Premium
Heterozygosity for P2Y12 receptor gene mutation associated with postoperative hemorrhage in a Greater Swiss Mountain dog
Author(s) -
Flores Rebecca S.,
Boudreaux Mary K.,
Vasquez Barbara,
Bristow Poppy,
Aronson Lillian R.,
SantoroBeer Kari,
Callan Mary Beth
Publication year - 2017
Publication title -
veterinary clinical pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 51
eISSN - 1939-165X
pISSN - 0275-6382
DOI - 10.1111/vcp.12533
Subject(s) - platelet , p2y12 , adenosine diphosphate , ristocetin , medicine , endocrinology , platelet activation , gene mutation , von willebrand factor , biology , mutation , gene , biochemistry , platelet aggregation
A 3‐year‐old, female Greater Swiss Mountain dog developed a hemoperitoneum following an exploratory laparotomy and ovariohysterectomy. Platelet count, PT , APTT , and plasma von Willebrand factor antigen concentration were within RI s. A buccal mucosal bleeding time (BMBT) was prolonged. Given the probability of a hereditary thrombopathia, the dog was administered desmopressin, fresh platelet transfusions, and aminocaproic acid to control hemorrhage. Subsequently, DNA testing for the P2Y12 receptor gene mutation identified the dog as being a heterozygote (carrier). Further platelet function testing was performed following complete recovery. Results of a repeat BMBT and a point‐of‐care screening test using the Platelet Function Analyzer‐100 (collagen/adenosine‐diphosphate [ADP] test cartridge) were within RI s. Flow cytometric studies demonstrated a marked reduction in fibrinogen binding to the dog's platelets in response to ADP ‐ adenosine diphosphate activation. Likewise, turbidimetric aggregometry revealed a complete absence of platelet aggregation in response to ADP . However, there were a normal aggregation response to the platelet agonist convulxin and a mild reduction in amplitude in response to γ‐thrombin. This is the first report of a dog heterozygous for the P2Y12 receptor gene mutation exhibiting a bleeding tendency and having evidence of impaired platelet function in vitro in response to ADP activation. Given that the mutant allele for the P2Y12 thrombopathia appears to be widespread in the Greater Swiss Mountain dog breed, veterinarians need to be aware that both homozygotes and heterozygotes for this platelet receptor mutation are at risk of developing life‐threatening bleeding following trauma or surgery.