5 Covid-19 facts worth keeping in mind as we deal with our pandemic anxiety

As an infectious disease physician who had the privilege of caring for many patients during the unsettling times of the early HIV epidemic and the more recent H1N1 pandemic influenza, I fully understand the widespread anxiety the current Covid-19 pandemic has inflicted on our society.

Here are 5 scientific facts that may be worth remembering as we try to deal with our pandemic anxiety.

 
1. On transmission in the community: For sure, Covid-19 is transmitted in the community but I am glad that it behaves more like influenza which is primarily contracted through close personal contact and droplets, and less like measles or chickenpox which are considered airborne with viral particles travelling lingering in the air for long periods of time. On average, a patient with Covid-19 may infect 2-3 susceptible contacts vs as many as 12 or more in the case of patients with measles or chickenpox (1, 2).

 
2. On transmission in healthcare settings: For sure, Covid-19 can be transmitted in the healthcare settings, just like other coronaviruses, such severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) coronaviruses. But the good news is that, in the absence of aerosol-producing procedures (eg, intubation, nebulizer therapy) it doesn’t seem to behave like an airborne virus (see above) and adherence to droplet and contact precautions, including donning of masks, gowns, eye protection and hand hygiene has been effective (3, 4).

 
3. On surface viability after cleaning/disinfection: For sure, the novel 2019 coronavirus SARS-CoV-2, the cause of Covid-19, can be found on surfaces outside of the body. But the good news is that, in contrast to hardy viruses such as norovirus, it succumbs to common disinfection and environmental cleaning procedures. That’s because  coronaviruses have a lipid envelope that easily falls apart under usual cleaning and disinfection of surfaces. That means that simple handwashing with soap and water (minimum 20 seconds), alcohol containing hand hygiene products, detergents and diluted bleach should easily inactivate it (5-9) and that’s good!

 
4. On the course of Covid-19: For sure, Covid-19 can make people very sick and, tragically, may be fatal on occasion. But compared to diseases caused by other recent respiratory coronaviruses such as MERS or SARS, the overall mortality associated with Covid-19 is much lower (often ~ 2.0-3.0% or lower vs 36.0% for MERS and ~10.0% for SARS) (1). In fact, the majority of patients (~80%) may have no symptoms or only have mild disease (10). I am thankful that we are not dealing with a transmissible respiratory virus that has mortality rates like that of MERS.

 
5. On the timing of this pandemic: We are fortunate that this is 2020 not 1918-19 when a particularly virulent form of influenza, dubbed as “the mother of all pandemics” infected some 500 million people (a third of the world’s population at the time) and accounted for an estimated 50 million deaths (11). Imagine fighting a pandemic without the technology to identify its cause. Imagine fighting a pandemic without access to the miracles of modern science and medicine, including antibiotics for secondary bacterial pneumonia, artificial ventilation, dialysis, ICU support, and capability to screen for an infectious agent.  Imagine fighting a pandemic without scientific tools to develop effective antimicrobials or vaccines. Imagine fighting a pandemic without the luxury of the internet.

 
As unprepared as we all feel in combatting Covid-19, I take solace in the fact that our armamentarium and collective determination to mount an effective response to this pandemic has never been better. Even during these uncertain times, I reflect on what could have been and remain optimistic. Be safe!

 

 

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References:
1. Fauci AS, Lane HC, Redfield RR. Covid-19—Navigating the uncharted. N Eng J Med 2020. DOI:10.1056/NEJMe2002387. https://www.nejm.org/doi/full/10.1056/NEJMe2002387
2. Delamater PL, Street EJ, Leslie TF, et al. Complexity of the basic reproduction number (R0). Emerg infect Dis 2019;25:1-4. https://wwwnc.cdc.gov/eid/article/25/1/17-1901_article
3. Seto WH, Tsang D, Yung RWH, et al. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet 2003;361:1519-20. https://www.sciencedirect.com/science/article/pii/S0140673603131686
4. Ng K, Poon BH, Puar THK, et al. COVID-19 and the risk to health care workers: a case report. Ann Intern Med. 2020, March 16. https://annals.org/aim/fullarticle/2763329/covid-19-risk-health-care-workers-case-report
5. van Doremalen N, Bushmaker, Morris DH, et al. Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1. N Engl J Med 2020. https://doi.org/10.1101/2020.03.09.20033217
6. Kampf G. Efficacy of ethanol against viruses in hand disinfection. J Hosp Infect 2018;98:331-38. https://www.sciencedirect.com/science/article/pii/S0195670117304693
7. Grayson ML, Melvani S, Druce J, et al. Efficacy of soap and water and alcohol-based hand-rub preparations against live H1N1 influenza virus on the hands of human volunteers Clin Infect Dis 2009;48:285-91. https://www.ncbi.nlm.nih.gov/pubmed/19115974/
8. Service RF. Does disinfecting surfaces really prevent the spread of coronavirus? Science 2020, March 12. https://www.sciencemag.org/news/2020/03/does-disinfecting-surfaces-really-prevent-spread-coronavirus
9. CDC. Norovirus. https://www.cdc.gov/vitalsigns/norovirus/index.html
10. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of Coronavirus disease 2019 in China. N Engl J Med 2020. First published Feb 28, 220, last updated March 6, 2020. https://www.nejm.org/doi/10.1056/NEJMoa2002032
11. Taubenberger JK, Morens DM. 1918 influenza: the mother of all pandemics. Emerg Infect Dis 2006;12:15-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291398/

