Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

Short answer: No! This is because most studies have shown frequently high ESR’s in stable “uninflamed” patients with chronic renal failure (CRF) (including those on dialysis) at levels often associated with infection, connective tissue disease, or malignancy in normal renal function. 1-4  

In fact, in a study involving patients with CRF, 57% of patients had markedly elevation of ESR (greater than 60 mm/h), with 20% having ESR greater than 100 mm/h; type or duration of dialysis had no significant effect on ESR levels.1 Another study reported a specificity for abnormal ESR of only 35% for commonly considered inflammatory conditions (eg, infections or malignancy) among patients with CRF. 2

But is it the chronic inflammation in diseased kidneys or the uremic environment that elevates ESR? A cool study compared ESR in CRF in patients who had undergone bilateral nephrectomies with those with retained kidneys and found no significant difference in the ESR between the 2 groups. 4  So it looks like it’s the uremic environment, not diseased kidneys themselves that result in elevated ESR in these patients.

The mechanism behind these observations seem to reside entirely within the patients’ plasma, not the erythrocytes. Within the plasma, fibrinogen (not gammaglobulins) seem to be the most likely factor explaining elevated ESR among patients with CRF. 1,2

Bonus pearl:  Did you know that ESR is nearly 100 years old, first described in 1921? 5

References

  1. Barthon J, Graves J, Jens P, et al. The erythrocyte sedimentation rate in end-stage renal failure. Am J Kidney Dis 1987;10: 34-40. https://www.ncbi.nlm.nih.gov/pubmed/3605082
  2. Shusterman N, Morrison G, Singer I. The erythrocyte sedimentation rate and chronic renal failure. Ann Intern Med 1986;105:801. http://annals.org/aim/fullarticle/700910
  3. Arik N, Bedir A, Gunaydin M, et al. Do erythrocyte sedimentation rate and C-reactive protein levels have diagnostic usefulness in patients with renal failure? Nephron 2000;86:224. https://www.ncbi.nlm.nih.gov/pubmed/11015011
  4. Warner DM, George CRP. Erythrocyte sedimentation rate and related factors in end-stage renal failure. Nephron 1991;57:248. https://www.karger.com/Article/PDF/186266
  5. Fahraeus R. The suspension stability of the blood. Acta Med Scan 1921;55:70-92. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0954-6820.1921.tb15200.x

 

If you liked this pearl, sign up under menu and receive future pearls straight into your mailbox! Thank you!

Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

How is prealbumin related to albumin?

Aside from being synthesized in the liver and serving as a transport protein in the blood, prealbumin (PA) doesn’t really have much in common with albumin. More specifically, PA is not derived from albumin and, in fact, the two proteins are structurally distinct from each other!

So where does PA get its name? PA is the original name for transthyretin (TTR), a transport protein that primarily carries thyroxine (T4) and a protein bound to retinol (vitamin A). The name arose because TTR migrated faster than albumin on gel electrophoresis of human serum.1

Because of its much shorter serum half-life compared to that of albumin ( ~2 days vs ~20 days),2 PA is more sensitive to recent changes in protein synthesis and more accurately reflects recent dietary intake (not necessarily overall nutritional status) than albumin. 3

But, just like albumin, PA may represent a negative acute phase reactant, as its synthesis drops during inflammatory states in favor of acute phase reactants such as C-reactive protein. 4 So be cautious about interpreting low PA levels in patients with active infection, inflammation or trauma.

 

Reference

  1. Socolow EL, Woeber KA, Purdy RH, et al. Preparation of I-131-labeled human serum prealbumin and its metabolism in normal and sick patients. J. Clin Invest 1965; 44: 1600-1609. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC292644/
  2. Oppenheimer JH, Surks MI, Bernstein G, and Smith JC. Metabolism of Iodine-131-labeled Thyroxine-Binding Prealbumin in Man. Science 1965; 149: 748-750. https://www.ncbi.nlm.nih.gov/pubmed/14330531
  3. Ingenbleek Y, Young VR. Significance of prealbumin in protein metabolism. Clin Chem Lab Med 2002; 40: 1281-1291. https://www.ncbi.nlm.nih.gov/pubmed/12553432
  4. Shenkin A. Serum prealbumin: is it a marker of nutritional status or of risk of malnutrition? Clin Chem 2006;52:2177 – 2179. http://clinchem.aaccjnls.org/content/52/12/2177

 

Contributed by Colin Fadzen, Medical Student, Harvard Medical School, Boston, MA.

 

If you liked this post, sign up under Menu and received future pearls right into your mailbox!

How is prealbumin related to albumin?

Should I routinely screen my patients with heart failure for iron deficiency?

