My patient with history of gastric bypass surgery now presents with right upper quadrant pain and gallstones. Is there a connection between gastric bypass surgery and gallstones?

An increased risk of new gallstones following gastric bypass surgery (GBS) has been reported by several studies (1-5).  More specifically, a study involving patients with baseline normal gallbladder ultrasound found that at 6 months following GBS 36% of patients developed gallstones and 13% developed sludge (4).  Similarly, a gallstone formation rate of 32% has been reported after GBS among patients who did not receive prophylactic treatment (5). 

New cholelithiasis following GBS may be largely attributed to rapid weight loss following this procedure, not the surgery itself or its related anatomical changes. Of interest, rapid weight loss, even by dieting, has been shown to increase the risk of gallstones (6).

However, overweight patients also have an increased risk of developing cholelithiasis at baseline, in part related to increased cholesterol secretion resulting in bile supersaturation with cholesterol (1).  Though weight loss may be expected to decrease this risk, rapid weight loss is thought to change the bile composition towards higher concentrations of calcium and cholesterol and increased production of gallbladder mucin, contributing to the pathogenicity of gallstone formation (5). 

In light of these findings, some have recommended routine prophylactic cholecystectomy as part of the GBS (7,8),  while others have argued against it (9,10), largely due to different observed rates of post-GBS symptomatic gallstones requiring cholecystectomies in various studies. Of note, post-operative ursodiol (ursodeoxycholic acid) may also reduce the incidence of post-GBS cholelithiasis (5,11). 
References

1. Everhart JE. Contributions of obesity and weight loss to gallstone disease. Ann Intern Med 1993;119(10):1029–35. https://www.ncbi.nlm.nih.gov/pubmed/8214980
2. Wudel LJ, Wright JK, Debelak JP, Allos TM, Shyr Y, Chapman WC. Prevention of gallstone formation in morbidly obese patients undergoing rapid weight loss: Results of a randomized controlled pilot study. J Surg Res 2002;102(1):50–6. https://www.ncbi.nlm.nih.gov/pubmed/11792152
3. Manatsathit W, Leelasincharoen P, Al-Hamid H, Szpunar S, Hawasli A. The incidence of cholelithiasis after sleeve gastrectomy and its association with weight loss: A two-centre retrospective cohort study. Int J Surg [Internet] 2016;30:13–8. Available from: http://dx.doi.org/10.1016/j.ijsu.2016.03.060 https://www.ncbi.nlm.nih.gov/pubmed/27063855
4. Shiffman M, Sugerman H, Kellum J, Brewer W, Moore E. Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. Am J Gastroenterol 1991;(86):1000–5. https://www.ncbi.nlm.nih.gov/pubmed/1858735
5. Sugerman H, Brewer W, Shiffman M, et al. A Multicenter, Placebo-Controlled, Randomized, Double-Blind, Prospective Trial of Prophylactic Ursodiol for the Prevention of Gallstone Formation Rapid Weight Loss. Am Jourmal Surg 1995;169(January):91–7. https://www.ncbi.nlm.nih.gov/pubmed/7818005

6. de Oliverira CIB, Chaim EA, da Silva BB. Impact of rapid weight reduction on risk of cholelithiasis after bariatric surgery. Obesity Surgery 2003;13:625-8.
7. Tarantino I, Warschkow R, Steffen T, Bisang P, Schultes B, Thurnheer M. Is routine cholecystectomy justified in severely obese patients undergoing a laparoscopic Roux-en-Y gastric bypass procedure? A comparative cohort study. Obes Surg 2011;21(12):1870–8. https://reference.medscape.com/medline/abstract/21863228
8. Amstutz S, Michel JM, Kopp S, Egger B. Potential Benefits of Prophylactic Cholecystectomy in Patients Undergoing Bariatric Bypass Surgery. Obes Surg 2015;25(11):2054–60. https://link.springer.com/article/10.1007%2Fs11695-015-1650-6
9. Karadeniz M, Gorgun M, Kara C. The evaluation of gallstone formation in patients undergoing Roux-en -Y gastric bypass due to morbid obesity. Turkish J Surg 2014;30(2):76–9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379817/
10. D’Hondt M, Sergeant G, Deylgat B, Devriendt D, Van Rooy F, Vansteenkiste F. Prophylactic Cholecystectomy, a Mandatory Step in Morbidly Obese Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass? J Gastrointest Surg 2011;15(9):1532–6. https://www.ncbi.nlm.nih.gov/pubmed/21751078
11. Miller K, Hell E, Lang B, Lengauer E. Gallstone Formation Prophylaxis after Gastric Restrictive Procedures for Weight Loss: A Randomized Double-Blind Placebo-Controlled Trial. Ann Surg 2003;238(5):697–702. https://www.ncbi.nlm.nih.gov/pubmed/14578732