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

5 Covid-19 facts worth keeping in mind as we deal with our pandemic anxiety

Why can’t my patient with alcohol-related liver disease be placed on the liver transplant list for at least 6 months after his last drink?

Although many centers impose a 6-month sobriety rule before patients can be listed for liver transplant, this rule has been increasingly challenged based on the results of more recent studies and ethical issues. 1-10

The argument for enforcing a 6-month sobriety rule is in part based on earlier studies (often small and/or single center) that reported an association between less than 6 months of sobriety before liver transplantation and relapse.5-6 Another frequently cited reason for postponing liver transplantation is to allow the liver enough time to recover from adverse effect of recent alcohol consumption before assessing the need for transplantation.6

Arguments against the 6-month sobriety rule include the very limited life-expectancy (often 3 months or less) of patients with severe alcohol-related liver disease who do not respond to medical therapy and increasing number of studies supporting earlier transplantation particularly in selected patients (eg, severe acute alcoholic hepatitis [SAAH], acute-on-chronic liver failure [ACLF]).1,7,9,10,

Further supporting a less stringent transplantation rule are a low rate (about 4%) of death or graft loss in alcohol-related liver disease patients who experience a relapse and lack of significant differences in survival between non-relapsers, occasional drinkers and problem drinkers.1 A 2019 multicenter, prospective study in the U.S. also found that early liver transplant for alcohol-related  liver disease was associated with comparable patient and graft survival as those without alcohol-related liver disease at 5 years post-transplant but increased risk of death at 10 years. 10

Bonus Pearl: Did you know that alcohol-related liver disease is now the most common diagnosis among patients undergoing liver transplantation in the U.S.? 10

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References

  1. Obed A, Stern S, Jarrad A, et al. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients. W J Gastroenterol 2015; 21:4423-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394109/
  2. Bramstedt KA, Jabbour N. When alcohol abstinence criteria create ethical dilemmas for the liver transplant team. J Med Ethics 2006;32:263-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579412/
  3. Kollmann D, Rashoul-Rockenschaub S, Steiner I, et al. Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post-tranplantation CDT monitoring for alcohol relapse assement— a retrospective study. Transplant International 2016;29:559-67. https://onlinelibrary.wiley.com/doi/epdf/10.1111/tri.12756
  4. Osorio RW, Ascher NL, Avery M, et al. Predicting recidivism after orthoptic liver transplantation for alcoholic liver disease. Hepatoloty 1994;20:105-110. https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.1840200117
  5. Carbonneau M, Jensen LA, Bain VG. Alcohol use while on the liver transplant waiting list: a single-center experience. Liver Transplantation 2010;16:91-97. https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/lt.21957
  6. Harnanan A. Challenging the “six-month sober” rule for liver transplants in Canada. McGill Journal of Law and Health. Dec 12, 2019. https://mjlh.mcgill.ca/2019/12/12/challenging-the-six-month-sober-rule-for-liver-transplants-in-canada/
  7. Lee BP, Mehta N, Platt L, et al. Outcomes of early liver transplantation for patients with severe alcoholic hepatitis. Gastroenterology 2018;155:422-430.e1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460480/
  8. Rice JP, Lee BP. Early liver transplantation for alcohol-associated liver disease: need for engagement and education of all stakeholders. Hepatol Communications 2019;3: 1019-21. https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep4.1385
  9. Lee BP, Vittinghoff E, Pletcher MJ, et al. Medicaid policy and liver transplant for alcohol-related liver disease. Hepatology; November 8, 2019 https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.31027
  10. Lee BP, Vittinghoff E, Dodge JL, et al. National trends and long-term outcomes of liver transplant for alcohol-associated liver disease in the United States. JAMA Intern Med 2019;179:340-48. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2720757?widget=personalizedcontent&previousarticle=2720750

