Introduction

Amylase is a digestive enzyme predominantly secreted by the pancreas and salivary glands, with minimal presence in other tissues.[1] The enzyme was first described in the early 1800s and is considered one of the earliest subjects of enzymology. Initially termed diastase, the enzyme was renamed amylase in the early 20th century.

The primary function of amylases is to hydrolyze glycosidic bonds in starch molecules, converting complex carbohydrates into simpler sugars. Amylase enzymes are classified into 3 main categories: α-, β-, and γ-amylases, each exhibiting specificity for distinct segments of carbohydrate molecules.[2] α-amylase occurs in humans, animals, plants, and microbes, whereas β-amylase is primarily restricted to microbes and plants. γ-amylase is present in both animals and plants.[3]

In 1908, Robert Wohlgemuth reported the presence of amylase in urine, establishing the enzyme's potential as a diagnostic laboratory analyte. Amylase is a standard laboratory test often ordered alongside lipase to evaluate suspected acute pancreatitis.

Etiology and Epidemiology

Elevation of amylase levels occurs in a variety of conditions, including pancreatic, salivary, and intestinal diseases, as well as conditions associated with decreased metabolic clearance and macroamylasemia.[4] Approximately 11% to 13% of patients with nonpancreatic abdominal pain exhibit elevated pancreatic enzyme levels.[5] In at least one study, 60% of asymptomatic patients living with HIV demonstrated abnormal amylase or lipase levels.[6] Upon admission, 26 of 208 patients (12.5%) with acute abdominal pain unrelated to pancreatic pathology presented with elevated serum amylase levels.

Abnormally elevated amylase values are observed in 35% of patients with liver disease.[7] Elevated amylase levels are also reported in approximately 16% to 25% of diabetic ketoacidosis cases.[8][9] In a cohort of 74 patients with surgically resectable lung cancer, 13 patients exhibited hyperamylasemia.[10]

Pathophysiology

Amylase is a heterogeneous, calcium-dependent metalloenzyme with a molecular weight typically ranging from 54 to 62 kDa. The compact structure of amylase facilitates efficient filtration through the glomeruli. Elimination occurs via both the renal and reticuloendothelial systems. The enzyme exists as 2 isoenzymes, pancreatic (P-type) and nonpancreatic (S-type), which arise from 2 closely linked loci on chromosome 1. Additional heterogeneity results from allelic variation, with 12 alleles identified for the S-type and 6 alleles for the P-type.[11] Both isoenzymes undergo posttranslational modifications, including deamidation, glycosylation, and deglycosylation, producing multiple isoforms. Amylase exhibits broad tissue distribution, with the highest P- and S-type activities located in the exocrine pancreas and salivary glands, respectively.[12]

P-type amylase is synthesized by pancreatic acinar cells and secreted into the intestinal tract via the pancreatic duct system. The enzymatic activity of P-type amylase is optimal under the slightly alkaline conditions of the duodenum.[13] The salivary glands exhibit the highest S-type amylase activity, thereby initiating starch hydrolysis during mastication and esophageal transit. Starch hydrolysis is terminated upon exposure to gastric acid.

S-type amylase is detectable in extracts from the testes, ovaries, fallopian tubes, Müllerian ducts, striated muscle, lungs, and adipose tissue, as well as in bodily fluids, including semen, colostrum, tears, and milk. Approximately 25% of plasma amylase is excreted by the kidneys, with the majority being reabsorbed in the proximal tubules.[14] The liver is considered the primary organ responsible for amylase elimination, resulting in a half-life of approximately 10 hours. Serum amylase levels are tightly regulated, reflecting a balance between production and clearance rates.[15] Elevated amylase concentrations may result from increased production, whether pancreatic or extrapancreatic, or from reduced clearance.

Genetic regulation likely contributes to the baseline determination of salivary amylase levels. In newborns, urinary amylase is predominantly of salivary origin, whereas salivary and pancreatic amylase isoenzymes increase with development. Functional integrity of amylase depends on the presence of calcium.[16] Full enzymatic activity requires specific anions, including chloride, bromide, nitrate, or monohydrogen phosphate, with chloride and bromide serving as the most effective activators. The pH optimum for enzymatic activity ranges from 6.9 to 7.0.[17]

The analyte amylase is an endoglycosidase enzyme of the hydrolase class that catalyzes the hydrolysis of 1,4-α-glucosidic linkages between adjacent glucose units in complex carbohydrates.[18] Linear polyglucans, such as amylose, and branched polyglucans, such as amylopectin and glycogen, are hydrolyzed at distinct rates.[19] In amylose, the enzyme cleaves the chains at alternate α-1,4-hemiacetal linkages (-C-O-C-), producing maltose and residual glucose. In branched polyglucans, enzymatic action generates maltose, glucose, and residual limit dextrins. The enzyme does not hydrolyze α-1,6-linkages at branch points.

Specimen Requirements and Procedure

Serum or heparinized plasma can serve as suitable samples. A particular study demonstrated that heparinized plasma samples produced significantly higher results than serum samples when using dry-film technology.[20] Amylase requires calcium ions for enzymatic activity. Therefore, chelating anticoagulants, including citrate, oxalate, and ethylenediaminetetraacetic acid, are unsuitable for plasma collection. Urine specimens obtained without preservatives, through random or timed methods, are considered valid samples.

Amylase is sometimes measured in ascitic, peritoneal, or pleural fluid. Elevated concentrations of this enzyme in these fluids can suggest pancreatitis or a tumor. In serum, enzymatic activity remains stable for up to 4 days at room temperature, 2 weeks at 5 °C, 1 year at −28 °C, or 5 years at −75 °C. Urine specimens should be analyzed within 12 hours at room temperature or within 5 days when stored at 5 °C. Freezing of urine specimens is not recommended.[21]

Diagnostic Tests

Amylase has historically played a central role in diagnosing acute pancreatitis. Assessment may be performed via blood or urine testing. Urine testing may be conducted using a clean-catch specimen or a 24-hour urine collection. Normal ranges for serum amylase vary across laboratories. Differentiation of pancreatic amylase from other isoforms remains clinically important. Elevated amylase levels with normal lipase values may indicate an extrapancreatic origin.

