2013 1 s Newsletter

Reference interval changes 2 Significance of ANCA 4 Type 1 diabetes 6 Inside Clinical Utility of Bone Turnover Markers 8 Ulysses Syndrome – is it the liver? 10 Test ordering standardisation 11 Order of Draw Quick Guide 12 DNA $ INRTroponineGFR $LDESR CBE HDLPCR $ $ PCRMBA LFT LFTMC&SPSARNA $ HbA1cRCF $ TFT For our Capatients and our population www.sapathology.sa.gov.au From the inside

transport improvement, will enable us to Complement method change From the Executive Director meet future challenges and maintain our hard earned reputation. To improve turnaround times for complement C3 and C4 results, As part of a highly regarded health system SA Pathology changed the method that provides outstanding patient care, and analyser platform to the integrated research and teaching activities ADVIA 2400 on 26 August 2013. we aim to continually improve the depth Results for both C3 and C4 using the and breadth of our services whilst returning new method are approximately value for money to South Australian 10% higher than those of the old taxpayers. method. The reference interval has As a clinical support service SA Pathology changed to reflect this shift and a recognises that it needs to positively paediatric range is included. IMVS is headed by Professor Ruth Salom a medical graduate respond to the changing clinical landscape who has specialised as a in order to meet the needs of hospitals, C3 Surgical Pathologist. clinicians and the community. We also recognise the need to manage demand and <4 weeks 0.58 to 1.08 g/L budget pressures, while ensuring our plans <3 months 0.67 to 1.24 g/L are consistent with the major developments <6 months 0.74 to 1.38 g/L MR KEN BARR IS EXECUTIVE that are occurring within the health system, DIRECTOR OF SA PATHOLOGY including the new Royal Adelaide Hospital <9 months 0.78 to 1.44 g/L and the South Australian Health and <10 years 0.80-1.50 g/L Medical Research Institute (SAHMRI), plus the major research and teaching goals >10 years and 0.85-1.60 g/L of the three universities. i am delighted to present this edition adults of the SA Pathology Newsletter (formerly SA Pathology will be explicitly moving the IMVS Newsletter). SA Pathology away from the ‘one hospital, one C4 0.12-0.36 is proud to be the public provider of laboratory’ model as advances in analytical, pathology services within South Australia transport and IT technology provide to ensure all our population, communities new opportunities for us to build a more DGA reference interval change and patients have 24/7 access to a flexible, efficient and effective state-wide comprehensive range of services, pathology network. SA Pathology changed the irrespective of their income and location. Deaminated Gliadin Antibody (DGA) Be assured that our services will continue method and analyser platform on The priorities and direction contained to be clinically led, and that patient safety 9 December 2013. Whilst the new within our 2013-16 strategic plan and improving health outcomes remains outline our clear intention to build on method is clinically identical to the our primary goal. We look forward to current method the results will be a longstanding record of quality and working with you so that we can continue considerably different. excellence as a regulated and accredited to provide the very best pathology service pathology service across all disciplines to support our patients and our population. New reference interval and our expanding Point of Care Testing The new reference interval for DGA network. Our plans for service, IT and Mr Ken Barr will be: <11 U/mL.

If you have any questions SA Pathology Newsletter Design Published by SA Pathology Sue Dyer Design regarding these changes Editorial Committee Photography please contact the John Bahnisch, Mark Fitz-Gerald, Ming Qiao, SA Pathology Photo and Imaging Immunology Consultant Dianne Zurcher and David Johnston Printing via SA Pathology Enquiries Contact Fivestar Print on (08) 8222 3000 [email protected] Cover: Ulysses and the Sirens ISSN 2203 – 2339 Print by John William Waterhouse 1891 ISSN 2203 – 2347 Online See page 10 for Ulysses syndrome

SA Pathology Newsletter > 1 – 2013 PAGE 2 DID YOU Red Blood Cell Folate (RCF) Q: What do I need to do KNOW? differently? SA Pathology has moved from serum folate to Red Blood Cell Folate (RCF) A: You will need to collect an testing as the standard measurement EDTA specimen (purple top). Citrate Blood Tubes to assess folate nutritional status. When collecting blood into Q: Can I specifically request citrate tubes (blue tops) you Due to the 120 day average lifespan serum folate testing? must fill to the indicator line. of the red cell, RCF folate is less Yes. Serum folate levels will susceptible to rapid changes in diet A: continue to be available on compared with serum folate, and will request. provide more reliable and accurate results. In practice this change will: Q: Can I request tests to n identify an additional 5% of differentiate between B12 patients with folate deficiency with and folate deficiencies? INDICATOR LINE spuriously high serum levels A: Yes. Specific tests to identify n more accurately reflect and differentiate between the patient’s folate status over the B12 and folate deficiencies, preceding 2 to 3 months. such as homocysteine and methylmalonic acid levels, BLOOD will continue to be performed. For B12 and RCF please collect both serum (white top) and whole blood (purple top).

