Is measurement of amylase and lipase useful in patients with renal insufficiency suspected of pancreatitis?

Depends on how high the serum levels are! Although the clearance of both amylase and lipase appears to be impaired in patients with significant renal insufficiency (eg,  creatinine clearance <50ml/min), serum levels greater than 2-4 times the upper limits of normal for these enzymes are still considered suggestive of pancreatitis in these patients1-3.

Interestingly, in hemodialysis patients, elevation of lipase may also be due to the lipolytic effect of heparin during this procedure.  That’s why obtaining serum lipase levels before, not after,  hemodialysis has been recommended4

Also fascinating is that most of the elevation of serum amylase in patients with significant renal insufficiency appears to be related to the elevation of salivary, not pancreatic, isoenzyme of amylase4.

Final fun fact: Did you know that at one time the diagnosis of pancreatitis was based on the activity of serum on starch (for amylase) and olive oil (for lipase)? 5

References

  1. Levitt MD, Rapoport M, Cooperband SR. The renal clearance of amylase in renal insufficiency, acute pancreatitis, and macroamylasemia. Ann Intern Med 1969;71:920-25. http://annals.org/aim/article/683643/renal-clearance-amylase-renal-insufficiency-acute-pancreatitis-macroamylasemia
  2. Collen MJ, Ansher AF, Chapman AB, et al. Serum amylase in patients with renal insufficiency and renal failure. Am J Gastroenterol 1990;85:1377-80. https://www.ncbi.nlm.nih.gov/pubmed/1699413
  3. Royce VL, Jensen DM, Corwin HL. Pancreatic enzymes in chronic renal failure. Arch Intern Med 1987;147:537-39. https://www.ncbi.nlm.nih.gov/pubmed/2435254
  4. Vaziri ND, Change D, Malekpour A, et al. Pancreatic enzymes in patients with end-stage renal disease maintained on hemodialysis. Am J Gastroenterol 1988;83:410-12. https://www.ncbi.nlm.nih.gov/pubmed/2450453
  5. Editorial. Pancreatic enzymes. N Engl J Med 1963;268:901-2. http://www.nejm.org/doi/pdf/10.1056/NEJM196304182681613
Is measurement of amylase and lipase useful in patients with renal insufficiency suspected of pancreatitis?

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

 

There are many causes of low serum haptoglobin besides hemolysis, including1-4:

  • Cirrhosis of the liver
  • Disseminated ovarian carcinomatosis
  • Pulmonary sarcoidosis
  • Elevated estrogen states
  • Repetitive physical exercise
  • Hemodilution
  • Blood transfusions
  • Drugs (eg, oral contraceptives, chlorpromazine, indomethacin, isoniazid, nitrofurantoin, quinidine, and streptomycin)
  • Iron deficiency anemia
  • Megaloblastic anemia (by destruction of megaloblastic RBC precursors in the bone marrow)
  • Congenital causes

Less well-known is that congenital haptoglobin deficiency (“anhaptoglobinemia”) may not be so rare in the general population at a prevalence of 1% among whites and 4% among African-Americans (>30% in blacks of West African origin)3. Measurement of serum hemopexin, another plasma protein that binds heme, may help distinguish between this condition and acquired hypohaptoglobinemia— in the absence of hemolysis, hemopexin levels should remain unchanged3,5.

Final Fun Fact: Did you know that serum haptoglobin is often low during the first 6 months of life?

References

  1. Shih AWY, McFarane A, Verhovsek M. Haptoglobin testing in hemolysis: measurement and interpretation. Am J Hematol 2014;89: 443-47. https://www.ncbi.nlm.nih.gov/pubmed/24809098
  2. Sritharan V, Bharadwaj VP, Venkatesan K, et al. Dapsone induced hypohaptoglobinemia in lepromatous leprosy patients. Internat J Leprosy 1981;307-310. https://www.ncbi.nlm.nih.gov/pubmed/7198620
  3. Delanghe J, Langlois M, De Buyzere M, et al. Congenital anhaptoglobinemia versus acquired hypohaptoglobinemia. Blood 1998;9: 3524. http://www.bloodjournal.org/content/bloodjournal/91/9/3524.full.pdf
  4. Haptoglobin blood test. https://medlineplus.gov/ency/article/003634.htm. Accessed August 6, 2017.
  5. Smith A, McCulloh RJ. Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front. Physiol 2015;6:187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485156/pdf/fphys-06-00187.pdf

 

In collaboration with Kris Olson, MD, MPH, Mass General Hospital, Boston, MA

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

Does oral iron cause false-positive stool guaiac test?