The lipase-to-amylase ratio helps distinguish gallstone-induced pancreatitis from alcoholic pancreatitis. Gallstone-associated pancreatitis typically produces greater increases in amylase, whereas alcohol-induced pancreatitis results in higher lipase elevations. A lipase-to-amylase ratio exceeding 2 has a 91% sensitivity and 76% specificity for alcoholic pancreatitis, whereas a ratio exceeding 5 has a 31% sensitivity and nearly 100% specificity for the same condition.[22] Alanine transaminase elevations reaching 3 times the upper limit of normal are highly specific for gallstone pancreatitis. Combined measurement of serum amylase and lipase enhances specificity compared with either test alone but does not substantially improve sensitivity.[23]

Testing Procedures

The amylase assay is performed using semiautomatic or fully automated analyzers based on photometric principles. Photometry involves measuring light absorption across the UV, visible, and infrared spectra to quantify analyte concentration in solution. Photometers use specific light sources and detectors, such as photodiodes, photoresistors, or photomultipliers, to convert light transmitted through the sample into corresponding electrical signals. The Beer-Lambert law is applied to calculate coefficients derived from transmittance measurements.[24] Test-specific calibration establishes the correlation between absorbance and analyte concentration, ensuring highly accurate quantification.[25]

P-type amylase can be distinguished from S-type amylase through selective inhibition of S-type using wheat germ inhibitor, temperature inhibition, immunoprecipitation, or immunoinhibition with monoclonal antibodies. Methods based on selective inhibition by monoclonal antibodies provide sufficient precision, reliability, practicality, and analytical speed for accurate measurement of P-type amylase.[26] Amylase isoforms may be separated by isoelectric focusing, ion-exchange chromatography, or gel or capillary electrophoresis employing electrophoretic endosmosis.[27]

Interfering Factors

Amylase assays generally resist interference from hemoglobin, bilirubin, or triglycerides. Specimens collected in tubes containing oxalate, citrate, or ethylenediaminetetraacetic acid may produce falsely decreased values due to chelation of essential amylase cofactors. Certain medications, including aspirin, morphine, antiretrovirals, and estrogen-containing drugs, can alter serum amylase concentrations.[28]

Elevated serum amylase activity can result from macroamylasemia, a condition characterized by the formation of macromolecular complexes. These complexes predominantly involve immunoglobulins, usually immunoglobulin A or G, although self-polymerization or association with other proteins may occur.[29] The complexes generally retain enzymatic activity but cannot undergo effective glomerular filtration. Consequently, delayed clearance increases serum amylase activity.[30] Macroamylasemia has been reported in up to 1.5% of hospitalized patients and accounts for as much as 28% of chronic or otherwise unexplained hyperamylasemia cases.[31]

Macroamylasemia is associated with autoimmunity, malignancy, cardiovascular disease, diabetes mellitus, and malabsorptive disorders. Consideration of macroamylasemia is warranted when evaluating asymptomatic patients with elevated serum amylase concentrations.[32] No specific treatment is required, as the condition is typically benign.[33]

Circulating pancreatic amylase concentrations are higher in female individuals with blood type O compared with those with blood type A, in whom pancreatic amylase concentrations tend to be lower.[34] Psychosocial stress elevates salivary amylase activity in healthy individuals, potentially increasing total serum amylase levels. Clinical studies have not confirmed whether psychosocial stress exerts a long-term effect on serum amylase levels.[35]

In cases of pancreatitis associated with hypertriglyceridemia, serum amylase concentrations may appear falsely normal. This discrepancy arises from inhibitory interference caused by elevated triglyceride levels, which affects the enzymatic assay. Dilution of the serum reduces the inhibitory effect, enabling recalculation to reveal the actual serum amylase concentration.[36]

Results, Reporting, and Critical Findings

Reference intervals for amylase vary among assay methods due to differences in substrates and reagent preparations.[37] Interpretation of patient blood test values should rely on reference limits established by the specific laboratory performing the assay. Each laboratory is recommended to establish unique reference ranges based on its testing methodology.[38] A significant proportion of individuals of African and Asian descent exhibit S-type amylase activity exceeding reference intervals established for White populations, resulting in elevated total amylase measurements without indicating pathology.[39]

Blood amylase activity in newborns is approximately 18% of adult values. Serum amylase activity shows no significant differences between male and female individuals. In healthy adults, pancreatic amylase typically constitutes 40% to 50% of total serum amylase activity. In most children younger than 6 months, serum pancreatic amylase activity is undetectable. Activity gradually increases thereafter, reaching adult levels by age 5 years, reflecting postnatal development of exocrine pancreatic function.[40] Measurement of this enzyme is not recommended for diagnosing acute pancreatitis in young children.[41]

No internationally standardized reference range has been established for serum amylase concentrations; reported reference intervals range from 20 to 300 U/L. Amylase levels exceeding 3 times the upper reference limit strongly suggest acute pancreatitis.[42] Values below this threshold are associated with alternative medical conditions. Abnormally low amylase values, although less common, occur in cystic fibrosis, chronic pancreatitis, diabetes mellitus, obesity, and chronic tobacco use.[43] Awareness of these potential etiologies is important when interpreting reduced amylase activity.[44]

Persistently elevated total amylase with normal lipase raises suspicion for macroamylasemia. Screening tests, including the amylase-creatinine clearance ratio (ACCR) and polyethylene glycol precipitation, help identify macroamylase.[45] ACCR is calculated using paired random urine and serum amylase and creatinine measurements. An ACCR below 1% suggests macroamylasemia. Each laboratory should evaluate the applicability of this threshold to its patient population and establish appropriate reference ranges when necessary.[46] An ACCR greater than 5% supports a diagnosis of acute pancreatitis.[47] Increased ACCR has also been reported in diabetic ketoacidosis, renal disease, and postoperative states.[48]

Clinical Significance

Amylase is primarily used in the diagnosis of pancreatic disease and remains a frequently measured enzyme due to readily available, cost-effective automated assays. Although amylase demonstrates high sensitivity for acute pancreatitis, limited specificity is evident, as elevations occur in numerous nonpancreatic conditions.[49] Acute pancreatitis is defined by the presence of at least 2 of 3 criteria: abdominal pain, serum amylase or lipase concentrations exceeding 3 times the upper reference limit, and characteristic findings on abdominal imaging. Ongoing evaluation of amylase's clinical utility reflects these limitations.[50] Alternative causes of hyperamylasemia should be considered in the presence of elevated amylase values without sufficient evidence of pancreatitis.[51]

Amylase does not predict the severity of an acute pancreatic episode and is not suitable for disease monitoring. The magnitude of serum enzyme activity elevation does not correlate with the extent of pancreatic involvement. However, a greater rise in amylase activity increases the likelihood of acute pancreatitis.

