the diagnosis of an infectious disease. This includes specimens that are being sent for: drug or alcohol testing cholesterol testing blood glucose level testing prostate specific antibody (PSA) testing testing to monitor kidney or liver function pregnancy testing tests for diagnosis of non-infectious diseases such as cancer biopsies

When the results on Mr. John Ready were called to the nurse, she was very surprised that the result of his CBC was normal. The nurse explained to the lab tech that Mr. John Ready had a known diagnosis of lower GI bleeding. His hemoglobin had been very low for the past 24 hours because of the internal bleeding, and she thought it was very surprising that his hemoglobin had normalized so quickly without having received a blood transfusion. Mr. Ready’s doctor decided the patient should be redrawn to ensure a correct result. The nurse further questioned if the phlebotomist could possibly have drawn the wrong patient because earlier that day Mr. Ready had been moved to room 831, and room 825 was presently occupied by a patient named Walter Redding. If Julie had checked the patient’s armband, she would have realized that the patient in 825 was the wrong patient.Relevant topics:Importance of patient ID, Patient identification continued, Specimen labeling, Specimen labeling Continued, Blood bank specimens

About 2-3% of women will develop gestational diabetes.Since women with gestational diabetes have a higher risk of losing their baby or having a baby with malformations, diagnosis and treatment of gestational diabetes is important.Pregnant women are screened for gestational diabetes at 28 weeks using a modified glucose tolerance test.Patients are given a 50 gm dose of Glucola, and blood is collected for glucose testing one hour later.If the glucose level is greater than 140 mg/dl, a 3 hour glucose tolerance test is required to confirm the diagnosis of gestational diabetes.

When evaluating Gram stains of clinical samples, keep in mind the source of material from which the smear was made. Bacteria found in cerebrospinal fluid (CSF), blood, tissue and specimens from other sterile sites are always significant. Gram stains of body fluids that are normally sterile must be examined carefully. For every one organism per oil immersion field, there are about 105 organisms per mL present in the sample! Examining stained smears of CSF sediment may assist the clinician in establishing a presumptive diagnosis. The Gram stain result and the results of other special stains could also guide in the selection of culture media. If bacteria are observed in a CSF specimen, it is important to determine and report whether the bacteria are inside or outside of white blood cells (intracellular or extracellular). The quantity of organisms seen and the amount and type of host cells are also important to report. Bacteria observed in specimens from the throat, genital tract and other areas containing normal flora suggest infection only if their composition and type varies significantly from the norm.

Jaundice was recognized in a day-old infant. Notice particularly the size variation (anisocytosis) of the erythrocytes on the infant's peripheral smear. What does this observation mean? Does it provide immediate information that might serve as guidance in expediting diagnosis and treatment? Note that normal-sized red blood cells, microcytes, microspherocytes, macrocytes, and nucleated red blood cells are all present. Red cell variations are expected findings in healthy neonates, but the variations here are exaggerated. Hyposplenic functional features may appear, including acanthocytes, spherocytes, and possibly Howell-Jolly bodies, especially if hemolysis is particularly vigorous. A high (3-7%) reticulocyte count is not unusual during the first three or four days after birth, however, the marrow in this jaundiced infant is proliferating vigorously in response to hemolysis. A call for more red cells is urgent. Immature red cells (in the form of nucleated red cells) and red cells with stippling of RNA (basophilic stippling) are readily identified. Red cell maturation sequence has not been totally processed in the marrow nor is all residual red cell debris removed by the spleen. In the lower photograph are reticulocytes stained by supravital stain (new methylene blue). Basophilic stippling (specks of RNA) stains with both supravital stains and with routine Wright-Giemsa stain.

The patient whose blood smear is shown in the photograph was a 32-year-old female from Virginia who came to the high country of Colorado to ski. The day after arrival, she experienced shortness of breath, fatigue, and upper abdominal pain. She was seen in a medical center in the mountains where a working diagnosis of altitude sickness was made. A CBC revealed RBCs 5.1 x 1012/L, hemoglobin 12.8g/dL, MCV 60fL, hematocrit 40.9%, and normal total WBC, differential, and platelet count. The RDW was normal. Further questioning revealed a previous diagnosis of heterozygous beta-chain thalassemia. No other abnormal hemoglobins were found on hemoglobin electrophoresis, but HbA-2 was elevated to 5%, supporting the diagnosis of beta thalassemia. The patient's poikylocytosis and anisocytosis may be a clue to an underlying erythrocyte abnormality. Persons with iron deficiency anemia may experience various degrees of hypoxia upon arriving at high altitudes. Those with sickle cell disease and thalassemia minor (as in this case) may experience bone pain or other symptoms of "crisis" and/or alteration in the appearance of their erythrocytes upon sudden high altitude exposure. The classic teaching is that in differentiating iron deficiency anemia from thalassemia, increased RDW would favor iron deficiency; normal RDW favors thalassemia.

