Acute liver failure due to iron overdose in an adult.

Zimmerman HJ. Deugnier YM, Loreal O, Turlin B, et al. There may end up being a number of
idiosyncratic component for the hepatotoxicity. Philadelphia, Lippincott, Williams & Wilkins, 1999,
ed 2, pp 346-347.
Reprint requests to Dr. she was not conscious of just about any drug allergies. J Toxicol Clin Toxicol
1987;25:347-359.
RELATED ARTICLE: key Points
Previous cases reported within the literature declare that the probability of hepatic injury raises
with increasing serum iron levels. We record a new case of severe hepatic injury in an adult who
overdosed upon iron tablets using suicidal intent. Thies JC, Teklote J, Clauer U, et al. Deferoxamine
had been administered, however the patient progressed in order to hepatic coma and also died 2
weeks later. Ten of those patients died along with three patients survived, a couple of involving
whom received chelation therapy, and one individual required liver transplantation. Peak serum iron
ranges occur approximately 6 hours following acute ingestion. Therefore, management with
intestinal decontamination, deferoxamine, and near monitoring should be considered, even with
peak serum levels lower than 400 [micro]g/dL. Most rights reserved. Therefore, the particular
decision to avoid therapy needs to be able to be based on the combination of clinical status, which
includes evidence of end-organ toxicity, urine color, and serum iron levels. Regardless of these
interventions, serum alanine aminotransferase (ALT) rose rapidly to end up being able to greater as
compared to 4,000 U/L on hospital day 2. There is actually certainly evidence for you to declare that
NAC is capable of reduce the severity of ischemia/reperfusion injury and also enhance postoperative
graft operate following liver transplantation. Neurologic examination ended up being unremarkable
as was her mental status. The Actual patient had had an altercation having a friend, and furthermore
the overdose has been together with suicidal intent. Henretig FM, Karl SR, Weintraub WH. Daram,
MD, and also Paul H. Am J Pathol 1966;49:1053-1067.
References
11. ME, and also the degree ended up being 109 mg/dL (normal range, 100 for you to 200 mg/dL). a
repeat course of intravenous deferoxamine was given and also oral acetylcysteine therapy has been
started. Regardless Involving Whether NAC helped our patient stay away from transplantation can
be unknown. Pharmacol Ther 1992;53:275-354.
15. Chronic iron overload states (eg, hereditary hemochromatosis) are generally connected with
chronic hepatitis as well as cirrhosis and also generally manifest throughout adulthood. Therefore,
physicians, especially those that do not necessarily routinely treat pediatric patients, tend to be
unfamiliar using hepatotoxicity associated for you to iron overdose. Our case had simply by far the
lowest reported serum level reported within the literature (340 [micro]g/mL). Nevertheless,
hepatotoxicity due to acute iron poisoning will be related having a high mortality rate. Right now
there was no family members history of liver disease.
In our case, NAC therapy was presented with once significant hepatotoxicity was evident. The Actual
emergency health-related service personnel brought the woman's towards the hospital right after
becoming called through the patient.
Serum creatinine (normal range,
0.5 - 1.5 mg/dL) 0.7 0.7 0.6
Serum bicarbonate (normal range,
23 - 27 mmol/L) twenty 19 19
Serum albumin (normal range, 3.5 - 4.5 g/dL) 3.9 3.0 3.0
Total bilirubin (normal range,
0.0 - 1.0 mg/dL) 0.3 3.1 2.3
Conjugated bilirubin (normal range,
0.0 - 0.3 mg/dL) 0.1 1.6 1.2
Alkaline phosphatase (normal range,
35 - 129 U/L) 59 87 84
Serum alanine aminotransferase (normal
range, 4 - 41 U/L) 14 4,048 3,618
Serum AST (normal range, 4 - 37 U/L) 17 2,417 1,993
PTT (normal range, 24.7 - 35.8 seconds) 34.4 35.3 39.5
Prothrombin time (normal range,
12.8 - 14.8 seconds) 14.5 46.3 51.5
International normalized ratio 1.0 5.0 5.8
Platelets (normal range,
150 - 400 k/[mm.sup.3]) 225 166 165
White blood cell count (normal range,
3.5 - 10.5 k/[mm.sup.3]) 8.4 7.8 6.9
Iron (normal range, 37 - 158 [micro]g/dL) 340 136 219
She reported not one other ingestion. (16) Apart from chelating iron, deferoxamine minimizes as
well as reverse lipid peroxidation. The Lady had been discharged about hospital day 6. Paul H. The
Girl temperature was 98.9[degrees]F, blood pressure had been 122/70 mm Hg, heart rate was 97
beats per minute, and also respiratory charge had been 22 per minute. link G, Pinson A, Hershko C.