The limited specificity of total amylase measurement has prompted evaluation of direct P-type amylase measurement for differential diagnosis in acute abdominal pain. Using a decision threshold of 3 times the upper reference limit, P-type amylase demonstrates specificity exceeding 90% for acute pancreatitis. Pancreatic amylase also improves sensitivity in the late phase of detection. A week after symptom onset, P-type amylase remains elevated in 80% of patients with uncomplicated pancreatitis, whereas only 30% exhibit persistent elevation of total amylase activity.[52]

Sustained elevation of serum P-type amylase renders measurement of total urinary amylase largely redundant. Historically, urinary testing was performed to enhance diagnostic sensitivity during the late phase of pancreatitis.[53]

Amylase inhibitors, including acarbose, have been used in the management of type 2 diabetes, demonstrating reductions in hemoglobin A1c and peak postprandial glucose levels. Acarbose also improves remission of dumping syndrome in patients following bariatric surgery. Additionally, this agent slows the progression of carotid artery thickening, thereby reducing cardiovascular risk.[54]

Elevated amylase concentrations occur in a broad range of conditions. A systematic, well-defined approach to hyperamylasemia is essential to prevent unnecessary hospitalization and ensure timely, appropriate management.[55] Biliary tract diseases, such as cholecystitis, may increase serum P-type amylase activity by up to 4-fold due to primary or secondary pancreatic involvement.[56]

Various intra-abdominal events can cause substantial elevations in serum P-type amylase, often exceeding 4-fold. These increases frequently result from leakage of P-type amylase from the intestine into the peritoneal cavity and circulation.[57] In renal insufficiency, serum amylase activity rises in proportion to the degree of renal impairment, typically not exceeding 5 times the upper reference limit.[58]

Cases of amylase-producing multiple myeloma have been reported. Increased amylase activity in most patients is due to salivary-type hyperamylasemia, specifically the sialyl type.[59] A common feature of myeloma cell lines associated with hyperamylasemia is a chromosome 1 translocation that contains the amylase gene. This association does not appear to be restricted to any specific immunoglobulin class. Onset of hyperamylasemia correlates with rapid disease progression, extensive bone destruction, and increased mortality. Therefore, serum amylase activity may serve as a prognostic tumor marker in multiple myeloma, decreasing with treatment and rising during relapse.[60][61]

Amylase isoenzymes in cases of ruptured ectopic pregnancy remain poorly characterized. In severe, late-diagnosed cases, the elevated isoenzyme may be pancreatic amylase due to pancreatic involvement associated with peritonitis, despite the presence of salivary amylase in the fallopian tube.[62]

Patients with pheochromocytoma or paraganglioma may exhibit hyperamylasemia, predominantly of the salivary isoenzyme. In such cases, elevated amylase activity may result from hypertensive crisis and vasoconstriction, causing tissue hypoxia, rather than direct tumor secretion. This increase in amylase activity is typically transient.[63] Salivary-type hyperamylasemia has also been observed in conditions unrelated to salivary gland pathology. These conditions include diabetic ketoacidosis, pneumonia, and postoperative states following a variety of surgical procedures, including extra-abdominal interventions such as coronary bypass surgery.[64] 

Benign pancreatic hyperenzymemia, also known as Gullo syndrome, was first described by Lucio Gullo. The condition is characterized by elevated serum concentrations of amylase, pancreatic isoamylase, lipase, and trypsin in asymptomatic individuals without evidence of pancreatic disease on imaging. The syndrome occurs as either a sporadic or a familial condition, and amylase activity may fluctuate, occasionally normalizing transiently.[65]

The etiology of benign pancreatic hyperenzymemia does not involve mutations in the CFTR, SPINK1, or PRSS1 genes. The condition cannot be attributed to mutations in genes associated with pancreatitis or other variants of PRSS1 or SPINK1.[66] Approximately 1 in 3 patients with chronic nonpathological pancreatic hyperenzymemia exhibit elevated fecal calprotectin concentrations. This finding suggests a potential link between intestinal ecology and alterations in pancreatic enzyme activity, warranting further investigation.[67]

Salivary hyperamylasemia has been observed following trauma or surgical procedures affecting the salivary glands. Radiation to the neck involving the parotid gland can result in duct obstruction or calculus formation. Chronic alcoholism and anorexia nervosa may cause subclinical salivary gland damage. In patients with alcoholism, approximately 10% exhibit salivary amylase activity 3 times higher than normal, often associated with chronic liver disease.[68]

Hyperamylasemia in anorexia nervosa is linked to vomiting, and elevated salivary amylase levels may indicate concealed emesis.[69] Pancreatitis can occur in these patients, particularly during refeeding. Measurement of plasma lipase or amylase isoenzymes may be warranted to differentiate pancreatitis from salivary hyperamylasemia.[70]

Hyperamylasemia may be associated with various tumors, either due to ectopic enzyme production by the tumor or to an inflammatory response by tumor cells, leading to significant release of the enzyme normally produced in these tissues into the circulation.[71] The elevated isoenzyme is almost exclusively of the salivary type in ovarian cancer, lung cancer, multiple myeloma, and pheochromocytoma.[72]

Amylase-producing tumors of the lung are rare, representing only 1% to 3% of all lung carcinomas, and typically exhibit the salivary amylase isoenzyme. These lung carcinomas are primarily adenocarcinomas, although hyperamylasemia has also been reported in small-cell carcinoma.[73] Amylase activity has been proposed as a tumor marker for monitoring treatment response in patients with amylase-producing lung carcinoma.[74]

Approximately 39% of patients demonstrate hyperamylasemia in ovarian carcinoma, predominantly of the salivary type. This finding suggests that salivary amylase may serve as an indicator for evaluating radiotherapy effectiveness in these cases.[75] 

Gut disorders, including mucosal inflammatory disease of the small intestine, mesenteric infarction, intestinal obstruction, appendicitis, and peritonitis, typically cause elevations in P-type isoamylase due to increased absorption of amylase from the intestinal lumen.[76] Gut perforation permits leakage of intestinal contents into the peritoneum, resulting in inflammation and amylase absorption across the inflamed peritoneum, which may produce hyperamylasemia.

Acidosis can induce hyperamylasemia and arises from 2 sources. Ketoacidosis increases both S- and P-type isoamylases, whereas nonketotic acidosis elevates only S-type isoamylase.[77]

Postoperative increases in amylase may elevate both S- and P-type isoamylases, with elevations of the salivary isoenzyme occurring more frequently.[78] Such elevations can follow procedures involving extracorporeal circulation or non-abdominal surgery. Approximately 30% of patients undergoing cardiac surgery have elevated S-type isoamylase levels.[79]

Rare cases of hyperamylasemia have been reported in association with systemic lupus erythematosus. Similar cases have also been described following ciprofloxacin therapy.[80] Additional causes of hyperamylasemia include pneumonia, which increases salivary amylase; cerebral trauma; burns; abdominal aortic aneurysms, which elevate pancreatic amylase; certain drugs, which may increase salivary or pancreatic amylase; anorexia nervosa and bulimia, which elevate salivary amylase; nonpathological factors affecting salivary or pancreatic amylase; and organophosphate poisoning.