Contributed in part by Nneka Ufere, MD, GI Division, Massachusetts General Hospital, Boston, MA

Why can’t my patient with alcohol-related liver disease be placed on the liver transplant list for at least 6 months after his last drink?

What’s causing an isolated GGT elevation in my patient with an abnormal alkaline phosphatase on her routine admission lab?

Although serum gamma-glutamyl transpeptidase or GGT is a very sensitive test for liver disease, especially of biliary origin, it’s by no means a very specific test. Besides the liver, GGT is found in the kidneys, pancreas, prostate, heart, brain, and seminal vesicles but not in bone (1-4).

 
Obesity, alcohol consumption and drugs are common causes of GGT elevation (2). As early as 1960s, elevated GGT was reported in such seemingly disparate conditions as diabetes mellitus, congestive heart failure, myocardial infarction, nephrotic syndrome and renal neoplasm (3). Nonalcoholic steatohepatitis, viral hepatitis, biliary obstruction, COPD, liver metastasis, drug-induced liver injury can all cause GGT elevation (1-4).

 
An isolated GGT does not necessarily indicate serious or progressive liver disease. That’s one reason it’s often not included in routine “liver panel” lab tests (1).

What to do when GGT is high but other liver panel tests such as ALT, AST, albumin, and bilirubin are normal? If your patient is at risk of acquired liver disease, then further workup may be necessary (eg, hepatitis B and C screening tests). Alcohol consumption should be queried. Don’t forget conditions associated with iron overload. If your patient is obese, diabetic or has elevated both lipids, an ultrasound of the liver to look for fatty liver should be considered. In the absence of risk factors, symptoms, or physical exam suggestive of liver disease, isolated GGT elevation should not require further investigation (1).

 
One good thing that may come out of finding an isolated elevated GGT is to encourage your patient to curb alcohol consumption or lose weight when indicated. But don’t rely on a normal GGT to rule out heavy alcohol consumption as it may miss 70% to 80% of cases (6)! 

 
Bonus Pearl: Did you know that GGT activity is thought to increase in alcohol use due to its role in maintaining intracellular glutathione, an anti-oxidant, at adequate levels to protect cells from oxidative stress caused by alcohol?

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References

1. Carey WD. How should a patient with an isolated GGT elevation be evaluated? Clev Clin J Med 2000;67:315-16. https://www.ncbi.nlm.nih.gov/pubmed/10832186
2. Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut 2018;67:6-19. https://gut.bmj.com/content/gutjnl/67/1/6.full.pdf
3. Whitfield JB, Pounder RE, Neale G, et al. Serum gamma-glutamyl transpeptidase activity in liver disease. Gut 1972;13:702-8. https://www.ncbi.nlm.nih.gov/pubmed/4404786
4. Tekin O, Uraldi C, Isik B, et al. Clinical importance of gamma glutamyltransferase in the Ankara-Pursaklar region of Turkey. Medscape General Medicine 2004;6(1):e16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140713/
5. Van Beek JHDA, de Moor MHM, Geels LM, et al. The association of alcohol intake with gamma-glutamyl transferase (GGT) levels:evidence for correlated genetic effects. Drug Alcohol Depend 2014;134:99-105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909645/

6. Bertholet N, Winter MR, Cheng DM, et al. How accurate are blood (or breath) tests for identifying self-reported heavy drinking among people with alcohol dependence? Alcohol and Alcoholism 2014;49:423-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060735/pdf/agu016.pdf

What’s causing an isolated GGT elevation in my patient with an abnormal alkaline phosphatase on her routine admission lab?

Why does my patient with alcoholic cirrhosis have macrocytic anemia?

Macrocytic anemia is commonly due to folate or vitamin B12 (cobalamin) deficiency.1 Deficiency in these vitamins can be related broadly to poor intake, poor absorption, or drug interference. In patients with chronic excess alcohol consumption, both intake and/or absorption of these vitamins may be affected.