Metabolic zonation of the liver: regulation as well as implications with regard to liver function. NAC
has relatively few facet effects, as well as the ability to give it intravenously has specific appeal
regarding iron poisoning cases where nausea and vomiting tend in order to be prominent. An
original iron level obtained approximately 6 hrs following ingestion has been 340 [micro]g/dL.
Abstract: Your bulk of acute iron toxicity cases exist in kids under 5 many a extended time of age. Br
Med J 1968;1:737-741.
The affected person underwent gastric lavage along with normal saline and also was started about
intravenous deferoxamine therapy with ten mg/kg hourly for a total of 6,000 mg. The Particular
patient's youthful age group argues against significant pre-event hepatic iron loading caused by
genetic hemochromatosis. Witzleben CL. no such "action line" graphs involving serum iron amounts
plotted against occasion right after ingestion tend to be available. Management associated with
metabolic acidosis as well as shock using constant monitoring for myocardial, hepatic, along with
renal involvement will be necessary.
Accepted October 19, 2004.
Laboratory parameter Day 4 Day 5 Day 6
Serum creatinine (normal range,
0.5 - 1.5 mg/dL) 0.4 0.6 0.6
Serum bicarbonate (normal range,
23 - 27 mmol/L) 22 19 25
Serum albumin (normal range, 3.5 - 4.5 g/dL) 2.7 3.0 3.2
Total bilirubin (normal range,
0.0 - 1.0 mg/dL) 2.3 2.4 2.8
Conjugated bilirubin (normal range,
0.0 - 0.3 mg/dL) 1.5 1.6 1.5
Alkaline phosphatase (normal range,
35 - 129 U/L) 85 85 107
Serum alanine aminotransferase (normal
range, 4 - 41 U/L) 2,642 1,657 1,438
Serum AST (normal range, 4 - 37 U/L) 630 188 97
PTT (normal range, 24.7 - 35.8 seconds) 33.8 32.9 29.2
Prothrombin occasion (normal range,
12.8 - 14.8 seconds) 38.8 29.0 15.1
International normalized ratio 4.0 2.7 1.1
Platelets (normal range,
150 - 400 k/[mm.sup.3]) 164 169 200
White blood cell count (normal range,
3.5 - 10.5 k/[mm.sup.3]) 9.3 6.8 9.9
Iron (normal range, 37 - 158 [micro]g/dL) 207 162 140
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1. the gastrointestinal mucosa adopted from the liver will always be the web site regarding
maximum concentration involving iron inside cases regarding acute iron poisoning. Your Woman
was seen 1 week later within the clinic. the patient reported no use of tobacco, alcohol, recreational
drugs, or perhaps alternative medicines. Hayashi, Division involving Gastroenterology as well as
Hepatology, Department involving Internal Medicine, Saint Louis College University of Medicine,
3635 Vista Avenue, FDT-9S, St Louis, MO 63110. Kozaki K, Egawa H, Garcia-Kennedy, R. (17)
Systemic hypotension and also pulmonary toxicity tend to be known adverse effects of deferoxamine
therapy. Clin Transplant 1995;9:85-87.
Sumanth R. The Actual affected person was given 140 mg involving N-acetylcysteine (NAC) per
kilogram entire body weight like a single oral loading dose followed by way of a dose associated with
70 mg associated with NAC per kilogram physique excess weight each and every 4 hours.
