Should I consider a direct oral anticoagulant (DOAC) for my patient with pancreatic cancer and pulmonary embolism?

Classically, anticoagulant (AC) of choice in active malignancy with venous thromboembolism (VTE) has been low-molecular weight heparin (LMWH) (eg, enoxaparin) because of trials showing its superiority over warfarin. But now the pendulum is swinging toward DOACs as an alternative mode of treatment.

A 2018 trial found that oral edoxaban (an Xa inhibitor) was noninferior to subcutaneous dalteparin (a LMWH) with the composite outcome of recurrent VTE or major bleeding.1 Overall, recurrent VTE was significantly lower in edoxaban (7.9% vs 11.3%) but had higher major bleeding (6.9% vs 4.05). Of note, edoxaban was initiated after 5 days of treatment with LMWH.

More recently, the 2020 Caravaggio trial, showed non-inferiority of apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) to dalteparin with recurrent VTE of 5.6% in the apixaban group vs 7.9% in the dalteparin.2 There was no significant difference in rates of major bleeding (3.8% vs 4%). A prior small study, the ADAM-VTE trial, compared apixaban to dalteparin in patients with malignancy and VTE.3 Apixaban had significantly lower VTE recurrence rates (0.7% to 6.3%) and non-significant lower major bleeding (0% vs 1.4%, p=0.138) consistent with the newer and larger trial. Of note, this trial excluded patients with brain tumor and had few patients with upper GI or hematologic malignancy.  

In addition, a pilot study, the SELECT-D trial, compared rivaroxaban to dalteparin.4 Rivaroxaban had significantly lower VTE recurrence (4% vs 11%), without a significant increase in major bleeding (6% vs 4%), but had an increased number of clinically relevant non-major bleeds (13% vs 4%), particularly in cancers of the upper GI tract.

Although decision regarding use of DOACs in patients with malignancy should be made on case-by-case basis, they are increasingly considered for treatment of VTE in this patient population with the strongest evidence supporting apixaban or the initial use of LMWH for 5 days followed by edoxaban.  

Contributed by Sean Mendez MD, Mass General Hospital, Boston, MA.

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References:  

  1. Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. doi: 10.1056/NEJMoa1711948. Epub 2017 Dec 12. PubMed PMID: 29231094.
  2. McBane Ii R, Loprinzi CL, Ashrani A, Perez-Botero J, Leon Ferre RA, Henkin S, Lenz CJ, Le-Rademacher JG, Wysokinski WE. Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE Trial. Thromb Haemost. 2017 Oct 5;117(10):1952-1961. doi: 10.1160/TH17-03-0193. Epub 2017 Aug 24. PubMed PMID: 28837207.
  3. Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro MR, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020 Mar 29;. doi: 10.1056/NEJMoa1915103. [Epub ahead of print] PubMed PMID: 32223112.
  4. Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. doi: 10.1200/JCO.2018.78.8034. Epub 2018 May 10. PubMed PMID: 29746227.

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 I consider a direct oral anticoagulant (DOAC) for my patient with pancreatic cancer and pulmonary embolism?

The chest CT of my patient with “B” symptoms shows hilar mass and mediastinal lymphadenopathy, highly suspicious for lymphoma or malignancy per radiology report. Should I still consider tuberculosis (TB) as a possibility?

Absolutely! TB often mimics malignancy, particularly lymphoma, both clinically and radiographically, even when sophisticated imaging techniques are used.1  

There are ample reports of TB being confused with mediastinal lymphoma, 1-6 with several reports also stressing abdominal TB mimicking malignancy. 7-10 As early as  1949, a  NEJM autopsy study emphasized “the difficulty in differentiating primary progressive TB and some types of lymphoma” and metastatic neoplasms, clinically and radiographically.  Over half-century later, despite major advancement in imaging techniques, TB is often confused for lymphoma or malignancy.

One reason for confusing TB with lymphoma is that primary TB can involve any pulmonary lobe or segment and is often associated with hilar and mediastinal adenopathy. 1 TB may also be overlooked in the differential diagnosis of mediastinal mass that often highlights neoplasms such as lymphoma, thymoma and germ cell tumors. 3 Lack of concurrent pulmonary infiltrates in the presence of mediastinal adenopathy may also veer clinicians away from TB diagnosis. 2,3,6 Unfortunately, even more sophisticated PET/CT scans may not be able to differentiate TB from lymphoma.5,6,9

Besides chest and abdomen, TB can also mimic malignancy in cervical nodes, bones (particularly the spine), bowels, and brain.1,2,6,8,9  To make matters worse, splenomegaly 2,10 and elevated LDH 3 may also be seen with TB and TB may coexist with lymphoma and other malignancies. 7,9,11

One of the best advices I ever received from a radiologist was “Think of TB anytime you think of lymphoma.”