Postprocedural balloon-assisted enteroscopy can also result in elevated amylase levels. Measurement of pancreatic isoenzyme concentrations, rather than total amylase, is recommended following these procedures.[81] Elevated pancreatic enzymes may be detected in patients with critical traumatic injuries, even in the absence of true pancreatitis.[82]

Quality Control and Lab Safety

The purpose of a clinical laboratory test is to assess underlying pathophysiology, aid diagnosis, provide guidance or supervision of treatment, and evaluate the likelihood of disease progression.[83] Implementing a quality management system is paramount in upholding the precision and reliability of laboratory tests.[84] Internal quality control is a cornerstone of a clinical laboratory's quality management system, systematically monitoring and verifying the accuracy and precision of laboratory test results.[85]

All aspects of laboratory operation, including internal quality control, must adhere to written standard operating procedures (SOPs).[86] The SOP for quality control should include all components of the program, including the selection of quality control materials, determination of statistical parameters to describe method performance, criteria for accepting quality control results, measurement frequency of quality control materials, corrective actions when problems arise, and the documentation and review processes. The SOP should specify authorized personnel responsible for setting acceptable control limits and interpretive rules for result release; reviewing performance parameters, including statistical quality control results; and granting authorization for exceptions to or modifications of established quality control policies and procedures.[87]

Quality control samples are periodically measured using the same method as clinical samples, and the results are analyzed to ensure that the measurement procedure meets performance requirements suitable for patient care. A quality control result within the acceptable range of the known value indicates that the measurement procedure is stable and operating as expected. This finding confirms that results for patient samples may be reported with a high probability of suitability for clinical use.

A quality control result outside the acceptable limits indicates suboptimal performance of the analytical measurement procedure. In such cases, patient sample values cannot be reported, and corrective action is required. After remedial measures are implemented, patient sample measurements are repeated along with quality control samples to ensure accuracy and reliability.[88] Adherence to good laboratory practice requires verifying that a method yields reliable results when tested on patient specimens.[89] 

For nonwaived tests, laboratory regulations mandate analysis of at least 2 control material levels at least once every 24 hours. Laboratories may assay quality control samples more frequently as needed to ensure the accuracy of results. Quality control samples must also be analyzed after an analyzer is calibrated or maintained to verify proper method performance.

Laboratories may implement an individualized quality control plan to reduce the frequency of quality control testing for assays with manufacturer-recommended intervals that are less frequent than regulatory requirements, such as once per month. The plan incorporates a risk assessment that evaluates potential error sources across all testing phases and establishes a tailored quality control strategy to minimize risk.[90]

Westgard multirules are applied to assess quality control runs. When a rule violation occurs, appropriate corrective and preventive actions must be completed before patient testing.[91]

Proficiency testing is a program designed to assess method performance by comparing results with those from other laboratories analyzing the same set of samples.[92] Proficiency testing providers distribute a set of samples among a group of laboratories for this purpose.

Each laboratory analyzes the proficiency testing samples in the same manner as patient samples and then reports the results to the proficiency testing provider for evaluation. The proficiency testing provider assigns a target value to the samples and evaluates whether the individual laboratory's results closely align with it, indicating acceptable method performance.[93] The acceptable performance criteria for the amylase assay, as defined by the Clinical Laboratory Improvement Amendments and the College of American Pathologists proficiency program, require results to fall within ±30% of the mean value of laboratory peer groups.[94]

If an unacceptable proficiency testing result is identified, the method must be investigated for possible causes, and any necessary corrective action must be taken.[95] Even when a proficiency testing result meets acceptability criteria, good laboratory practice requires investigation of results that deviate by more than approximately 2.5 SD from the peer group mean. An SD of 2.5 corresponds to only a 0.6% probability that the result falls within the expected distribution for the peer group, warranting consideration of a potential method problem.[96] Investigative steps, reviewed data, and conclusions from the review must be documented in a written report on the unacceptable proficiency testing result, which the laboratory director should review.

Ensuring laboratory safety is paramount in clinical laboratories, where precise and reliable results are essential for patient diagnosis and treatment.[97] Maintaining a secure environment requires strict adherence to safety protocols.

Personal protective equipment, including lab coats, gloves, goggles, and masks, must be used to protect against potential hazards.[98] Chemical safety measures include proper labeling, storage, and handling of chemicals, with hazardous substances confined to designated areas. Biological safety requires the use of biosafety cabinets and stringent protocols for managing potentially infectious materials.

Regular maintenance and calibration of equipment, along with staff training on safe operation, are crucial for preventing accidents and ensuring accurate results. Well-defined procedures for handling emergencies, including accidents, spills, or exposures, must be established. Staff must also have a clear understanding of the locations of safety equipment and evacuation routes.[99]

Fire safety precautions, including the availability of fire extinguishers and proper storage of flammable materials, are critical. Electrical safety measures, such as regular equipment maintenance and ensuring proper grounding, reduce the risk of electrical hazards.[100] Safe handling and disposal of sharps, along with appropriate management of chemical and biohazardous waste, are essential to protect laboratory personnel. Rigorous training on safety protocols, combined with comprehensive documentation of incidents, procedures, and training, fosters a culture of safety and ensures compliance with regulatory standards.[101] A comprehensive approach to laboratory safety remains indispensable for preserving both the accuracy of test results and the well-being of personnel in clinical settings.

Enhancing Healthcare Team Outcomes

Effective interprofessional communication is essential when interpreting abnormal serum amylase values, particularly in distinguishing pancreatic from nonpancreatic etiologies.[102] Clinicians, advanced practitioners, and laboratory professionals must recognize that amylase lacks specificity and may be elevated in diverse conditions, including salivary gland disorders, gastrointestinal pathology, renal impairment, and macroamylasemia. Clear communication of these diagnostic limitations by laboratory personnel reduces diagnostic anchoring and prevents unnecessary downstream investigations.

Interprofessional teams evaluating abnormal serum amylase concentrations should prioritize clinical severity scoring systems, such as the Ranson criteria or APACHE II (Acute Physiology and Chronic Health Evaluation II), rather than relying on absolute enzyme values. Integration of additional markers, including blood urea nitrogen, hematocrit, and C-reactive protein, improves risk stratification for organ failure and pancreatic necrosis.

Vigilance for diagnostic pitfalls remains necessary, including hypertriglyceridemia-associated pancreatitis, in which lipase may represent the only reliable biochemical marker. Specialist consultation should be considered for persistent or unexplained hyperamylasemia. Health systems may support optimal management through electronic decision-support tools. Early imaging and clinical judgment remain particularly important in older patients because of reduced diagnostic sensitivity of pancreatic enzyme measurements.

From a care coordination and patient safety perspective, lipase testing should be prioritized over amylase when pancreatitis is suspected, as lipase has superior diagnostic specificity and remains elevated for longer. In contrast, amylase concentrations often normalize within 3 to 5 days. This distinction is particularly relevant when delays occur between symptom onset and clinical presentation, and failure to recognize this temporal pattern may result in false reassurance or misdiagnosis.[103]

Routine or simultaneous ordering of amylase and lipase is neither cost-effective nor evidence-based. Guidelines from the American College of Gastroenterology emphasize that ordering both assays does not improve diagnostic accuracy and increases healthcare costs without proportional patient benefit. Laboratory stewardship initiatives, supported by pathologists, pharmacists, and quality managers, guide appropriate test utilization and promote high-value care.[104]

Nurses and allied health professionals contribute by ensuring accurate specimen acquisition, timely transport, and appropriate documentation of clinical context. In contrast, pharmacists identify medication-related causes of hyperamylasemia and help prevent unnecessary therapeutic interventions.[105] Shared decision-making, standardized diagnostic pathways, and transparent communication of assay limitations improve diagnostic accuracy, reduce unnecessary testing, enhance patient outcomes, and optimize team performance in the evaluation of amylase abnormalities.[106]

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

Pieper-Bigelow C, Strocchi A, Levitt MD. Where does serum amylase come from and where does it go? Gastroenterol Clin North Am. 1990 Dec;19(4):793-810. [PubMed: 1702756]

2.