Even in the absence of anemia, screening for iron deficiency (ID) has been recommended in patients with heart failure (HF) with reduced ejection fraction (HFrEF) by some European and Australia-New Zealand cardiology societies. 1

In contrast, the 2017 American College of Cardiology/American Heart Association/Heart Failure Society of America guidelines do not mention routine screening for ID in such patients but instead state (under “Anemia”) that in patients with NYHA class II and III HF and ID (ferritin < 100 ng/mL or 100 to 300 ng/mL plus transferrin saturation <20%), IV iron replacement “might be reasonable” to improve functional status and quality of life (IIb-weak recommendation).2

As these guidelines are primarily based on data derived from patients with HFrEF, whether patients with HF with preserved (eg, >45%) ejection fraction (HFpEF) should undergo routine screening for ID is even less clear due to conflicting data based on limited small studies 3,4

What is known is that up to 50% or more of patients with HF with or without anemia may have ID. 5 Although most studies involving ID and HF have involved patients with HFrEF, similarly high prevalence of ID in HFpEF has been reported. 6,7

A 2016 meta-analysis involving patients with HFrEF and ID found that IV iron therapy alleviates HF symptoms and improves outcomes, exercise capacity and quality of life irrespective of concomitant anemia; all-cause and cardiovascular mortality rates were not significantly impacted, however.8  

Fortunately, larger trials in the setting of acute and chronic systolic HF are underway (Affirm-AHF, 9 IRONMAN 10).  Stay tuned!

Bonus Pearl: Did you know that iron deficiency directly affects human cardiomyocyte function by impairing mitochondrial respiration  and reducing its contractility and relaxation?11

References

  1. Silverberg DS, Wexler D, Schwartz D. Is correction of iron deficiency a new addition to the treatment of the heart failure? Int J Mol Sci 2015;16:14056-74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490538/
  2. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure. Circulation 2017;136:e137-e161. https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000509
  3. Kasner M, Aleksandrov AS, Westermann D, et al. Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. International J of Cardiol 2013;168:12:4652-57. https://www.ncbi.nlm.nih.gov/pubmed/23968714
  4. Enjuanes C, Klip IT, Bruguera J, et al. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol 2014;174:268-275. https://www.ncbi.nlm.nih.gov/pubmed/24768464
  5. Drodz M, Jankowska EA, Banasiak W, et al. Iron therapy in patients with heart failure and iron deficiency: review of iron preparations for practitioners. Am J Cardiovasc Drugs 2017;17:183-201. https://www.ncbi.nlm.nih.gov/pubmed/28039585
  6. Bekfani T, Pellicori P, Morris D, et al. Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life. Clin Res Cardiol 2018, July 26. Doi: 10. 1007/s00392-018-1344-x. https://www.ncbi.nlm.nih.gov/pubmed/30051186
  7. Nunez J, Dominguez E, Ramon JM, et al. Iron deficiency and functional capacity in patients with advanced heart failure with preserved ejection fraction. International J Cardiol 2016;207:365-67. https://www.internationaljournalofcardiology.com/article/S0167-5273(16)30185-1/abstract
  8. Jankowska EA, Tkaczynszyn M, Suchocki T, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Failure 2016;18:786-95. https://www.ncbi.nlm.nih.gov/pubmed/26821594
  9. https://clinicaltrials.gov/ct2/show/NCT02937454
  10. https://clinicaltrials.gov/ct2/show/NCT02642562
  11. Hoes MF, Beverborg NG, Kijlstra JD, et al. Iron deficiency impairs contractility of human cardiomyoctyes through decreased mitochondrial function. Eur J Heart Failure 2018;20:910-19. https://www.ncbi.nlm.nih.gov/pubmed/29484788  

 

If you liked this post, sign up under Menu and receive future pearls right into your mailbox!

Should I routinely screen my patients with heart failure for iron deficiency?

Why is my hospitalized patient with alcohol withdrawal syndrome so thrombocytopenic?

Although thrombocytopenia associated with chronic alcoholism may be related to complications of cirrhosis (eg, platelet sequestration in spleen due to portal hypertension, poor platelet production, and increased platelet destruction) (1), it may also occur in the absence of cirrhosis due to the direct toxic effect of alcohol on platelet production and survival (2).

 
In a prospective study of patients ingesting the equivalent of a fifth or more daily of 86 proof whiskey admitted for treatment of alcohol withdrawal—without evidence of severe liver disease, infection or sepsis— 81% had initial platelet counts below 150,000/µl, with about one-third having platelet counts below 100,000 µl (as low as 24,000/ul) (3).

 
In most patients, 2-3 days elapsed before the platelet count began to rise significantly, peaking 5-18 days after admission. Others have also reported that platelet counts rise within 5-7 days and normalize in a few weeks after alcohol withdrawal (1); bleeding complications have been uncommon in this setting.

