Moldy sweet clover poisoning, also called dicumarol poisoning, is typically a herd-level hemorrhagic toxicosis that develops after chronic ingestion of moldy sweet clover. Hemorrhage is the most common clinical sign; prolonged blood clotting times help to confirm diagnosis and determine treatment. Direct confirmation can be challenging due to limited availability of dicumarol testing; however, response to removal of moldy sweet clover feed and to treatment with blood transfusions and vitamin K1 supports the diagnosis.
In the 1920s, cattle in North America developed a fatal hemorrhagic disease. Various potential causes, including pathogenic organisms and nutritional deficiencies, were investigated. It was observed that damp conditions caused haystacks to mold and spoil, and that within several weeks of eating the hay, sheep and cattle developed uncontrollable hemorrhages that were generally fatal in 30–50 days. Feeding trials and chemical analyses later definitively identified the cause as spoiled or moldy sweet clover (Melilotus officinalis and M alba; see image) hay or silage.
Courtesy of Dr. Cecil Brownie.
Etiology of Moldy Sweet Clover Poisoning in Animals
As sweet clover spoils and becomes moldy, coumarins in the plant are converted to toxic dicumarol (also spelled "dicoumarol"), a potent vitamin K antagonist and anticoagulant. Any method of hay storage that allows molding of sweet clover increases the likelihood of dicumarol formation in the hay and subsequent poisoning of animals consuming the hay. Weathered, large, round hay bales, particularly the outer portions, usually contain the highest concentrations of dicumarol.
Dicumarol inhibits the body's regeneration of vitamin K in a dose-dependent manner. As vitamin K becomes less available, production of vitamin K–dependent coagulation factors (II [prothrombin], VII, IX, and X) decreases, lessening an animal's ability to clot blood appropriately. Dicumarol concentrations of 20–30 mg/kg of hay ingested over several weeks are usually necessary to cause sweet clover poisoning in cattle.
Dicumarol crosses the placenta in pregnant animals, and neonates may be affected at birth.
All species of animals studied to date are susceptible to moldy sweet clover poisoning, but most instances occur in cattle and, to a limited extent, sheep, pigs, and horses.
Coumarins are found in plants other than sweet clover, including sweet vernal grass (Anthoxanthum odoratum) and sweetgrass (Hierochloe odorata); however, in the US, sweet clover is the plant most commonly linked to dicumarol poisoning in animals.
Clinical Findings and Lesions of Moldy Sweet Clover Poisoning in Animals
Clinical signs of moldy sweet clover poisoning are a result of spontaneous bleeding due to decreased production of clotting factors. Because dermal pigmentation and hair can obscure small hemorrhages, the first indication of dicumarol poisoning is often death of one or more animals in a herd. However, on closer observation, poisoned animals may be stiff or lame as a result of bleeding into muscles and joints. Hematomas, epistaxis, or GI bleeding may also be observed.
Death is generally caused by massive hemorrhage or bleeding after injury, surgery, or parturition. Neonatal deaths rarely occur without clinical signs in the dam. Animals that survive may be clinically affected by anemia resulting from blood loss.
The time between consumption of toxic moldy sweet clover and the appearance of clinical signs varies greatly and depends on the dose (dicumarol concentration in the sweet clover variety and amount eaten) and duration of exposure. Animals that are younger, smaller, and/or have preexisting liver disease are at higher risk for poisoning. If the dicumarol content of the ration is low or variable, animals may consume it for months before clinical signs develop.
Diagnosis of Moldy Sweet Clover Poisoning in Animals
Clinical evaluation
Prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests
Dicumarol testing
Because moldy sweet clover poisoning occurs with continuous consumption of moldy hay or silage over relatively long periods, the condition is diagnosed by identifying compatible clinical signs and lesions and by documenting prolonged blood clotting times and decreased plasma prothrombin concentrations (hypoprothrombinemia). The nature of the coagulopathy can be confirmed in the laboratory when clotting times are prolonged. Prothrombin time is the first to be prolonged; activated partial thromboplastin time becomes prolonged as illness progresses.
Detection of dicumarol in blood and livertissue samples is less commonly used for diagnosis because few diagnostic laboratories offer dicumarol testing.