Gastroenterology 1992;102:2050-2059.
20. N Engl J Med 1954;251:995-999.
10. Fatal iron intoxication in late pregnancy. on physical examination, she was fatigued as well as
drowsy yet easily aroused along with coherent. Tenenbein M. Syndromes of Environmental
Hepatotoxicity, within Zimmerman HJ (ed): Hepatotoxicity. all of these patients were younger than
18 many years of age.
13. the [alpha]-1 antitrypsin phenotype was heterozygous. Luongo MA, Bjornson SS. (18) Moreover,
NAC replenishes glutathione, which can offer general hepatoprotective outcomes for assorted leads
to associated with hepatic injury. These points will be discussed also because the pathophysiology
regarding iron hepatotoxicity along with general remedy measures together with feedback about the
use of NAC within this setting.
19. Severe iron poisoning handled together with enteral and also intravenous deferoxamine. in all of
these 13 cases, hepatotoxicity developed within 48 hours involving ingestion. Nearly All iron toxicity
involves the intestinal tract, including nausea and also vomiting in order to diarrhea and
hematemesis. she had absolutely no latest travel history. Even though this phenotype confers a
rather higher danger for hepatic as well as pulmonary disease related for you to [alpha]-1
antitrypsin, this really is merely speculative inside the absence of a liver biopsy. Whole bowel
irrigation will benefit cases in which the actual abdominal film reveals pills beyond the pylorus.
Transfusional iron overload: the relationship between tissue iron concentration along with hepatic
fibrosis in thalassemia.
Treatment regarding acute iron poisoning consists involving early decontamination of the gut and
chelation together with parenteral deferoxamine therapy. Acute iron poisoning within children, role
regarding chelating agents. in a research associated with NAC inside non-acetaminophen-induced
acute liver failure, 4 associated with seven patients survived. Hepatotoxicity inside acute iron
poisoning. The Particular liver inside ferrous sulfate poisoning, the statement regarding 3 fatal cases
in children plus an experimental study. Transpl Int 1998;11(suppl 1):S390-S392.
18. a MEDLINE as well as PubMed search utilizing the particular terms NAC, Mucomyst, iron
poisoning, iron toxicity, as well as iron-induced liver failure did not yield just about any report of the
use of NAC inside the remedy regarding iron-induced hepatic dysfunction. The Girl ended up being
negative with regard to anti-hepatitis The virus IgM, hepatitis B surface antigen, as well as hepatitis
C virus antibodies. (15) Deferoxamine can be generally administered like a continuous intravenous
infusion from 15 mg/kg for each hour. Liver pathology throughout genetic hemochromatosis: a
report on 135 homozygous cases and their bioclinical correlations. Shortly thereafter, the lady had
nausea and one episode associated with scant hematemesis together with epigastric pain and one
episode regarding watery diarrhea. Unfortunately, zero genetic testing has been performed within
our case.
17. Gastric lavage using a large-bore oral gastric tube using normal saline can be recommended.
The Particular case reminds physicians in which severe iron hepatotoxicity in adults, although rare,
can easily occur. Laboratory and other test outcomes from town hospital are usually as shown
throughout Table one (day one of hospitalization). Assessment involving management guidelines in
acute iron ingestion. Ben-Ari Z, Vaknin H, Tur-Kaspa R. Maybe 5% involving these hospitalized will
die or even require liver transplantation.
5. tests for additional hepatotoxins (eg, acetaminophen), hepatatrophic viruses, along together with
other causes involving acute liver injury had been negative. Hepatogastroenterology 2000;47:786-
789.
**********
The poorer prognosis connected together with hepatic involvement within iron poisoning compared
with acetaminophen poisoning might end up being due to several histologic patterns of injury.
