A 4-year-old 6-lb (2.7-kg) spayed domestic shorthaired cat was presented to an emergency clinic for evaluation of lethargy and flatulence of four hours’ duration.
The previously healthy cat had ingested 2 or 3 tablespoons of onions cooked in butter about 10 to 12 hours before the lethargy and flatulence had started. Assuming each tablespoon of onion was about 15 g, the approximate amount of onion ingested was 11 to 16.6 g/kg.
The emergency veterinarian contacted the ASPCA Animal Poison Control Center (APCC). The ASPCA APCC veterinarian discussed the potential risk of oxidative damage to the red blood cells (RBCs) from the onion ingestion and a treatment plan.
A urinalysis, complete blood count (CBC), serum chemistry profile and blood smear (stained with new methylene blue) were performed (Table 1). Microscopic examination of RBCs showed Heinz bodies in almost every RBC. Hemoglobin and bilirubin were present in the urine. The packed cell volume (PCV) and total protein concentration were 43.6% and 8 g/dl, respectively, and the PCV stayed between 30% and 35% when checked every eight hours for 24 hours.
Plasma-Lyte (Baxter) intravenous fluids were started at twice the maintenance rate to maintain perfusion and to protect the kidneys. Diluted N-acetylcysteine (20% solution diluted to 5% in sterile water) was administered; 380 mg (140 mg/kg) was given initially by mouth, and then 190 mg (70 mg/kg) was given every six hours for four additional treatments. The cat’s heart and respiration rates were checked every four hours at the emergency clinic and stayed within the normal range.
The cat remained quiet, alert and responsive. Dark stool and dark urine were noted about 28 hours and 30 hours, respectively, after ingestion. Blood work was repeated about 24 hours after ingestion, and the results were within the normal range except for slightly elevated alanine transaminase (ALT) activity (126.4 U/L; reference range = 10 to 100 U/L).
The cat was transferred to its primary veterinarian and was hospitalized for an additional 24 hours. Intravenous fluids were continued—lactated Ringer’s solution at half the maintenance rate—and a final dose of diluted N-acetylcysteine was given. Blood work was rechecked about 48 hours after ingestion and revealed a low normal blood urea nitrogen concentration (16 mg/dl; reference range = 16 to 36 mg/dl), decreased alkaline phosphatase (ALP) activity (< 10 U/L; reference range = 14 to 111 U/L) and elevated ALT activity (150 U/L; reference range = 12 to 130 U/L). At discharge, the cat’s PCV was 32% and remained the same when rechecked five and nine days after exposure. It was reported that the cat did well at home and did not develop any further clinical signs.
Onions are part of the Amaryllidaceae family. The genus Allium also includes garlic, chives and leeks.1 A true onion is known as Allium cepa.1 Onions can be found growing wild in yards and gardens, in food (raw, cooked or in powdered forms) and in medicinal supplements.2
Allium species contain sulfoxides (sulfur-containing compounds), which are hydrolyzed into thiosulfinates and further broken down into disulfides when the plant is disturbed (crushed or chewed).2 These compounds give the onion its strong odor, taste and pharmacologic effects.2 The disulfide compounds are readily absorbed by the gastrointestinal tract and oxidize RBC membranes, resulting in hemolysis, Heinz body formation and methemoglobinemia in dogs and cats.2
The most toxic disulfide is dipropyl disulfide (N-propyl disulfide).3 N-propyl disulfide is thought to contribute to RBC injury by oxidizing free sulfhydryl groups in the hemoglobin. This decreases the activity of glucose-6 phosphate dehydrogenase, leading to a reduction of glutathione concentration in the RBCs.2 Glutathione is an important antioxidant in the RBC and acts as a reducing agent for sulfhydryl groups in hemoglobin.4 Reduced glutathione in RBCs can increase hemoglobin’s susceptibility to oxidative damage.4