ANTICOAGULANT Did you know? > Mandatory folate The reason is that the ratio of fortification of flour blood to anticoagulant is critical has been in place since 2009 in Australia. for clotting tests. An under-filled tube will have too much citrate making results Clinically related questions invalid; similarly, overfilling Please contact Professor Luen Bik To, Haematology Clinical Director on the tube dilutes the citrate (08) 8222 3633 or Dr Penelope Coates, Chemical Pathology Clinical Director concentration invalidating the on (08) 8222 3391. result. Collection by vacuum is the method preferred as this takes Warfarin reversal guidelines To aid decision making in this patient the correct amount of blood. group the recently updated Warfarin However if the tubes are old the In-patients receiving warfarin and Reversal Guidelines are now available vacuum may be reduced resulting experiencing bleeding is a relatively on the SA Pathology internet site. in under filling; please replace old common event, with approximately From the Home page go to: For or defective tubes. 2-3% of such individuals having a Clinicians | Quick Guide for Clinicians major complication each year. | Emergency Information. Over or under filled samples will be rejected and a new sample will Patients on warfarin will also often Further advice can be obtained be required. This applies to all have high INR values without from the duty haematologist on-call tube sizes. clinically evident bleeding. Guidelines through the RAH switch board, for the management of both bleeding phone (08) 8222 4000. For additional information please and non-bleeding patients with call the Haemostasis Reference an elevated INR result have been Laboratory on (08) 8222 3918. developed by the Australian Society of Haemostasis and Thrombosis.

SA Pathology Newsletter > 1 – 2013 PAGE 3 www.sapathology.sa.gov.au Significance of ANCAANCAANCA

Dr Tatjana Banovic – Consultant pathologist – Immunology

Anti neutrophil cytoplasmic antibodies (ANCA) are associated with a spectrum of systemic vasculitic conditions affecting small and medium vessels throughout the body.

The syndromes of small vessel False positive results have been vasculitides (SVV) systemic reported in a variety of disorders vasculitides are characterised by: including infections, drug-induced vasculitis, other autoimmune diseases, n overlapping clinical and histological malignancies and inflammatory bowel features with frequent involvement disease (IBD). Conversely, negative of major organs results have been reported in patients n the need for aggressive with biopsy proven vasculitides. immunosuppressive treatment Results therefore should always be n serious morbidity and a significant evaluated in the context of other mortality. laboratory and clinical findings and should not be used as the principal The management of these vasculitides indication for treatment. often requires critical and timely decision making to prevent the There are three major patterns consequences of disease and the associated with a positive ANCA The ANCA group of autoantibodies are directed hazards of mistreatment. The screen: against cytoplasmic components in human importance of understanding the neutrophilis 1 Cytoplasmic or cANCA tests for ANCA used in the diagnosis cannot be overemphasised. 2 Perinuclear or pANCA Confirmation 3 Atypical-ANCA pattern There are many different antigen Screening specificities in the ANCA group The limits of ANCA testing need The atypical ANCA pattern has of autoantibodies but only two to be understood. To maximise the been reported in IBD, cystic fibrosis, have proven clinical associations, predictive value of ANCA screening autoimmune liver disease, drug- anti proteinase 3 (PR3) and anti it should only be performed on induced ANCA and rheumatic myeloperoxidase (MPO) antibodies. appropriately selected patients. diseases. In rheumatoid arthritis the Tests for other ANCA specificities The clinical indications of suspected prevalence of atypical-ANCA has been are not currently clinically useful ANCA-associated vasculitis include: detected in 20 – 70% of patients and and none have been proven specific been associated with more severe or diagnostically important for any n glomerulonephritis and long-standing disease. particular disease. Therefore all n pulmonary haemorrhage positive ANCA screens must have n cutaneous vasculitis, especially their identity confirmed to PR3 and with systemic features MPO antibodies. n multiple lung nodules n chronic destructive disease of the upper airways; long standing Results should be evaluated sinusitis or otitis in context of other laboratory n subglottic tracheal stenosis n retro-orbital mass. and clinical findings