 
Perhaps even more intriguing is the report of the association between thrombocytopenia in early alcohol withdrawal and the development of delirium tremens or seizures (sensitivity and specificity ~ 70%, positive predictive value less than 10% but with a negative predictive value of 99%) (4)! In fact, the authors suggested that, if their findings are corroborated, a normal platelet count could potentially be used to identify patients at low risk of alcohol withdrawal syndrome and therefore outpatient therapy. 

References
1. Mitchell O, Feldman D, Diakow M, et al. The pathophysiology of thrombocytopenia in chronic liver disease. Hepatic Medicine: Evidence and Research 2016;8 39-50. https://www.dovepress.com/the-pathophysiology-of-thrombocytopenia-in-chronic-liver-disease-peer-reviewed-article-HMER
2. Cowan DH. Effect of alcoholism on hemostasis. Semin Hematol 1980;17:137-47. https://www.ncbi.nlm.nih.gov/pubmed/6990498
3. Cowan DH, Hines JD. Thrombocytopenia of severe alcoholism. Ann Intern Med 1971;74:37-43. http://annals.org/aim/article-abstract/685069/thrombocytopenia-severe-alcoholism.

4. Berggren U, Falke C, Berglund KJ, et al. Thrombocytopenia in early alcohol withdrawal is associated with development of delirium tremens or seizures. Alcohol & Alcoholism 2009;44:382-86. https://www.ncbi.nlm.nih.gov/pubmed/19293148

If you like this pearl, sign up under menu and receive future pearls right into your mailbox!

Why is my hospitalized patient with alcohol withdrawal syndrome so thrombocytopenic?

Is it possible to have acute pancreatitis with normal serum lipase?

Yes! Although an elevated serum lipase has a negative predictive value of 94%-100% for acute pancreatitis (1), there are ample reports in the literature of patients with CT findings of pancreatitis in the presence of abdominal symptoms but with normal serum lipase and/or amylase (2,3).

A case series and review of literature of acute pancreatitis with normal lipase and amylase failed to reveal any specific risk factors for such observation (2). More specifically, the etiologies of acute pancreatitis in the reported cases have varied, including drug-induced, cholelithiasis, alcohol, hypertriglyceridemia, and postoperative causes.

But what accounts for this phenomenon? Many cases have been associated with the first bout of pancreatitis without evidence of pancreatic calcifications which makes the possibility of a “burned-out” pancreas without sufficient acinar cells to release lipase as a frequent cause unlikely. Other potential explanations for normal lipase in acute pancreatitis have included measurement of serum lipase at a very early phase of the disease before significant destruction of acinar cells has occurred (increases in 3-6 h, peaks at 24 h [4]) and more rapid renal clearance of serum lipase due to tubular dysfunction (2).

Of note, unlike amylase, lipase is totally reabsorbed by renal tubules under normal conditions (5). Thus, it’s conceivable that even a reversible tubular dysfunction may lead to increased clearance of serum lipase and potentially lower its levels.
References
1. Ko K, Tello LC, Salt J. Acute pancreatitis with normal amylase and lipase. The Medicine Forum. 2011;11 Article 4. https://jdc.jefferson.edu/tmf/vol11/iss1/4/
2. Singh A, Shrestha M. Acute pancreatitis with normal amylase and lipase-an ED dilemma. Am J Emerg Med 2016;940.e5-940.e7. https://www.ncbi.nlm.nih.gov/pubmed/26521195
3. Limon O, Sahin E, Kantar FU, et al. A rare entity in ED: normal lipase level in acute pancreatitis. Turk J Emerg Med 2016;16:32-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882216/
4. Shah AM, Eddi R, Kothari ST, et al. Acute pancreatitis with normal serum lipase: a case series. J Pancreas (Online) 2010 July 5;11:369-72. PDF
5. Lott JA, Lu CJ. Lipase isoforms and amylase isoenzymes: assays and application in the diagnosis of acute pancreatitis. Clin Chem 1991;37:361-68. https://www.ncbi.nlm.nih.gov/pubmed/1706232
If you liked this post, sign up under menu to receive future P4P pearls right into your mailbox!

Is it possible to have acute pancreatitis with normal serum lipase?

Can I rule out primary adrenal insufficiency by obtaining a single morning serum cortisol level in my hospitalized patient with unexplained hyponatremia?

Primary adrenal insufficiency (PAI) can be confidently ruled out when the morning (eg, 6 AM) serum cortisol level is greater than 17 ug/dl. Lower cut-off values are associated with lower probability of excluding PAI: > 10 ug/dl, 62%-67% and ≥5 ug/dl, 36%. 1,2 Conversely, PAI is highly likely when the morning serum cortisol level is less than 3 ug/dl. 3

Since many patients may have serum cortisol levels between 3 ug/dl and 17 ug/dl (ie, in the “indeterminate” range), confirmatory testing commonly performed through cosyntropin stimulation test (CST) is often necessary.

