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Acanthocytosis and Other Hematological and Serum Biochemical

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Acanthocytosis and Other Hematological and Serum Biochemical ACANTHOCYTOSIS AND OTHER HEMATOLOGICAL AND SERUM BIOCHEMICAL PAMMETERS M THE DIAGNOSIS OF CmHEMANGIOSARCOMA A Thesis Presented to The Faculty of Graduate Studies of The University of Guelph by MARGO SUSAN TANT (n partial fuifilment of requirernents for the degree of Doctor of Veterinary Science February, 1998 Q Margo Susan Tant, 1998 National Library Bibliotheque nationale du Canada Acquisitions and Acquisitions et Bibliographie Services seMces bibliographiques 395 Wellington Street 395, rue Weilingtori ûüawaON KIAM ûaawaON K1AON4 Canada canada The author has granted a non- L'auteur a accorde une licence non exclusive licence dowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or sell reproduire, prêter, distri'buer ou copies of this thesis in microfom, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/nlm, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom t Ni la thèse ni des extraits substantiels may be printed or othemise de celle-ci ne doivent être imprimés reproduced without the author's ou auttement reproduits sans son ~ermission. autorisation. ABSTRACT ACANTHOCYTOSIS AND OTHER HEMATOLOGICAL AND SERUM BIOCHEMICAL PARAMETERS iN THE DIAGNOSIS OF CANINE HEMANGIOSARCOMA Margo Susan Tant Advisor: University of Guelph, 1998 Dr. J. H. Lumsden A retrospective case-control study was conducted using the records of 80 dogs with visceral hemangiosarcoma (HSA) and 200 dogs with various diseases that had features simila. to HSA. Al1 dogs were older than one year of age, had histologically confirxned disease, and had a complete blood count performed prior to the ha1 diagnosis. A standard protocol was used to count acanthocytes in the blood film of each dog. Acanthocyte count had a diagnostic sensitivity of 53.8% (and specificity of 61.5%) at a cutpoint of 21 acanthocyte/2000 red blood cells. A diagnostic specificity of 100% (and sensitivity of 7.5%) was achieved at a cutpoint of Hl acanthocytes/2000 red blood ceiis, which represented a marked acanthocytosis. The precision of acanthocyte count was poor to fair due to the subjective nature of identifjing acanthocytes. Although dogs with acanthocytes were more likely to have HSA (P = 0.02), and dogs with HSA had higher acanthocyte counts than controls (P = 0.003), acanthocyte count had Mted utility as a diagnostic test There was no level of acanthocytosis at which HSA could be ruled out and, although HSA could be ruled in at counts >71 acanthocyted2OOO red blood celis, ody a smdpercentage of dogs with HSA would be detected at this level. A multivariable logistic regsession analysis was performed using demographic, hematology, and serum biochernistry data for the study population. The resulthg predictive model for HSA included age greater than 8 years, Golden retriever breed, anemia, and thrombocytopenia. The mode1 had a sensitivity of 83.9% and a specificity of 80.9% in predicting the presence of HSA. In a related rnodel, acanthocyte count was retained as a significant variable, demonstrating that although acanthocyte count may not be useW. as a separate diagnostic test for HSA, it cm contribute to diagnostic certainty in the context of other findings. Hypoalbuminemia and elevated senun akaline phosphatase were associated with the absence of HSA, but inclusion of these variables did not improve the diagnostic performance of the logistic model. Therefore, although select serum biochemistry variables may help to deout HSA, a biochemistry profile is unlikely to contribute to the certainty of the diagnosis. 1 would like to thank the members of my advisory cornmittee for their advice and assistance in the preparation of this thesis, and in particdar, Dr. Tim Lumsden for his endless patience, Dr. Robert Jacobs for the generous use of his cornputer software, Dr. Brian Wilcock for his refieshing perspective fiom the other side, and Dr. Breoda Bo~ett for her detailed appraisd of my work, and for her interest and encouragement. I am deeply indebted to those who bravely agreed to count acanthocytes for me as pari of the multi-rater studies, including Dr. Th Lumsden, Dr. Robert Jacobs, Dr. Krk Ruotsalo, and Mn. Phyilîs Few - I truiy couldn't have done it without you. Dr. Frank Pollari fiom the Department of Population Medicine worked tirelessly with me on the logistic regression, and aiso helped with the statisticai analysis in the acanthocyte study. Thank you Frank, for being a good sport, and for your patience and humour throughout. The OVC Computer Support Group, including Mrs. Wendy Woodhouse and Ms. Elizabeth Reemeyer, and the Staff of the Medical Records Depariment, were instrumental in helping me find my study population, and without their help the project would have remained just an interesting idea The Pet Trust Fund is also gratefûlly acknowledged for its hanciai support of my research. To my fellow graduate students - especidy Krys Grodecki and Kris Ruotsaio, who were mentors and colieagues, but more importantiy, invaluable fnends and supporters; and Emma Michel (nee Hamilton) who shed with me that trial-by-fie known as Statistics, and stayed on to become a good fiiend - my special thanks for making the experîence more enjoyable. 1 thank my family for their love and support durhg the last three years; in particular, my parents for instilling the value of education, and the importance of nnishing what you start, and my sisten Uea and Judy for their encouragement when things were bleakest, and for cheerfully hunting down obscure journal articles for me. My most heartfelt appreciation is reserved for my husband, Alan Sippel, who has been my anchor throughout, and without whom this project would have been neither started nor completed. His direct contribution as the infamous "disinterested third party" (if the studies were properly blinded it's al1 his fault) was crucial. But of greater importance was his confidence in me, his moral support, and his patience. TABLE OF CONTENTS ......................................................... LIST OF TABLES ......................................................... v LIST OF FIGURES ...................................................................... .................................. vi CHAPTER I Prevalence ...........*........................... $. ...............*....*1 Biology of Hemangiosarcoma ................ ................................................................ 2 Age. Sex. and Breed .............................................................. ........................................ 3 Etiology .......................................................... .............................................................. 5 Chcal Course and Prognosis ......................................................................................6 Visceral Hemangiosarcorna.................................................................................................. 6 Cutaneous Hemangiosarcoma .............................................................................................. 8 Diagnostic Findings ......................................................................................................8 Hematological Changes in Dogs with Hemangiosarcoma .......................................... 10 Erythron .............................................................................................................................. 10 Leukon ................................................................................................................................ 12 PIatelets .............................................................................................................................. 13 Acanthocytes ............................................................................................................ 14 Acanthocytes in Humans .................................................................................................... 14 Acanthocytes in Animals ................................................................................................... 17 Acanthocytes in Canine Hemangiosarcoma ....................................................................... 18 CHAPTER II: CHAPTER III EVALUATIONOF ACANTHOCYTE COUNTAS A DIAGNOSTICTEST FOR CANIhE HEMANGIOSARCOMA...................................................................................................... 33 Introduction ................... .. ...................................................................................... 33* ................................................ Materials and Methods ................................................ 34 Def~tionand Criteria for Inclusion and Exclusion .......................................................... 34 Acanthocyte Smdy .......................................................................................................... 35 Analysis ................ .. ......................................................................................................... 37 Resuits .......................... ...... ......................................................................................... 39 Blood Film Smdy ............................................................................................................... 42 Photographic Study .........................................................................................................
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