SA Pathology Newsletter > 1 – 2013 PAGE 4 What is ANCA? ANCA is a group of autoantibodies directed against cytoplasmic components in human neutrophils, the two main antigenic targets being proteinase-3 (PR3) and myeloperoxidase (MPO). Clinical studies done at SA Pathology have found the combination of an ANCA screen and confirmation tests yield the best diagnostic information.

If an ANCA screen on initial sensitivity around 60% for Other factors besides diagnostic presentation is positive but negative microscopic polyangiitis and 50% tests need to be considered before for both PR3 and MPO antibodies it for Churg Strauss syndrome. About deciding to administer toxic is more likely to be related to other 25% of patients with Wagner’s immunosuppressive therapy, they diseases than ANCA associated Granulomatosis are also anti MPO include the: vasculitides. However results must positive. Anti MPO levels do not n probability of improvement be interpreted in context with appear to reflect the disease activity and potential side effects with clinical findings as it may represent of patients with primary vasculitides additional biopsy investigations a limited form of disease. Patients and the effects of treatment are not for whom there is a high index of well documented. n consequences and costs of suspicion should be monitored with mistreating nonvasculitic disorders PR3 and MPO antibodies, which may Anti MPO antibody is occasionally n consequences and costs of delaying become detectable as the disease found in other forms of or missing the diagnosis. progresses. glomerulonephritis. It is present in about 30 – 40% of patients with anti In the appropriate clinical setting for Clinical associations glomerular basement membrane those patients with renal findings (GBM) disease, and these patients suggestive of vasculitis, initiation of To date only PR3 and MPO antibodies appear to have a better prognosis immunosuppression based on ANCA have been shown to be of value in the than those with GBM antibodies results alone without renal biopsy diagnosis of vasculitides. alone. Antibodies also occur in drug- appears justified. induced lupus and occasionally The strongest disease association in certain other connective tissue In other clinical settings, a positive is between anti PR3 antibody and diseases. ANCA screen and MPO/PR3 Wagner’s granulomatosis, which has antibodies are not sufficient for been reported in about 80% of active In general, anti MPO and anti PR3 diagnostic decisions on patient cases, however sensitivity varies do not occur in the same patient treatment. Positive ANCA results according to disease activity and concurrently. in these settings must be confirmed extent. The more limited forms have with biopsy investigation. sensitivities in the order of 67%, When to treat? while generalised forms are nearly In a successfully treated vasculitis Systemic necrotising vasculitides 100% of patients. patient ANCA levels should disappear are serious life threatening or decrease significantly. If this is diseases, fatal if untreated. Since PR3 antibody levels appear to not the case, or the levels reappear, the introduction of combination parallel disease activity. In general a clinical exacerbation is likely to corticosteroid and cyclophosphamide high levels of anti-PR3 antibodies occur within the next few weeks or therapy clinical outcomes have indicate active vasculitis and a sharp months. ¥ rise in levels signifies disease flare. improved dramatically. The current Monitoring ANCA levels may be useful treatment schemes also include in discriminating between a disease aggressive immunosuppressive flare and non-specific infections in therapy. patients with SVV. Treatment should be started early The presence of anti MPO antibody as there is good evidence that the strongly suggests necrotising extent of organ involvement at onset vasculitis. It has a reported determines the ultimate prognosis, hence prompt diagnosis is critical.

SA Pathology Newsletter > 1 – 2013 PAGE 5 www.sapathology.sa.gov.au Type 1 early diabetes: diagnosis

Drs Jessica Philips, Jenny Couper, Jan Fairchild, Alexia Peña and Elaine Tham – essential Paediatric; Endocrinology Women’s and Children’s Hospital

Every day in Australia two children will be diagnosed with type 1 diabetes. Currently Australia has the world’s sixth highest rate for new diagnoses of type 1 diabetes. The incidence is highest amongst teenagers, with a second smaller peak amongst 5-9 year olds, but it can occur at any age, including infancy.

