leviathan

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Had a weird case about a month ago, curious to see what others would do, and differential diagnosis, investigative workup etc. Identifying details have been changed to protect confidentiality. I will start the post with all the details when I took over her care. I can post the autopsy results at the end.

This was a 77 year old woman, admitted with acute abdominal pain. PMHx of hypertension and gout, appy/chole. Living independently, married, non smoker, reasonably healthy lady. CT scan of her abdomen showed some mural thickening and possible inflammatory/infectious changes in 25 cm of the small bowel. Clinically had peritonitis too. Went to the OR for an ex lap and ran the bowel which apparently looked fine, and just had some adhesions that were lysed. She's now post-op day 2, starting to eat a little bit, abdominal pain has resolved, starting to mobilize etc. However she was nauseated and vomited in the morning. She was on room air at that time with no issues.

In the evening she acutely drops her sats to the 70s coming up to the mid 80s on a non-rebreather. EKG shows a new right bundle branch block. Before I got there her sats recovered to the 90s and the surgeon decided to send for CT which is negative for PE but shows bibasilar airspace disease. Abdomen which shows improvement in the prior ischemic changes and no other new findings. When I see her she's now on high flow nasal O2 on 60% fio2, sats are 98, BP 130s, feeling much better, though still tachycardic in the 120s and probably too sick for the wards so I brought her to the ICU for closer monitoring (our stepdown unit was closed at the time). I figured she just aspirated and probably would recover quickly over the next 24hrs or so.

Shortly after arrival to the ICU she has a generalized tonic clonic seizure, and is now post-ictal. I decide to intubate her to protect her airway and send for a CT head which shows nothing acute. However she then very quickly ends up on very high doses of levophed to maintain a MAP of 65. She is anuric, cold, mottled and lactate is climbing.
 

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Labwork at this time:
WBC 0.8 (was 4.8 in the morning). Hgb 11 (was 10 earlier) Platelet count 90 (from 150). No schistocytes on smear. INR up to 1.9 and PTT up (was on dalteparin).
Extended lytes, urea, creatinine all normal.

Liver enzymes and bilirubin normal. Albumin 20.
 

Hork Bajir

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Interesting case. Multiple organ systems failing without clear driving process. Curious what her labs are, any clues there? Almost smells like vasculitis.
 
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Test for covid x2 and precautions until both back, broad spectrum abx (if not already done).

Tte--does she look dry? What is right heart doing after surgeons treated her presumed ischemic bowel? Did she get a ton of fluids over the last few days?
 

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Interesting case. Multiple organ systems failing without clear driving process. Curious what her labs are, any clues there? Almost smells like vasculitis.
Labs as above. I also wondered if there could be some systemic thing going on. For what it's worth, ANCAs, ANA, complements were all normal. Anything else you'd request for systemic processes? CRP was 400.

In this day and age, Covid test?
Echo? Even bedside Echo? Right heart looks like?
Troponins? How’s her abdominal exam?
As you might have guessed that was tested. COVID-19, RSV, Influenza PCR all negative. Abdomen was soft, non tender, and no concern for compartment syndrome.

Echo showed global LV dysfunction, EF about 30-35%. No known history of this so presumed to be on the basis of her acute illness. Troponins only mildly increased. Her ECG showed a right bundle branch block which was new, and that resolved with no major ST changes. RV size and function normal. No pericardial effusion. Lungs sliding well no pneumothorax. She was oxygenating reasonably well.

Test for covid x2 and precautions until both back, broad spectrum abx (if not already done).

Tte--does she look dry? What is right heart doing after surgeons treated her presumed ischemic bowel? Did she get a ton of fluids over the last few days?
She had a history of ESBL in a urine culture from 6 months prior, unclear why she had ESBL, but I put her on meropenem, vancomycin. Added hydrocort 50 q6h as well because I wondered if she had some sort of systemic inflammatory process and also due to the pressor requirements . She didn't seem dry on exam, IVC dilated and no variability (i dont believe in IVC but thats for another discussion), but also no stroke volume variability with passive leg raise (measured via LVOT VTI). I did empirically try 2 litres of fluid which didn't help urine output (she was anuric), or vasopressor requirements. As she had a low EF, cold, mottled, I changed her from levophed to epinephrine which didn't seem to help. Right heart was functioning well. With all the drips running she was getting plenty of fluid and so I wondered if I was overloading the RV as well, but it wasn't dilated and function was good.