Zakowski JJ, Bruns DE. Biochemistry of human alpha amylase isoenzymes. Crit Rev Clin Lab Sci. 1985;21(4):283-322. [PubMed: 2578342]

3.

Azzopardi E, Lloyd C, Teixeira SR, Conlan RS, Whitaker IS. Clinical applications of amylase: Novel perspectives. Surgery. 2016 Jul;160(1):26-37. [PubMed: 27117578]

4.

Reynolds TM. Amylase. Br J Hosp Med (Lond). 2009 Jan;70(1):M8-9. [PubMed: 19357566]

5.

Chase CW, Barker DE, Russell WL, Burns RP. Serum amylase and lipase in the evaluation of acute abdominal pain. Am Surg. 1996 Dec;62(12):1028-33. [PubMed: 8955242]

6.

Argiris A, Mathur-Wagh U, Wilets I, Mildvan D. Abnormalities of serum amylase and lipase in HIV-positive patients. Am J Gastroenterol. 1999 May;94(5):1248-52. [PubMed: 10235202]

7.

Pezzilli R, Andreone P, Morselli-Labate AM, Sama C, Billi P, Cursaro C, Barakat B, Gramenzi A, Fiocchi M, Miglio F, Bernardi M. Serum pancreatic enzyme concentrations in chronic viral liver diseases. Dig Dis Sci. 1999 Feb;44(2):350-5. [PubMed: 10063922]

8.

Rizvi AA. Serum amylase and lipase in diabetic ketoacidosis. Diabetes Care. 2003 Nov;26(11):3193-4. [PubMed: 14578269]

9.

Muniraj T, Dang S, Pitchumoni CS. PANCREATITIS OR NOT?--Elevated lipase and amylase in ICU patients. J Crit Care. 2015 Dec;30(6):1370-5. [PubMed: 26411523]

10.

Lenler-Petersen P, Grove A, Brock A, Jelnes R. alpha-Amylase in resectable lung cancer. Eur Respir J. 1994 May;7(5):941-5. [PubMed: 8050552]

11.

Goldberg DM, Spooner RJ. Amylase, isoamylase and macroamylase. Digestion. 1975;13(1-2):56-75. [PubMed: 1104398]

12.

Barbieri JS, Riggio JM, Jaffe R. Amylase testing for abdominal pain and suspected acute pancreatitis. J Hosp Med. 2016 May;11(5):366-8. [PubMed: 27160507]

13.

Motoo Y. [Amylase]. Nihon Rinsho. 2004 Nov;62 Suppl 11:387-9. [PubMed: 15628424]

14.

Peyrot des Gachons C, Breslin PA. Salivary Amylase: Digestion and Metabolic Syndrome. Curr Diab Rep. 2016 Oct;16(10):102. [PMC free article: PMC6825871] [PubMed: 27640169]

15.

Otsuki M. [Usefulness of amylase isoenzyme determination for the diagnosis of pancreatic diseases]. Nihon Rinsho. 1995 May;53(5):1184-91. [PubMed: 7541479]

16.

Berk JE, Fridhandler L. Clinical application of amylase isoenzyme analysis. Am J Gastroenterol. 1975 Jun;63(6):457-63. [PubMed: 1146802]

17.

Brault D, Bonnefoy A, Houry S, Dreux B, Bunodière M, Huguier M. [Acute pancreatitis and biochemical markers. Isoamylase]. Pathol Biol (Paris). 1985 Mar;33(3):195-9. [PubMed: 2409510]

18.

Rompianesi G, Hann A, Komolafe O, Pereira SP, Davidson BR, Gurusamy KS. Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of acute pancreatitis. Cochrane Database Syst Rev. 2017 Apr 21;4(4):CD012010. [PMC free article: PMC6478262] [PubMed: 28431198]

19.

Ismail OZ, Bhayana V. Lipase or amylase for the diagnosis of acute pancreatitis? Clin Biochem. 2017 Dec;50(18):1275-1280. [PubMed: 28720341]

20.

Giavarina D, Lippi G. Blood venous sample collection: Recommendations overview and a checklist to improve quality. Clin Biochem. 2017 Jul;50(10-11):568-573. [PubMed: 28242283]

21.

Lippi G, von Meyer A, Cadamuro J, Simundic AM. Blood sample quality. Diagnosis (Berl). 2019 Mar 26;6(1):25-31. [PubMed: 29794250]

22.

King LG, Seelig CB, Ranney JE. The lipase to amylase ratio in acute pancreatitis. Am J Gastroenterol. 1995 Jan;90(1):67-9. [PubMed: 7528469]

23.

Lankisch PG, Petersen M. Lipase/amylase ratio: not helpful in the early etiological differentiation of acute pancreatitis. Z Gastroenterol. 1994 Jan;32(1):8-11. [PubMed: 7511857]

24.

Oshina I, Spigulis J. Beer-Lambert law for optical tissue diagnostics: current state of the art and the main limitations. J Biomed Opt. 2021 Oct;26(10) [PMC free article: PMC8553265] [PubMed: 34713647]

25.

Mäntele W, Deniz E. UV-VIS absorption spectroscopy: Lambert-Beer reloaded. Spectrochim Acta A Mol Biomol Spectrosc. 2017 Feb 15;173:965-968. [PubMed: 27727137]

26.

Gromashevskaia LL, Bogatyr' TV. [Serum amylase isoenzymes: their sources and clinical value of their determination (review of the literature)]. Lab Delo. 1986;(8):451-7. [PubMed: 2429044]

27.

Takagi Y, Ishii T. [Methods of serum enzyme determination and its clinical significance: amylase inhibitors--with special reference to their application in the quantitative analysis of amylase isoenzymes in the human body fluids]. Rinsho Byori. 1983 Jun;Suppl 55:61-8. [PubMed: 6197542]

28.

Hamdan II, Afifi F, Taha MO. In vitro alpha amylase inhibitory effect of some clinically-used drugs. Pharmazie. 2004 Oct;59(10):799-801. [PubMed: 15544061]

29.

Klonoff DC. Macroamylasemia and other immunoglobulin-complexed enzyme disorders. West J Med. 1980 Nov;133(5):392-407. [PMC free article: PMC1272350] [PubMed: 6162278]

30.