A combination of genetic and ketoacidosis (DKA), a life threatening Symptoms environmental factors is thought complication and the leading cause of Children with type 1 diabetes usually to precipitate the autoimmune death in children with type 1 diabetes. present with a 2-6 week history of destruction of the pancreas which Recognising the symptoms and signs polyuria, polydipsia, and weight loss. leads to Type 1 diabetes. Despite of the disease and starting insulin Bedwetting is also common. years of research, improvements in early can prevent morbidity and insulin and insulin delivery devices mortality. These symptoms are often attributed a cure remains elusive. to urinary tract infections or The following case study illustrates psychogenic polydipsia. If these Over 30% of children with type 1 the importance of early diagnosis and early symptoms are not recognised diabetes still present in diabetic treatment. and ketoacidosis develops, vomiting, abdominal pain, dehydration, reduced consciousness and hyperventilation CASE STUDY will ensue, and can be mistaken for gastroenteritis, acute abdominal pain, Mia is 4 years old. Her mother takes her to the GP as she is concerned Mia asthma or pneumonia. might have a bladder infection. She has been going to the toilet frequently and has started wetting the bed again after being mostly dry overnight for Diagnosis over a year. Today Mia complained of a sore tummy. She has had no fever or vomiting, but has been quite thirsty. Once suspected, type 1 diabetes can be easily diagnosed with a blood glucose Mia has no significant past medical Because of the glucosuria, her meter. The diagnosis is made if the history. Her grandfather has type 2 BGL is checked and is 14mmol/L. blood glucose level (BGL) is elevated: diabetes. Her GP thinks Mia may have type n fasting BGL ≥7mmol/L or 1 diabetes and asks them to return n random BGL ≥11.1mmol/L Her GP agrees a urinary tract in the morning for a fasting blood infection is likely, though is glucose level. A fasting BGL, oral glucose tolerance wondering about type 1 diabetes. test (OGTT) or an HbA1c are not Overnight Mia starts vomiting and required for diagnosis. Waiting for the Her urinalysis results are: the abdominal pain worsens. Her results of extra tests will only delay mother takes her to the emergency Specific gravity 1.01 the diagnosis and management. department. Her BGL on arrival is pH 5.0 18mmol/L with blood ketones of Testing blood or urine ketones will Leukocytes negative 3.7mmol/L. A blood gas shows a help determine if ketoacidosis is likely. metabolic acidosis with a pH of Nitrites negative 7.15 and bicarbonate of 10mmol/L. Children diagnosed with type 1 diabetes require immediate referral Ketones + Mia is admitted to the paediatric intensive care unit and an insulin to a hospital with paediatric services Glucose +++ infusion started. to commence insulin and organise multidisciplinary education and management.

SA Pathology Newsletter > 1 – 2013 PAGE 6 RESEARCH SPOTLIGHT Leading Light Award

Children with diabetes can deteriorate Polyuria, polydipsia, bedwetting and quickly, and it is not uncommon for weight loss are usual early symptoms. a child to present in severe DKA whilst waiting to have a fasting BGL. A random blood glucose level >11.1mmol/L, in a symptomatic child The fasting BGL is not necessary is enough to make the diagnosis. for a symptomatic patient with Associate Professor Susan Branford Fasting blood glucose, OGTT or elevated random BGL. Very early on Associate Professor Susan Branford HbA1c are not necessary to make the in the disease post-prandial BGLs of the Leukaemia Unit, Department diagnosis and can delay treatment. are the first to rise and fasting BGLs of Molecular and Genetic Pathology, remain normal. Early diagnosis and immediate Centre for Cancer Biology at SA Pathology won the Australian referral to a doctor experienced in Summary Society for Medical Research (ASMR) the management of type 1 diabetes SA Leading Light Award in September Type 1 diabetes can occur at any age, in children can prevent diabetic this year. and is easily diagnosed if suspected. ketoacidosis. This prestigious award recognises the exceptional research output by mid-career researchers who have pursued their own research direction, Children with diabetes can and highlights the outstanding work being undertaken by up and coming deteriorate quickly researchers in South Australia. The award was presented by Professor Ian Frazer.