Lactate as the night progressed was now 25. Platelets were down to 30, INR 2.6, transaminases now in the thousands. She remained anuric.
 
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chessknt

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I'm definitely on heart failure (left leading to right probably ? Critical illness cardiomyopathy) now given everything else even if the tte shows right heart looks ok. With other imaging not showing obvious infectious source and infectious workup normal I think uncontrolled sepsis is not causing this. Rapidly progressive vasculitis over several hours also seems unlikely especially since there is no consumptive coagulopathy occuring (eg ttp).

Lactate that bad with pan organ failure is probably past the point of no return but it's time to add crrt to get fluid off and add some inotrope to try to keep her alive long enough for it to maybe work. I liked the epi trial, would also add vaso. Goals of care to try to make no cpr since the writing is on the wall.

Edit--saw the dropping plt. If hb is stable and no schistocytes on repeat I'm going to attribute this to critical illness but otherwise ttp is back on the table especially since her initial odd bowel findings were never explained.
 
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leviathan

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I'm definitely on heart failure (left leading to right probably ? Critical illness cardiomyopathy) now given everything else even if the tte shows right heart looks ok. With other imaging not showing obvious infectious source and infectious workup normal I think uncontrolled sepsis is not causing this. Rapidly progressive vasculitis over several hours also seems unlikely especially since there is no consumptive coagulopathy occuring (eg ttp).

Lactate that bad with pan organ failure is probably past the point of no return but it's time to add crrt to get fluid off and add some inotrope to try to keep her alive long enough for it to maybe work. I liked the epi trial, would also add vaso. Goals of care to try to make no cpr since the writing is on the wall.
Yeah LV function was not great though not terrible either. Though i had asked the nurses to stop the levophed the reality is when the epi was added they were never able to wean the levo off. Vaso was added at some point during the night as well due to refractory hypotension.

Good thoughts about vasculitis unlikely being so rapid in nature, but there was evidence of consumptive coagulopathy with the platelets were dropping and INR /PTT were going up in a DIC picture, along with all the evidence of mottling in the extremities. I believe ctastrophic antiphospholipid antibody syndrome (CAPS) can present this rapidly, and I did test anti cardiolipin, lupus anticoagulant and PTT dade were all normal.

We did start to dialyze fluid off the patient at this point when oxygenation was worse. I didn't mention but ventilation/oxygenation were never terrible up front but I think the fluid start to catch up with her.

The patient was able to wean off all vasopressors and inotropes 48 hours after the initial event, but the platelets continued to fall more, the mottling got even worse (her toes/fingers were starting to look black), and she was still not waking up. An EEG was done as well given the seizure that happened, but was almost a complete flatline and no obvious seizure activity, and this was off all sedation.

We met with the family and given the multi organ failure and likelihood of either not surviving or needing a very prolonged course in ICU, the decision was made to withdraw care.

Still curious to hear if anyone would order other investigations, if anyone has thoughts on what might have tied together a woman with ?bowel ischemia, seizures, renal failure, cardiac involvement, etc. Her blood cultures, urine cultures were negative. Sputum cultures did grow light E.coli, which was resistant to pip tazo (glad i did the meropenem).
 
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Hork Bajir

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I’ve also seen cases of fulminant hepatic failure present similarly, if not quite as dramatically. No liver findings on her CT though?
 
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chocomorsel

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Labs as above. I also wondered if there could be some systemic thing going on. For what it's worth, ANCAs, ANA, complements were all normal. Anything else you'd request for systemic processes? CRP was 400.


As you might have guessed that was tested. COVID-19, RSV, Influenza PCR all negative. Abdomen was soft, non tender, and no concern for compartment syndrome.

Echo showed global LV dysfunction, EF about 30-35%. No known history of this so presumed to be on the basis of her acute illness. Troponins only mildly increased. Her ECG showed a right bundle branch block which was new, and that resolved with no major ST changes. RV size and function normal. No pericardial effusion. Lungs sliding well no pneumothorax. She was oxygenating reasonably well.


She had a history of ESBL in a urine culture from 6 months prior, unclear why she had ESBL, but I put her on meropenem, vancomycin. Added hydrocort 50 q6h as well because I wondered if she had some sort of systemic inflammatory process and also due to the pressor requirements . She didn't seem dry on exam, IVC dilated and no variability (i dont believe in IVC but thats for another discussion), but also no stroke volume variability with passive leg raise (measured via LVOT VTI). I did empirically try 2 litres of fluid which didn't help urine output (she was anuric), or vasopressor requirements. As she had a low EF, cold, mottled, I changed her from levophed to epinephrine which didn't seem to help. Right heart was functioning well. With all the drips running she was getting plenty of fluid and so I wondered if I was overloading the RV as well, but it wasn't dilated and function was good.