Although the standard CST involves measuring serum cortisol levels at baseline, 30 min, and 60 min with peak cortisol level <18 ug/dl indicative of PAI, several studies have reported that a single post-CST cortisol level obtained at 60 min may also be diagnostic. 3

 

References

  1. Erturk E, Jaffe CA, Barkan AL. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J Clin Endocrinol Metab 83;2350-54. https://www.ncbi.nlm.nih.gov/pubmed/9661607
  2. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016;101:364-89. https://academic.oup.com/jcem/article/101/2/364/2810222
  3. Odom DC, Gronowski AM, Odom E, et al. A single, post-ACTH cortisol measurement to screen for adrenal insufficiency in the hospitalized patient. J Hosp Med 2018;13: E1-E5. https://www.ncbi.nlm.nih.gov/pubmed/29444197
Can I rule out primary adrenal insufficiency by obtaining a single morning serum cortisol level in my hospitalized patient with unexplained hyponatremia?

Should I order a blood transfusion based on the hemoglobin (Hgb) or the hematocrit (Hct)?

Despite the frequent interchangeability of Hgb (g/dL) and Hct (%) by a ratio of ~1:3, directly-measured blood Hgb levels may be preferred for assessing the need for blood transfusion for at least 3 reasons:

First, in contrast to the widely-used automated measurements of Hct, Hgb is not affected by conditions that affect the size of the RBCs or the mean corpuscular Hgb concentration (MCHC). This is because the Hct is not a direct measure of Hgb; rather it’s the proportion of blood occupied by RBCs which, in automated systems, is derived by multiplying the number of RBCs by the mean corpuscular volume (MCV).1-3

This may not be a significant issue when MCHC is normal, but when MCHC is abnormal, HCT may not accurately reflect the blood Hgb concentration. For example, in patients with hypochromic iron deficiency anemia with RBCs containing less hemoglobin (ie, low MCHC), the Hct may overestimate blood Hgb levels. Conversely in hereditary spherocytosis with its attendant low RBC volume and high MCHC, the Hct may underestimate Hgb levels.

Second, Hct results may also be more subject to technical factors in the lab. For example, blood at room temperature between 6-24 h may be associated with RBC swelling and increased Hct without any change in its Hgb concentration.4

Finally, national and international guidelines on blood transfusion generally target Hgb, not Hct results.5-7

For a related pearl, go to https://pearls4peers.com/2016/11/01/should-i-use-a-hemoglobin-level-of-7-or-8-gdl-as-a-threshold-for-blood-transfusion-in-my-hospitalized-patient.

 

References

  1. Tefferi A, Hanson CA, Inwards DJ. How to interpret and pursue an abnormal complete blood cell count in adults. Mayo Clin Proc 2005;80:923-36. https://www.ncbi.nlm.nih.gov/pubmed/16007898
  2. Macdougall IC, Ritz E. The Normal Haematocrit Trial in dialysis patients with cardiac disease: are we any the less confused about target hemoglobin? Nephrol Dial Transplant 1998;13:3030-33. https://academic.oup.com/ndt/article-pdf/13/12/3030/9907456/3030.pdf
  3. Kelleher BP, Wall C, O’Broin SD. Haemoglobin, not haematocrit, should be the preferred parameter. Nephrol Dial Transplant 2001;16:1085-87. https://www.ncbi.nlm.nih.gov/pubmed/11328933
  4. Hayuanta HH. Can hemoglobin-hematocrit relationship be used to assess hydration status? CDK-237/vol 43 no.2, th. 2016 http://www.kalbemed.com/Portals/6/20_237Opini-Can%20Hemoglobin-Hematocrit%20Relationship%20Be%20Used%20to%20Assess%20Hydration%20Status.pdf
  5. Blood transfusion. NICE guideline, November, 2015. https://www.nice.org.uk/guidance/ng24/chapter/Recommendations#fresh-frozen-plasma-2 uk
  6. National Blood Authority: Australia. Patient blood management, November 2016. https://www.blood.gov.au/system/files/documents/nba-patient-blood-management-resource-guide-nov_2016_v3_sm_web_file.pdf
  7. Carson JL, Guyatt G, Heddle NM, et al. Clinical practice guidelines from the AAABB: red blood cell transfusion thresholds and storage. JAMA 2016; 316:2025-2035. https://www.ncbi.nlm.nih.gov/pubmed/27732721

 

If you like this pearl, don’t forget to sign up for future pearls delivered directly to your mailbox from “Oceans of Knowledge”!

Should I order a blood transfusion based on the hemoglobin (Hgb) or the hematocrit (Hct)?