A cat’s hemoglobin is considered two or three times more sensitive to oxidative damage than a dog’s or a person’s is because cats have eight free sulfhydryl groups on their hemoglobin, whereas dogs and people have four and two sulfhydryl groups, respectively.2,5 Heinz bodies are commonly observed in cats (1% to 10% is considered normal)4,6,7 and circulate longer in cats than in dogs because cats have nonsinusoidal spleens that are inefficient at removing Heinz body-containing RBCs.4 Cats, compared with other mammals, have an increased dependence of glutathione against oxidative damage in their erythrocytes.8 Feline hemoglobin also dissociates into dimers 10 times faster than hemoglobin dissociates in other species.4
In cats, ingesting 5 g/kg or more of onion is considered a risk for causing oxidative damage to hemoglobin and for anemia.2 There is also a secondary concern for renal damage due to hemoglobinuria.2,9 The onset time for developing anemia can be as soon as 12 hours after ingestion, but it is typically delayed up to two to five days after the exposure.2 Initial clinical signs of onion toxicosis in cats can be nonspecific. According to information available in the ASPCA APCC toxicology database, the most common signs reported in cats are vomiting, diarrhea and lethargy.10
Some of the common toxic agents that can cause clinical signs similar to onion toxicosis and should be considered as potential toxins in cases such as this one are zinc, copper, propylene glycol, benzocaine, phenazopyridine, dl-methionine, acetaminophen and moth balls that contain naphthalene.2 Other conditions such as autoimmune hemolytic anemia, blood parasites (Mycoplasma haemofelis, Babesia canis, Mycoplasma suis), diabetes mellitus, hepatic lipidosis, hyperthyroidism, lymphoma, neoplasms and other hereditary diseases that affect RBCs should also be considered as differential diagnoses.2
Onion toxicosis is diagnosed based on a history of exposure, clinical signs and laboratory findings.2 Blood tests that can aid in diagnosis include a CBC with a differential and reticulocyte count, evaluation of a peripheral blood smear to detect Heinz bodies in RBCs, a methemoglobin concentration, and a serum chemistry profile focusing on bilirubin concentration and renal values. Urine should also be evaluated for the amount of output and for hemoglobinuria. Renal functions can be compromised if hemoglobin is present in the urine.2,9
Clinical signs of onion toxicosis include gastrointestinal signs (vomiting, diarrhea, anorexia) and behavior changes (depression, lethargy, weakness).2,5 Patients may experience dyspnea, exercise intolerance or collapse because of the body’s inability to carry oxygen properly.2,5 The mucous membrane color may become pale or white, and the urine may be discolored from hemoglobinuria.2,5
Decontamination (emesis and activated charcoal) should be considered in patients not exhibiting clinical signs with significant (> 5 g/kg), recent exposures (within two hours of ingestion).2,5,10 The decision to decontaminate also depends on the cat’s health history (e.g. seizures, cardiac issues, age). Take caution when inducing emesis.5,9 In cats, emesis can be induced with dexmedetomidine (40 µg/kg intramuscularly).11 The effects of dexmedetomidine can be reversed with atipamezole.11 This protocol is recommended in cats since they do not readily vomit from 3% hydrogen peroxide. Activated charcoal (1 to 3 g/kg orally) can be administered.11
The ASPCA APCC generally recommends that asymptomatic cats that have been successfully decontaminated be monitored at home by owners. Changes in behavior, exercise intolerance, pale or white mucous membranes and urine color changes are all consistent findings of Heinz body hemolytic anemia and should be reported to the veterinarian.2 Daily PCV measurement and blood smear analysis are recommended for five days since the onset of clinical signs can be delayed.2 Gastrointestinal signs should be managed with antiemetics and a bland diet. If the cat does not develop clinical signs and there are no changes in blood work, no further care is needed.
