Research Updates: A simple blood smear as a diagnostic test to predict death secondary to heatstroke in dogs?

A number of prognostic factors for survival of dogs with heatstroke have been reported. Commonly encountered historical, clinical, or laboratory findings associated with increased mortality include a comatose state upon admission, a high body condition score, a longer time between onset of heatstroke and presentation to a veterinarian, hypoglycemia, increased serum creatinine concentration, and abnormal results on a coagulation profile. In people, the presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients has been correlated with a poorer outcome. Red blood cell (RBC) morphologic abnormalities are commonly noted in dogs with heatstroke; NRBCs are particularly common in affected dogs, but have not been reported in people with heatstroke.

The goal of this prospective study was to evaluate whether the presence of NRBCs correlates with heatstroke-associated complications such as disseminated intravascular coagulation (DIC), acute intrinsic renal failure, and death and to determine whether the presence or number of peripheral NRBCs offers superior prognostic information. Forty dogs with environmental or exertional heatstroke were identified based on history and clinical signs. Serum chemistry profiles, complete blood counts with smear evaluation, and coagulation profiles including prothrombin time (PT) and partial thromboplastin time (PTT) were performed in each dog. The NRBC results were analyzed by absolute NRBC count and by relative NRBC number, defined as the number of NRBCs per 100 white blood cells (WBCs).

In total, 95% of dogs with heatstroke had NRBCs noted in circulation at presentation. Both the absolute NRBC count and median relative NRBC number at presentation were significantly higher in nonsurvivors than in survivors. When NRBC results were further subdivided by stage of development, the proportion of rubricytes vs. metarubricytes (i.e. early vs. late RBC precursors/total NRBC) was significantly higher in nonsurvivors compared with survivors. Acute intrinsic renal failure and DIC were diagnosed in 42% and 58% of dogs, respectively, of which 81% and 82% of affected dogs did not survive. The median relative NRBC number at presentation was significantly higher in dogs with acute intrinsic renal failure (48 NRBCs/100 WBCs) and DIC (55 NRBCs/100 WBCs) compared with dogs without acute intrinsic renal failure (9 NRBCs/100 WBCs) or DIC (2 NRBCs/100 WBCs). The relative NRBC number significantly correlated with PT and PTT, with dogs with DIC having a significantly increased relative NRBC number.

Data analysis of this population of dogs with heatstroke allowed the authors to conclude that a relative NRBC ≥ 18% at presentation was a sensitive (91%) and specific (88%) predictor of death. Finally, the median relative NRBC number 24 hours after admission was not significantly different between survivors (0.5%) and nonsurvivors (2.5%).

COMMENTARY

Heatstroke in dogs is a severe disease associated with a guarded prognosis. The overall mortality range is 50% to 64%. The poor prognosis associated with heatstroke is likely due to the high prevalence of DIC and acute intrinsic renal failure in affected dogs, presumptively because of systemic organ damage. The authors of this study suggest that the increased release of NRBCs from the bone marrow may likewise be a marker of severe hyperthermia-induced organ injury. This increased release of NRBCs may explain why nonsurvivors, which presumptively have more severe organ injury, had a higher percentage of early erythroid precursors (rubricytes) than survivors.

The overall mortality of dogs enrolled in this study was 55%, with 91% (20 of 22) of the nonsurvivors dying or being euthanized within 36 hours of presentation. The authors have provided compelling evidence that blood smear evaluation in dogs with heatstroke may be a rapid and reliable method to assess and predict the likelihood of heatstroke patients developing severe complications such as acute intrinsic renal failure and DIC, as well as the likelihood of a good outcome. This adjunctive diagnostic test will be particularly useful for general practitioners because of its simplicity, practicality, and cost-effectiveness. But keep in mind that although highly correlative, a number of patients that survived to be discharged had a high relative NRBC number, and many nonsurvivors had absolute NRBC numbers that overlapped with the range noted in survivors.

Aroch I, Segev G, Loeb E, et al. Peripheral nucleated red blood cells as a prognostic indicator in heatstroke in dogs. J Vet Intern Med 2009;23(3):544-551.

The information in "Research Updates" was provided by Erika Meler, DVM, MS, and Barrak Pressler, DVM, PhD, DACVIM, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.