The shelf-life of stored red blood cells (RBCs) is typically 42 and 35 days for human and canine RBCs, respectively. Given that blood is a precious and limited resource, both human and veterinary blood banks typically dispense the oldest RBC units first to reduce wastage. 

However, accumulating evidence suggests that transfusion of RBCs stored ≥ 14 days is associated with increased rates of morbidity and mortality in hospitalized human patients.

In our study of healthy dogs receiving autologous RBC transfusions stored for 7 (fresh) and 28 (old) days, administration of old, but not fresh, RBC units was associated with a pro-inflammatory cytokine response, exemplified by monocyte chemoattractant protein (MCP)-1, and accompanied by increased neutrophil counts and decreased platelet counts.

We propose to evaluate markers of inflammation, hemolysis, and endothelial activation in a randomized clinical trial in which client-owned dogs with primary immune-mediated hemolytic anemia (IMHA) and immune-mediated thrombocytopenia (IMT) would receive fresh (stored <7 days) or old (stored 21-28 days) RBCs. If we document that transfusion of “older” RBCs to dogs with IMHA and IMT is associated with an increased inflammatory response, this study would provide the basis for a larger multi-center study to evaluate the effect of duration of RBC storage on morbidity and mortality in anemic canine patients, potentially changing our current transfusion practice. 

 Brief background:

Transfusion of RBCs stored ≥ 14 days may be associated with increased rates of infection, thrombosis, morbidity, and mortality in hospitalized human patients, especially those with trauma, after surgery, or in an ICU.

Our choice of enrolling dogs with IMHA and IMT to evaluate potential adverse effects of “old” RBC transfusions is based on:

  1. A retrospective study of 3,187 canine patients that received RBC transfusions at MJR VHUP, in which a logistic regression model indicated that for dogs with hemolysis (n=514), 89% of which had immune-mediated hemolytic anemia, longer duration of PRBC storage was a negative risk factor for survival; for every 7 day increase in storage, there was a 0.79 lesser odds of 30 day survival (95% CI 0.64-0.97; P=0.025).
  2. Our preliminary data from autologous PRBC transfusions in healthy dogs in which there was evidence of a pro-inflammatory cytokine response, exemplified by MCP-1.  Interestingly, increased serum concentrations of MCP-1 and interleukin (IL)-18 have been documented in dogs with IMHA compared with controls and were independently associated with mortality. 
  3. Dogs with blood loss anemia due to IMT will be included for comparison since they are hypothesized to have less inflammation than dogs with IMHA prior to transfusion. 

Study design: Prospective, randomized clinical trial enrolling 60 client-owned dogs with primary IMHA and 60 dogs with IMT deemed to be in need of a RBC transfusion. 

Benefits to client for participation in study (total value ~ $1300):

  • CBC (pre- and 24 hour post-transfusion)
  • Blood type
  • Blood crossmatch (n=2)
  • PRBC transfusion (n=2)
  • Two nights of hospitalization (excluding ES/ICU)

Study Investigators: Beth Callan (Penn Vet) and Eldad Hod (Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital)

Funding Sources: AKC Canine Health Foundation and Penn Vet’s Companion Animal Research Fund

Trial Duration: January 2014-December 2015

Contact:

For more information and to enroll in this trial, please contact Beth Callan at 215-898-3999 or callan@vet.upenn.edu