Lactate as the night progressed was now 25. Platelets were down to 30, INR 2.6, transaminases now in the thousands. She remained anuric.
Infarcted liver? I had initially asked about the Liver enzymes in my first post but then deleted it when read your post and you said it was normal.
But now things are progressing. A lactate that high, gotta come from somewhere or isn’t getting cleared. As in a bad liver. Was there an abdominal scan after the surgery? Edit, I see they scanned the belly after all. And since she got contrast I am assuming all her abd vessels are ok as well?
Not an expert on vasculitis tho.
Ammonia high?
 
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leviathan

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Infarcted liver? I had initially asked about the Liver enzymes in my first post but then deleted it when read your post and you said it was normal.
But now things are progressing. A lactate that high, gotta come from somewhere or isn’t getting cleared. As in a bad liver. Was there an abdominal scan after the surgery?

Ammonia high?
Liver probably packed it in by the second day there but originally was fine. I never did dopplers of the liver but i suppose it's still possible the initial event was ischemic liver. But she got sick before the liver enzymes went up rather than after.
 

Hork Bajir

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Maybe a silly thought, but could this all be driven by diffuse thrombosis from HIT? Assuming she was exposed to heparinoids at some point. Clots in her brain, liver, kidneys, bowel, etc touching off a DIC picture
 
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chessknt

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Maybe a silly thought, but could this all be driven by diffuse thrombosis from HIT? Assuming she was exposed to heparinoids at some point. Clots in her brain, liver, kidneys, bowel, etc touching off a DIC picture
Hitt possible but the inciting bowel event shouldn't have happened unless she was on lovenox at home.
 

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Maybe culture negative endocarditis showering emboli through the aorta?

I would add liver US to look at inflow and outflow for potential thrombosis.

Pancreatitis?

Seems like a very rough case
 
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leviathan

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Pancreas + liver looked normal on both CT scans. I can't remember if I checked a lipase. If it helps steer anyone in one direction, I also checked a ferritin and it came back at 79,000.
 
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chessknt

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Having treated several people with hlh (all but one died) it can be quite a bitch if that is what you are hinting at. Very hard to diagnose in a timely fashion and would help explain her neutropenia in the absence of sepsis. I can't say I've seen it present as seizure and rapid deterioration over a period of 8 hours though.
 
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economycian

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Sounds suspicious for CAPS or TTP.

I would send ADAMs test and start plasmapharesis, although at that stage given the extent of organ ischemia and patients age, withdrawing sounds like an appropriate decision too
 
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chocomorsel

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Having treated several people with hlh (all but one died) it can be quite a bitch if that is what you are hinting at. Very hard to diagnose in a timely fashion and would help explain her neutropenia in the absence of sepsis. I can't say I've seen it present as seizure and rapid deterioration over a period of 8 hours though.
This. Etiology Covid 19. Lol. That virus activates everything. I say she has a false negative test.
Ok, could be some other cause.
I have only ever seen HLH/MAS once in an SLE patient.
 
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chessknt

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What’s CAPS? Not an internist or practicing Intensivist here.
catastrophic antiphospholipid syndrome--A dramatic presentation where massive clotting occurs everywhere and looks like TTP. I was peripherally involved in a single case in all of training--it is super rare.

Both HLH and CAPS usually have an autoimmune association but this lady doesnt have any.
 
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economycian

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Was the ferritin measured before or after the ALT went into the 1000s?
 
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lymphocyte

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I also wonder about HLH given a bicytopenia, markedly high ferritin, and overall being sick as dog ****. What did the spleen look like clinically or on the CT scan?

I live in the land of Q-fever and have seen associated HLH three times - i.e. it's not always autoimmune related. I now check ferritin +/- lipids fairly often whenever I wonder about septic mimics.
 
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PTPoeny

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Did she have any (even mild) symptoms a month or two before presentation? Any fevers with the initial presentation? If yes MIS-C (or whatever they are calling it in adults, Google says there are now adult case reports) should be strongly considered and COVID antibody testing sent.

Probably too late now with the multi-organ failure and flat EEG to do any MIS-C specific treatment even if the story fits.
 

MoMoGesiologist

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Cancer with paraneoplastic NMDA encephalitis and clots/DIC everywhere? What’s the autopsy results!?
 