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

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My patient with history of gastric bypass surgery now presents with right upper quadrant pain and gallstones. Is there a connection between gastric bypass surgery and gallstones?

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  https://pearls4peers.com/2019/07/26/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   

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?

Is there a connection between my patient’s blood type and risk of thromboembolic events?

There seems to be, given the weight of the evidence to date suggesting that non-blood group O may be associated with non-valvular atrial fibrillation (NVAF)-related peripheral cardioembolic complications, myocardial infarction (MI) and ischemic stroke. 1-4

A 2015 retrospective Mayo Clinic study involving patients with NVAF adjusted for CHADS2 score found significantly lower rate of peripheral embolization in those with blood group O compared to those with other blood groups combined (3% vs 2%, O.R. 0.66, 95% CI, 0.5-0.8); rates of cerebral thromboembolic events were not significantly different between the 2 groups, however. 1

A 2008 systematic review and meta-analysis of studies spanning over 45 years reported a significant association between non-O blood group and MI, peripheral vascular disease, cerebral ischemia of arterial origin, and venous thromboembolism.2 Interestingly, the association was not significant for angina pectoris or for MI when only prospective studies were included.  Some studies have reported that the association between VWF and the risk of cardiovascular mortality may be independent of blood group. 5,6

Although the apparent lower risk of thromboembolic conditions in O blood group patients may be due to lower levels of von Willebrand factor (VWF) and factor VIII in this population 1,4, other pathways likely  play a role.7  

As for why the rate of peripheral (but not cerebral) thromboembolic events in NVAP is affected by blood group, it is suggested that, because of their size, larger clots (facilitated by lower VWF levels) may bypass the carotid and vertebral orifices in favor of their continuation downstream to the “peripheral bed”.1

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References

  1. Blustin JM, McBane RD, Mazur M, et al. The association between thromboembolic complications and blood group in patients with atrial fibrillation. Mayo Clin Proc 2015;90;216-23. https://www.sciencedirect.com/science/article/abs/pii/S002561961401043X
  2. Wu O, Bayoumi N, Vickers MA, et al. ABO (H) groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemostasis 2008;6:62-9. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2007.02818.x
  3. Medalie JH, Levene C, Papier C, et al. Blood groups, myocardial infarction, and angina pectoris among 10,000 adult males. N Engl J Med 1971;285:1348-53. https://www.nejm.org/doi/pdf/10.1056/NEJM197112092852404
  4. Franchini M, Capra F, Targher G, et al. Relationship between ABO blood group and von Willebrand factor levels: from biology to clinical implications. Thrombosis Journal 2007, 5:14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042969/
  5. Meade TW, Cooper JA, Stirling Y, et al. Factor VIII, ABO blood group and the incidence of ischaemic heart disease. Br J Haematol 1994;88:601-7. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.1994.tb05079.x
  6. Jager A, van Hinsbergh VW, Kostense PJ, et al. von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn Study. Arterioscl Thromb Vasc Biol 1999;19:3071-78. https://www.researchgate.net/publication/12709043_von_Willebrand_Factor_C-Reactive_Protein_and_5-Year_Mortality_in_Diabetic_and_Nondiabetic_Subjects_The_Hoorn_Study
  7. Sode BF, Allin KH, Dahl M, et al. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type. CMAJ 2013.DOI:10.1503/cmaj.121636. https://www.ncbi.nlm.nih.gov/pubmed/23382263
Is there a connection between my patient’s blood type and risk of thromboembolic events?

Should I routinely treat my patients with acute COPD exacerbation with antibiotics?