Email: hayaship@slu.edu
12. (6) Occasionally, the particular gastrointestinal symptoms are severe using shock, but overall
merely 20% of poisonings require hospitalization. The Woman's latest sexual get in touch with was
limited to her boyfriend. Though it cannot be routinely suggested in most cases regarding iron
poisoning associated hepatotoxicity, it is actually a therapy to be considered if the prothrombin some
moment and bilirubin tend to be rapidly rising.
4. The Actual efficacy regarding N-acetylcysteine like a hepatoprotective agent throughout liver
transplantation. Individual account of ingestion occasion can be often suspect in overdose cases, but
visualization of pill fragments upon emesis in the emergency space delivers a few corroboration in
the patient history. (3,5) The Actual oldest case reported is a 30-year-old pregnant woman within the
36th week regarding gestation. The Particular affected person had been minimally symptomatic and
she or he ultimately stood a complete recovery.
Key Words: acetylcysteine, deferoxamine, hepatotoxicity, iron intoxication, iron poisoning
3. (20) Any prospective, randomized, double-blinded, placebo-controlled trial regarding NAC inside
acute liver failure not necessarily brought in by acetaminophen overdose is currently being
completed by the US Acute Liver Failure Research Team (21). (5) Together With small literature
upon and also relative rarity associated with adult cases, the actual clinician may be taken off guard
by simply iron hepatotoxicity as well as disregard the possibility beyond the time for anyone
personally to consider transfer to a transplant center.
16. Schauben JL, Augenstein WL, Cox J, Sato R. the great majority involving iron overdoses have a
relatively benign course, with total recovery. Milchak LM, Douglas Bricker J. There is certainly small
evidence to aid this intervention. (3) Acetaminophen poisoning is actually related with a a lot more
centrilobular involvement in contrast for you to iron poisoning, which is associated primarily with
necrosis of the periportal areas, the particular web site regarding hepatic regeneration. Your
presence regarding genetic hemochromatosis could have increased susceptibility as reports
involving acute iron induced hepatic necrosis are already reported along with vitamin C ingestion,
the vitamin C causing an acute surge in serum iron. National Institutes involving Wellness website.
Deferoxamine therapy was prompt, and serum iron ranges by absolutely no means once again rose
over 300 [micro]g/dL.
14. Moreover, clinical hepatic injury will be uncommon with many signs stemming in the intestinal
tract (eg, nausea, vomiting, diarrhea). Unlike acetaminophen levels, serum iron amounts do not
necessarily seem to correlate well with likelihood of hepatotoxicity. N-acetylcysteine within acute
hepatic failure (non-paracetamol induced). The Woman's liver function--related exams had been
typical about presentation. Serum antinuclear antibody, antimitochondrial antibodies, and also anti-
smooth muscle mass antibodies were undetectable. Though peak serum iron degree (340
[micro]g/dL) has been significantly lower compared to in which reported to cause hepatotoxicity
(>1,700 [micro]g/dL), rapid along with significant elevations within aminotransferases (>4,000 U/L),
total bilirubin (5 mg/dL), along with prothrombin moment (50 seconds) occurred inside 48 hours. et
al. Within an experimental study regarding acute ferrous sulfate overdose throughout rabbits,
mitochondrial swelling using loss associated with cristae beginning inside the periportal region was
observed. Gebhardt R. Remedy along with deferoxamine has been prompt and also followed by
empiric N-acetylcysteine once liver injury ended up being apparent. Indeed, early lavage regarding
ingested pills would be throughout collection with the few achievement inside intestinal
decontamination and also subsequent reduced serum iron levels. Hepatic Failure credited to huge
iron ingestion effectively treated with liver transplantation. Unlike acetaminophen levels, iron
amounts do not provide reliable danger stratification regarding liver injury.
Case Report
9. Accessible from http:www.clinicaltrials.gov/ct/show/NCT00004467?order-1. Whenever
prothrombin serious amounts of bilirubin began in order to increase, your woman had been
transferred to our facility in your event liver transplantation became necessary.