Bonus Pearl: Did you know that TB lymphadenitis is the most common form of extrapulmonary TB with the majority involving the mediastinum? 4

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References

  1. Tan CH, Kontoyiannis DP, Viswanathan C, et al. Tuberculosis: A benign impostor. AJR 2010;194:555-61. https://www.researchgate.net/publication/41509877_Tuberculosis_A_Benign_Impostor
  2. Smith DT. Progressive primary tuberculosis in the adult and its differentiation from lymphomas and mycotic infections. N Engl J Med 1949;241:198-202. https://www.ncbi.nlm.nih.gov/pubmed/18137399
  3. Maguire S, Chotirmall SH, Parihar V, et al. Isolated anterior mediastinal tuberculosis in an immunocompetent patient. BMC Pulm Med 2016;16:24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739107/
  4. Tang SS, Yang ZG, Deng W, et al. Differentiation between tuberculosis and lymphoma in mediastinal lymph nodes: evaluation with contrast-enhanced MDCT. Clin Radiol 2012;67:877-83. https://www.sciencedirect.com/science/article/abs/pii/S0009926012001079
  5. Hou S, Shen J, Tan J. Case report: Multiple systemic disseminated tuberculosis mimicking lymphoma on 18F-FDG PET/CT. Medicine 2017;96:29(e7248). https://journals.lww.com/md-journal/Pages/ArticleViewer.aspx?year=2017&issue=07210&article=00005&type=Fulltext
  6. Tian G, Xiao Y, Chen B, et al. Multi-site abdominal tuberculosis mimics malignancy on 18F-FDG PET/CT: Report of three cases. World J Gastroenterol 2010;16:4237-4242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932932/
  7. Dres M, Demoule A, Schmidt M, et al. Tuberculosis hiding a non-Hodgkin lymphoma “there may be more to this than meets the eye”. Resp Med Case Rep 2012;7:15-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920344/
  8. Banerjee Ak, Coltart DJ. Abdominal tuberculosis mimicking lymphoma in a patient with sickle cell anemia. Br J Clin Pract 1990;44:660-61. https://www.ncbi.nlm.nih.gov/pubmed/2102179?dopt=Abstract
  9. Gong Y, Li S, Rong R, et al. Isolated gastric varices secondary to abdominal tuberculosis mimicking lymphoma: a case report. Gastroenterology 109;19:78. https://www.ncbi.nlm.nih.gov/pubmed/31138138
  10. Uy AB, Garcia Am Manguba A, et al. Tuberculosis: the great lymphoma pretender. Int J Cancer Res Mol Mech 2016; 2(1):doi http://dx.doi.org/10.16966/2381-3318.123
  11. Nayanagari K, Rani R, Bakka S, et al. Pulmonary tuberculosis with mediastinal lymphadenopathy and superior veno caval obstruction, mimicking lung malignancy: a case report. Int J Sci Study 2015;2:211-14. https://www.ncbi.nlm.nih.gov/pubmed/31138138
The chest CT of my patient with “B” symptoms shows hilar mass and mediastinal lymphadenopathy, highly suspicious for lymphoma or malignancy per radiology report. Should I still consider tuberculosis (TB) as a possibility?

Is my patient with gout at higher risk of cancer?

Although the association of gout with cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus or obesity is well known, increasingly number of epidemiologic studies support the association of gout with higher risk of malignancy. 1,2

A 2015 meta-analysis of 3 studies involving over 50,000 persons concluded that gout was an independent risk factor for cancer, particularly urological, gastrointestinal and lung cancers. 1

A population-based study of comorbidities in over 2 million persons in Sweden found that in addition to an increased risk of diabetes mellitus, hypertension, chronic heart failure, chronic kidney disease and alcohol abuse, gout was associated with increased risk of malignancy: odds ratio 1.3 (1.2-1.5) in men and 1.1 (1.1-1.2) in women. 2

Although serum uric acid has been considered to have anti-oxidant properties, a prospective study of over 28,000 women followed over a median of 15.2 years did not find high serum acid levels to be protective of cancer.3 In fact, uric acid levels > 5.4 mg/dL at the time of subject enrollment was independently associated with increased risk of total cancer mortality and deaths from a variety of malignant neoplasms, including those of breast, female genital organs, and nervous systems. 3 In a similar prospective study involving men, high uric acid levels (>6.7 mg/dL) were associated with increased risk of mortality from gastrointestinal, respiratory and intrathoracic organ malignancies. 4

Whether the observed association between gout and higher risk of malignancy is causal or due to the company that gout often keeps (eg, lifestyle) is unclear.

