Overview of Sweet Clover Poisoning

During the process of spoiling, the coumarins in sweet clover are converted to toxic dicumarol, a potent vitamin K antagonist and anticoagulant. Any method of hay storage that allows molding of sweet clover promotes the likelihood of formation of dicumarol in the hay. Weathered, large round bales, particularly the outer portions, usually contain the highest concentrations of dicumarol. When toxic hay or silage is consumed for several weeks, dicumarol alters proenzymes required for synthesis of prothrombin, resulting in hypoprothrombinemia (by preventing formation of the active enzyme). It probably also interferes with synthesis of factor VII and other vitamin K–dependent coagulation factors (see Hemostatic Disorders). Dicumarol concentrations of 20–30 mg/kg of hay ingested throughout several weeks are usually required to cause poisoning in cattle. The toxic agent crosses the placenta in pregnant animals, and newborn animals may be affected at birth. All species of animals studied are susceptible, but instances of poisoning involve cattle and, to a limited extent, sheep, pigs, and horses.

Clinical signs are referable to hemorrhages that result from faulty blood coagulation. The time between consumption of toxic sweet clover and appearance of clinical disease varies greatly and depends on the dicumarol content of the particular sweet clover variety being fed, age of the animals, and amount of feed consumed. If the dicumarol content of the ration is low or variable, animals may consume it for months before signs of disease appear.

The first indication of dicumarol poisoning may be the death of one or more animals. In affected animals, the first signs may be stiffness and lameness, due to bleeding into the muscles and joints. Hematomas, epistaxis, or GI bleeding may also be seen. Death is generally caused by massive hemorrhage or bleeding after injury, surgery, or parturition. Neonatal deaths rarely occur without signs in the dam.

Poisoning occurs when sweet clover hay or silage is consumed continually for relatively long periods. Diagnosis is made by identifying compatible signs and lesions and markedly prolonged blood clotting time or demonstration of reduced plasma prothrombin concentrations. The nature of the coagulopathy can be confirmed in the laboratory when the prothrombin time is prolonged. Sweet clover poisoning is normally a herd problem, making conditions that affect individual animals,such as blackleg, pasteurellosis, bracken fern poisoning, and aplastic anemia, less likely causes.

Rodenticide poisoning (see Rodenticide Poisoning) is the primary differential diagnosis in which such large hemorrhages are also likely to occur. Congenital or inherited diseases affecting coagulation factors or blood platelets (eg, hemophilia A) may produce similar large hemorrhages but with largely different morbidity.

The hypoprothrombinemia, hemorrhages, and anemia can be immediately corrected, to a degree, by IV administration of whole blood. This may be difficult in large animals, because effective dosages range from 2–10 L of fresh blood per 1,000 lb (450 kg) body wt. Care should be taken to ensure that donor animals are not receiving sweet clover feed. All clinically affected animals should receive a transfusion, which can be repeated if necessary. In addition, all severely affected animals should receive parenteral administration of synthetic vitamin K₁ (phytonadione). SC or IM injection is recommended to avoid the substantial risk of anaphylaxis; SC vitamin K₁ may not be as effective as IM treatment. The usual dosage recommended for cattle is 1 mg/kg, bid-tid for 2 days. Although it is more costly, vitamin K₁ is more effective than K₃ (menadione). Because reversal of the dicumarol by vitamin K₁ requires synthesis of coagulation proteins, several hours are required for significant improvement in homeostasis, and >24 hr is required to completely restore coagulation. Either vitamin K₁ or a blood transfusion is sufficient to correct mild cases if additional exposure is stopped.

Cultivars of sweet clover low in coumarin and safe to feed (eg, Polara) have been developed. If one of these is not available, the only certain method of prevention 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 be used to avoid severe poisoning. A 7- to 10-day period on the sweet clover hay, followed by an equal time on the alternative hay, can prevent poisoning, but it will not completely prevent prolonged bleeding times. Because some animals have higher risks of serious hemorrhage (surgical candidates or pending parturition), they should not receive sweet clover hay for a minimum of 2–3 wk, and preferably ≥4 wk, before surgery or parturition.