Quality Corner – Crohn’s Disease, Tachycardia, Thrombocytosis; Angioedema – Treatment and Disposition

Author: Christine Kulstad, MD (EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Welcome to Quality Corner, an emDocs series evaluating tough cases and potential areas for improvement. The cases described below are based on ED bouncebacks, with all identifying details removed, and are limited to what was documented in the medical record.

Case 1 – Crohn’s Disease

A 25-year-old male with a past medical history of Crohn’s disease and anemia presented with diffuse abdominal pain, vomiting, and diarrhea for 2 days. He had a heart rate of 130 on arrival, but otherwise normal vital signs. His abdominal exam did not show focal tenderness or peritonitis. A CBC, CMP, lipase, UA, and lactate were ordered. He was given 2 L of IVF. His labs were unremarkable except for a hemoglobin of 9.3 and a platelet count of 615. He was discharged with iron supplementation and instructed to keep his upcoming appointment with his gastroenterologist in 10 days.

He returned 16 hours later with persistent pain. At that point, it was noted that his heart rate at the time of discharge was 115. Repeat blood work showed a hemoglobin of 6.5 and an elevated ESR and CRP. He was given more IVF, 2 units of pRBCs, ciprofloxacin, and metronidazole, and then admitted with a GI consult.

There are several things to consider in this case, from documentation to systems problems to knowledge review.

1. Crohn’s patients often have GI bleeding, but this was not documented (history or exam) on the first visit. His second visit note says he had been having blood in stool x 3 days. We all know history can change from one provider to another, but get in the habit of asking and documenting this. No doubt his history of anemia provided false reassurance that his hemoglobin of 9.3 was not serious.

2. Next a common system issue – he was discharged with tachycardia. It frequently happens that vitals are measured after the order to discharge and are not always seen by the responsible provider. Check that abnormal vitals have normalized prior to discharge, or explain why you think they don’t need to.

3. It’s also advisable to have at least 2 exams documented on every patient you see with abdominal pain. If the patient is being discharged, the second documented exam should say he/she is better and tolerating PO.

4. Last, knowledge review – This patient had platelets > 600 on the first visit. Thrombocytosis occurs in infections, postsurgical states, malignancy, post-splenectomy state, acute blood loss, iron deficiency, or as a side effect of certain medications (Tefferi, 2017). Think of it as an even less specific inflammatory marker – something to explain if you’re sending someone home.

For Crohn’s flares, there is no agreed upon scoring system to determine severity. Reviewing the medications list can provide some clue to baseline severity- none vs sulfasalazine vs immunomodulators or biologics. Checking an ESR and CRP can assist, though these are not always included in the standard abdominal pain work-up (AS., 2013). Physical exam remains critical – tender masses or peritonitis suggest more severe flare.

Ideally, management of this chronic disease would be initiated with the input of your friendly local gastroenterologist, but this may not easy to obtain at all hours in every ED. In the patient with mild to moderate disease, treatment has traditionally started with medications like sulfasalazine or mesalamine, although they are no longer recommended by the American College of Gastroenterology due to lack of effect. For an acute flare, start steroids such as prednisone 40-60 mg daily (Lichtenstein GR, 2009). Be generous with supportive care, as IVF and anti-emetics may keep them from bouncing back. Outpatient care is appropriate, assuming they have follow-up or that it can be arranged. For those who have more severe disease including a concerning exam, elevated inflammatory markers, or fever, order a CT with IV contrast. Start antibiotics (ciprofloxacin/metronidazole or rifaximin if allergic) and steroids (Lichtenstein GR, 2009) (AS., 2013). These patients should be admitted with a GI consult.


  • Make sure abnormal vitals have normalized, or explain why they didn’t need to.
  • Thrombocytosis is non-specific but may be found with blood loss and infection.
  • Check ESR/CRP on most Crohn’s flares to help determine severity.
  • Consult GI for further input regarding evaluation and management.

Additional reading:

Tefferi, A (2017). Approach to the patient with thrombocytosis. In L. K. Leung (Ed.), UpToDate. https://www.uptodate.com/contents/approach-to-the-patient-with-thrombocytosis

Cheifetz AS. Management of active Crohn disease. JAMA. 2013 May 22;309(20):2150-8. doi: 10.1001/jama.2013.4466.