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leviathan

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Gross inspection on autopsy was pretty unremarkable. Heavy lungs (every autopsy i see has that line), lung consolidation as well, nutmeg appearing liver, grade 3/4 atherosclerosis in the LAD, etc. The terminal ileum was a bit dusky but not frankly infarcted or ischemic.

It's been a month and I'm still waiting to hear back on the bone marrow biopsy, the liver+kidney histopathologic analysis etc. The brain just had some neurofibrillary tangles / plques but nothing to suggest a vasculitis.

At the end of the day, I think she may have just had an aspiration pneumonitis with an extremely overwhelming inflammatory response causing DIC, microvascular clotting, the high ferritin (79,000) etc. I feel like I may never get a definitive answer on it.
 
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chocomorsel

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Gross inspection on autopsy was pretty unremarkable. Heavy lungs (every autopsy i see has that line), lung consolidation as well, nutmeg appearing liver, grade 3/4 atherosclerosis in the LAD, etc. The terminal ileum was a bit dusky but not frankly infarcted or ischemic.

It's been a month and I'm still waiting to hear back on the bone marrow biopsy, the liver+kidney histopathologic analysis etc. The brain just had some neurofibrillary tangles / plques but nothing to suggest a vasculitis.

At the end of the day, I think she may have just had an aspiration pneumonitis with an extremely overwhelming inflammatory response causing DIC, microvascular clotting, the high ferritin (79,000) etc. I feel like I may never get a definitive answer on it.
Damn. Way to string us along. Thought you had an answer and were testing us. You are giving us hints and everything like someone who's got answers.
And we may never know? That sucks. I don't like it. I need answers.
 
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leviathan

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Damn. Way to string us along. Thought you had an answer and were testing us. You are giving us hints and everything like someone who's got answers.
And we may never know? That sucks. I don't like it. I need answers.
Trust me, I need answers too. It wasn't my intent to string anyone along, though. I just didn't want to influence your thought process by knowing what I knew up front. I'm hopeful that I'll get some answers soon and will update you all with the results! I didn't expect the gross inspection to reveal anything, so it's all gonna (hopefully) come down to tissue/histopathology results. But my working diagnosis would just be an HLH-like inflammatory reaction to a chemical aspiration (or maybe bacterial given the positive sputum culture for E.coli).
 
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IIRC, the sky high ferritins actually make a diagnosis of HLH less likely. It should be up (500s to 1000s) but past the 10,000 mark, it's less likely than other autoimmune/inflammatory conditions.
 

chocomorsel

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IIRC, the sky high ferritins actually make a diagnosis of HLH less likely. It should be up (500s to 1000s) but past the 10,000 mark, it's less likely than other autoimmune/inflammatory conditions.
Didn't know this. The one I took care of had Ferittins in the 60K range if I remember correctly. She got Anikinra and came back from death. It was on my renal rotation and she looked like death at only 29 years old.
 
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MoMoGesiologist

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Does the geriatric crowd even mount that impressive of an inflammatory response? I can see a young person getting immune hyperactivation. This case sounds like sepsis. The way things were phrased made it seem like we were all missing something. Sometimes it really just is sepsis.
 

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IIRC, the sky high ferritins actually make a diagnosis of HLH less likely. It should be up (500s to 1000s) but past the 10,000 mark, it's less likely than other autoimmune/inflammatory conditions.

That’s not my understanding. Ferritin of over 10000 is usually only one of two things.. HLH or stills. Or massive liver injury.
 
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chocomorsel

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Does the geriatric crowd even mount that impressive of an inflammatory response? I can see a young person getting immune hyperactivation. This case sounds like sepsis. The way things were phrased made it seem like we were all missing something. Sometimes it really just is sepsis.
Even if it was sepsis, wouldn’t the resultant inflammation/immune response cause those numbers?
Are you saying the numbers aren’t accurate? Because she’s old?
Or that sepsis would cause such a crazy immune response whereas HLH wouldn’t?
 

chessknt

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Does the geriatric crowd even mount that impressive of an inflammatory response? I can see a young person getting immune hyperactivation. This case sounds like sepsis. The way things were phrased made it seem like we were all missing something. Sometimes it really just is sepsis.

Maybe... Seems dramatic without a clear source to me (belly cleared by CT and didn't respond to appropriate early abx). If she had massive aspiration and horrible oxygenation issues then I could get on board but the aspiration was assumed in this case and didn't seem to cause a significant local inflammatory reaction in the lungs aside from what the CT scanner picked up in the bases.