The answer is “NO”! With an estimated 20% to 50% of acute chronic obstructive pulmonary disease (COPD) exacerbations attributed to noninfectious factors (1,2), routine inclusion of antibiotics in the treatment of this condition is not only unnecessary but potentially harmful.

 
Although the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommends the use of antibiotics in patients who have dyspnea, increased sputum volume, and increased sputum purulence—or at least 2 of these 3 criteria when sputum purulence is one of them (3)—, these recommendations are not based on robust evidence and have not been widely corroborated (2,4-6).

 
That’s why the findings of a 2019 New England Journal of Medicine study (PACE) supporting the use of serum C-reactive protein (CRP) as an adjunctive test in COPD exacerbation is particularly welcome (1). In this multicenter randomized controlled trial performed in the U.K., the following CRP guidelines (arrived from prior studies) were provided to primary care clinicians to be used as part of their decision making in determining which patients with COPD exacerbation may not need antibiotic therapy:

 
• CRP less than 20 mg/L: Antibiotics unlikely to be beneficial
• CRP 20-40 mg/L: Antibiotics may be beneficial, mainly if purulent sputum is present
• CRP greater than 40 mg/L: Antibiotics likely to be beneficial

 
Adoption of these guidelines resulted in significantlly fewer patients being placed on antibiotics without evidence of harm over a 4-week follow-up period (1).  Despite its inherent limitations (eg, single country, outpatient setting), CRP testing may be a step in the right direction in curbing unnecessary use of antibiotics in COPD exacerbation.  

 

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References

 
1. Butler CC, Gillespie D, White P, et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med 2019;381:111-20. https://www.ncbi.nlm.nih.gov/pubmed/31291514
2. Llor C, Moragas A, Hernandez S, et al. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:716-23. https://www.ncbi.nlm.nih.gov/pubmed/22923662
3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019 (http://www.goldcopd.org).
4. Brett AS, Al-Hasan MN. COPD exacerbations—A target for antibiotic stewardship. N Engl J Med 2018;381:174-75. https://www.ncbi.nlm.nih.gov/pubmed/31291521
5. Miravitlles M, Moragas A, Hernandez S, et al. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest 2013;144:1571-7. https://www.ncbi.nlm.nih.gov/pubmed/23807094
6. Van Vezen P, Ter Riet G, Bresser P, et al. Doxycycline for outpatient-treated acute exacerbations of COPD: a randomized double-blind placebo-controlled trial. Lancet Respir Med 2017;5:492-9. https://www.ncbi.nlm.nih.gov/pubmed/28483402

Should I routinely treat my patients with acute COPD exacerbation with antibiotics?

Should I routinely select antibiotics with activity against anaerobes in my patients with presumed aspiration pneumonia?

Anaerobes have been considered a major cause of aspiration pneumonia (AP) based on studies published in 1970’s (1-3). More recent data, however, suggest that anaerobes no longer play an important role in most cases of AP (4-7) and routine inclusion of specific anti-anaerobic drugs in their treatment is no longer necessary.

 
An important reason for anaerobes not playing an important role in AP in the current era is the change in the demographics of patients who may be affected. Patients reported in older studies often suffered from alcohol use disorder, drug ingestion, seizure disorders and acute cerebrovascular accident. In contrast, more recent data show that AP often occurs in nursing home residents, the elderly with cognitive impairment, and those with dysphagia, gastrointestinal dysmotility or tube feeding (8,9).

 
In addition, many cases of AP reported in older studies involved delay of 4 or more days before seeking medical attention and, not surprisingly, often presented with lung abscess, necrotizing pneumonia, empyema, or putrid sputum, features that are relatively rare in the current era.

 
Further supporting the diminishing role of anaerobes in AP, are recent microbiological studies of the respiratory tract in AP revealing the infrequent isolation of anaerobes and, even when isolated, often coexisting with aerobic bacteria. The latter observation is important because, due to the alteration in the redox potential (9,10), treatment of aerobic bacteria alone may lead to less oxygenation consumption and less favorable environment for survival of anaerobes in the respiratory tract.

 
We should also always consider the potential adverse effects of unnecessary antibiotics with anaerobic activity in our frequently debilitated patients, including gastrointestinal dysbiosis (associated with Clostridiodes difficile infections and overgrowth of antibiotic-resistant pathogens such as vancomycin-resistant enterococci (VRE), hypersensitivity reactions, drug interactions, and central nervous system toxicity (11,12).

