Hot Seat Case #39 Denouement: 5 yo at OSH who “doesn't look right”

by Katie Donnelly, Children’s National
with Paul Mullan, Children's National, on the Hot Seat

The Case
This is a case of a 5 yo girl being transferred from an OSH because she “doesn’t look right” who has tachypnea and emesis.  The challenge in this case is how to approach a patient with initial findings of hepatosplenomegaly and leukocytosis. 

For a complete case presentation, please click here. 

Here's How You Answered Our Questions 

In light of this CXR, would you order any additional studies while awaiting the results of the bloodwork? 

Less than 3 years PEM experience (fellows, PAs/NPs, pediatricians) n=10

More than 3 years PEM experience (PEM attendings, pediatricians) n=12

PEM providers of all years experience agreed.  The majority would obtain an EKG.  Several would also get an ECHO with Cardiology consult.

Case continues: You receive a call from the lab with a critical WBC 800,000. The CMP is still pending. You go to assess the patient, who is clinically unchanged.  

One more question for you

What is your next management priority?

Less than 3 years PEM experience (fellows, PAs/NPs, pediatricians) n=9

More than 3 years PEM experience (PEM attendings, pediatricians) n=12

PEM providers with less than 3 years experience gave a normal saline bolus and started 1.5 x MIVFs (no potassium, as worried about tumor lysis).  One person stated that "other" for tumor lysis labs.  PEM providers with more than 3 years experience ordered 1.5x MIVFs followed by NS bolus/"other".  Three people put "other" for "more labs (LFTs, LDH, uric acid)," "I-stat electrolytes and gas," and "consider rasburicase."

Clinical Reasoning 

Thank you to the several attendings that left very insightful comments about this case!  Overall themes include the need to obtain tumor lysis labs (iStat lytes, gas, LDH, uric acid, Ca, Phos, Mg, CMP).  Additional excellent discussion topics include the use of rasburicase vs allopurinol.  Also, in the setting of hyper-leukocytosis, one should think about PICU admission for central line access and leukapheresis.  For complete comments, click here.

“If the WBC is really 800K (not 80K), with huge hepatosplenomegaly, this is leukemia until proven otherwise… With WBC that high, the serum K level is much more accurate on a non-spun specimen (such as from an I-Stat instead of sending to the lab), as leukemic WBCs are typically "leaky". Rasburicase is better than allopurinol in this setting in getting uric acid under control”. - Dewesh Agrawal, Children's National

“One of the big risks of hyper-leukocytosis is sludging, which can lead to high-output cardiac failure or stroke. My next step would be to get the kid to a place where he/she could get a big honkin' 7F line in the groin for an exchange transfusion [plasmapheresis]…You can do some hemodilution with IVF but have to be careful not to give any bulky fluids (PRBCs) since they can precipitate stroke.  Rasburicase is super $$$$, so not sure the role if the patient is getting exchanged regardless.” – David Mathison, Children's National

“Plasmapheresis is when plasma is removed and donor plasma is given. Used in TTP, HUS, Autoimmune diseases , Good pastures etc.”  VS.  “Exchange transfusion is where you remove blood (not plasma) and replace it with good donor blood example : sickle cell with acute chest syndrome where blood removed from sickler and transfused again with normal blood” – Breanna Barger, Johns Hopkins

“The highest priority is plasmapheresis, so moving her to the PICU is the focused goal… no longer recommended to alkalinize the urine because of the risk of precipitating Ca-phos product.” – Jennifer Chapman, Children's National

“Can't ignore a WBC of 800k… If blasts are seen, you have your diagnosis. While waiting for plasmapheresis and transfer to the PICU, giving a NS bolus would probably be beneficial for the marked leukocytosis. Perhaps check an EKG (+/- ECHO) before doing so to make sure you're not fluid overloading a 'sick' heart… and calls to the Hem/Onc, Cardiology.” – Jamil Madati, Children's National

From the Hot Seat
by Paul Mullan, Children's National

DDx for HSM that's likely cancer-related with that WBC and mediastinal mass:

- Leukemia, Lymphoma

- Neuroblastoma

- Hepatic cancer (less common than above types; screen with alpha-fetoprotein and CT).

- Histiocytic (these are hard to remember but I have an assortment of specific findings I look for and if I don't see at least a couple of these, this falls lower on ddx:  cytopenias or cytopenic suggested symptoms noted, skin findings papular or seborrheic, diabetes insipidus symptoms, lymphadenopathy, loose teeth - although that picture suggests maybe some loose ones!). 

The hyperleukocytosis (>50-100K WBC) pushes me toward the dx of ALL in a major way (esp Tcell ALL with that mediastinal mass ugliness on CXR), so the oncology fellow is on their way in from home to look at the slide, but in the ED at this moment I'm worried about potential for leukostasis (that is, when hyperleukocytosis causes symptoms which can affect many organ systems) - so by system, what to worry about, and what to do about it...

1. CNS:  increase ICP, bleed, seizures, AMS, focal deficits, CVA, coma; no signs of this now in this patient; continue to monitor.