I still think her right heart may have **** the bed just by her age, delayed presentation, and the association of mesenteric ischemia with massive reflexive ivf bolus which may have accelerated her precipitous decline by takatsubos acutely. Hlh/caps is possible but given how extraordinarily rare they are if I was putting money down id go with old fashioned volume overload
 
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MoMoGesiologist

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Even if it was sepsis, wouldn’t the resultant inflammation/immune response cause those numbers?
Are you saying the numbers aren’t accurate? Because she’s old?
Or that sepsis would cause such a crazy immune response whereas HLH wouldn’t?
I’m sure the numbers are accurate. I’m just wondering how often the old get HLH. A lot of times old people don’t mount a great immune response, don’t get as tachy, as high of white counts, etc. Just very hard to differentiate sepsis from HLH IMO. I wonder what this pts HLH score was.
 

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My thoughts - I think the transient heart block is confounding and secondary to acuity of illness rather than part of the primary pathology. I'm leaning toward the ferritin being related to the ALF. I don't buy that she didn't have schisto's regardless of the smear. I think aggressive fluid removal was the right play. If she was someone I thought had a fighting chance I'd push for pheresis and have ECMO consult (though I dont think either were worthwhile in this case). Maybe trying an immunomodulator like anakinra, but it feels futile.

I wonder if she had something like nonocclusive mesenteric ischemia and just hadn't been nonviable when she was opened. Frustrating case. Hope you eventually get an answer.

IIRC, the sky high ferritins actually make a diagnosis of HLH less likely. It should be up (500s to 1000s) but past the 10,000 mark, it's less likely than other autoimmune/inflammatory conditions.

That’s not my understanding. Ferritin of over 10000 is usually only one of two things.. HLH or stills. Or massive liver injury.


Key notes - Hyperferritinemia is much more specific for HLH in peds than adults. Extreme hyperferritinemia is unusual in HLH (~20% with ferritin >50k). In extreme hyperferritinemia (>50k), HLH prevalence is about 20% (other differential being renal failure, hepatocellular injury, infectious, malignancy).
 
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chocomorsel

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My thoughts - I think the transient heart block is confounding and secondary to acuity of illness rather than part of the primary pathology. I'm leaning toward the ferritin being related to the ALF. I don't buy that she didn't have schisto's regardless of the smear. I think aggressive fluid removal was the right play. If she was someone I thought had a fighting chance I'd push for pheresis and have ECMO consult (though I dont think either were worthwhile in this case). Maybe trying an immunomodulator like anakinra, but it feels futile.

I wonder if she had something like nonocclusive mesenteric ischemia and just hadn't been nonviable when she was opened. Frustrating case. Hope you eventually get an answer.






Key notes - Hyperferritinemia is much more specific for HLH in peds than adults. Extreme hyperferritinemia is unusual in HLH (~20% with ferritin >50k). In extreme hyperferritinemia (>50k), HLH prevalence is about 20% (other differential being renal failure, hepatocellular injury, infectious, malignancy).
Great input. Although I think ECMO in a 77 year old is a bit extreme.
I was leaning towards Liver injury or mesenteric ischemia myself but with follow up CT not showing deadgut, I left the mesenteric one alone and still think it could be liver infarction or now possibly HLH driving this whole thing. Still think the Covid test is wrong though. She got the Covid and it’s the driver for all this. Haha
Hope we get answers.
 
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WheezyBaby

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Great input. Although I think ECMO in a 77 year old is a bit extreme.
I was leaning towards Liver injury or mesenteric ischemia myself but with follow up CT not showing deadgut, I left the mesenteric one alone and still think it could be liver infarction or now possibly HLH driving this whole thing. Still think the Covid test is wrong though. She got the Covid and it’s the driver for all this. Haha
Hope we get answers.

I forgot about the repeat CT as I read through the thread, I'd nix that etiology. I agree covids a possibility, but I havent heard of it leading to an initial presentation like this case. Not to say it can't. Womp womp
 
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IL-2RA would help rule out HLH in this case. If normal, it's off the table. If >2400 - now you got a serious discussion.

Can't just use ferritin and other lab markers which have endless confounding variables in cases like this.
 

chessknt

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IL-2RA would help rule out HLH in this case. If normal, it's off the table. If >2400 - now you got a serious discussion.

Can't just use ferritin and other lab markers which have endless confounding variables in cases like this.

That would take over a week to get back where I am, pt would be dead by then.
 
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