Enzootic Hematuria

Stacey R. Byers

Definition and Etiology

Enzootic hematuria is a disease of chronic or intermittent hematuria that occurs in a wide variety of ruminants and is most commonly associated with chronic ingestion of bracken fern (Pteridium spp.).

associated with enzootic hematuria.¹³ Enzootic hematuria occurs after ingestion of large quantities of the responsible ferns (approximating the animal's body weight), usually over a period of 1 to 3 months, and is different from acute bracken poisoning. Acute bracken poisoning manifests as acute coagu­lopathy or fulminant septicemic crisis associated with severe bone marrow suppression (see Chapter 54).

Clinical Signs and Differential Diagnoses

Protracted, possibly intermittent, hematuria is the first clinical sign detected in most animals. Blood clots may be voided and can cause urethral obstruction. Chronic blood loss eventually results in tachycardia, tachypnea, exercise intolerance, pale mucous membranes, and a decline in productivity and body condition. A thickened bladder wall and bladder tumors may be palpated per rectum. Proliferative changes or overt neoplasia of the bladder may cause dysuria, pollakiuria, and, rarely, obstruction of the bladder trigone. Depending on the magnitude and duration of fern ingestion, hematuria may last for months to years before severe debilitation or death occurs.

Examination of serum for evidence of hemolysis and analysis of sediment from a freshly voided urine sample for intact RBCs allow for differentiation of hematuria from the hemoglobinuria found in hemolytic diseases. Icterus, also characteristic of ruminant hemolytic disorders, is not found in cases of enzootic hematuria. Hematuria may be evident in a UTI, but pyuria and bacteriuria are marked, and anemia, if present, is usually mild.

Ultrasonography or cystoscopy examination of the urinary bladder may help with antemortem diagnosis.^4-6 Diagnosis is often made on necropsy.

Clinical Pathology

Severe, regenerative anemia is often seen with enzootic hematuria. However, evidence of a regenerative response may not be present if bone marrow suppression exists or chronic blood loss induces iron deficiency. The platelet, segmented neutrophil, and lymphocyte counts may be reduced. Clotting profiles show increased antithrombin III and protein S activities.⁴ Urinalysis reveals hematuria, proteinuria, and variable pyuria.

Pathophysiology

All parts of the ferns are toxic to ruminants. The ferns contain multiple compounds that have irritant, mutagenic, carcinogenic, and immunosuppressive activities and cause a variety of medical conditions in addition to enzootic hematuria. The carcinogenic compound, ptaquiloside, appears to be the primary compound that leads to the bladder tumors. A synergistic interaction between ptaquiloside and bovine papilloma virus type 2 is thought to induce many of the bladder tumors.^1,3,7,8 Ptaquiloside is also found in the milk and meat of animals grazing the ferns and has been found to increase the risk of esophageal and gastric tumors in humans.^3,9

Bladder carcinomas from cows with enzootic hematuria have been shown to express both cyclooxygenase-1 (COX-1) and COX-2 at a high level relative to normal controls when evaluated by immunohistochemical methods.¹⁰ The efficacy of COX-2 inhibitor drugs on cancer prevention or treatment in cattle at risk for bladder tumors has yet to be investigated.

Epidemiology

Enzootic hematuria has a worldwide geographic distribution as the plants are found almost everywhere.

Necropsy Findings

Tissue pallor from anemia is often appreciated. The bladder wall is thickened, and the mucosa hemorrhagic and ulcerated. Microscopic examination of the bladder wall reveals capillary engorgement, intramural hemorrhage, and metaplasia of the bladder epithelium. Several types of bladder tumors and mixed-origin neoplasms may be present. Metastasis of epithelial neoplasms to the regional lymph nodes or other organs can occur.¹¹

Treatment and Prevention

Treatment of enzootic hematuria is limited to reduction or elimination of the responsible ferns from the diet. Forage improvement may help limit incorporation of the plant into hay. A program of early culling may help prevent low productivity from anemia and neoplasia. Hematuria will cease if bracken feeding is discontinued before the onset of tumor formation.