 
Thus, the weight of the evidence does not justify routine anaerobic coverage of AP in today’s patients.

 

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References
1. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. Am J Med. 1974;56(2):202-7. https://www.ncbi.nlm.nih.gov/pubmed/4812076
2. Bartlett JG, Finegold SM. Anaerobic pleuropulmonary infections. Medicine (Baltimore). 1972;51(6):413-50. https://www.ncbi.nlm.nih.gov/pubmed/4564416
3. Bartlett JG, Gorbach SL. The triple threat of aspiration pneumonia. Chest. 1975;68(4):560-6. https://www.ncbi.nlm.nih.gov/pubmed/1175415
4. Finegold SM. Aspiration pneumonia. Rev Infect Dis. 1991;13 Suppl 9:S737-42. https://www.ncbi.nlm.nih.gov/pubmed/1925318
5. Bartlett JG. How important are anaerobic bacteria in aspiration pneumonia: when should they be treated and what is optimal therapy. Infect Dis Clin North Am. 2013;27(1):149-55. https://www.ncbi.nlm.nih.gov/pubmed/23398871
6. El-Solh AA, Pietrantoni C, Bhat A, Aquilina AT, Okada M, Grover V, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med. 2003;167(12):1650-4. https://www.ncbi.nlm.nih.gov/pubmed/12689848
7. Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest. 1999;115(1):178-83. https://www.ncbi.nlm.nih.gov/pubmed/9925081
8. Bowerman TJ, Zhang J, Waite LM. Antibacterial treatment of aspiration pneumonia in older people: a systematic review. Clin Interv Aging. 2018;13:2201-13. https://www.ncbi.nlm.nih.gov/pubmed/30464429
9. Mandell LA, Niederman MS. Aspiration Pneumonia. N Engl J Med. 2019 Feb 14;380(7):651-663. doi: 10.1056/NEJMra1714562. https://www.ncbi.nlm.nih.gov/pubmed/30763196
10. Walden, W. C., & Hentges, D. J. (1975). Differential effects of oxygen and oxidation-reduction potential on the multiplication of three species of anaerobic intestinal bacteria. Applied microbiology, 30(5), 781–785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC187272/
11. Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis. 2001;1(2):101-14. https://www.ncbi.nlm.nih.gov/pubmed/11871461
12. Bhalla A, Pultz NJ, Ray AJ, Hoyen CK, Eckstein EC, Donskey CJ. Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients. Infect Control Hosp Epidemiol. 2003;24(9):644-9. https://www.ncbi.nlm.nih.gov/pubmed/14510245

 

Contributed by Amar Vedamurthy, MD, MPH, Mass General Hospital, Boston, MA

Should I routinely select antibiotics with activity against anaerobes in my patients with presumed aspiration pneumonia?

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?

Should my patient with cirrhosis and esophageal varices be considered for partial splenic embolization?

 

Although limited, the weight of the evidence suggests that patients with cirrhosis and esophageal varices may benefit from partial splenic embolization (PSE).

A 2006 small randomized-controlled trial comparing PSE and endoscopic ligation vs. endoscopic ligation alone in patients with cirrhosis, thrombocytopenia and esophageal varices reported reduced risk of recurrence of varices, progression to variceal bleeding and death over a mean follow-up of 4.8 years. 1

A 2016 meta-analysis of PSE in the management of gastroesophageal variceal hemorrhage arrived at a similar conclusion with respect to reducing the risk of recurrence of varices, variceal hemorrhage and mortality. 2 The studies included in this meta-analysis, however, were small with only 1 randomized-controlled trial (RCT) in the series.