Wiederkehr JC, Wiederkehr BA, Wiederkehr HA, Carvalho CA. Nonspecific hyperamylasemia: a case report. JOP. 2013 Jan 10;14(1):74-6. [PubMed: 23306339]

31.

Cutolo M, Sulli A, Barone A, Picciotto A, Mangraviti S, Seriolo B, Accardo S. Macroamylasemia: a possible cause of unexplained hyperamylasemia in rheumatoid arthritis. Br J Rheumatol. 1995 Mar;34(3):290-2. [PubMed: 7537158]

32.

Ishizuka T, Yasuda K, Kajita K, Sakata S, Kimura M, Ito Y, Miura K. Macroamylasemia associated with thyroid cancer, elevated serum thyroxine-binding globulin (TBG), chronic pancreatitis and gastrointestinal polyposis. Gastroenterol Jpn. 1986 Aug;21(4):385-90. [PubMed: 2429888]

33.

Lam R, Muniraj T. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Dec 11, 2022. Hyperamylasemia. [PubMed: 32644699]

34.

Peng YF, Goyal H, Lin H, Liu DC, Li L. Serum amylase activity altered by the ABO blood group system in Chinese subjects. J Clin Lab Anal. 2019 Jun;33(5):e22883. [PMC free article: PMC6595472] [PubMed: 30938472]

35.

Santos SVMD, Silva LAD, Terra FS, Souza AV, Espindola FS, Marziale MHP, Teixeira RR, Robazzi MLDCC. Association of salivary alpha-amylase with anxiety and stress in nursing professionals. Rev Lat Am Enfermagem. 2021;29:e3468. [PMC free article: PMC8432589] [PubMed: 34468625]

36.

Melnick S, Nazir S, Gish D, Aryal MR. Hypertriglyceridemic pancreatitis associated with confounding laboratory abnormalities. J Community Hosp Intern Med Perspect. 2016;6(3):31808. [PMC free article: PMC4942506] [PubMed: 27406459]

37.

Gräsbeck R. Reference values, why and how. Scand J Clin Lab Invest Suppl. 1990;201:45-53. [PubMed: 2244183]

38.

Liu W, Bretz F, Cortina-Borja M. Reference range: Which statistical intervals to use? Stat Methods Med Res. 2021 Feb;30(2):523-534. [PMC free article: PMC8008401] [PubMed: 33054684]

39.

Lim E, Miyamura J, Chen JJ. Racial/Ethnic-Specific Reference Intervals for Common Laboratory Tests: A Comparison among Asians, Blacks, Hispanics, and White. Hawaii J Med Public Health. 2015 Sep;74(9):302-10. [PMC free article: PMC4578165] [PubMed: 26468426]

40.

Gillard BK, Simbala JA, Goodglick L. Reference intervals for amylase isoenzymes in serum and plasma of infants and children. Clin Chem. 1983 Jun;29(6):1119-23. [PubMed: 6189641]

41.

Morgenstern T, Niessen KH, Teufel M. [Value of isoamylases in the diagnosis of exocrine pancreatic insufficiency in childhood]. Monatsschr Kinderheilkd. 1984 Sep;132(9):661-5. [PubMed: 6208482]

42.

Furey C, Buxbaum J, Chambliss AB. A review of biomarker utilization in the diagnosis and management of acute pancreatitis reveals amylase ordering is favored in patients requiring laparoscopic cholecystectomy. Clin Biochem. 2020 Mar;77:54-56. [PubMed: 31899279]

43.

Nakajima K. Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation. World J Diabetes. 2016 Mar 25;7(6):112-21. [PMC free article: PMC4807301] [PubMed: 27022442]

44.

Nakajima K, Nemoto T, Muneyuki T, Kakei M, Fuchigami H, Munakata H. Low serum amylase in association with metabolic syndrome and diabetes: A community-based study. Cardiovasc Diabetol. 2011 Apr 17;10:34. [PMC free article: PMC3102610] [PubMed: 21496338]

45.

Banks PA, Sidi S, Gelman ML, Lee KH, Warshaw AL. Amylase-creatinine clearance ratios and serum amylase isoenzymes in moderate renal insufficiency. J Clin Gastroenterol. 1979 Dec;1(4):331-5. [PubMed: 95609]

46.

Terui K, Hishiki T, Saito T, Mitsunaga T, Nakata M, Yoshida H. Urinary amylase/urinary creatinine ratio (uAm/uCr)--a less-invasive parameter for management of hyperamylasemia. BMC Pediatr. 2013 Dec 13;13:205. [PMC free article: PMC3878803] [PubMed: 24330759]

47.

Hansen SEJ, Langsted A, Varbo A, Madsen CM, Tybjærg-Hansen A, Nordestgaard BG. Low and high pancreatic amylase is associated with pancreatic cancer and chronic pancreatitis. Eur J Epidemiol. 2021 Sep;36(9):975-984. [PubMed: 34482515]

48.

Boybeyi O, Ergür AT, Dursun ZE, Gülerman F. Amylase/creatinine clearance ratio in diabetic ketoacidosis: a case report. J Pediatr Endocrinol Metab. 2014 Nov;27(11-12):1243-5. [PubMed: 25153214]

49.

Treacy J, Williams A, Bais R, Willson K, Worthley C, Reece J, Bessell J, Thomas D. Evaluation of amylase and lipase in the diagnosis of acute pancreatitis. ANZ J Surg. 2001 Oct;71(10):577-82. [PubMed: 11552931]

50.

Smith RC, Southwell-Keely J, Chesher D. Should serum pancreatic lipase replace serum amylase as a biomarker of acute pancreatitis? ANZ J Surg. 2005 Jun;75(6):399-404. [PubMed: 15943725]

51.

Yang RW, Shao ZX, Chen YY, Yin Z, Wang WJ. Lipase and pancreatic amylase activities in diagnosis of acute pancreatitis in patients with hyperamylasemia. Hepatobiliary Pancreat Dis Int. 2005 Nov;4(4):600-3. [PubMed: 16286272]

52.

Ashraf H, Colombo JP, Marcucci V, Rhoton J, Olowoyo O. A Clinical Overview of Acute and Chronic Pancreatitis: The Medical and Surgical Management. Cureus. 2021 Nov;13(11):e19764. [PMC free article: PMC8684888] [PubMed: 34938639]

53.

Pham A, Forsmark C. Chronic pancreatitis: review and update of etiology, risk factors, and management. F1000Res. 2018;7 [PMC free article: PMC5958317] [PubMed: 29946424]

54.

Hiele M, Ghoos Y, Rutgeerts P, Vantrappen G. Effects of acarbose on starch hydrolysis. Study in healthy subjects, ileostomy patients, and in vitro. Dig Dis Sci. 1992 Jul;37(7):1057-64. [PubMed: 1618053]

55.

Garrison R. Amylase. Emerg Med Clin North Am. 1986 May;4(2):315-27. [PubMed: 2422011]

56.