On transfer in order to our intensive care unit, her vital indicators remained stable. Iron poisoning:
report involving 3 cases and a overview of therapeutic intervention. Your Woman had mild icterus
and also persistent epigastric tenderness together with nausea as well as occasional emesis.
Olenmark M, Biber B, Dottori O, Rybo G. This particular patient took 5,000 mg regarding elemental
iron (70 mg/kg involving body weight), designed a peak ALT regarding 6,000 U/L, prothrombin
duration of 43 seconds, as well as total bilirubin involving 18.7 mg/dL. Ferrous sulfate toxicity: a
new overview of autopsy findings. Your trend inside serum aminotransferases and prothrombin
period is proven in the Figure. Physical examination had been within normal limitations except
regarding mild epigastric tenderness. (8,9) Also, the actual periportal location receives the blood
richest in oxygen and also iron, both associated with that are substrates pertaining to free radical
generation. We located few other biochemical or serologic markers to become able to suggest an
underlying chronic liver disorder or perhaps cirrhosis. NAC might end up being considered if severe
hepatotoxicity occurs.
* Acute liver failure via iron overdose will be unusual in youngsters as well as uncommon throughout
adults.
21. Coronary Heart cells within culture: a model of myocardial iron overload and chelation. J Lab
Clin Med 1985;106:147-153.
Copyright 2005, Gale Group. (13,14) Liver biopsy might happen to be useful here however was
clinically unjustified. Pestaner JP, Ishak KG, Mullick FG, Centeno JA. (10)
Discussion
This case associated with acute iron poisoning along with associated liver injury will be of curiosity
for two reasons: (1) acute iron hepatotoxicity is actually uncommon in older adults and (2) the
measured peak serum level of iron was well under in which reported to become able to cause liver
injury. (11,12) Hepatotoxicity according to idiosyncratic reactions is typically not necessarily dose-
dependent or even serum level--dependent and presumably comes from the hypersensitivity sort of
reaction. Toxicol Lett 2002;126:169-177.
We document a new case regarding an adult using severe hepatotoxicity after iron overdose despite
relatively reduced serum iron levels. Hayashi, MD
* Deferoxamine along with early referral into a liver transplant center remain mainstay
interventions.
The authors have got not necessarily received any monetary scholarships through any kind of supply
whatsoever.
Iron is a known hepatotoxin. An electron microscopic study regarding ferrous sulfate induced liver
damage. (1,2) Hepatotoxicity connected along with acute iron coverage is scatporn actually unusual
along with mostly confined towards the pediatric age group group, along with just sporadic studies
associated with adult cases. Barr DG, Fraser DK. J Pathol 1975;116:83-95.
Once hepatotoxicity occurs, the particular mortality price can be as high as 50% or even a lot more
(3,4); liver transplantation continues to always be able to be reported, yet again, primarily in the
pediatric setting. The Particular effects of glutathione along with vitamin E in iron toxicity in isolated
rat hepatocytes. (7) Tenenbein et al reviewed 13 cases of acute iron poisoning connected using
hepatotoxicity. Idiosyncratic acute hepatitis brought in by paracetamol inside two patients with
melanoma treated with good dose interferon-[alpha]. Also, hepatotoxicity has been connected simply
with serum iron ranges greater compared to 1,700 [micro]g/dL. A New literature research for adult
cases regarding iron poisoning associated along with hepatotoxicity yielded only three cases which
were older compared to 15 many many years of age. Iron catalyzes hydroxyl radical formation, that
initiates lipid peroxidation. Clin Pediatr 1990;29:316-321.
8. Your Woman was unclear about why the particular iron tablets were in the woman's own home.
the highest serum iron level measured was 492 [micro]g/dL after approximately 15 hrs associated
with ingestion. (3) The Actual highest serum iron degree measured in our case was just 340
[micro]g/dL, measured approximately six hours right after reported ingestion. J Toxicol Clin Toxicol
2001;39:721-726.