2. Blood/Lytes:  

a.Tumor lysis syndrome (TLS) ; this usually begins after chemo starts but can occur prior to chemo. CMP might be pending, but double check that it's not being done and in meantime add some more labs:  Istat with lytes, uric acid, LDH, CBC, T&S, DIC panel.  Reducing wbc can happen with chemo, leucopheresis, or hydroxyurea but this will happen in ICU so not really our acute issue right now. Prophylaxis and treatment for TLS (according to most recent American Society of Clinical Oncology guidelines - by Coiffier B,et al JCO 2008;26(16): 2767-2778.) is two fold: 

1st: Hydration  with D5 1/4 NS at 3L/m2/day with goal of equal ins and outs; if already oliguric or in renal failure, d/w renal/onco on how they prefer to hydrate. 

2nd: Uric acid reduction. Two choices: allopurinol and rasburicase. The ASCO guidelines recommend first determining if patient is low risk, intermediate risk, or high risk; another fun article (Brit J Hem 2010;149:578-586) details this risk classification, but assuming this is leukemia, the >100k puts this pt in high risk zone regardless of leukemic subtype or LDH level. High risk patients get rasburicase (medium risk gets allopurinol or rasburicase; low risk gets nothing but monitoring); given contraindication to rasburicase is G6PD, definitive testing for this condition is recommended. Rasburicase is expensive but cost effectiveness studies show that it decreases ICU days, renal failure incidence, etc. and ends up saving money.  

- As Jen stated, alkalinization is no longer recommended - it was never proven effective and can increase precipitation of CaPhos crystals in urine.

- Hyperuricemia: can lead to uric acid crystallization in kidneys  -->  acute renal failure; see uric acid reduction tx above.

- Hyperkalemia (can also be spurious from leukemic blast degradation; Istat is most accurate), worry about EKG changes that lead to VT/VF/arrest; treat if >6 with standard hyperK tx and NO iv or po potassium intake. 

- Hyperphosphatemia: leads to n/v/d (worsens hydration state which is key for TLS) and can cause lethargy/seizures which makes one think of CNS leucostasis symptoms and thus complicates the workup; if Ca x Phos is >70, can get CaPho precipitation in kidneys;  therapy is hydration and phosphate binders (calcium carbonate, aluminum hydroxide) ; if severe or not decreasing, then hemodialysis. 

- Hypocalcemia: can lead to cramps/tetany and worse cases hypotension/arrhythmias.  If symptomatic, given ca gluc 50 mg/kg IV slowly with ekg monitoring.

b. DIC and thrombocytopenia; except for the photo that shows bleeding around the gums (vs tartar?), no indication of this for now, but have sent the labs above.

2. Lungs: hypoxemia (can get false low pO2 on ABG because leucocytes use up the O2), respiratory distress (made worse in her by this mediastinal mass on CXR - I would NOT get a chest CT as laying these patients down can precipitate resp failure - I would sit her up in bed, add O2 by NRB facemask, and see if this helps her tachypneic state.

3. Renal failure: from the uric acid or ca-phos deposition; if oliguric or in renal failure, discuss with renal about IVF and diuretic management

4. Cardiac failure (get an EKG; heart failure is still a possibility with the HSM and tachypnea, but I would not necessarily get cards to the ED unless EKG was abnormal; myocarditis a possibility as a secondary infection, but unlikely as a primary one with >800k wbc, unless lab called and said white count was a lab error)

5. Less common in ED: GI (bleeds, abd pain), priapism, clitoral enlargement, dactylitis, many others.   

Disposition is certainly to the ICU in this symptomatic child with high interventional needs. 

The Denouement
by Katie Donnelly, Children’s National

The case was modified somewhat for the Hot Seat presentation and the actual case follows:

This 5 year old female initially presented to an referring hospital with a WBC count of 300 and a chest x-ray  that was concerning for cardiomegaly.  Repeat CBC at our institution (less then 8 hours later!) was notable for a WBC of 803 with 81% blasts, a hemoglobin of 6.4 and platelets of 30. Her uric acid was 8.6 and her LDH was 3,522.  Her potassium was initially reported as 20, repeat of 4, the erroneous result was attributed to her massive leukocytosis.  She had a bedside ultrasound which showed normal heart size and function and hepatosplenomegaly. Her repeat chest XR above was concerning for an anterior mediastinal mass. She was started on hyperhydration with one and a half times maintenance fluids without potassium  and rasburicase for hyperuricemia. She was admitted to the PICU.  Hematology and Transfusion Medicine were consulted and the patient underwent leukapheresis given her significant risk for stroke which reduced her WBC count to 500.  Her peripheral flow cytometry was consistent with Acute T-cell Lymphoma and she has started chemotherapy.  

Please answer the two quick questions below. The data helps inform our future case design. Thanks for participating.

Like the Hot Seat? Don't miss a case. Subscribe for email updates of new posts by adding subscribing in the field at the top of this page or by clicking here.

The Hot Seat is a recurrent online case series aimed at facilitating asynchronous sharing of PEM knowledge and experience. Faculty are placed on The Hot Seat and publish their opinions without knowing the case or its outcomes. Cases are based on real cases and written by PEM fellows at Children's National in DC, Johns Hopkins in MD, and INOVA Fairfax in VA to highlight teaching points. Emily Willner is the faculty advisor for the Hot Seat.