Lichtenstein GR, Hanauer SB, Sandborn WJ; Practice Parameters Committee of American College of Gastroenterology. Management of Crohn’s disease in adults. Am J Gastroenterol. 2009 Feb;104(2):465-83; quiz 464, 484. doi: 10.1038/ajg.2008.168.

Case 2 – Angioedema

A 53-year-old woman presented with right sided facial swelling to her lips and lower face but without airway obstruction. She had a history of hypertension and had been taking lisinopril for 7 months. She was treated with methylprednisolone, diphenhydramine, and ranitidine. After a brief observation in the ED, it was documented that her swelling improved and that she was tolerating PO. She was told to stop lisinopril, start losartan, and was discharged. She returned 4 hours later with worsening swelling and was admitted to the MICU for airway monitoring.

1. How do we treat angioedema? Many people start with the treatments for anaphylaxis with H1 and H2 blockers, steroids, and possibly IM epinephrine. These medications will likely have no effect if the cause is angioedema, but if the cause is not clear cut, they are relatively benign medications to try. The biggest downside may be the delay to using more effective therapies. First a brief review: ACE-I’s inhibit the angiotensin converting enzyme (ACE) which degrades bradykinin. The excess bradykinin is thought to lead to edema in susceptible individuals. Two medications have been developed to treat hereditary angioedema and have been tried in ACE-I induced angioedema (Riha HM, 2017). The first, ecallantide, inhibits production of bradykinin. Mechanistically, it seems unlikely to reverse the edema that is already in place, and low quality studies show mixed results (Riha HM, 2017). The second medication, icatibant, is a bradykinin receptor antagonist, so it sounds more promising. A small study published in the NEJM in 2015 did show a positive effect, but the drug’s expense limited its adoption (Baş M, 2015). That was probably a good thing as a larger RCT by Sinert et al published in 2107 showed no effect (Sinert R & group., 2017).

So what can you use? FFP. It contains the ACE enzyme which degrades existent bradykinin and improves edema in 2-4 hours. Give 2 units, if your patient can tolerate the volume (Guyer, 2017). Although there has not been an RCT to demonstrate its effectiveness, it is widely available, relatively inexpensive, and has case reports to support its use. The only problem is the delay inherent in administering FFP, which typically requires typing and time to thaw.  It can also worsen the condition due to the presence of several other factors associated with angioedema, thus warranting close monitoring of the patient.

2. The next question (assuming immediate airway intervention is not needed) that complicates management of these patients is disposition. Can you ever send them home from the ED? Do all have to go to the MICU? It helps to know that the swelling peaks over minutes to hours. If the patient started noticing lip swelling 24 hours ago and finally gave into their significant other nagging them to get it checked out, it’s unlikely to progress to airway closure. The swelling will typically last 24-72 hours, but can persist for up to 5 days (Guyer, 2017). When/where to admit will depend on the practice patterns in your hospital, how long the patient has been affected, and the risk tolerance of both you and your patient.

3. Discharge instructions – Foremost, advise the patient to avoid ACE-I in the future. Update their EMR to reflect the involved medication as an allergy. Secondly, the patient will likely need another medication to treat their hypertension. In the ideal setting, the patient’s primary care provider will choose the agent. However, many of our patients lack timely access to a PCP and may need you to prescribe something. Two systematic reviews suggested the recurrence of angioedema with an ARB was up to 10%, making it seem a risky choice (Haymore BR, 2008)(Beavers CJ, 2011).  Another meta-analysis found the risk of angioedema related to ARB use to be equal to that of placebo (Makani H, 2012), justifying their use in patients in whom this class may be superior to other anti-hypertensive medications. This is another time when shared decision making will help.


  • Angioedema peaks in hours and can last for days.
  • FFP is the most reliable treatment, which may work in 2-4 hours.
  • Disposition depends on length of symptoms and available monitoring.
  • Instruct your patient to avoid ACE-I in the future. ARBs can be used in this patient population, but have some risk.

Additional reading:

Riha HM, Summers BB, Rivera JV, Van Berkel MA. Novel Therapies for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review of Current Evidence. J Emerg Med. 2017 Nov;53(5):662-679.

Baş M, Greve J, Stelter K, Havel M, Strassen U, Rotter N, Veit J, Schossow B, Hapfelmeier A, Kehl V, Kojda G, Hoffmann TK. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015 Jan 29;372(5):418-25.