Table. the lowest serum iron degree connected with liver injury has been reported being 1,700
[micro]g/dL (range regarding 1,700 for you to 21,680 [micro]g/dL, obtained 2 in order to 72 hrs
following ingestion). Monitoring associated with liver enzymes, prothrombin time, bilirubin, along
with mental status can be prudent in most cases. Ann Emerg Med 1983;12:306-309.
Laboratory parameter Day one Day 2 Day 3
6. Acetaminophen hepatotoxicity: what can we know, what don't we know, and also what do we do
next? Hepatology 2004;40:23-26.
* one must monitor liver enzymes, bilirubin, international normalized ratio, and also mental status in
every iron overdose cases.
7. Apart from bowel decontamination along with deferoxamine administration, diligent monitoring
along with supportive care are generally imperative. Nevertheless, animal studies have proposed a
task for NAC in protection against iron-induced lipid peroxidation. Klein-Schwartz W, Oderda GM,
Gorman RL, et al. The Girl liver enzymes, prothrombin time, and also bilirubin also improved (see
Table). Ann Intern Med 2001;134:345.
Hepatotoxicity due to iron poisoning remains relatively unusual within pediatric patients as well as
distinctly rare throughout adults. Indeed, cases associated with no hepatotoxicity despite very high
serum levels tend to be reported. Every one hundred mg of deferoxamine binds approximately 9 mg
associated with elemental iron producing the actual feroxamine-iron complex, that is excreted from
the kidney, imparting a new vin-rose discoloration towards the urine. Accessed on December 28,
2004.
Conclusion
At admission, your affected person vomited noticeable pill fragments. The Girl ended up being upon
absolutely no medications except occasional ibuprofen pertaining to headaches. Kaplowitz N. Acute
liver failure caused by iron overdose: Laboratory data over
the span of hospitalization (a)
Iron overdose typically happens in kids younger when compared with 5 numerous a prolonged time
of age, that blunder the particular iron pills pertaining to candy. Your Ex laboratory values only with
that visit included the serum ALT involving 362 U/L, international normalized ratio regarding 0.9,
prothrombin time of 13.4 seconds, and furthermore the total bilirubin ended up being 0.9 mg/dL.
Ceruloplasmin level was within regular limits, as had been an [alpha]-1 antitrypsin level.
Over the particular subsequent 4 days, your patient's clinical condition, including the epigastric
tenderness and also nausea, improved. J Emerg Med 1990;8:309-319.
2. Disappearance in the vin-rose discoloration with the urine continues in order to be considered an
end point pertaining to chelation therapy; however, normal urine colour inside the existence of
higher serum iron levels has been reported. (19) Indeed, a quantity of centers give NAC for virtually
most cases involving fulminant hepatic failure. Gale Team is a Thomson Corporation Company.
An 18-year-old woman ended up being admitted to some community hospital, 4 to be able to 5 hrs
after a one-time ingestion associated with approximately 100 ferrous sulfate pills (120 mg associated
with elemental iron per kilogram physique weight). she was asymptomatic and following up with the
psychiatry service.
The reason for such hepatic susceptibility with this type of reduced degree of iron is unclear. Fabris
P, Dalla Palma M, de Lalla F. (4) Therefore, literature upon adult iron hepatotoxicity is scant. most
likely there is several component of an idiosyncratic reaction, as has been suggested pertaining to
cases of acetaminophen toxicity occurring with lower than expected levels. Risdon RA, Barry M,
Flynn DM. The Lady had simply no physical examination findings suggestive associated with
cirrhosis. Urine and also serum drug screens, such as acetaminophen amounts obtained with
admission, had been negative. Biol Trace Element Res 1999;69:191-198.. (3)
* Peak serum ranges involving iron may not predict hepatotoxicity.
From your Division associated with Gastroenterology as well as Hepatology, Department of Internal
Medicine, Saint Louis College College regarding Medicine, St Louis, MO.
(a) AST, aspartate amino transferase; PTT, partial thromboplastin time.
[FIGURE one OMITTED]
Even within the pediatric population, severe as well as fatal hepatotoxicity is actually very unusual
representing approximately 1% of all iron poisonings