Hiatt JR, Calabria RP, Passaro E, Wilson SE. The amylase profile: a discriminant in biliary and pancreatic disease. Am J Surg. 1987 Nov;154(5):490-2. [PubMed: 2445215]

57.

Jeong IH, Jung YS, Kim H, Kim BW, Kim JW, Hong J, Wang HJ, Kim MW, Yoo BM, Kim JH, Han JH, Kim WH. Amylase level in extrahepatic bile duct in adult patients with choledochal cyst plus anomalous pancreatico-biliary ductal union. World J Gastroenterol. 2005 Apr 07;11(13):1965-70. [PMC free article: PMC4305718] [PubMed: 15800987]

58.

Collen MJ, Ansher AF, Chapman AB, Mackow RC, Lewis JH. Serum amylase in patients with renal insufficiency and renal failure. Am J Gastroenterol. 1990 Oct;85(10):1377-80. [PubMed: 1699413]

59.

Mizuno S, Hanamura I, Ota A, Karnan S, Narita T, Ri M, Mizutani M, Goto M, Gotou M, Tsunekawa N, Shikami M, Iida S, Hosokawa Y, Miwa H, Ueda R, Nitta M, Takami A. Overexpression of salivary-type amylase reduces the sensitivity to bortezomib in multiple myeloma cells. Int J Hematol. 2015 Nov;102(5):569-78. [PubMed: 26341959]

60.

Shigemura M, Moriyama T, Shibuya H, Obara M, Endo T, Hashino S, Yokouchi H, Asaka M, Shimizu C, Chiba H, Nishimura M. Multiple myeloma associated with sialyl salivary-type amylase. Clin Chim Acta. 2007 Feb;376(1-2):121-5. [PubMed: 16979610]

61.

Ross CM, Devgun MS, Gunn IR. Hyperamylasaemia and multiple myeloma. Ann Clin Biochem. 2002 Nov;39(Pt 6):616-20. [PubMed: 12564849]

62.

Mitura K, Romanczuk M. Ruptured ectopic pregnancy mimicking acute pancreatitis. Ginekol Pol. 2009 May;80(5):383-5. [PubMed: 19548460]

63.

Ho ET, Gardner DS. Paraganglioma with acute hyperamylasaemia masquerading as acute pancreatitis. Singapore Med J. 2011 Dec;52(12):e251-4. [PubMed: 22159946]

64.

Wan S, Arifi AA, Chan CS, Ng CS, Wan IY, Lee TW, Yim AP. Is hyperamylasemia after cardiac surgery due to cardiopulmonary bypass? Asian Cardiovasc Thorac Ann. 2002 Jun;10(2):115-8. [PubMed: 12079932]

65.

Gullo L. Benign pancreatic hyperenzymemia. Dig Liver Dis. 2007 Jul;39(7):698-702. [PubMed: 17531557]

66.

Birtolo C, Migliori M, Drewes AM, Tomassetti P, Imbrogno A, Fusaroli P, Casadei R, Ricci C, Stanghellini V, De Giorgio R. Benign Pancreatic Hyperenzymemia: Lights on a Clinical Challenge. Pancreas. 2017 Jan;46(1):5-7. [PubMed: 27977626]

67.

Pezzilli R, Barassi A, Morselli-Labate AM, Fantini L, Tomassetti P, Campana D, Casadei R, Finazzi S, d'Eril GM, Corinaldesi R. Fecal calprotectin and elastase 1 determinations in patients with pancreatic diseases: a possible link between pancreatic insufficiency and intestinal inflammation. J Gastroenterol. 2007 Sep;42(9):754-60. [PubMed: 17876545]

68.

Bloch RS, Weaver DW, Bouwman DL, Berger G. Alcohol-induced salivary hyperamylasemia. J Surg Res. 1984 Apr;36(4):389-94. [PubMed: 6200693]

69.

Scheutzel P, Gerlach U. [Alpha-amylase isoenzymes in serum and saliva of patients with anorexia and bulimia nervosa]. Z Gastroenterol. 1991 Jul;29(7):339-45. [PubMed: 1950041]

70.

Monteleone P, Scognamiglio P, Monteleone AM, Mastromo D, Steardo L, Serino I, Maj M. Abnormal diurnal patterns of salivary α-amylase and cortisol secretion in acute patients with anorexia nervosa. World J Biol Psychiatry. 2011 Sep;12(6):455-61. [PubMed: 21745126]

71.

Yamamoto H, Kuroda R. [Amylase producing tumor]. Ryoikibetsu Shokogun Shirizu. 1994;(4):17-9. [PubMed: 7516440]

72.

Vuković A, Kuna K, Lončar Brzak B, Vučičević Boras V, Šeparović R, Šekerija M, Šumilin L, Vidranski V. THE ROLE OF SALIVARY AND SERUM CA125 AND ROUTINE BLOOD TESTS IN PATIENTS WITH OVARIAN MALIGNANCIES. Acta Clin Croat. 2021 Mar;60(1):55-62. [PMC free article: PMC8305365] [PubMed: 34588722]

73.

Otsuki M, Yuu H, Maeda M, Saeki S, Yamasaki T. Amylase in the lung. Cancer. 1977 Apr;39(4):1656-63. [PubMed: 856449]

74.

Zhang J, Zhang L, Pan S, Gu B, Zhen Y, Yan J, Zhou Y. Amylase: sensitive tumor marker for amylase-producing lung adenocarcinoma. J Thorac Dis. 2013 Aug;5(4):E167-9. [PMC free article: PMC3755679] [PubMed: 23991331]

75.

Guo S, Lv H, Yan L, Rong F. Hyperamylasemia may indicate the presence of ovarian carcinoma: A case report. Medicine (Baltimore). 2018 Dec;97(49):e13520. [PMC free article: PMC6310503] [PubMed: 30544453]

76.

Obiekwe BC, Chard T. What do placental function tests predict? Observations on placental lactogen levels in growth retardation and fetal distress. Eur J Obstet Gynecol Reprod Biol. 1982 Nov;14(2):69-73. [PubMed: 7173482]

77.

Serene TEL, G SV, Padmakumar JS, Terence HCW, Keem LJ, Bei W, Winston WWL. Predictive value of post-operative drain amylase levels for post-operative pancreatic fistula. Ann Hepatobiliary Pancreat Surg. 2018 Nov;22(4):397-404. [PMC free article: PMC6295369] [PubMed: 30588532]

78.

Kasapoğlu F, Ozmen OA, Coşkun H, Erişen L, Onart S. Evaluation of amylase levels in the neck drainage and serum for early diagnosis of the pharyngocutaneous fistula. Kulak Burun Bogaz Ihtis Derg. 2009 Mar-Apr;19(2):67-70. [PubMed: 19796002]

79.