The family (cited in the previous case history) was from a region of Thailand where the physician knew HbE carriers are prevalent. Homozygous hemoglobin E is common in Southeast Asia and presents with very mild anemia and seldom requires transfusion. Over 30 million people in the world are HbE carriers, making this abnormal hemoglobin almost as common as HbS. Hemoglobin E is uncommon in North America and in Europe, but with changing immigration patterns, hemoglobinopathy E cannot be ignored. Peripheral blood smear findings of target cells, microspherocytes, red cell hypochromia, a few red blood cell fragments, and nucleated red blood cells require evidence from hemoglobin electrophoresis to establish a diagnosis. Clinically, a very important and severe syndrome is hemoglobin E/beta thalassemia in which there is hemolysis requiring repeated transfusions. The patient has a severe anemia, low MCV (50's), and high RBC. This is characteristic of Hgb E/beta thalassemia.

Laboratory data must be presented to clinicians in a user friendly way to promote effective decision making. Databases must be designed to provide clear information that leads quickly to the best patient care outcome. We continue learning how to collect and retrieve laboratory data from our machines, but we are not always in tune to how entry and retrieval of data is geared to and, more directly, influences patient care outcomes. Examples of blood cell abnormalities on a peripheral blood smear that may immediately direct the physician to a specific diagnosis are: (1) presence of target cells as found in thalassemia or hemoglobinopathies and target cells in liver disease, particularly with obstructive jaundice; (2) burr cells as a signal of chronic renal disease and uremia; and (3)atypical neutrophil inclusions relating to genetic disorders. Critical appraisal of such observations could add valuable clues for a diagnosis. Laboratory professionals must establish a set of principles for orderly observation of blood cell morphology, have a clear vision of the applications of their work, and understand the potential clinical implications of their reports and interpretations. Emphasis on values and relevance focuses on patient care outcomes and their dependency on prompt availability of results and contextual interpretations.

Examples of conditions in which spherocytes can be seen include hereditary spherocytosis and immune hemolytic anemias (i.e., ABO incompatibility). Spherocytes can also form in conditions where there has been a direct physical or chemical injury to the cells. An example would be a smear from an individual who has suffered severe burns. In hereditary spherocytosis, a condition where spherocytes are numerous, the MCHC value will be at the upper limits of normal, or about 36. The identification of spherocytes on the smear of a patient with hereditary spherocytosis can aid significantly in the diagnosis of the disorder. In Artifactual spherocytes can appear when blood is stored for a prolonged period of time.

It is important to differentiate in vitro changes which are secondary to preparing the slide, from in vivo morphology, which is the result of the pathophysiological condition of the patient. Examining erythrocytes in the critical viewing area is extremely important in making this distinction. The determination of the clinical significance of the morphology reported is the responsibility of the physician, who must correlate the blood smear findings with the clinical diagnosis, and other laboratory parameters.

Another example of an echinocyte is seen in the center of this slide. In rare instances, echinocytes circulate in vivo in uremia, following heparin injection, in certain congenital anemias and in pyruvate kinase deficiency. Plastic slides must be used to verify the presence of in vivo echinocytes. Since echinocytes do not aid in the diagnosis of these conditions, their main importance lies in the fact that they are artifactual and reversible and must be distinguished from acanthocytes.

Another example of a target cell (or codocyte) is seen in the center of this slide. Notice that the hemoglobin in the center of this cell is somewhat lighter in appearance than in the previous slide. A second codocyte can be seen in the upper left portion of the slide. Codocytes appear in conditions which cause the surface of the red cell to increase disproportionately to its volume. This may result from a decrease in hemoglobin, as in iron deficiency anemia, or an increase in cell membrane. Target cells have excess membrane cholesterol and phospholipid and decreased cellular hemoglobin. Examples of other conditions in which target cells may be present include thalassemias, hgb C disease, post splenectomy and obstructive jaundice. Since their presence can be the result of an in vitro artifact, their value in clinical diagnosis is limited.