Moldy sweet clover poisoning is typically a herd problem affecting numerous animals, which contrasts sharply with diseases that affect individual animals, such as blackleg, pasteurellosis (hemorrhagic septicemia), bracken fern poisoning, and aplastic anemia. A more likely alternative diagnosis for hemorrhagic disease involving many animals would be anticoagulant rodenticide poisoning, which can be differentiated from sweet clover poisoning by examining feed and looking for potential exposures. Congenital or inherited diseases affecting coagulation factors or blood platelets (eg, hemophilia A) can produce hemorrhagic disease similar to sweet clover poisoning, but with an obviously inherited pattern affecting individuals within a lineage.
Treatment of Moldy Sweet Clover Poisoning in Animals
Whole blood transfusion
Parenteral vitamin K1 (phytonadione) administration
Change of feed; removal of moldy sweet clover feed
Hypoprothrombinemia, hemorrhages, and anemia due to moldy sweet clover poisoning can be immediately corrected, to a degree, by IV administration of whole blood. This can be difficult in large animals because effective doses are large, from 2–10 L of fresh blood per 450 kg (1,000 lb) body weight. Care should be taken to ensure that donor animals are not also consuming moldy sweet clover feed. All clinically affected animals should receive transfusions, which can be repeated if necessary.
All severely affected animals should be administered synthetic vitamin K1 (phytonadione) parenterally, preferably intramuscularly (1 mg/kg, IM, every 8 or 12 hours for 2 days). IV administration of vitamin K1 is not recommended, as a substantial risk for anaphylaxis is associated with this route. Subcutaneous administration of vitamin K1 may not be as effective as intramuscular treatment. Although it is more costly, vitamin K1 is more effective than vitamin K3 (menadione). Because reversal of dicumarol poisoning by vitamin K1 requires synthesis of coagulation proteins, substantial improvement in homeostasis requires several hours, and > 24 hours is required to completely restore coagulation.
Typically, either blood transfusion or vitamin K1 administration is sufficient to correct mild cases of moldy sweet clover poisoning once additional exposure to spoiled feed is stopped.
All animals in the herd should be switched to unspoiled feed, and all moldy sweet clover feed should be removed and discarded.
Prevention of Moldy Sweet Clover Poisoning in Animals
Cultivars of sweet clover that are low in coumarin have been developed (eg, Polara) and are safe to feed. If one of these is not available, the only certain method for preventing moldy sweet clover poisoning is to avoid feeding sweet clover hay or silage. Although well-cured sweet clover is not dangerous, the absence of visible spoilage is insufficient evidence of safety.
Alternating sweet clover hay suspected of containing dicumarol with other roughage, such as alfalfa or a grass-legume hay mixture, can prevent severe poisoning. A 7- to 10-day period on sweet clover hay, followed by equal time on an alternative hay, is effective; however, this method will not completely prevent prolonged bleeding times.
Some animals are at higher risk for serious hemorrhage (surgical candidates or animals pending parturition) and should not be fed sweet clover hay for a minimum of 2–3 weeks (preferably ≥ 4 weeks) before surgery or parturition.
Key Points
Moldy sweet clover hay or silage can produce an anticoagulant toxin (dicumarol) and cause herd-level hemorrhagic toxicosis.
Most of the herd will likely be affected by the time clinical signs (hemorrhage, acute death) are noticed.
Blood transfusions and administration of intramuscular vitamin K1 are recommended for treating affected animals.
Removal of moldy sweet clover feed is required to prevent further exposure.
For More Information
US Department of Agriculture, Agricultural Research Service. Plants Poisonous to Livestock in the Western States. Agriculture Information Bulletin Number 415. Rev. April 2011.
Plants affecting the blood. In: Knight A, Walter RG. A Guide to Plant Poisoning of Animals in North America. Teton NewMedia/International Veterinary Information Service (IVIS); last updated May 7, 2004.
Sweet clover poisoning. In: Chase C, Lutz K, McKenzie E, Tibary A, eds. Blackwell's Five-Minute Veterinary Consult: Ruminant. 2nd ed. Wiley-Blackwell; 2017:779.
Also see pet owner content regarding sweet clover poisoning.
