Red Maple Toxicity: Hemolysis and Anemia

Hematotoxicology: Toxicants/Toxins Causing Hemolysis and Anemia

Red Maple (Acer rubrum)

• Found throughout the entire eastern US and Canada.
• Gallic acid and tannins are the toxic oxidants.
• Horses, ponies, and Grevy’s zebra are susceptible.
• A toxic dose is 0.5-0.8% of body weight following consumption of wilted or dried leaves; the bark is also toxic.
• Tannic acid metabolizes into gallic acid in the equine ileum via Klebsiella pneumoniae or Enterobacter cloacae.
• Gallic acid metabolizes further into pyrogallol in the equine ileum via K. pneumoniae or E. cloacae.
• Pyrogallol is absorbed in the equine ileum and interacts with iron (Fe) to form free radicals.
• Oxidative damage of hemoglobin (Hb) leads to the precipitation of oxidized Hb as Heinz bodies in red blood cells (RBCs).
• RBCs containing Heinz bodies are removed by the spleen, causing extravascular hemolysis.
• Damage to RBC membranes results in altered permeability and intravascular hemolysis.
• These processes lead to severe progressive anemia.
• Hemoglobin filtered in the kidney can precipitate in renal tubules, causing renal failure.
• Clinical signs are more likely in fall/late summer or after storms.
• Depression, anorexia, acute hemolytic anemia with weakness, increased respiratory and heart rates, cyanosis, icterus, red-brown urine, decreased PCV, Heinz bodies, proteinuria, weakness, coma, and death are clinical signs.
• Abortion may occur in pregnant mares.
• Peracute death from tissue anoxia may occur.
• Diagnosis includes a history of exposure to red maple leaves (primarily July to October), clinical signs, and ruling out other causes of hemolytic anemia.
• Differential diagnoses include equine infectious anemia, piroplasmosis, ehrlichiosis, onion toxicosis, nitrate/nitrite toxicosis, Brassica toxicosis, and naphthalene toxicosis.
• Avoid stressing poisoned animals during treatment.
• Decontamination involves using activated charcoal early in the toxicosis.
• Supportive care includes IV fluids, whole-blood transfusion, Oxyglobin, and oxygen.
• Ascorbic acid and methylene blue are treatment options.
• Horses respond poorly to methylene blue, as it may oxidize Hb to MetHb (potential contraindication).
• Pain relief can be provided via NSAIDs, pentazocine, or butorphanol.
• Aggressive therapy is often unrewarding.

Allium (Onion, Garlic, Leek, Chives)

• Herbaceous plants with bulbs with both domesticated and wild varieties.
• Found throughout North America.
• N-propyl disulfide and other disulfides are the toxic principles.
• Exposure occurs from ingestion of cull onions, fresh raw onions, cooked onions, minced onions, and garlic.
• Wild onions rarely cause toxicity but may impart odor in milk.
• Cats, dogs, and cattle are most susceptible; goats and sheep appear resistant.
• Akitas, Shibas, and Tosas are highly susceptible.
• Cats' RBCs are highly susceptible to oxidative damage because of a high number of –SH groups.
• Dogs: 11-15g/kg bw (raw onions), 5.5g/kg bw (minced dehydrated onions)
• Dogs: 2.5-15mg/kg bw encapsulated garlic powder
• Cattle: 40g/kg bw
• Sheep: 50g/kg bw
• N-propyl disulphide affects RBC membrane and Hb.
• It inhibits the enzyme glucose-6-phosphate dehydrogenase (G6PD), impairing the hexose monophosphate pathway in RBCs.
• Depletion of NADPH occurs, impairing glutathione regeneration, which results in the oxidation of Hb.
• Oxidized Hgb precipitates in the RBCs to form Heinz bodies.
• RBCs with Heinz bodies are removed in the spleen or undergo hemolysis, leading to anemia.
• Cats are highly sensitive because their Hb is more susceptible to oxidation.
• G6PD is responsible for the generation of cellular reducing power (NADPH).
• Anorexia, vomiting, salivation, lethargy, weakness, ataxia, collapse, recumbency, tachypnea, tachycardia, exercise intolerance, pale or icteric mucous membranes, onion odor in breath and onion flavor in milk, and death are clinical signs.
• Hemoglobinemia, hemoglobinuria (dark red-brown urine), reduced PCV and hematocrit, Heinz body hemolytic anemia, and elevated WBC count are clinical signs.
• Pregnant animals may abort.
• Diagnosis is based on hematological parameters and urine appearance, as well as a history, clinical signs, and examination of pasture or property for Allium spp.
• Treatment includes emesis (within 1 hour), gastric lavage (within 2-4 hours), and activated charcoal plus cathartic (e.g., sorbitol) for decontamination.
• Maintain cardiovascular support with IV fluids to maintain hydration and protect kidneys, oxygen supplementation, whole blood transfusion, or Oxyglobin.

Bracken Fern (Pteridium aquilinum)

• Bracken fern is a native perennial herb.
• Occurs throughout the US, with young plants and rhizomes being the most toxic.
• Toxic principles include thiaminase, ptaquiloside, and cyanogenic glycoside.
• Ptaquiloside causes death of precursor cells in bone marrow.
• Ptaquiloside causes urinary tract neoplasia by causing DNA alkylation and induction of protooncogenes.
• Ptaquiloside is secreted in milk, causing neoplasia in mice.
• Aplastic anemia in cattle and sheep is the most common syndrome in North America.
• Other diseases caused by Bracken Fern include enzootic bovine hematuria and tumors of the upper GI tract following prolonged low dose exposure.
• Progressive retinal degeneration in sheep depends on animal age, duration, and rate of exposure.
• Suppression of bone marrow activity occurs after >3-4 weeks of exposure, resulting in aplastic anemia.
• Severe pancytopenia with acute onset of fever, lethargy, and loss of appetite occurs.
• Hemorrhaging via natural orifices, bloody stool and urine, and nasal hemorrhage occur.
• Enzootic Hematuria results in intermittent blood loss in urine from hemorrhages and tumors in the urinary bladder.
• This occurs after prolonged (2 years) consumption of low levels.