The general agreement in the literature is that oral iron supplementation does not cause a false-positive guaiac-based fecal occult blood test (GFOBT).

GFOBT is based on rapid oxidization of α-guaiaconic acid to “guaiacum blue”, with hemoglobin serving as a catalyst through a non-enzymatic or “pseudoperoxidase” action. Although in vitro Fe3+ may serve as an oxidizing agent, this reaction is possible only under acidic conditions not found in the stool (pH ≥ 6-7)1.  Also, in the absence of a catalyst, Fe3+ alone would not be expected to cause rapid (within 30 seconds) conversion of α-guaiaconic acid to guaiacum blue1

Although a number of earlier clinical studies reported false-positive GBFOBT because of oral iron supplementation, subsequent investigations have uniformly failed to confirm these findings2. Potential reasons for earlier false-positive GBFOBT results include false interpretation of the color change—eg, green instead of blue— particularly when the discoloration is weakly positive, and non-standardized method of stool collection with the possibility of stool sample contamination by toilet water.

Other fascinating facts: Did you know that guaiac plant extract was used for centuries for treatment of syphilis and that the earliest application of guaiac testing was in forensic medicine in 1800s?

References

  1. McDonnell WM, Ryan JA, Seeger DM, Elta GH. Effect of iron on the guaiac reaction. Gastroenterology. 1989 Jan;96(1):74-8. https://www.ncbi.nlm.nih.gov/pubmed/2909440
  2. Anderson GD, Yellig TR, Krone RE. An investigation into the effects of oral iron supplementation on in vivo hemoccult stool testing. Am J Gastroenterol 1990;85:558-561. https://www.ncbi.nlm.nih.gov/pubmed/218661

Contributed by Brian Li, Medical Student, Harvard Medical School

Does oral iron cause false-positive stool guaiac test?

Should male patients with suspected urinary tract infection routinely undergo a prostate exam?

Yes! That’s because any urinary tract infection (UTI) in men has the potential for prostatic involvement1 —-as high as 83% by one report2.  

To make the matters more confusing, patients with acute bacterial prostatitis (ABP) often present with symptoms just like those of UTI such as urinary frequency, dysuria, malaise, fever, and myalgias3.  In the elderly, atypical presentation is not uncommon (eg, confusion, incontinence, fall)4.  Under these circumstances, bacteriuria and pyuria may also be related to ABP and the prostate exam should be an important part of your evaluation.

Although the sensitivity of prostate tenderness on digital rectal exam varies widely for ABP (9%-100%), a painful exam should raise suspicion for ABP, and by itself may be an independent predictor for clinical and bacteriologic failure of therapy1. Along with tenderness, fluctuance of prostate, particularly in the setting of voiding difficulties and longer duration of symptoms, may also suggest the presence of prostatic abscess5,6

But be gentle when performing a prostate exam and don’t massage it because you could potentially cause bacteremia and worsening of sepsis!1,7