Medeiros MM, Fernandes GH, Pinto NS, Silveira VA. Clinical and subclinical pancreatitis in a cohort of patients diagnosed with systemic lupus erythematosus. Clin Exp Rheumatol. 2011 Sep-Oct;29(5):776-82. [PubMed: 21962107]

80.

Kopáčová M, Bureš J, Rejchrt S, Vávrová J, Bártová J, Soukup T, Tomš J, Tachecí I. Risk Factors of Acute Pancreatitis in Oral Double Balloon Enteroscopy. Acta Medica (Hradec Kralove). 2016;59(3):84-90. [PubMed: 27638962]

81.

Herman R, Guire KE, Burd RS, Mooney DP, Ehlrich PF. Utility of amylase and lipase as predictors of grade of injury or outcomes in pediatric patients with pancreatic trauma. J Pediatr Surg. 2011 May;46(5):923-6. [PubMed: 21616253]

82.

Bayot ML, Lopes JE, Zubair M, Naidoo P. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jan 26, 2024. Clinical Laboratory. [PubMed: 30570979]

83.

Wadhwa V, Rai S, Thukral T, Chopra M. Laboratory quality management system: road to accreditation and beyond. Indian J Med Microbiol. 2012 Apr-Jun;30(2):131-40. [PubMed: 22664426]

84.

Kinns H, Pitkin S, Housley D, Freedman DB. Internal quality control: best practice. J Clin Pathol. 2013 Dec;66(12):1027-32. [PubMed: 24072731]

85.

Westgard JO. Internal quality control: planning and implementation strategies. Ann Clin Biochem. 2003 Nov;40(Pt 6):593-611. [PubMed: 14629798]

86.

Skitek M, Martinello F, Jerin A. How to Really Understand and Improve the System of Internal Quality Control and External Quality Assessment in the Accreditation Process of the Medical Laboratory? EJIFCC. 2022 Apr;33(1):23-27. [PMC free article: PMC9092718] [PubMed: 35645692]

87.

Mishra B, Das BKL, Khan SA, Gelal B, Niraula A, Chaudhari RK, Lamsal M. Knowledge of Internal Quality Control for Laboratory Tests among Laboratory Personnel Working in Department of Biochemistry in a Tertiary Care Center: A Descriptive Cross-sectional Study. JNMA J Nepal Med Assoc. 2023 Feb 01;61(258):167-170. [PMC free article: PMC10088986] [PubMed: 37203967]

88.

Nichols JH. Verification of method performance for clinical laboratories. Adv Clin Chem. 2009;47:121-37. [PubMed: 19634779]

89.

Kearney E. Internal quality control. Methods Mol Biol. 2013;1065:277-89. [PubMed: 23996371]

90.

Bayat H. Selecting multi-rule quality control procedures based on patient risk. Clin Chem Lab Med. 2017 Oct 26;55(11):1702-1708. [PubMed: 28236626]

91.

Miller WG, Jones GR, Horowitz GL, Weykamp C. Proficiency testing/external quality assessment: current challenges and future directions. Clin Chem. 2011 Dec;57(12):1670-80. [PubMed: 21965556]

92.

Shahangian S. Proficiency testing in laboratory medicine: uses and limitations. Arch Pathol Lab Med. 1998 Jan;122(1):15-30. [PubMed: 9448012]

93.

Laubender RP, Geistanger A. Selection of within-run quality control rules for laboratory biomarkers. Stat Med. 2021 Jul 20;40(16):3645-3666. [PubMed: 33876446]

94.

Kristensen GB, Meijer P. Interpretation of EQA results and EQA-based trouble shooting. Biochem Med (Zagreb). 2017 Feb 15;27(1):49-62. [PMC free article: PMC5382861] [PubMed: 28392726]

95.

Earley MC, Astles JR, Breckenridge K. Practices and Perceived Value of Proficiency Testing in Clinical Laboratories. J Appl Lab Med. 2017 Jan;1(4):415-420. [PMC free article: PMC6941662] [PubMed: 31903445]

96.

Wagar EA, Yuan S. The laboratory and patient safety. Clin Lab Med. 2007 Dec;27(4):909-30, viii-ix. [PubMed: 17950905]

97.

Ejilemele AA, Ojule AC. Health and safety in clinical laboratories in developing countries: safety considerations. Niger J Med. 2004 Apr-Jun;13(2):182-8. [PubMed: 15293842]

98.

Cornish NE, Anderson NL, Arambula DG, Arduino MJ, Bryan A, Burton NC, Chen B, Dickson BA, Giri JG, Griffith NK, Pentella MA, Salerno RM, Sandhu P, Snyder JW, Tormey CA, Wagar EA, Weirich EG, Campbell S. Clinical Laboratory Biosafety Gaps: Lessons Learned from Past Outbreaks Reveal a Path to a Safer Future. Clin Microbiol Rev. 2021 Jun 16;34(3):e0012618. [PMC free article: PMC8262806] [PubMed: 34105993]

99.

Adyanthaya S, Jose M. Quality and safety aspects in histopathology laboratory. J Oral Maxillofac Pathol. 2013 Sep;17(3):402-7. [PMC free article: PMC3927343] [PubMed: 24574660]

100.

Ionescu G, Neguţ M, Combiescu AA. [Biosafety and biosecurity in the medical laboratory. Update and trends]. Bacteriol Virusol Parazitol Epidemiol. 2007 Jul-Dec;52(3-4):91-9. [PubMed: 19326721]

101.

Logie JJ, Cox M, Sharkey J, Williams A. A multidisciplinary approach to an unusual cause of hyperamylasaemia. BMJ Case Rep. 2015 Jul 06;2015 [PMC free article: PMC4493173] [PubMed: 26150631]

102.

Beauregard JM, Lyon JA, Slovis C. Using the literature to evaluate diagnostic tests: amylase or lipase for diagnosing acute pancreatitis? J Med Libr Assoc. 2007 Apr;95(2):121-6. [PMC free article: PMC1852619] [PubMed: 17443244]

103.

White TE, Wong WB, Janowiak D, Hilborne LH. Strategies for laboratory professionals to drive laboratory stewardship. Pract Lab Med. 2021 Aug;26:e00249. [PMC free article: PMC8339222] [PubMed: 34381860]

104.

Ravi P, Pfaff K, Ralph J, Cruz E, Bellaire M, Fontanin G. Nurse-pharmacist collaborations for promoting medication safety among community-dwelling adults: A scoping review. Int J Nurs Stud Adv. 2022 Dec;4:100079. [PMC free article: PMC11080473] [PubMed: 38745597]

105.

Montori VM, Ruissen MM, Hargraves IG, Brito JP, Kunneman M. Shared decision-making as a method of care. BMJ Evid Based Med. 2023 Aug;28(4):213-217. [PMC free article: PMC10423463] [PubMed: 36460328]

Disclosure: Muhammad Zubair declares no relevant financial relationships with ineligible companies.

Disclosure: Thiruvengadam Muniraj declares no relevant financial relationships with ineligible companies.