Sinert R, Levy P, Bernstein JA, Body R, Sivilotti MLA, Moellman J, Schranz J, Baptista J, Kimura A, Nothaft W; CAMEO study group. Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema. J Allergy Clin Immunol Pract. 2017 Sep – Oct;5(5):1402-1409.e3.

Guyer, A. B. (2017, Oct). ACE inhibitor-induced angioedema. (S. Saini, Ed.) Retrieved from UptoDate: https://www.uptodate.com/contents/ace-inhibitor-induced-angioedema

Haymore BR, Y. J. (2008, Nov). Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis. Ann Allergy Asthma Immunol, 101(5), 495-9.

Makani H, M. F.-P. (2012, Aug). Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors. Am J Cardiol, 110(3), 383-91.

Beavers CJ, D. S. (2011, Apr). The role of angiotensin receptor blockers in patients with angiotensin-converting enzyme inhibitor-induced angioedema. Ann Pharmacother, 45(4), 520-4.


The post Quality Corner – Crohn’s Disease, Tachycardia, Thrombocytosis; Angioedema – Treatment and Disposition appeared first on emDOCs.net - Emergency Medicine Education.

Quality Corner – The Bleeding Fistula and Neutropenic Fever

Author: Christine Kulstad, MD (EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Welcome to Quality Corner, a new emDocs series evaluating tough cases and potential areas for improvement. The cases described below are based on ED bouncebacks, with all identifying details removed, and are limited to what was documented in the medical record.

Case 1 – The Bleeding Fistula

A 52-year-old man was sent from his hemodialysis (HD) center for an AV fistula problem. He had completed his dialysis session, but the center was unable to stop the bleeding afterwards. He arrived with normal vital signs and no other complaints. Of note, he was taking warfarin and had an INR of 6. The initial provider documented that the bleeding was controlled with one stitch, the patient was briefly observed, and he was discharged. He returned to the ED 2 days later with a complaint of non-functional fistula and was admitted for an angioplasty of his fistula. Could this have been avoided?

Bleeding from AV fistulas can be life threatening due to the poor function of platelets in renal failure, the use of anticoagulation during HD, and the frequent presence of aneurysms at the fistula site. This patient had the additional bleeding risk factor of a supra-therapeutic INR. For life or limb threatening bleeding, application of a suture or even a tourniquet at the bleeding site is clearly appropriate. For less severe bleeding, start simple and add therapies as needed. First apply direct pressure, which has probably been tried at the dialysis center, so add topical agents to promote clotting like Gelfoam, thrombin powder, or whichever combat dressing your hospital uses. If the bleeding has not stopped, give IV DDAVP to improve platelet function. The dose is ten-fold higher than when used for DI, and it has an onset of action within one hour (Hedges SJ, 2007). Estrogens can be used for bleeding in renal failure but take up to 6 hours for maximal effect (Hedges SJ, 2007). Literature review found no studies evaluating topical TXA for this specific indication, but there is evidence of its effectiveness for stopping bleeding in operative settings and epistaxis. In this patient, reversal of INR should be considered, depending on his reason for anti-coagulation and the difficulty of controlling the bleeding. PCC would be preferred, as it would reverse his anticoagulation in about 30 minutes (Leissinger CA, 2008) and not require as much volume as FFP for this HD patient.

Take Home Points:

  • Avoid sutures or tourniquets for AV fistulas (or grafts) unless life or limb threatening bleeding is occurring.
  • Many topical agents – from thrombin powder to combat dressings to TXA – exist to help stop the bleeding.
  • IV DDAVP improves the platelet dysfunction in renal failure patients.

Case 2 – Neutropenic Fever

A 24-year-old male with a PMH of ALL currently undergoing chemotherapy, came to the ED for fever. His initial vital signs were HR 102, Temp 37.2, RR 16, BP 128/70.  He had no symptoms to suggest a source of infection. His evaluation included a normal UA and CXR, unremarkable BMP, and a CBC that showed an absolute neutrophil count of 150. He was given IVF and pain control in the ED, and felt improved. He was then discharged with instructions to follow-up with his oncologist.

He returned 24 hours later with a complaint of persistent fevers and pus draining from his PICC line. His heart rate on this visit was 128, with a normal temperature. He was given broad spectrum antibiotics and admitted for neutropenia and PICC line infection. At both visits, he reported a Tmax at home of 102 F, although he was never febrile in the ED. Although it may have been examined, no mention was made of his PICC line in the chart for his first visit, only the ubiquitous “Skin: warm and dry”.