Fun fact: Did you know that among mammals, only humans, great apes and certain breeds of dogs (eg, Dalmation) produce elevated levels of uric acid in the urine and blood? 5

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References

  1. Wang W, Xu D, Wang B, et al. Increased risk of cancer in relation to gout: a review of three prospective cohort studies with 50,358 subjects. Mediators of Inflammation 2015, Article ID 680853, 6 pages. https://www.ncbi.nlm.nih.gov/pubmed/26504360
  2. Wandell P. Gout and its comorbidities in the total population of Stockholm. Preventive Medicine 2015; 81:387-91. ISSN 0091-7435. https://www.ncbi.nlm.nih.gov/pubmed/26500085
  3. Strasak AM, Rapp K, Hilbe W, et al. The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28000 older Austrian women. Ann Onc 2007;18:1893-97. https://www.ncbi.nlm.nih.gov/pubmed/17785768
  4. Strasak Am, Hilbe RK, Oberaingner W, et al. Serum uric acid and risk of cancer mortality in a large prospective male cohort. Cancer Causes Control 2007;18:1021-9. https://www.ncbi.nlm.nih.gov/pubmed/17665312
  5. Bannasch D, Safra N, Young A, et al. Mutations in the SLC2A9 gene cause hyperuriosuria and hyperuricemia in the dog. PLOS Genet 2008;4:e1000246. https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000246&type=printable
Is my patient with gout at higher risk of cancer?

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 teardrop 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 teardrop 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 patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

Yes! Arterial thromboembolism—just as venous thromboembolism— is more common in patients with cancer.

In a large 2017 epidemiologic study involving patients 66 years of age or older, the 6-month cumulative incidence of MI was nearly 3-fold higher in newly-diagnosed cancer patients compared to controls, with the excess risk resolving by 1 year. 1 These findings were similar to a previous report involving patients with newly-diagnosed cancer, although in that study the overall coronary heart disease risk remained slightly elevated even after 10 years. 2

In addition, the incidence of coronary events and unstable ischemic heart disease during the 2 year period prior to the diagnosis of cancer is 2-fold higher among cancer patients suggesting that ischemic heart disease may be precipitated by occult cancer. 3

The association of cancer and thromboembolic coronary events may be explained through several mechanisms, including development of a prothrombotic or hypercoagulable state through acute phase reactants, abnormal fibrinolytic activity and increased activation of platelets which are also significantly involved in the pathophysiology of acute coronary syndrome (ACS). 4 Coronary artery embolism from cancer-related marantic endocarditis may also occur.5

More specific to our case, primary brain tumors may be associated with a hypercoagulable state through expression of potent procoagulants such as tissue factor and tissue factor containing microparticles, with a subset producing carbon monoxide, another procoagulant. 6

So our patient’s MI prior to his surgery for brain tumor diagnosis might have been more than a pure coincidence!

Bonus Pearl: Did you know that cancer-related prothrombotic state, also known as  “Trousseau’s syndrome” was first described in 1865 by Armand Trousseau, a French physician who diagnosed the same in himself and died of gastric cancer with thrombotic complications just 2 years later? 7,8

References

  1. Navi BB, Reinder AS, Kamel H, et al. Risk of arterial thromboembolism in patients with cancer. JACC 2017;70:926-38. https://www.ncbi.nlm.nih.gov/pubmed/28818202
  2. Zoller B, Ji Jianguang, Sundquist J, et al. Risk of coronary heart disease in patients with cancer: A nationwide follow-up study from Sweden. Eur J Cancer 2012;48:121-128. https://www.ncbi.nlm.nih.gov/pubmed/22023886
  3. Naschitz JE, Yeshurun D, Abrahamson J, et al. Ischemic heart disease precipitated by occult cancer. Cancer 1992;69:2712-20. https://www.ncbi.nlm.nih.gov/pubmed/1571902
  4. Lee EC, Cameron SJ. Cancer and thrombotic risk: the platelet paradigm. Frontiers in Cardiovascular Medicine 2017;4:1-6. https://www.ncbi.nlm.nih.gov/pubmed/29164134
  5. Lee V, Gilbert JD, Byard RW. Marantic endocarditis-A not so benign entity. Journal of Forensic and Legal Medicine 2012;19:312-15. https://www.ncbi.nlm.nih.gov/pubmed/22847046
  6. Nielsen VG, Lemole GM, Matika RW, et al. Brain tumors enhance plasmatic coagulation: the role of hemeoxygenase-1. Anesth Analg 2014;118919-24. https://www.ncbi.nlm.nih.gov/pubmed/24413553
  7. Thalin C, Blomgren B, Mobarrez F, et al. Trousseau’s syndrome, a previously unrecognized condition in acute ischemic stroke associated with myocardial injury. Journal of Investigative Medicine High Impact Case Reports.2014. DOI:10.1177/2324709614539283. https://www.ncbi.nlm.nih.gov/pubmed/26425612
  8. Samuels MA, King MA, Balis U. CPC, Case 31-2002. N Engl J Med 2002;347:1187-94. https://www.nejm.org/doi/pdf/10.1056/NEJMcpc020117?articleTools=true