References

  1. Etienne M, Chavanet P, Sibert L, et al. Acute bacterial prostatitis: heterogeneity in diagnostic criteria and management. Retrospective multicentric analysis of 371 patients diagnosed with acute prostatitis. BMC Infectious Diseases 2008;8:12. https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/1471-2334-8-12?site=bmcinfectdis.biomedcentral.com
  2. Ulleryd P, Zackrisson B, Aus G, et al. Prostatic involvement in men with febrile urinary tract infection as measured by serum prostate-specific antigen and transrectal ultrasonography. BJU Int 1999;84:470-4. http://onlinelibrary.wiley.com/doi/10.1046/j.1464-410x.1999.00164.x/pdf
  3. Krieger JN, Nyberg L, Nickel JC. NIH consensus definition and classification. JAMA 1999;282:236-37. http://jamanetwork.com/journals/jama/article-abstract/1030245
  4. Harper M, Fowlis. Management of urinary tract infections in men. Trends in Urology Gynaecology & Sexual Health. January/February 2007. http://onlinelibrary.wiley.com/doi/10.1002/tre.8/pdf
  5. Lee DS, Choe HS, Kim HY, et al. Acute bacterial prostatitis and abscess formation. BMC Urology 2016;16:38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936164/
  6. Oliveira P, Andrade JA, Porto HC, et al. Diagnosis and treatment of prostatic abscess. International Braz J Urol 2003;29: 30-34. http://www.scielo.br/pdf/ibju/v29n1/v29n1a06.pdf
  7. Lipsky BA, Byren I, Hoey CT. Treatment of bacterial prostatitis. Clin Infect Dis 2010; 50:1641-52. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/50/12/10.1086/652861/2/50-12-1641.pdf?Expires=1501276981&Signature=X5SLG2Pq5IpbsjDigES70~Nk6g5onrPwhrFClIAFIvdFiEyCsc1~2aWN9LpR~56DlGqxjmZuIX33JtOn-tURGG0puEwnulZDEDXFjFt6fXucSgtKMDOmGXSKoMvgtPZe86nduJMNDuaifEZXITpDXjSLXAJXVamJ-bbSUMEqSysnCCMxZx~5MaAb6WEikqG5Vi~Xnp58fXABG7BJS~ZFRn2~BTlVEEvmIIDDaY5cJjgUcN7SNOhs0rOS71WzlNtlXSqnXffZEdFSJ~iDcbyRL-wh-9OZqZ2fwojdk8Be89DsKJg8rIh8dlLc5O7v92yL~cZ6iieiP8xTGOU-21tVeA__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q
Should male patients with suspected urinary tract infection routinely undergo a prostate exam?

Should I order serum procalcitonin on my patient with suspected infection?

 

Two things to ask before you order procalcitonin (PCT): 1. Will it impact patient management?; and 2. If so, will the result be available in a timely manner ie, within hours not days?

Whatever the result, PCT should always be interpreted in the context of the patient’s illness and other objective data. Not surprisingly then, as a “screening” test, PCT may be more useful in patients with low pre-test likelihood of having bacterial infection, not dissimilar to the use of D-dimer in patients with low pre-test probability of pulmonary embolism1.  

Several potential clinical uses of this biomarker have emerged in recent years,  including:1,2

  1. Helping decide when to initiate antibiotics in patients with upper acute respiratory tract infections and bronchitis. A normal or low PCT supports viral infection.
  2. Helping decide when to discontinue antibiotics (ie, when PCT normalizes) in community-acquired or ventilator-associated pneumonia.
  3. Helping monitor patient progress with an expected drop in PCT of about 50% per day (half-life ~ 24 hrs) with effective therapy.

Few caveats…

PCT may be unremarkable in about a third of patients with bacteremia (particularly caused by less virulent bacteria, including many gram-positives)3.  

PCT levels are lowered by high-flux membrane hemodialysis, so check a baseline level before, not after, hemodialysis4.

Lastly, despite its higher specificity for bacterial infections compared to other biomarkers such as C-reactive protein, PCT may be elevated in a variety of non-infectious conditions, including pancreatitis, burns, pulmonary edema or aspiration, mesenteric infarction (ischemic bowel), cardiogenic shock, and hypotension during surgery2.

 

References:

  1. Schuetz P, Muller B, Chirst-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections (review). Evid-Based Child Health (A Cochrane Review Journal) 2013;8:4;1297-137. http://onlinelibrary.wiley.com/doi/10.1002/ebch.1927/pdf
  2. Gilbert GN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol 2010;48:2325-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897488/pdf/0655-10.pdf
  3. Yan ST, Sun LC, Jia HB. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med 2017;35:779-83. https://www.ncbi.nlm.nih.gov/m/pubmed/27979420/#fft
  4. Grace E, Turner RM. Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy. Clin Infect Dis 2014;59:1761-7. https://www.ncbi.nlm.nih.gov/pubmed/25228701
Should I order serum procalcitonin on my patient with suspected infection?

My patient with cirrhosis and suspected infection has a normal serum C-reactive protein (CRP). Does cirrhosis affect CRP response to infection?

 

CRP is primarily synthesized by the liver mainly as a response to IL-6 production in inflammatory states1.  Lower CRP production may then be expected in cirrhotic patients with significant infections and several studies support this view2

In a particularly convincing study involving E. coli-infected patients with bacteremia, the median CRP level in cirrhotic patients was about 40% that of non-cirrhotic patients (62 mg/L vs 146 mg/L)3.  In another study involving bacteremic patients with or without liver dysfunction, median CRP level was about 60% that of  patients with preserved liver function (81 mg/L vs 139 mg/L)4.  Some investigators have reported a cut-off CRP value of 9.2 mg/L as a possible screening test for bacterial infections in patients with cirrhosis with a sensitivity and specificity of 88% (AUROC 0.93)5.