Although folate deficiency is increasingly rare in many developed countries due to mandatory folate fortification of flour and uncooked-grain, alcohol use can be associated with malnourishment severe enough to causes folate deficiency. In addition, alcohol itself can alter folate metabolism and absorption.  More specifically, chronic alcohol consumption has been shown to be associated with decreased folate absorption by the small intestine, altered intrahepatic processing and distribution between the systemic and enterohepatic folate circulations as well as increased folate urinary excretion. 2 Though uncommon,3 alcohol can also be associated with a food B12 malabsorption process, whereby despite adequate intake, B12 is not released or absorbed from food. 4

But what if serum folate and B12 levels return as normal in our patient with macrocytosis? It turns out that alcohol consumption, independent of folate or B12 deficiency, may also cause macrocytosis. 5 Though the exact mechanism is unknown, it may be related to alcohol’s direct toxicity or that of its metabolites; alcohol is oxidized to acetaldehyde, which affects membranes of red blood cells (RBCs) and their precursors by forming adducts with erythroid proteins,6 and interfering with cell division.7 Interestingly, alcohol-related macrocytosis may appear before anemia is detected and can resolve within 2-4 months of abstinence.

In addition to alcohol, cirrhosis itself may be associated with macrocytic anemia caused by lipid deposition on RBC membranes.1

See also a related pearl at  www.Pearls4Peers.com

References

  1. Hoffbrand V, Provan D. ABC of clinical haematology: macrocytic anaemias. BMJ 2011;314(7078):430–430. https://www.ncbi.nlm.nih.gov/pubmed/9040391
  2. Medici V, Halsted CH. Folate, alcohol, and liver disease. Mol Nutr Food Res 2013;57(4):596–606. https://www.ncbi.nlm.nih.gov/pubmed/23136133
  3. Bode C, Bode CJ. Effect of alcohol consumption on the gut. Best Pract Res Clin Gastroenterol [Internet] 2003;17(4):575–92. https://www.sciencedirect.com/science/article/pii/S1521691803000349
  4. Dali-Youcef N, Andrès E. An update on cobalamin deficiency in adults. QJM 2009;102(1):17–28. https://academic.oup.com/qjmed/article/102/1/17/1502492
  5. Savage DG, Ogundipe A, Allen RH, Stabler SP, Lindenbaum J. Etiology and diagnostic Evaluation of macrocytosis. Am J Med Sci [Internet] 2000;319(6):343–52. http://dx.doi.org/10.1016/S0002-9629(15)40772-4 https://www.ncbi.nlm.nih.gov/pubmed/10875288
  6. Latvala J, Parkkila S, Melkko J, Niemelä O. Acetaldehyde adducts in blood and bone marrow of patients with ethanol-induced erythrocyte abnormalities. Mol Med 2001;7(6):401–5. https://www.ncbi.nlm.nih.gov/pubmed/11474133
  7. Wickramasinghe SN, Malik F. Acetaldehyde causes a prolongation of the doubling time and an increase in the modal volume of cells in culture. Alcohol Clin Exp Res 1986;10(3):350–4. https://www.ncbi.nlm.nih.gov/pubmed/3526962

 

Contributed by Kim Schaefer, Harvard medical student, Boston, MA

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Why does my patient with alcoholic cirrhosis have macrocytic anemia?

My patient with anemia has an abnormally high mean red blood cell corpuscular volume (MCV). What conditions should I routinely consider as a cause of his macrocytic anemia?

Anemia with mean corpuscular volume (MCV) above the upper limit of normal (usually ≥ 100 fL) is considered macrocytic anemia. The numerous causes of macrocytic anemia can be divided into major categories (1,2) (Figure 1).

First, a reticulocyte production index should be calculated and if elevated the MCV can be above the normal range due to the large size of reticulocytes. Once high MCV is not thought to be related to reticulocytosis, the majority of macrocytic anemias can be categorized according to one of two major mechanisms: 1. Liver disease; and  2. Impairment of DNA synthesis, which includes nutritional deficiencies (folate, B12), drug effect (e.g co-trimoxazole, anti-neoplastic agents and certain anti-retroviral drugs) and “idiopathic” causes (myelodysplastic syndromes).

Mild macrocytosis can also be seen in hypothyroidism and hypoproliferative anemias such as aplastic anemia.  Macrocytosis without anemia or liver disease can also be a manifestation of heavy alcohol intake.

