Sweet Clover Poisoning: Introduction - The Merck Veterinary Manual

Sweet Clover Poisoning: Introduction

Sweet clover poisoning, an insidious hemorrhagic disease, is seen in animals that consume toxic quantities of spoiled sweet clover ( Melilotus officinalis and M alba ) hay or silage.

Melilotus spp (sweet clover)

Etiology:

During the process of spoiling, the harmless natural coumarins in sweet clover are converted to toxic dicumarol. 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 levels of dicumarol. When toxic hay or silage is consumed, hypoprothrombinemia results, presumably because dicumarol combines with the proenzyme required for synthesis of prothrombin (by preventing formation of the active enzyme). It probably also interferes with synthesis of factor VII and other coagulation factors. (See hemostatic disorders, Hemostatic Disorders: Introduction .) Dicumarol levels of 20-30 mg/kg of hay 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 have involved mainly cattle and, to a limited extent, sheep, pigs, and horses.

Clinical Findings and Lesions:

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 the 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 be seen. Death may occur suddenly with little preliminary evidence of disease and is caused by massive hemorrhage or bleeding after injury, surgery, or parturition. Neonatal deaths rarely occur without signs in the dam.

Hemorrhage is the characteristic necropsy finding; large extravasations of blood are common in subcutaneous and connective tissues.

Diagnosis:

This is based on a history of continuous consumption of sweet clover hay or silage over relatively long periods, compatible signs and lesions, and markedly prolonged blood clotting time or demonstration of reduced prothrombin content of the plasma. The nature of the coagulopathy can be confirmed in the laboratory when the prothrombin time (PT) is prolonged. Sweet clover poisoning is normally a herd problem; signs of hemorrhage or slow blood clotting in only one animal from a group makes this diagnosis unlikely. Most diseases with hemorrhagic manifestations, such as blackleg, pasteurellosis, bracken fern poisoning, and aplastic anemia, can be readily differentiated based on clinical, pathologic, and hematologic findings. This is the only commonly acquired disease, except purpura hemorrhagica (common only in horses) and rodenticide poisoning ( Rodenticide Poisoning: Introduction), in which such large hemorrhages occur.

Congenital or inherited diseases affecting coagulation factors or blood platelets (eg, hemophilia A) also may be characterized by large hemorrhages.

Treatment:

The hypoprothrombinemia, hemorrhages, and anemia can be immediately corrected, to a degree, by IV administration of whole blood. Recommended dosages range from 2-10 L of fresh blood per 1,000 lb (450 kg) body wt. Animals used as a source of blood must not be receiving sweet clover feed. All animals with marked signs 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. There appears to be little advantage in outcome from IV administration. The usual dose 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) in experimental studies and is the preferred treatment. Because reversal of the dicumarol by vitamin K₁ requires synthesis of coagulation proteins, significant improvement in homeostasis requires several hours, and >24 hr is required to completely restore coagulation. Either vitamin K₁ or a blood transfusion is sufficient to correct mild cases of intoxication if feeding toxic hay is stopped.

Prevention:

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. There is no quick chemical test for dicumarol, but suspect feed can be fed to rabbits, which develop fatal hemorrhages more rapidly than cattle. This can be combined with periodic determination of PT in the rabbits to speed up the test results. Unfortunately, some rabbits are refractory to dicumarol, which complicates negative test results.

A simple management technique involves alternating sweet clover hay suspected of containing dicumarol with other roughage such as alfalfa or a grass-legume hay mixture. A 7- to 10-day period on the sweet clover hay is followed by an equal time on the alternate hay. Alternating the forage can successfully prevent poisoning but does not completely prevent prolonged bleeding times. Some animals are at greater risk of serious hemorrhaging at calving (or lambing). They should not receive sweet clover hay for a minimum of 2-3 wk, and preferably 4 wk, prior to parturition. The goal is to allow the animal’s clotting system to fully reestablish competency before a hemorrhagic stress. Dehorning and castration should also be avoided in animals consuming sweet clover hay at least until a full withdrawal period has been achieved.