Treatment for cats exhibiting clinical signs may include administration of oxygen support for hypoxia, blood transfusions, intravenous fluids for management of shock and to support renal function, and gastrointestinal management.2,5,9 Daily blood work is recommended, and treatment should continue until signs resolve.2,5,9
N-acetylcysteine administration is recommended because it is a glutathione precursor. Glutathione plays an important protective role against oxidative damage.5 A study conducted in 44 healthy cats confirmed antioxidant supplementation with ascorbate, vitamin E and N-acetylcysteine had minimal effect in cats with Heinz body anemia.12 Denamarin (Nutramax) and Denosyl (Nutramax) (20 mg/kg once a day) were recommended as an alternative to N-acetylcysteine because of the ease of administration and availability. Treatment with these agents can be discontinued after five days if the cat does not develop clinical signs. If clinical signs develop, administration of the antioxidants should continue until clinical signs resolve.
Cats are considered more sensitive to onion toxicosis than other species are. Exposures > 5 g/kg can result in gastrointestinal upset, oxidative damage of hemoglobin (resulting in hemolysis), Heinz body anemia, methemoglobinemia and secondary renal damage from hemoglobinuria.1,2,4,5 If anemia develops, it is generally regenerative unless there is a preexisting health condition.5 In cats, the main concern is that large ingestions may cause anemia or methemoglobinemia to develop so rapidly that the cat does not have time to regenerate the RBCs that are being oxidized.
Symptomatic and supportive care, including administration of intravenous fluids, N-acetylcysteine, blood transfusions, and oxygen support, may be necessary for several days until the RBCs have time to regenerate.1 Heinz bodies will gradually disappear over one to four weeks, RBCs will regenerate within 10 to 12 days, and the hemoglobinuria will subside in one or two days once the source of onions is removed.1,5,13
1. Burrows GE, Tyrl RJ. Liliaceae juss. In: Toxic plants of North America. Ames: Iowa State Press, 2001;751-756.
2. Cope RB. Allium species poisoning in dogs and cats. Vet Med 2005;100:562-566.
3. Cheeke PR. Onion poisoning of livestock. In: Natural toxicants in feeds, forages, and poisonous plants, 2nd ed. Danville, Ill: Interstate Publishers, 1998;305-306.
4. Robertson JE, Christopher MM, Rogers QR. Heinz body formation in cats fed baby food containing onion powder. J Am Vet Med Assoc 1998;212(8):1260-1266.
5. Simmons DM. Onion breath. Vet Tech J 2001;22:424-427.
6. Brockus CW. Erythrocytes In: Latimer KS, Mahaffey EA, Prasse KW, eds. Duncan and Prasse’s veterinary laboratory medicine. 4th ed. Ames, Iowa: Blackwell Publishing Company, 2003;20.
7. Thrall MA, Weiser G, Allison R, et al. Erythrocyte morphology. Veterinary hematology and clinical chemistry. Ames, Iowa: Blackwell Publishing, 2006;76-76, 109-110.
8. Fettman MJ. Comparative aspects of glutathione metabolism affecting individual susceptibility to oxidant injury. Compend Contin Educ Pract Vet 1991;13(7):1079-1087.
9. Bough M. Food-associated intoxications. In: Poppenga RH, Gwaltney-Brant SM, eds. Small animal toxicology essentials. Ames, Iowa: Wiley-Blackwell, 2011;207-208.
10. AnTox Database. Urbana, Ill: ASPCA Animal Poison Control Center, 2002-2014.
11. Plumb DC. Atipamezole; charcoal, activated; and medetomidine. In: Veterinary drug handbook. 7th ed. Ames: Iowa State Press, 2011;120,260,846.
12. Hill AS, O’Neill S, Rogers QR, et al. Antioxidant prevention of Heinz body formation and oxidative injury in cats. Am J Vet Res 2001; 62:370-374.
13. Hackner SG. Hematologic emergencies: anemia. In: Drobatz KJ, Costello MF, eds. Feline emergency & critical care medicine. Ames, Iowa: Wiley-Blackwell, 2001;379-407.