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My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

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

Short answer: often not! 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. 1-4  

In fact, in a study involving patients with CRF, 57% of patients had markedly elevated 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

 

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

What is the significance of Terry’s or Lindsay’s nails in my hospitalized patient?

Terry’s nails were first described in 1954 in patients with hepatic cirrhosis (prevalence 82%, majority related to alcohol abuse) (1). Since then, they have been reported in a variety of other conditions, including adult-onset diabetes mellitus (AODM), chronic congestive heart failure, chronic renal failure, pulmonary tuberculosis, and Reiter’s syndrome (2).

A 1984 study found Terry’s nails in 25% of hospitalized patients (3).  In this study, cirrhosis, chronic congestive heart failure, and AODM were significantly associated with Terry’s nails, while pulmonary tuberculosis, rheumatoid arthritis and cancer were not. The presence of Terry’s nails may be particularly concerning in patients 50 y of age or younger as it increases the relative risk of cirrhosis, chronic congestive heart failure or AODM by 5-fold (18-fold for cirrhosis alone) in this age group (3).

Terry’s nails should be distinguished from Lindsay’s nails or “half and half” nails. Although both nail abnormalities are characterized by an opaque white proximal portion, Terry’s nails have a thinner distal pink to brown transverse band no more than 3 mm wide (3) (Fig 1), while the same anomaly is wider and occupies 20%-60% of the nail bed in Lindsay’s nails (Fig 2). Of interest, Lindsay’s nails have been reported in up to 40% of patients with chronic kidney disease (4,5).

References

1. Terry R. White nails in hepatic cirrhosis. Lancet 1954;266:757-59. https://www.ncbi.nlm.nih.gov/pubmed/13153107 
2. Nia AM, Ederer S, Dahlem K, et al. Terry’s nails: a window to systemic diseases. Am J Med 2011;124:603-604. https://www.ncbi.nlm.nih.gov/pubmed/21683827 
3. Holzberg M, Walker HK. Terry’s nails: revised definitions and new correlations. Lancet 1984;1(8382):896-99. https://www.ncbi.nlm.nih.gov/pubmed/6143196 
4. Pitukweerakul S, Pilla S. Terry’s nails and Lindsay’s nails: Two nail abnormalities in chronic systemic diseases. J Gen Intern Med 31;970.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945547/ 
5. Gagnon AL, Desai T. Dermatological diseases in patients with chronic kidney disease 2013;2:104-109.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891143/

Figure 1. Terry’s nails in a patient with end-stage liver disease

Figure 2. Lindsay’s nails in a patient with chronic kidney disease

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What is the significance of Terry’s or Lindsay’s nails in my hospitalized patient?

Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

Although there are many potential sources for Klebsiella sp. bacteremia, C. difficile infection (CDI) itself may be associated with GI translocation of enteric organisms.

A retrospective study of over 1300 patients found an incidence of 1.8% for CDI-associated bacteremia. E. coli, Klebsiella sp. , or Enterococcus sp. accounted for 72% of cases. History of malignancy, neutropenia (at the time of CDAD), and younger age (mean 59 y) were among the risk factors.1 Another study reported over 20 cases of bacteremia caused by C. difficile plus other bacteria often of enteric origin such the aforementioned organisms, Bacteroides sp, Candida sp, and Enterobacter sp.2

CDI is thought to predispose to bacterial translocation through the GI tract by alteration of mucosal indigenous microflora, overgrowth of certain pathogens, and presence of inflammation in the mucosa.3 Interestingly, C. difficile toxin A or B may play an active role in the bacterial adherence and penetration of the intestinal epithelial barrier.4  

Bonus pearl: Did you know that C. difficile may be found in the normal intestinal flora of 3% of healthy adults, 15-30% of hospitalized patients, and up to 50% of neonates? Why neonates seem immune to CDI is another fascinating story!