Collectively, these data suggest that although CRP response may be diminished in patients with advanced liver disease and acute infection, its synthesis is still maintained.

References

  1. Pieri G, Agarwal B, Burroughs AK. C-reactive protein and bacterial infection in cirrhosis. Ann Gastroenterol 2014;27:113-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982625/pdf/AnnGastroenterol-27-113.pdf
  2. Ha YE, Kang C-I, Joo E-J, et al. Usefulness of C-reactive protein for evaluating clinical outcomes in cirrhotic patients with bacteremia. Korean J Intern Med 2011;26:195-200. http://pubmedcentralcanada.ca/pmcc/articles/PMC3110852/pdf/kjim-26-195.pdf
  3. Park WB1, Lee KD, Lee CS et al. Production of C-reactive protein in Escherichia coli-infected patients with liver dysfunction due to liver cirrhosis. Diagn Microbiol Infect Dis. 2005 Apr;51(4):227-30. https://www.ncbi.nlm.nih.gov/pubmed/15808312
  4. Mackenzie I, Woodhouse J. C-reactive protein concentrations during bacteraemia: a comparison between patients with and without liver dysfunction. Intensive Care Med 2006;32:1344-51. https://www.ncbi.nlm.nih.gov/pubmed/16799774
  5. Papp M, Vitalis Z, Altorjay I, et al. Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infection. Liver Int 2011;603-11. https://www.ncbi.nlm.nih.gov/pubmed/22145664

 

My patient with cirrhosis and suspected infection has a normal serum C-reactive protein (CRP). Does cirrhosis affect CRP response to infection?

How should I interpret a positive urine pneumococcal antigen when my suspicion for pneumococcal disease is very low?

The popular urine pneumococcal antigen (UPA) (based on the C-polysaccharide of Streptococcus pneumoniae cell wall) has been a valuable diagnostic tool in diagnosing invasive pneumococcal infections, but may be associated with up to nearly 10% rate of false-positivity in hospitalized patients1.  Three factors have often been cited as the  cause of false-positive UPA results: a. Nasopharyngeal carriage; b.Prior invasive pneumococcal infection and;  c. Pneumococcal vaccination.

Among adults with nasopharyngeal carriage of S. pneumoniae, particularly those with HIV infection, 12-17% of positive UPA tests may be false-positive1. In patients with recent invasive pneumococcal disease, UAP may remain positive in over 50% of patient at 1 month and about 5% at 6 months1,2.

Among persons receiving the 23-valent polysaccharide pneumococcal vaccine (PPV), over 20% may have a positive UPA up to 30 hours following immunization, some potentially longer1.  In fact, the manufacturer of UPA assay recommends that UPA not be obtained within 5 days of receiving PPV. There is reason to believe that conjugated pneumococcal vaccine may be associated with the same phenomenon3.

So in a hospitalized patient with low suspicion for pneumococcal disease but a positive UAP, it would be wise to first exclude the possibility of PPV administration earlier during hospitalization before the sample was obtained1,4.

 

References

  1. Ryscavage PA, Noskin GA, Bobb A, et al. Incidence and impact of false-positive urine pneumococcal antigen testing in hospitalized patients. S Med J 2011;104:293-97.
  2. Andre F, Prat C, Ruiz-Manzano J, et al. Persistence of Streptococcus pneumoniae urinary antigen excretion after pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis 2009;28:197-201.
  3. Navarro D, Garcia-Maset Leonor, Gimeno C, et al. Performance of the Binax NOW Streptococcus pneumoniae urinary assay for diagnosis of pneumonia in children with underlying pulmonary diseases in the absence of acute pneumococcal infection. J Clin Microbiol 2004; 42: 4853-55.
  4. Song JY, Eun BW, Nahm MH. Diagnosis of pneumococcal pneumonia: current pitfalls and the way forward. Infect Chemother 2013;45:351-66.

 

How should I interpret a positive urine pneumococcal antigen when my suspicion for pneumococcal disease is very low?