Macrocytic anemia in liver disease is due to excess lipid deposition in the red blood cell (RBC) membrane, not impairment of DNA synthesis. Enlarged RBCs are usually round and  often have a targeted appearance in liver disease; acanthocytes (spur cells) may also be present (Fig 2). In contrast, in disorders of impaired DNA synthesis, enlarged RBCs are often oval-shaped (macro-ovalocytes) (Fig 3).

Other common abnormalities seen with macrocytic anemia include hypersegmented neutrophils (eg, induced by B12 or folate deficiency), and in the case of myelodysplastic syndromes, hypogranulated neutrophils and Pelger-Huet neutrophil abnormalities.

Bonus pearl: Did you know that the MCV unit, fL, stands for femtoliters or 1/1,000,000,000,000,000 L? 

macroalgo

Figure 1. Major causes of macrocytic anemia. MDS: myelodysplastic syndrome.

 

Macrocytic_Anemia_Figure 1

Fig 2. Round macrocytes with targeting and abundant acanthocytes (spur cells) in a patient with hepatic cirrhosis.

 

Macrocytic_Anemia_Figure 2

Fig 3. Oval macrocytes in a patient with large granular cell leukemia and an MCV of 125 fL who received cyclophosphamide.

References

  1. Ward PC. Investigation of Macrocytic Anemia. Postgrad Med 1979; 65: 203-207. https://www.ncbi.nlm.nih.gov/pubmed/368738
  2. Green R, Dwyre DM. Evaluation of macrocytic anemias. Semin Hematol 2015; 52: 279-286. https://www.sciencedirect.com/science/article/abs/pii/S0037196315000554

 

Contributed by Tom Spitzer, MD, Director of Cellular Therapy and Transplantation Laboratory, Massachusetts General Hospital, Boston, MA.

My patient with anemia has an abnormally high mean red blood cell corpuscular volume (MCV). What conditions should I routinely consider as a cause of his macrocytic anemia?

My patient with cocaine and alcohol addiction is admitted with repeated convulsions during which he seems totally conscious. What could I be missing?

Consider strychnine poisoning as a cause of recurrent generalized tonic clonic seizures and muscle spasm with clear sensorium either during or following the episode. 1-4 In contrast to the cortical source of most seizures, convulsions due to strychnine poisoning are due to the blocking of the action of spinal and brain-stem inhibitory neurons resulting in overwhelming muscle rigidity, not unlike that seen in tetanus.

Although strychnine was found in various tonics and cathartic agents and was a common cause of accidental death in children under 5 years of age in early 20th century, it is still used in various rodenticides and pesticides.3  Today, it may be used intentionally in suicide attempts as well as an adulterant in street drugs, such as amphetamines, heroin and especially cocaine. 1,3,5

The initial symptoms of strychnine poisoning include nervousness, a hyperalert state, and confusion. These symptoms may be followed by severe muscle rigidity throughout the body often in response to minimal stimuli, such as physical contact, bright lights, noise and medical procedures.3, 6,7  Interestingly, strychnine also has an excitatory action on the medulla and enhances the sensation of touch, smell, hearing and sight.6  The cause of death is usually respiratory arrest due to prolonged muscle spasms, often complicated by rhabdomyolysis and associated renal failure.1

So among the numerous causes of seizures, think of strychnine as another potential cause when there is no concurrent loss of consciousness or the expected postictal state.

Bonus Pearl: Did you know that strychnine may be present in street drugs with a variety of names such as “back breakers”, “homicide”, “red rock opium”, “red stuff” and “spike”? 7

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References

  1. Wood DM, Webser E, Martinez D, et al. Case report: survival after deliberate strychnine self-poisoning, with toxicokinetic data. Critical Care 2002;6:456-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC130147/
  2. Santhosh GJ, Joseph W, Thomas M. Strychnine poisoning. J Assoc Physicians India 2003;51:736. https://www.ncbi.nlm.nih.gov/pubmed/14621058
  3. Libenson MH, Young JM. Case records of Massachusetts General Hospital. A 16 years boy with an altered mental status and muscle rigidity. N Engl J Med 2001;344:1232-9. https://www.nejm.org/doi/full/10.1056/NEJM200104193441608
  4. Smith BA. Strychnine poisoning. J Emerg Med 1990;8: 321-25. https://www.ncbi.nlm.nih.gov/pubmed/2197324
  5. O’Callaghan WG, Ward M, Lavelle P, et al. Unusual strychnine poisoning and its treatment: report of eight cases. B Med J 1982;285:478. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1499293/
  6. Burn DJ, Tomson CRV, Seviour J, et al. Strychnine poisoning as an unusual cause of convulsions. Postgrad Med J 1989;65:563-64. https://www.ncbi.nlm.nih.gov/pubmed/2602253
  7. Radosavljevic J, Jeffries WS, Peter JV. Intentional strychnine use and overdose—an entity of the past? Crit Care Resusc 2006;8: 260-61. https://www.ncbi.nlm.nih.gov/pubmed/16930120

 

My patient with cocaine and alcohol addiction is admitted with repeated convulsions during which he seems totally conscious. What could I be missing?