Young Investigator world diabetes day Recognising risk 14 November Award Raising awareness KNOW THE DIABETES WARNING SIGNS! within the community about the four common signs of diabetes – weight loss, increased Frequent Weight thirst, increasing urination loss urination and fatigue, reduces the number of children diagnosed late as in Mia’s case. A recent Australian Dr Julia Kuliwaba Lack of Excessive energy thirst study demonstrated that SA Pathology’s Dr Julia Kuliwaba, a population awareness a researcher in surgical pathology, is campaign was effective the recipient of an International Bone If your child shows these signs, in reducing the number seek immediate medical attention. and Mineral Society (IBMS) 2013 Sun of children who present Valley Young Investigator Award – the in DKA by 64%. ¥ Alice L. Jee Award – for her research investigating the pathophysiology of

Diabetes can affect children at any age. If left untreated, diabetes is deadly. osteoarthritis. The award was presented at the 43rd

www.worlddiabetesday.org/dka International Sun Valley Workshop on Musculoskeletal Biology, Sun Valley, Idaho, in August 2013.

SA Pathology Newsletter > 1 – 2013 PAGE 7 www.sapathology.sa.gov.au

Clinical utility of bone BTMturnover markers Dr Devika Thomas

Osteoporosis is a major public health issue. Diagnosis relies on a bone mineral density (BMD) measurement, using dual energy X ray absorptiometry, and is defined as a bone density more than 2.5 standard deviations below the young normal (peak bone) values at the lumbar spine or the hip. Bone turnover markers (BTM) can be used as a complement to BMD in monitoring treatment response as well as fracture prediction in patients with osteoporosis.

Bone Turnover Markers serum. Total alkaline phosphatase Which markers? may be used in place of bone specific Fasting morning serum CTX and BTM are products of bone formation alkaline phosphate in the absence of P1NP are convenient measures of and resorption. Bone is dynamic liver disease. bone turnover. Diurnal variations and tissue with formation and resorption effects of food intake affect marker occurring concurrently at many Bone resorption levels, and serial collections for multi-cellular bone remodelling units, Products of osteoclasts and terminal monitoring should be collected under hence the measurement of BTM telopeptides of mature type 1 the same conditions, at the same reflects bone turnover and rates of collagen (like serum crosslaps – time of day and analysed by the same formation and resorption. CTX) are bone resorption markers. laboratory to minimise biological and Currently CTX is the most widely analytical variability. Bone formation used bone resorption marker having Products of osteoblasts (osteocalcin, replaced the urine-based crosslinks Who to test and when? bone specific alkaline phosphatase) test. Products of osteoclasts are not and type 1 procollagen extension BTM testing is not a screen for routinely measured in clinical products (P1NP) are markers of bone osteoporosis and has not been practice. formation that can be measured in validated as a diagnostic test, which still requires bone density measurement. However, BTM testing is useful for monitoring the treatment BONE BONE RESORPTION response to antiresorptive agents in CTX RELEASED patients with osteoporosis, and in the early recognition of non responders. This is an important indication because alternative treatment may P1NP RELEASED be offered to non responders. BTM testing may be requested prior BONE FORMATION to commencement of treatment. Following initiation of anti-resorptive therapy it is useful to measure BTM again at three to six months to ensure BONE adequate response, followed by re-assessment once or twice a year while treatment continues.