The IDSA defines fever in neutropenic patients as either a single oral temp of greater than 38.3 C or a temperature greater than 38.0 C for more than 1 hour (Freifeld AG & America.). Our patient, with his single oral temp of 102 F (38.9 C), easily qualifies. As a reminder, neutropenia is technically defined by an ANC of less than 1500 cells µL, although a patient with “neutropenic fever” is usually one with severe neutropenia defined by an ANC < 500 cells/µL (Freifeld AG & America., 2011). Our patient was severely neutropenic but did not have a fever in the ED, which likely falsely reassured his provider. Patients with documented fever at home should be treated as if febrile in the ED. Patients, and even providers, are not as accurate in determining fever by symptoms or touch (Singh M, 2003).

The potential sources of fever in the neutropenic patient are considerable, but the most common identified cause is bacteremia (Freifeld AG & America., 2011). All patients should have blood cultures and a CBC with differential ordered, and a UA and CXR should be strongly considered. A good physical exam must be performed, including careful examination of the skin, especially indwelling lines. Digital rectal exam or rectal temp should be avoided, as it may allow GI flora to cross the mucosa. Additional findings, like abdominal tenderness or neck stiffness, guide further testing.

Broad spectrum antibiotics should be given within 60 minutes of patient presentation. Monotherapy with an anti-pseudomonal beta-lactam like cefepime, imipenem, or piperacillin-tazobactam is appropriate for most patients. If patients have pneumonia, skin or soft tissue infections, suspected catheter infection, or are septic, add vancomycin – Vanc/Zosyn for all your sepsis needs (Freifeld AG & America., 2011).

Most of these patients will be admitted, however, carefully selected patients can be discharged. They must look and feel well, display normal vitals, and have excellent follow-up. The decision to discharge should be made in conjunction with their oncologist. The CISNE (Clinical Index of Stable Febrile Neutropenia) score can also help support that decision (Carmona-Bayonas A, 2011) (Coyne CJ, 2017).  Like all clinical decision rules, it’s important to apply to patients it was designed for, namely well-appearing patients. It uses a 7-day outcome of complications: hypotension, arrhythmia, heart or renal failure, major bleeding, respiratory failure, DIC, acute abdomen, or delirium, which seem reasonable as serious patient-oriented outcomes. Most of the score components are easy to determine, except the ECOG score– a marker of the effect of illness on patients. It ranges from Asymptomatic to Dead, with the middle ground being symptomatic with greater or less than 50% of your day spent in bed. Both can be found on MDCalc.

Importantly, discharged patients should receive a dose of antibiotics in the ED and continue oral antibiotics at home. ASCO guidelines recommend a fluoroquinolone + amoxicillin/clavulanate or fluoroquinolone+ clindamycin (Flowers CR S. J., 2013) in the PCN allergic patient.

Take Home Points:

  • Neutropenic patients with a measured temperature greater than 38 C, even at home, need rapid, thorough evaluation.
  • Patients with neutropenic fever should have blood cultures and broad spectrum IV antibiotics within 60 minutes of arrival to the ED.
  • Carefully selected patients with excellent follow up can be managed as outpatients, with oral antibiotics.

References/Further Reading:

Carmona-Bayonas A, G. J.-B. (2011). Prognostic evaluation of febrile. Br J Cancer., 105(5), 612-7.

Coyne CJ, L. V. (2017). Application of the MASCC and CISNE Risk-Stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department. Ann Emerg Med, 69(6), 755-64.

Flowers CR, S. J. (2013). Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol, 31(6), 794-810.

Flowers CR, S. J. (n.d.). Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of C.

Freifeld AG, B. E., & America., I. D. (2011). Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis, 52(4), e56-93.

Hedges SJ, D. S. (2007). Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol, 3(3), 138-53.

Leissinger CA, B. P. (2008). Role of prothrombin complex concentrates in reversing warfarin anticoagulation: A review of the literature. Am J Hematol., 83, 137-43.

Singh M, P. M. (2003). Accuracy of perception and touch for detecting fever in adults: a hospital-based study from a rural, tertiary hospital in Central India. Trop Med Int Health., 8(5), 408-14.


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