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. 

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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

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

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

Should my patient with suspected alcoholic hepatitis undergo liver biopsy?

Although a characteristic clinical history and biochemical pattern of liver injury can strongly suggest the diagnosis of alcoholic hepatitis (AH), a definitive diagnosis is confirmed with liver biopsy only. In fact, in 30% of patients clinically diagnosed as having AH, a liver biopsy may lead to an alternative diagnosis.1Understandably, many physicians are reluctant to proceed with biopsy in this fragile patient population given the associated risks, notably bleeding. For this reason, most patients with AH are clinically diagnosed without a liver biopsy. However, there are certain instances in which a biopsy can be helpful, including when:2

  • Diagnosis of AH is in doubt
  • Suspicion for another disease process that may be contributing in parallel to AH is high
  • Obtaining prognostic data or identification of advanced hepatic fibrosis or cirrhosis in AH is desired

Thus, liver biopsy findings may influence short- and long-term management in AH. For these reasons, the European Association for the Study of the Liver recommends consideration of a liver biopsy in patients with AH.3 To minimize the bleeding risk, the transjugular approach is preferred.

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References

  1. Mookerjee RP, Lackner C, Stauber R, et al. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis. J Hepatol 2011; 55:1103-1111 Link
  2. Altamirano J, Miquel R, Katoonizadeh A, et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014;146: 1231-1239. PDF
  3. European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol 2012; 57:399-420. PDF

Contributed by Jay Luther, MD, Gastrointestinal Unit, Mass General Hospital, Boston, MA.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Should my patient with suspected alcoholic hepatitis undergo liver biopsy?

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

My 35 year old patient with chronic alcoholism blames benign prostatic hypertrophy for his difficulty voiding. Could his bladder dysfunction be related to his alcoholism?

Several case reports in the literature have stressed the association of bladder dysfunction (BD) with chronic alcohol abuse1,2.  Although some cases may be associated with concurrent thiamine deficiency (with its attendant neuropathy), other cases of BD do not appear to be. The mechanism of BD in this setting may be related to the toxic effect of alcohol on peripheral, autonomic and/or central nervous systems2,3.

Binge drinking may also be associated with urinary retention, with spontaneous atraumatic urinary bladder rupture having been reported on several occasions4. Lastly, alcohol withdrawal alone may precipitate urinary retention5.  

Unfortunately, many cases of abdominal pain due to urinary retention in the setting of alcohol abuse or withdrawal may be mistakenly attributed to ascites or other causes5.  High index of suspicion for BD is essential to minimize its complications.

In our patient, given the low prevalence of benign prostatic hypertrophy in men less than 40 years of age, urinary retention due to alcohol-related BD is more likely.

 

References

  1. Yuan R, Carcciolo VJ, Kulaga M. Chronic abdominal distension secondary to urinary retention in a patient with alcoholism. JAMA 2002;287;318-19.
  2. Sheremata WA, Sherwin I. Alcoholic myelopathy with spastic urinary bladder. Dis Nerv Syst 1972;33:136-139.
  3. Mellion M, Gilchrist JM, De La Monte S. Alcohol-related peripheral neuropathy: nutritional, toxic or both? Muscle Nerve 2011;43:309-16.
  4. Muneer M, Abdelrahman H, El-Menyar A, et al. Spontaneous atraumatic urinary bladder rupture secondary to alcohol intoxication: a case report and review of literature. Am J Case Rep 2015;16:778-81.
  5. Iga J-I, Taniguchi T, Ohmori T. Acute abdominal distension secondary to urinary retention in a patient after alcohol withdrawal. Alcohol Alcoholism 2005;40:86-87.
My 35 year old patient with chronic alcoholism blames benign prostatic hypertrophy for his difficulty voiding. Could his bladder dysfunction be related to his alcoholism?