ABSTRACT
BACKGROUND: In humans, fresh frozen plasma (FFP) loses factor V and VIII activities after 1 year. It then becomes frozen plasma (FP), and theoretically is unsuitable for use in patients with coagulopathies. These findings have not been reported for dogs. HYPOTHESIS: Canine FP is hemostatically active after 5 years of storage. ANIMALS: Fresh plasma (Group FsP; n = 15) and 5-year-old FP (Group FzP; n = 10) from blood bank donors. METHODS: Group FsP and Group FzP samples were evaluated by thromboelastography (TEG), one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), fibrinogen, and antithrombin. Fresh plasma (n = 6) and a subset of Group FzP (n = 8) were evaluated for clotting factor activities (V, VIII, IX, X). A 2nd experiment using short-term storage of thawed FP under suboptimal conditions (refrigerated [4°C] or refrozen [-20°C]) by TEG was performed to simulate general practice storage capabilities. RESULTS: Group FzP had shorter reaction time (P = .0007) and larger angle (P = .0004) compared with Group FsP by TEG, suggesting hypercoaguability. Factor VIII and X activities were lower in Group FzP (P = .02 and .005, respectively). Fibrinogen, OSPT, and APTT were significantly lower or longer for Group FzP than Group FsP (P < .05), but most values remained within reference intervals for dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Five-year-old canine FP stored at -30°C is hemostatically active and should be clinically evaluated in patients with coagulopathies. If active, the monetary savings of using older plasma will be substantial.
Subject(s)
Dogs , Hemostatics/pharmacology , Plasma , Thrombelastography/veterinary , Animals , Blood Coagulation Factors/metabolism , Blood DonorsABSTRACT
Osteosarcoma (OS) is the most commonly diagnosed malignant bone tumor in humans and dogs, characterized in both species by extremely complex karyotypes exhibiting high frequencies of genomic imbalance. Evaluation of genomic signatures in human OS using array comparative genomic hybridization (aCGH) has assisted in uncovering genetic mechanisms that result in disease phenotype. Previous low-resolution (10-20 Mb) aCGH analysis of canine OS identified a wide range of recurrent DNA copy number aberrations, indicating extensive genomic instability. In this study, we profiled 123 canine OS tumors by 1 Mb-resolution aCGH to generate a dataset for direct comparison with current data for human OS, concluding that several high frequency aberrations in canine and human OS are orthologous. To ensure complete coverage of gene annotation, we identified the human refseq genes that map to these orthologous aberrant dog regions and found several candidate genes warranting evaluation for OS involvement. Specifically, subsequenct FISH and qRT-PCR analysis of RUNX2, TUSC3, and PTEN indicated that expression levels correlated with genomic copy number status, showcasing RUNX2 as an OS associated gene and TUSC3 as a possible tumor suppressor candidate. Together these data demonstrate the ability of genomic comparative oncology to identify genetic abberations which may be important for OS progression. Large scale screening of genomic imbalance in canine OS further validates the use of the dog as a suitable model for human cancers, supporting the idea that dysregulation discovered in canine cancers will provide an avenue for complementary study in human counterparts.