Immunoglobulin G and phosphatidylserine in regenerative and nonregenerative immune-mediated anemias of dogs.

BACKGROUND: Although precursor-targeted immune-mediated anemia (PIMA) is thought to be caused by immune targeting of erythroid precursors (nucleated RBCs, nRBCs), its pathogenesis is unknown. Immunoglobulin G (IgG) or phosphatidylserine (PS) may promote nRBC destruction in PIMA. HYPOTHESIS: Dogs with PIMA have increased nRBC IgG and PS, and dogs with immune-mediated hemolytic anemia (IMHA) have increased RBC PS compared to healthy dogs. ANIMALS: Blood from 20 healthy dogs and from dogs with IMHA (11) or other (non-IMHA) conditions (9), and marrow aspirates with or without blood from 10 healthy dogs and from dogs with PIMA (17) or other (non-IMHA, non-PIMA) conditions (7). METHODS: Marrow nRBC stages were separated by density gradient. Flow cytometry was used to assess the percentage of RBCs or nRBCs with increased IgG or PS. RESULTS: Red blood cell (RBC) IgG positivity was increased in 9/11 IMHA dogs and 0/9 non-IMHA dogs. Red blood cell PS positivity was increased in 10/11 IMHA dogs and 2/9 non-IMHA dogs. Five of 17 PIMA dogs had increased nRBC IgG positivity in mid- or late-stage fractions, whereas all 7 non-PIMA dogs were negative. Mid- and late-stage erythroid precursor PS was significantly higher in PIMA dogs compared to healthy dogs. Five of 14 PIMA dogs had increased RBC IgG positivity. CONCLUSIONS: Immunoglobulin G and PS may promote destruction of nRBCs in PIMA dogs; PS may promote destruction of RBCs in IMHA dogs.

Use of fresh platelet concentrate or lyophilized platelets in thrombocytopenic dogs with clinical signs of hemorrhage: a preliminary trial in 37 dogs.

OBJECTIVE: To examine the safety and feasibility of using lyophilized platelets (LYO) and fresh platelet concentrate (FRESH) in bleeding thrombocytopenic dogs. DESIGN: Preliminary prospective randomized clinical trial. SETTING: Two private referral centers and 3 university teaching hospitals. ANIMALS: Thirty-seven dogs with a complaint of hemorrhage associated with thrombocytopenia (platelet count <70 × 10(9) /L [70,000/µL], a hematocrit >15%, and that had received neither vincristine nor platelet-containing transfusions within 72 h of enrollment were studied. INTERVENTIONS: Animals were randomized to receive LYO or FRESH, dosed according to weight. Physical examination, complete blood counts, and coagulation testing (prothrombin time and activated partial thromboplastin time) were performed at enrollment. Physical examinations were also performed immediately post transfusion, and at 1 and 24 h after transfusion. Complete blood counts were repeated immediately post transfusion and at 24 h. Collected data included bleeding score (BLS), response to transfusion, adverse reactions, hospitalization time, need for additional transfusions, survival to discharge, and 28-d survival. MEASUREMENTS AND MAIN RESULTS: Twenty-two dogs received LYO and 15 received FRESH. There was no difference between groups in age, weight, BLS, platelet count, white blood cell count, hematocrit, or presence of melena. There was no difference between groups in transfusion reaction rates, the need for additional transfusions, 24-h BLS, hospitalization time, survival to discharge, or 28-d survival. CONCLUSIONS: Transfusion of LYO was feasible and associated with a low transfusion reaction rate in this limited study of thrombocytopenic canine patients presenting with mild-to-severe hemorrhage. LYO were easy to use and provided storage advantages over FRESH. Further study of this product, including examination of efficacy and platelet life span, is warranted.

SCID dogs: similar transplant potential but distinct intra-uterine growth defects and premature replicative senescence compared with SCID mice.

We have previously described DNA-dependent protein kinase (DNA-PKcs) mutations in horses and dogs that result in deficits in V(D)J recombination, DNA repair, and SCID. In this paper, we document substantial developmental growth defects in DNA-PKcs-deficient dogs that are not apparent in SCID mice. Fibroblast cell strains derived from either fetal or adult SCID dogs proliferate poorly in culture and undergo premature replicative senescence, somewhat reminiscent of cells derived from Ku-deficient mice. A limited number of animals have been immune reconstituted (by bone marrow transplantation) so that they can be maintained in a normal environment for long periods. Several of these animals have developed conditions associated with premature ageing at 2-3 years of age, roughly 20% of their expected lifespan. These conditions include intestinal malabsorption and primary neural cell neoplasia. These results suggest that DNA-PKcs deficiency is not tolerated equally in all species, perhaps providing insight into why DNA-PKcs deficiency has not been observed in humans. Finally, this study demonstrates the feasibility of maintaining SCID dogs for extended periods of time and documents their utility for bone marrow transplantation studies and as hosts for the propagation of xenografts. In sum, SCID dogs may present researchers with new possibilities for the development of animal models of human disease.