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An Investigation of the Multifaceted Platelet Dysfunction in Dogs with Naturally-Occurring Chronic Kidney Disease

Dudley, Alicia A

Abstract Details

2014, Master of Science, Ohio State University, Comparative and Veterinary Medicine.
Bleeding is a complication of chronic kidney disease (CKD) in humans and can occur despite normal coagulation times and platelet counts. These abnormalities are caused, in part, by platelet dysfunction and abnormal platelet-vessel wall interactions. Dogs with experimentally induced CKD have prolonged mucosal bleeding times, however this test is variable and error prone. In dogs with naturally occurring CKD, coagulation defects and platelet dysfunction have not been evaluated using new point-of-care tests of platelet function and global coagulation. Our objective was to compare platelet function between healthy dogs and dogs with CKD using the PFA-100 and thromboelastography (TEG) and to determine if changes in these tests can be explained by alterations in platelet GPIb and GPIIb-IIIa expression, membrane receptors for vWF and fibrinogen, respectively or in changes in platelet activation as determined by platelet P-selectin expression. Blood samples from 11 dogs with naturally occurring CKD and 10 healthy control dogs were collected. Routine CBC with platelet count, serum biochemistry and urinalysis with urine protein to creatinine ratio were performed in both groups. Platelet function was assessed by measuring PFA-100 closure times (CT) using collagen and epinephrine (Col+EPI) or collagen and adenosine diphosphate (Col+ADP) agonists. Reaction time (R), clot formation time (K), alpha-angle, maximal amplitude (MA) and global clot strength (G) TEG variables were analyzed. Soluble coagulation factor function testing was performed including PT, aPTT, fibrinogen concentration and AT activity. Platelet GPIb, GPIIb-IIIa and P-selectin expression was assessed by flow cytometry and expressed as mean fluorescence intensity (MFI). Hematocrit was significantly decreased in CKD dogs (p < 0.0001). Platelet counts were not different between groups (p = 0.57). Dogs with CKD had significantly prolonged PFA-100 Col+ADP CT compared to healthy dogs (p = 0.01). No significant difference in Col+EPI CT was found between healthy and CKD dogs. There was a significant increase in TEG MA (p < 0.01) and G (p = 0.01) and a significant decrease in K-time (p = 0.035) in dogs with CKD compared to healthy controls. The remaining TEG variables (R, and angle) were not significantly different between CKD and healthy dogs. CKD dogs had increased platelet GPIIb-IIIa and P-selectin MFI compared with control dogs (p = 0.01 and 0.03 respectively). There was no difference in GPIb MFI between groups. No correlation was found between platelet surface receptor expression and any TEG value or PFA-100 closure times. Dogs with CKD appear to have platelet dysfunction despite normal platelet counts. However, despite platelet dysfunction, these patients are hypercoagulable based on their significantly elevated MA and G TEG values. This discrepancy may be explained by the significantly decreased hematocrit and significantly increased fibrinogen concentrations in CKD dogs. However, platelet receptor expression cannot be used to explain changes in platelet function and changes in whole blood coagulation identified in these patients. Additional studies are needed to identify the underlying platelet defect(s) in dogs with CKD and what role they play in whole body coagulation, as well as their clinical significance.
Julie Byron, DVM, MS, DACVIM (Advisor)
Mary Jo Burkhard, DVM, PhD, DACVP (Committee Member)
Emma Warry, BVSc (HONS), DACVIM (Committee Member)
80 p.

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Citations

  • Dudley, A. A. (2014). An Investigation of the Multifaceted Platelet Dysfunction in Dogs with Naturally-Occurring Chronic Kidney Disease [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1405012077

    APA Style (7th edition)

  • Dudley, Alicia. An Investigation of the Multifaceted Platelet Dysfunction in Dogs with Naturally-Occurring Chronic Kidney Disease. 2014. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1405012077.

    MLA Style (8th edition)

  • Dudley, Alicia. "An Investigation of the Multifaceted Platelet Dysfunction in Dogs with Naturally-Occurring Chronic Kidney Disease." Master's thesis, Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1405012077

    Chicago Manual of Style (17th edition)