A 2019 small retrospective of patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement with or without PSE found a significant benefit in primary shunt patency (period between placement and first shunt dysfunction), but not secondary shunt patency (period between placement and permanent shunt dysfunction) or mortality over a 5-year follow-up.3

Adverse effects of PSE include post-embolization syndrome—a constellation of symptoms such as fever, pain, and nausea/vomiting— reported in 78%-100% of patients. More severe complications up to 15%-30% may also occur with PSE, particularly when around 70% or more of splenic volume is embolized. These complications include pleural effusion/ascites, spontaneous bacterial peritonitis, pulmonary embolism, liver failure, portal vein thrombosis and splenic abscesses which may develop between 10 days to 3 months following the procedure.  Up to 6% of patients undergoing PSE may die of the procedure-related complications. 4-6  

For these reasons, careful selection of patient for PSE and limiting the extent of splenic necrosis to 50% with close monitoring of clinical and ultrasound follow-up, particularly in patients with a volume of splenic necrosis >50%,  have been suggested.6

 

Fun fact: Did you know that splenic embolization was first performed by Frank E. Maddison of Madison, Wisconsin, in 1973 using autologous clot to treat recurrent gastrointestinal hemorrhage arising from esophageal varies?

 

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References

 

  1. Ohmoto K, Yoshioka N, Tomiyama Y, et al. Improved prognosis of cirrhosis patients with esophageal varices and thrombocytopenia treated by endoscopic variceal ligation plus partial splenic embolization. Digestive Diseases and Sciences 2006;51:352-58. https://link.springer.com/article/10.1007/s10620-006-3137-8
  2. Wang P, Liu R, Tong L, et al. Partial splenic embolization has beneficial effects for the management of gastroesophageal variceal hemorrhage. Saudi J Gastroenterol 2016;22:399-406. http://europepmc.org/articles/PMC5184739/
  3. Wan Y-M, Li Y-H, Xu Z-Y, et al. Comparison of TIPS alone and combined with partial splenic embolization (PSE) for the management of variceal bleeding. European Radiology 2019; https://doi.org/10.100/s00330-019-06046-6
  4. N’Kontchou G, Seror O, Bourcier V, et al. Partial splenic embolization in patients with cirrhosis: efficacy, tolerance, and long-term outcome in 32 patients. Eur J Gastroenterol Hepatol 2005;17:179-84. https://www.ncbi.nlm.nih.gov/pubmed/15674095
  5. Hadduck TA, McWilliams JP. Partial splenic artery embolization in cirrhotic patients. World J Radiol 2014;28:6:160-168. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037542/
  6. Smith M, Ray CE. Splenic artery embolization as an adjunctive procedure for portal hypertension. Semin Intervent Radiol 2012;29:135-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444868/
  7. Maddison FE. Embolic therapy of hypersplenism. Invest Radiol 1973;8:280-281. https://journals.lww.com/investigativeradiology/Citation/1973/07000/Embolic_Therapy_of_Hypersplenism.54.aspx

 

Contributed in part by Theodore R. Pak, MD, PhD, Mass General Hospital, Boston, Massachusetts.

Should my patient with cirrhosis and esophageal varices be considered for partial splenic embolization?

My previously healthy patient developed a viral illness with fever and headache few days after swimming in a community pool. Can swimming pools be a source of viral infection?

Yes! Swimming pools have been implicated in the transmission of a variety of pathogens,  including enteric viruses (eg, echovirus, coxackie virus, hepatitis A virus, norovirus) which account for nearly one-half of all swimming pool-related outbreaks.  Adenoviruses also account for a significant number of swimming pool outbreaks.1,2

The most commonly reported symptoms in swimming pool outbreaks have been gastroenteritis, respiratory symptoms and conjunctivitis. However, aseptic meningitis and hepatitis may also occur. 1

Because viruses cannot replicate in the environment outside of host tissues, their presence in swimming pool is the result of direct contamination by those in the water who may shed viruses through unintentional fecal release or through body fluids, such as saliva, mucus, or vomitus.  The finding of E. coli in 58% of pool water samples in 1 CDC study suggests the presence of stool as a primary source of infection.3

On average, each person has 0.14 grams (range 0.1 gram to 10 grams) of fecal material on their perianal surface that could rinse into the water if pre-swim shower with soap is omitted.4-5 Coupled with the potential for inadequate disinfection or chlorination of pool water, it is not surprising that swimming pools may serve as a source of infection.  

CDC recommends keeping feces and urine out of the water, checking the chlorine level and pH before getting into the water and not swallowing the water you swim in.3 

Bonus pearl: Did you know that pool water has also been associated with Cryptosporidium and Giardia and waterslides with E.coli-0157 outbreaks?