 

References

  1. Censullo A, Grein J, Madhusudhan M, et al. Bacteremia associated with Clostridium difficile colitis: incidence, risk factors, and outcomes. Open Forum Infectious Diseases, Volume 2, Issue suppl_1, 1 December 2015, 943, https://doi.org/10.1093/ofid/ofv133.659 https://academic.oup.com/ofid/article/2/suppl_1/943/2635179
  2. Kazanji N, Gjeorgjievski M, Yadav S, et al. Monomicrobial vs polymicrobial Clostridum difficile bacteremia: A case report and review of the literature. Am J Med 2015;128:e19-e26. https://www.amjmed.com/article/S0002-9343(15)00458-1/abstract
  3. Naaber P, Mikelsaar RH, Salminen S, et al. Bacterial translocation, intestinal microflora and morphological changes of intestinal mucosa in experimental models of Clostridium difficile infection. J Med Microbiol 1998; 47: 591-8. https://www.ncbi.nlm.nih.gov/pubmed/9839563 
  4. Clostridium difficile toxins may augment bacterial penetration of intestinal epithelium. Arch Surg 1999;134: 1235-1242. https://jamanetwork.com/journals/jamasurgery/fullarticle/390434
Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

My bed-bound, debilitated patient is being transferred to a long-term facility (LTF). Should I continue the venous thromboembolism (VTE) prophylaxis she has been receiving in the hospital?

There are no randomized-controlled studies that examine the effectiveness of VTE prophylaxis in debilitated patients following discharge from the hospital, and currently  the literature does not recommend prophylaxis for chronic immobility as a single risk factor for VTE (1). However, given the expected morbidity, potential mortality and hospital readmission associated with VTE,  prophylaxis should be considered in residents of LTFs with the following comorbidities (2):

  • Acute exacerbation of congestive heart failure
  • Acute exacerbation of chronic obstructive pulmonary disease
  • Acute infection (e. g. pneumonia, urosepsis, skin and soft tissue infections, infectious diarrhea)
  • Acute exacerbation of inflammatory/autoimmune diseases
  • Active malignancy
  • Immobility and prior VTE

 

Unless contraindicated, patients should receive prophylactic doses of unfractionated heparin, enoxaparin, or other approved drugs. Mechanical VTE prophylaxis should be used only when the risk of bleeding is considered unacceptably high or when there are drug intolerances or adverse effects.

The need for VTE prophylaxis should be reassessed regularly taking into account patient’s overall health status, mobility, drug tolerance and goals of care.

 

References

  1. Pai M, Douketis JD. Preventing venous thromboembolism in long-term care residents: Cautious advice based on limited data. Cleveland Clin J Med 2010;77: 123-130.  https://www.ncbi.nlm.nih.gov/pubmed/20124270    
  2. Robinson Am. Venous thromboembolism prophylaxis for chronically immobilized long-term care residents. Ann Long-Term Care 2013;10:30. https://www.managedhealthcareconnect.com/article/venous-thromboembolism-prophylaxis-chronically-immobilized-long-term-care-residents
My bed-bound, debilitated patient is being transferred to a long-term facility (LTF). Should I continue the venous thromboembolism (VTE) prophylaxis she has been receiving in the hospital?

Besides malignancy, what other causes of cachexia should we usually consider in our hospitalized patients?

Although cachexia , a loss of >5% body weight over 12 months,  has been reported in about 30% of patients with cancer, many other chronic conditions  commonly encountered in our hospitalized patients may also be a culprit.  In fact, cachexia is not infrequent in CHF (20%), COPD (20%), kidney failure (40%), or rheumatoid arthritis (10%) (1,2).  We also shouldn’t overlook HIV and tuberculosis as a cause.

Cachexia is a multifactorial disease which does not fully reverse with nutritional support.  Numerous mediators have been implicated, including cytokines such as tumor-necrosis factor-α, and interleukin [IL]-1 and -6, as well as transforming growth factors such as myostatin and activin A (2). 

In patients with CHF, angiotensin II appears to be a key mediator, associated with insulin resistance, depletion of  ATP in skeletal muscles, poor appetite, reduction in insulin-like growth factor-1 (IGF-1), and an increase in glucocorticoid and IL-6 levels.  All these factors contribute to “cardiac cachexia” through muscle wasting, reduced food intake and lower muscle regeneration. 

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References

  1. Morely JE, Thomas DR, Wilson M-M G. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 2006;83:735-43. https://www.ncbi.nlm.nih.gov/pubmed/16600922
  2. Yoshida T, Delafontaine P. Mechanisms of cachexia in chronic disease states. Am J Med Sci 2015;35:250-256. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587350/
Besides malignancy, what other causes of cachexia should we usually consider in our hospitalized patients?