SA Pathology Newsletter > 1 – 2013 PAGE 8

Follow up with BTM testing is still When monitoring treatment response BTM limitations useful even without a baseline value, the target would be a 30% fall in bone n There is no consensus on the if the blood samples are collected resorption markers within weeks of use and interpretation of BTM under recommended conditions commencing therapy. The desirable and no recommendations in (ie: morning fasting samples) and limit for P1NP in postmenopausal clinical guidelines. analysed by the same laboratory to women is <75 ug/L. minimise variabilities. n Reference intervals and desirable Table 1 P1NP reference range limits vary between laboratories. Clinical Utility FEMALES n The baseline BTM level cannot be BTM are not specific to a disease used for diagnosis of osteoporosis, and therefore cannot be used for AGE P1NP (ug/L) it does not direct treatment choice diagnosis, however raised bone <30 years 25-90 nor will it predict treatment resorption as reflected by raised CTX outcome. may suggest bone loss and loss of 30-39 years 15-80 n Only a fall in BTM greater than bone microarchitecture not captured 40-49 years 15-60 the least significant change by bone density measurements. >50 years 15-75 (30% for serum markers) may be Therefore changes in BTM precede regarded as a response to changes in BMD. MALES treatment and proof of compliance. AGE P1NP (ug/L) BTM are raised in Paget’s n It is not known to what extent disease, osteoporosis and other >25 years 15-80 BTM should fall to optimise anti- conditions where bone turnover fracture efficacy. is high, such as rheumatoid n Bone markers may be higher in BTM are also useful in recognising arthritis, hyperparathyroidism and patients with renal failure and non compliance and sometimes, hyperthyroidism. They are also dialysis dependent patients due helps identify those who may take generally higher in patients with renal to accumulation over time, and the medication incorrectly (i.e. taking impairment due to low clearance. may not directly reflect bone bisphosphonate tablets with food or turnover rate. Monitoring therapy calcium tablets). There is no consensus on a BTM Summary target with as many as 50% of women Fracture prediction with osteoporosis having a BTM in There is clear and convincing evidence BTM can be used to identify patients the premenopausal range. The aim from epidemiological studies that with high bone turnover who may be of treatment would be to return BTM BTM are an independent predictor at greater risk of fragility fracture. to premenopausal levels. In patients of fractures, particularly of the spine Comparison between baseline and treated with anti-resorptive agents, and hip. Elevated CTX levels are subsequent BTM levels can be used levels of serum CTX of <400ng/L or associated with significantly increased to monitor treatment response and at least 30% reduction from baseline risk of fragility fractures. However patient compliance. In patients treated level should be the therapeutic target. there is no evidence to support BTM with anti-resorptive agents, at least for predicting fractures in individual 30% reduction from baseline level P1NP has been shown to convincingly patients and fracture calculators do should be the therapeutic target. ¥ and significantly rise after treatment not incorporate BTM as yet. with teriparatide. When treated with anti resorptive agents such as bisphosphonates, strontium ranelate and denosumab, BTM fall significantly compared to baseline values.

SA Pathology Newsletter > 1 – 2013 PAGE 9 www.sapathology.sa.gov.au Ulysses syndrome – is it the liver? Dr Devika Thomas

This interesting case highlights the value of clinical history when interpreting test results, particularly those like liver enzymes with significant non-specificity. It reminds us that context is crucial to unravelling the complex web of influences that produce any set of test results. For more on the liver function tests refer to IMVS Newsletter 57.

CASE STUDY Discussion Liver enzyme patterns are used A 20 year old football player was admitted to the Emergency Department to classify liver disease into two with a fractured mandible. Routine biochemistry tests revealed elevated broad categories – cholestatic AST, ALT and LD with normal GGT, ALP and bilirubin. There were no clinical disease (biliary obstruction) or or historical findings to explain the elevated Liver Function Test (LFT) results. hepatocellular disease. GGT and ALP Following surgical repair of the mandible the patient’s GP was informed of are mainly located on cell membranes the results and requested follow up. Repeat results by the GP revealed and particularly line the biliary the following. cannaliculi, therefore they are raised in any obstructive biliary disease anti mitochondrial, anti LKM and ASSAY RESULT RANGE (cholestasis, metastatic lesions). anti smooth muscle – all negative Bilirubin 9 umol/L (2-24) They may also be induced by alcohol n Ceruloplasmin, alpha 1 and a variety of medications, anti- GGT 13 U/L (<60) antitrypsin, haptoglobin, serum convulsants being the most common. protein electrophoresis and ALP 90 U/L (30-110) coagulation studies were normal Transaminases (ALT and AST ALT 130 U/L* (<55) n Iron studies showed normal iron are intracellular enzymes that are AST 339 U/L* (<45) status released due to cellular injury, and are elevated in viral hepatitis and n Chest, abdominal and pelvic LD 363 U/L* (110-230) in cell destruction due to toxins CT scans – normal and medications such as high dose n Liver biopsy revealed normal paracetamol. Levels may rise 2 to The GP organised a liver and biliary hepatic and biliary tree histology 100 fold. Other causes of raised ultrasound which was normal. The Repeat liver function tests confirmed transaminases are non alcoholic patient was then referred to the liver ALT, AST and LD remained elevated steatohepatitis, haemochromatosis clinic. Subsequent investigations while GGT, ALP and bilirubin were and autoimmune liver disease. were as follows: normal. n ALT and AST had risen to AST and LD are also found in red 220 and 684 U/L respectively The patient was referred to a blood cells and muscle cells including haematologist but no haematological cardiac cells. Intravascular haemolysis n Hepatitis A IgG, Hepatitis B cause was found for the abnormal or haemolysis of the sample after surface antigen and Hepatitis C results. Following consultation collection often raises LD and AST. In antibody tests were negative with a chemical pathologist, and some haematological diseases LD may n CMV and EBV IgM serology tests considering the patient’s routine of be markedly elevated (myelodysplasia – negative playing football most days, a CK level and pernicious anaemia). n Autoantibody tests including was requested, which was 2605 U/L ANCA, ANA, ENA, dsDNA, (250U/L). If cardiac causes are suspected then a troponin T assay is recommended