When the results on Mr. John Ready were called to the nurse, she was very surprised that the result of his CBC was normal. The nurse explained to the laboratory technologist that Mr. John Ready had a known diagnosis of lower GI bleeding. His hemoglobin had been very low for the past 24 hours because of the internal bleeding, and she thought it was very surprising that his hemoglobin had normalized so quickly without having received a blood transfusion. Mr. Ready’s doctor decided the patient should be redrawn to ensure a correct result. The nurse further questioned if the phlebotomist could possibly have drawn the wrong patient because earlier that day Mr. Ready had been moved to room 831, and room 825 was presently occupied by a patient named Walter Redding. If Julie had properly identified the patient by asking him to state his name and then checking the name and identification number on the wristband, she would have realized that the patient in 825 was the wrong patient.

Semen analysis has become an important screening test when evaluating male infertility. Infertility has been defined as the failure of a couple to conceive after one year of unprotected intercourse. The results of the semen analysis may provide sufficient information for a diagnosis or may indicate the need for additional testing.

According to the CDC guidelines, patients with clinical illness consistent with uncomplicated influenza who reside in an area where influenza viruses are circulating may not require diagnostic influenza testing for clinical management. Most mild cases of H1N1 infection are self-limiting and do not require confirmation. However, if a patient is hospitalized due to the severity of the symptoms, or if the diagnosis of the patient will provide needed information to the physician to direct clinical care, infection control decisions, or management of close contacts, diagnostic influenza testing should be done. In any case, if a decision to use antiviral treatment is made, the treatment should commence as soon as possible, without waiting for the results of confirmatory diagnostic tests.

Renal epithelial fragments of collecting duct origin are composed of three or more cuboidal cells. These fragments indicate a more severe form of renal tubule injury with basement membrane disruption. Proximal and distal convoluted tubule renal epithelial cells are not found in fragment form. In addition to the indication of severe tubule damage, proper identification of these fragments is important to avoid a false positive diagnosis of low-grade transitional cell carcinoma. Transitional cell carcinoma is a type of cancer seen in 71% of cases of malignant tumors of the ureter.

Symptoms of TB can mimic other diseases and the physician must consider the patient's history as well as physical symptoms before making a final diagnosis.

Dohle bodies are seen in a number of conditions, including infections, burns, measles, leukemia and chemotherapy. Dohle bodies are classified as pathological in the sense that they are only present when the body is responding to an unusually severe stress or stimulus. This severe stress may cause the cytoplasm of some cells to mature improperly. Their presence does not aid in the diagnosis of the disorders in which they are found, but they are frequently seen along with toxic granulation and/or vacuoles in cases of infection or burns.

The following pages in this presentation includes a series of white blood cell abnormalities that may be identified in a peripheral blood smear. Many of the cases will simulate the practice of a peripheral smear review by a hematology morphologist. He/she must asses what responses in patient care may be triggered by the clinician attempting to interpret the reported findings on a peripheral smearObservations of white blood cell abnormalities in the peripheral blood smear should be reported so as to direct the physician to an immediate specific diagnosis, such as: (1) atypical lymphocytes suggesting infectious mononucleosis rather than leukemia, (2) toxic granules in neutrophils as in acute infections, or atypical granules suggesting a genetic disorder, (3) an unusual mix of cells, such as too many or too few neutrophils, monocytes, or other myeloid cells, and (4) the presence of giant platelets, myelocytes, or other cells suggesting a myelodysplastic syndrome.In summary, laboratory data should be presented to clinicians in a user friendly way to promote effective decision making. The design of the data base of information must be directed toward providing clinically helpful information clearly and quickly in order to facilitate appropriate action in terms of optimizing patient care outcomes.d

A 17-year-old young woman was admitted to the hospital with abdominal pain and a tentative diagnosis of appendicitis.The total white blood count was 14,500 cells/cumm with a left shift and neutrophils with changes tagged by the arrow in the photographs (see blue arrow).The bluish-staining, blurred accumulations in the cytoplasm (Doehle bodies), are located at the cell periphery in neutrophils with toxic changes.Doehle bodies are remnants of endocytoplasmic reticulum and are products of cytokine activity in the induction and shortened activity of neutrophil activation.They are often present in conditions with increased neutrophil lysosomal activity, manifest as toxic granulation.In this case, the presence of Doehle bodies serves as markers for infection-induced leukocytosis and supports the diagnosis of acute appendicitis.