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References

  1. Bonadonna L, La Rosa G. A review and update on waterborne viral diseases associated with swimming pools. Int j Environ Res Public Health 2019;16, 166. Doi:10.3390/ijerph16020166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352248/
  2. Keswick BH, Gebra CP, Goyal SM. Occurrence of enteroviruses in community swimming pools. Am J Public Health 1981;71:1026030. https://www.ncbi.nlm.nih.gov/pubmed/6267950
  3. CDC.Microbes in pool filter backwash as evidence of the need for improved swimmer hygiene—Metro-Atlanta, Georgia, 2012. MMWR 2013;62:385-88. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6219a3.htm
  4. Gerba CP. Assessment of enteric pathogen shedding by bathers during recreational activity and its impact on water quality. Quant Microbiol 2000; 2:55-68 https://arizona.pure.elsevier.com/en/publications/assessment-of-enteric-pathogen-shedding-by-bathers-during-recreat
  5. CDC. Model Aquatic Health Code. 8.0 Annexes: fecal/vomit/blood contamination response Annex (6.0 policies and management), 2008. https://www.cdc.gov/healthywater/pdf/swimming/pools/mahc/structure-content/mahc-fecal-vomit-blood-contamination-response-annex.pdf
  6. CDC. Surveillance of waterborne disease outbreaks and other health events associated with recreational water—United States, 2007-2008 and surveillance of waterborne disease outbreaks associated with drinking water—United States, 2007-2008. MMWR 2011;60. 1-76. https://www.ncbi.nlm.nih.gov/pubmed/21937976

 

 

My previously healthy patient developed a viral illness with fever and headache few days after swimming in a community pool. Can swimming pools be a source of viral infection?

What is the significance of teardrop cells (dacrocytes) on the peripheral smear of my patient with newly-discovered pancytopenia?

The presence of teardrop cells (dacrocytes) (Figure below) in the peripheral blood, named for their tear drop shape, is a prominent feature of myelophthisic (marrow infiltrative) conditions, including myelofibrosis, hematologic malignancies, cancer metastatic to the bone marrow, and granulomatous diseases. Teardrop cells may also be seen in beta-thalassemia, autoimmune and microangiopathic hemolytic anemia and severe iron deficiency (1-4).

 
When evaluating patients with leucoerythroblastic smears (defined by the presence of early myeloid and erythroid forms), the presence of teardrop cells can be helpful in distinguishing often malignant marrow infiltrative conditions from a benign reactive process.  Conditions where teardrop cells are seen with high frequency may also have extramedullary hematopoiesis, particularly in the spleen (1,2).

 
The mechanism of tear drop cell formation may be multifactorial but appears to involve distortion of the red cells as they pass through marrow or splenic sinusoids. Teardrop cells resulting from conditions such as cancer metastatic to the bone marrow likely involve primarily a marrow origin of the cells whereas primary myelofibrosis with prominent extramedullary hematopoiesis include a splenic mechanism of tear drop cell formation (2).

 
Supporting the possible splenic contribution to teardrop cell formation is the observation that teardrop cells may be reduced in number or eliminated entirely after splenectomy in patients with myelofibrosis and autoimmune hemolytic anemia (1,4).

Teardrop

Figure. Teardrop cells

References

1. DiBella NJ, Sliverstein MN, Hoagland HC. Effect of splenectomy on teardrop-shaped erythrocytes in agnogenic myeloid metaplasia. Arch Intern Med 1977; 137: 380-381. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/586447
2. Gutgemann I, Heimpel H, Nebe CT. Significance of teardrop cells in peripheral blood smears. J Lab Med 2014; DOI: 10.1515/labmed-2014-0005 https://www.researchgate.net/publication/272430111_Significance_of_teardrop_cells_in_peripheral_blood_smears
3. Korber C, Wolfler A, Neubauer M, Robier Christoph. Red blood cell morphology in patients with β-thalassemia minor. J Lab Med 2016-12-10 | https://www.researchgate.net/publication/311564128_Red_blood_cell_morphology_in_patients_with_b-thalassemia_minor DOI: https://doi.org/10.1515/labmed-2016-0052
4. Robier C, Klescher D, Reicht G,Amouzadeh-Ghadikolai O, Quehenberger F, Neubauer M. Dacrocytes are a common morphologic feature of autoimmune and microangiopathic haemolytic anaemia. Clin Chem Lab Med. 2015;53:1073-6. https://www.ncbi.nlm.nih.gov/pubmed/25503671

Contributed by Tom Spitzer, MD, Director of Cellular Therapy and Transplantation Laboratory,  Massachusetts General Hospital, Boston, MA.
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What is the significance of teardrop cells (dacrocytes) on the peripheral smear of my patient with newly-discovered pancytopenia?