SA Pathology Newsletter > 1 – 2013 PAGE 10 ‘Ulysses syndrome’ is the term used to describe an unnecessary complication of the diagnostic decision making process Test ordering standardisation where false-positive diagnostic test MBA LFT results or clinical decisions trigger a Historically ordering an MBA panel If you request an LFT plus an complex diagnostic has been something of a ‘movable additional chemistry test from work-up to elucidate feast’. Everyone seems to have their the MBA suite then you will receive the nature of what is, own interpretation on what should a full MBA report. in fact, not a disease. be reported with an MBA. The syndrome is To clarify this situation SA Pathology LFT named after Classical has implemented consistent panel Greek hero Ulysses, who fought in definitions for the basic chemistry Albumin the Trojan War (1194 to 1184 BC) tests. Total Protein and subsequently took 20 years to Total Bilirubin return home to Greece; however If you request an MBA, or any of all his harrowing diversions proved the test panels listed below, you GGT will receive the tests as listed. unnecessary. ALP

MBA ALT Electrolytes AST along with an ECG and clinical history. AST and LD are abundant Urea LDH (coming) in skeletal muscle. Although ALT Anion Gap is regarded as a liver specific RFT or ECU? transaminase, it is also present in Creatinine skeletal muscle and with persistent Glucose SA Pathology has also now muscle injury ALT may also be standardised on ECU as the renal released. Urate function panel. Note that glucose Phosphate is not included in the ECU panel and should be separately requested, History lesson Total Calcium and a grey top sample collected. A good history would have given Albumin The grey top provides a more stable the clue to severe muscular exertion collection environment for glucose as a potential cause. In this case, Total Protein and hence results are more persistent exertions in the form Total Bilirubin accurate. of severe exercise lead to the consistently elevated AST, ALT, LD GGT and CK from skeletal muscle. ALP ECU (The half life of ALT is up to 57 hours ALT Electrolytes while that of AST and CK are less than 24 hours.) AST Anion Gap Urea The differential diagnosis could have LDH been supported by requesting the Total Cholesterol Creatinine patient to have a repeat blood test Globulins eGFR after a few days rest to confirm that the cause was indeed exertion. Calculated Ionised n For more information The ‘health dollar’ is a premium Calcium please speak to a SA Pathology commodity, and in this case it’s easy eGFR Marketing representative to see how much time effort and money could have been saved by MBA LFT including a good history with the Multiple Biochemical Analysis Liver Function Test request. ¥ RFT ECU > for list of acronyms Renal Function Test Electrolytes, Creatinine, Urea see page 12

