Postparturient Hemoglobinuria in Dairy Cows
Postparturient hemoglobinuria is a sporadic condition seen worldwide that most commonly affects individual high-yielding dairy cows at the onset of lactation. It is characterized by development of acute intravascular hemolysis often associated with hemoglobinuria and leading to potentially life-threatening anemia. Beef and nonlactating cattle are rarely affected. The exact cause is unknown, but phosphorus depletion or hypophosphatemia, as well as copper deficiency and possibly hemolyzing substances contained in certain feeds have been incriminated as potential causative or predisposing factors. Severe intracellular phosphorus depletion of RBCs is known to increase osmotic fragility of the RBCs, possibly predisposing to intravascular hemolysis.
Although marked hypophosphatemia is a common finding in affected animals, the vast majority of hypophosphatemic dairy cows do not develop postparturient hemoglobinuria, suggesting that hypophosphatemia is not the sole causative factor. Cases of postparturient hemoglobinuria observed in New Zealand are believed to be associated with copper deficiency, potentially making RBCs more susceptible to oxidative stress. Other potential causes are hemolytic or oxidative plant toxins (often from Brassica spp, sugar beets, or green forage).
Clinical cases of postparturient hemoglobinuria are rare, but when they occur the case fatality rate is considerable (10%–30%). In general, the disorder remains clinically inapparent until the PCV drops below 20%. As intravascular hemolysis continues, affected cows display a drop in milk production, anorexia, and lethargy. Signs of marked hemolytic anemia, such as pale and icteric mucous membranes, tachycardia, tachypnea, and hemoglobinuria with dark brown or red urine, become readily apparent. Cases of spontaneous recovery, in which intravascular hemolysis stops without therapeutic intervention are frequent. Cows that survive the hemolytic crisis may take several weeks to recover completely.
Diagnosis of postparturient hemoglobinuria is usually made by recognition of clinical signs, particularly dark urine and anemia during the characteristic stage of lactation. Hemoglobinuria may best be diagnosed by noting failure of the urine to clear with centrifugation (excluding hematuria) and presence of concurrent severe anemia. Jaundice becomes apparent after a few days of hemolysis. Intravascular hemolysis caused by babesiosis or theileriosis may be excluded by blood smear analysis, and standard laboratory methods can be used to exclude leptospirosis or bacillary hemoglobinuria.
Diagnostic testing and feed or pasture analysis can be performed to identify toxic plants and deficiency of phosphorus, copper, and other antioxidants. Blood phosphorus concentrations are unreliable indicators for diagnosis of this condition because cases with normal or even elevated blood phosphorus concentrations have been reported. Normal or high serum phosphorus concentrations in animals with postparturient hemoglobinuria have been explained by massive intravascular hemolysis releasing large amounts of phosphorus from the intracellular space into plasma.
Transfusion of 4–6 liters of whole blood is the only known treatment for postparturient hemoglobinuria consistently reported as effective. Blood transfusion, however, is only indicated in the most severe cases, with PCV <15%. Affected cows should be restrained in a calm environment, avoiding physical stress as much as possible and allowing easy access to water and feed. Color of the urine, demeanor of the animals, and the PCV should be followed closely to identify animals requiring blood transfusion. Oral drenches with fluids to maintain hydration may be needed in depressed animals. Oral treatment with 200–300 g of sodium phosphate salts every 12 hours (which may be preceded by IV infusion with monosodium dihydrogen phosphate (60 g in 300 mL of sterile water), is suitable to rapidly correct hypophosphatemia but does not stop hemolysis. Copper glycinate (120 mg available copper) has been recommended in cases in which copper deficiency is suspected as the underlying cause.
The efficacy of these treatments to prevent further hemolysis is not documented. No sodium phosphate or copper glycinate solution approved for parenteral administration by the FDA is currently available for use in ruminants. The use of these compounds in dairy cows is therefore extra-label. Correction of mineral deficiencies and elimination of plant toxins from the diet may help prevent recurrence.
Postparturient hemoglobinuria is most commonly found in high-producing dairy cows at the onset of lactation.
The exact cause is unknown, but hypophosphatemia, copper deficiency, toxic plant exposure, and presence of hemolyzing substances in certain feeds have been proposed as predisposing factors.
Many cows do not display clinical signs until the PCV falls below 20%. Once that occurs, mortality risk may be 10%–30%.
Transfusion of whole blood is indicated for severe cases.