My 65 year old patient on chronic warfarin happens to have diffuse tracheobronchial calcification on her chest X-ray. Could warfarin be the culprit?

Absolutely! Although tracheobronchial calcification (TBC) is often found as part of normal aging process in the elderly, especially women, long-term warfarin use has also been implicated as a cause of TBC, even among those with less advanced age (1-4).

In a cohort of patients 60 years of age or older, radiographic evidence of trachea and bronchi calcification was found in 47% of patients on warfarin (mean age 64 years, mean duration of treatment 6 years) compared to 19% of controls (1). A positive correlation between the duration of warfarin therapy and increased levels of calcification was also found.  Fortunately, TBC is a benign finding and has no health consequences.

As for the mechanism for this rather intriguing phenomenon, the inhibition of a vitamin K-dependent protein that prevents calcification of cartilaginous tissue seems to be the most plausible (1). Although we often think of vitamin-K dependent factors in relation to the coagulation cascade, several vitamin K-dependent proteins also play an important role in the inhibition of calcification in soft tissues and blood vessels (eg, matrix Gla protein-MGP) (5,6).

In fact, rats maintained on warfarin undergo calcification of cartilage and elastic connective tissue, while exposure of the fetus to warfarin during pregnancy is associated with calcifications in and around joints, airway and nasal cartilages (4,7). These observations further support a causative role of warfarin in inducing TBC.

 

Bonus Pearl: Did you know that MGP deficiency in humans is known as the Keutel syndrome, a rare autosomal recessive disease characterized by several characteristic physical features, including severe cartilage calcifications and depressed nasal bridge?

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References

  1. Moncada RM, Venta LA, Venta ER, et al. Tracheal and bronchial cartilaginous rings: warfarin sodium-induced calcification. Radiology 1992;184:437-39. https://pubs.rsna.org/doi/10.1148/radiology.184.2.1620843
  2. Thoongsuwan N, Stern EJ. Warfarin-induced tracheobronchial calcification. J thoracic Imaging 2003;18:110-12. https://journals.lww.com/thoracicimaging/Abstract/2003/04000/Warfarin_Induced_Tracheobronchial_Calcification.12.aspx
  3. Nour SA, Nour HA, Mehta J, et al. Tracheobronchial calcification due to warfarin therapy. Am J Respir Crit Care Med 2014;189:e73. https://www.atsjournals.org/doi/full/10.1164/rccm.201305-0975IM
  4. Joshi A, Berdon WE, Ruzal-Shapiro C, et al. CT detection of the tracheobronchial calcification in an 18 year-old on maintenance warfarin sodium therapy. AJR Am J Roentgenol 2000;175:921-22. https://www.ajronline.org/doi/full/10.2214/ajr.175.3.1750921
  5. Wen L, Chen J, Duan L, et al. Vitamin K-dependent proteins involved in bone and cardiovascular health (review). Molecular Medicine Reports 2018;18:3-15. https://www.spandidos-publications.com/mmr/18/1/3/abstract \
  6. Theuwissen E, Smit E, Vermeer C. The role of vitamin K in soft-tissue calcification. Adv Nutr 2012; 3:166-173. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648717/pdf/166.pdf

7.      Price PA, Williamson MK, Haba T, et al. Excessive mineralization with growth plate closure in rats on chronic warfarin treatment. Proc Natl Acad Sci  U.S.A 1982;79:7734-8. https://www.ncbi.nlm.nih.gov/pubmed/6984192

My 65 year old patient on chronic warfarin happens to have diffuse tracheobronchial calcification on her chest X-ray. Could warfarin be the culprit?