SA Pathology Newsletter > 1 – 2013 PAGE 11 www.sapathology.sa.gov.au Order of Draw Vacuum Blood Collection System Quick Guide Surgery Draw – Quick Guide The volume of blood taken should be age appropriate and minimal. Please consider patient weight (patient blood volume) and frequency of collection. Enquiries 8222 3000 Order of Draw Contents Test The SA Pathology Order of Draw Quick Guide Bactec Aerobic (blue) has recently been updated. Whilst many of the Blood Cultures (paired bottles) Anaerobic (purple) tests and tubes remain the same there have Blue been a number of significant updates including Sodium Coag Studies the introduction of the ‘yellow top’ for tissue 3.5mL Citrate INR, APTT, PT, Fibrinogen, D-Dimer typing and platelet clumping. White PSA, Tumour Markers, Iron Studies, B12, Folate, Drugs, GEL Hormone Levels, EPG, CRP, TFT, ECU, LFT, CK, LD, Ca, (Serum - Fast Clotting) For comprehensive information on all the 8mL Phos, Creatinine, Magnesium, Lipids, Troponin, Lithium, Green/Black tests SA Pathology provides please visit our Vitamin D, Auto antibody tests, Viscosity web site at www.sapathology.gov.au or Heparin Cholinesterase, Lymphocyte Surface Markers, 8mL Cytogenetics, Clozapine, Perhexiline, T Cell subsets, HLA-B27 simply scan the QR code with your Pink smartphone to go direct to the Pathology EDTA transfusion: G&S, G&M, Direct Anti-globulin(Coombs), Collection Guide page. 6mL Cord Blood, Transfusion Reaction, Antibody Screen PurPle 4ml: CBE, ESR, Haemoglobin, HbA1c, Haemoglobinopathy/Thalassaemia Screen, EDTA Red Cell Folate, Lead, Mercury, Haemochromatosis, 4mL 9mL Cyclosporin, Tacrolimus 9ml: Blood borne Viral PCR tests: RNA, DNA, Viral Load, PurP le/YelloW Genotype, Molecular Genetic Tests EDTA + GEL 5mL Homocysteine, Ammonia, PTH YelloW ACD 9mL Tissue Typing, Platelet ‘Clumping’ GreY Fluoride AHEEEHAPEHJOEPJDMEOINMAKHKDBBJBLJFCPPDBBLFCJOPAHEEEHA Glucose, Alcohol, Lactate BNFFFNBPIOJKIDNLMDADAKMGAHFHALEHAHMCFKEDNDAOMPBNFFFNB 4mL EDTA KCPCODFDGAILPFHFOFKOOCAJEAEHANODJPEOAEEEDGPIHFFFIFEJC OAOHBLFBBNEMLGPGJHGAPOCFCDEEAMGAGOMGADEAOHPNEPDCGNJME LDFOIEFBPAGEEIONCAJOLCBJNAKEMDMKAGOFDHDAPCGFCNPACAHBB AHLBBNFDIABJKGMGPKJLMBIKLILOMHIHLMFGEDMGEPHNHONNCNIFC LHANAHFHAMLHLGAOEBHAOHKOAHFHACDEDCDEABNIBFOIAHFHAJPBE MFGFEAFHGJICGGKKLBNEFMEMACBCBEHJOOGLBKDGLLICEEBBGCNCB GNNCPKFELHMFKENENBKJHJMAFDCFABCHLCNNGJPEGKPPBAOBNDGKD JEJMCKFBCHALAGIAHPHJDIOLIPLGGAHCHOCDFIMBGJOJKBMFNILFF Scan for Pathology Collection Guide BIGNBNFONGKGJAIAEHAJPDCBAHPBIOHNGGOBCOAFKKOGPMFIMCNJJ MNNFNNEHAHNKJKFAPILIJNLKAHFHAOHDKBGNCPGOGKGIAHFHALGDC APBBBPAPKPHJAAFCFPFOAGDAHABHFFFCAEDOBDEEGOPPDAFDANNMF HHHHHHHPPHHPHPHPPHHPPPHHPPPPPPPHHHHHPHPHPHPPHPHHPHPHP

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ACRONYMS CMV Allergy Test Requests Cytomegalovirus The test information sheet, ‘Allergen LFT EBV Testing Guidelines’ contains Liver Function Tests Epstein Barr Virus recommendations related to ordering. GGT ANCA You can read or print the guidelines Gamma Glutamyl Transferase Anti Neutrophil Cytoplasmic Antigen on the SA Pathology web site. From the home page go to: For ALP ANA Clinicians | Pathology Collection Guide Alkaline Phosphatase Anti Nuclear Antibody and type ‘allergy’ into the search box; ALT ENA click on the More Info link. Alanine Aminotransferase Extractable Nuclear Antigen Antibody For clinical questions please AST dsDNA phone SA Pathology Enquiries on Aspartate Amino Transferase Double stranded DNA antibody (08) 8222 3000 and ask for the LD LKM Immunopathology Registrar or on Lactate Dehydrogenase Liver-Kidney Microsomal Antibody call Immunopathologist.

CK CT The SA Pathology Allergy Test Creatine Kinase X-ray Computed Tomography Request form has been discontinued.

SA Pathology enquiries > Metropolitan 8222 3000 > Regional and Country 1800 188 077

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