Macrothrombocytopenia in Dog Breeds Inherited macrothrombocytopenia is due to a mutation in the gene encoding Beta 1-tubulin.1 This mutation has been identifi ed in approximately 90% of Cavalier King Charles Spaniels (CKCS), as well as other breeds:1,2,3

Norfolk Terriers Shih Tzus

Chihuahuas Jack Russell Terriers

Labrador Retrievers Havanese

Poodles Boxers

English Toy Spaniels Cocker Spaniels

Labradoodles Bichon Frise

Maltese Cairn Terriers

Mixed Breeds

In one study, marked thrombocytopenia (< 100,000) was noted in over 51% of CKCS, with macrothrombocytes identifi ed in as many as 33% of the population.4 The tubulin mutation results in defective fragmentation of the megakaryocyte cytoplasm, causing the platelets to stay together.1

Dogs a� ected with macrothrombocytopenia are often asymptomatic despite low platelet number, and show normal platelet crits due to increased platelet size that allow for normal platelet function and coagulation times.1 Clinical bleeding is not a characteristic of this syndrome.2 Greyhounds have lower platelet counts than other dog breeds for unknown reasons.1

Hematologic Changes Suggesting Macrothrombocytopenia Changes noted in hematology to suggest macrothrombocytopenia may include some or all of the following:

• A low platelet number ranging from as low as 30 x 10^9/l to 150 x 10^9/l.1,5

• An increased mean platelet volume (MPV) noted on the CBC results (MPV > 11.1 fl ).5

• Presence of macrothrombocytes on a blood fi lm (see image above).

• Plateletcrit should be normal or just below reference interval.6

• An increased lymphocyte (LYM) count, which is elevated as the impedance counter counts the macroplatelets as white blood cells (specifi cally, lymphocytes).7

UNDERSTANDING INHERITED MACROTHROMBOCYTOPENIA(GIANT PLATELET DISORDER)

Chapter 7 - Evaluation of Hemostasis: Coagulation and Platelet Disorders by John Harvey from Veterinary Hematology A Diagnostic Guide and Color Atlas 2012, Fig 7-26, page 211

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1 Stokol T. Disorders of haemostasis [Chapter 6]. BSAVA Manual of Canine and Feline Clinical Pathology, Third Edition. 2016: 114. 2 Sharkey L, Heinrich D. In-Clinic Hematology: The Blood Film Review. Today’s Veterinary Practice. 2015;5(4):43-53. 3 https://www.vetmed.auburn.edu/faculty/boudreaux-mary/4 Cowan SM, Bartges JW, Gompf RE, et al. Giant platelet disorder in the Cavalier King Charles Spaniel. Experimental Hematology. 2004;32(4):344-350.5 B. Davis, M. Toivio-Kinnucan, S. Schuller, and M.K. Boudreaux Mutation in b1-Tubulin Correlates with Macrothrombocytopenia in Cavalier King Charles Spaniels. J Vet Intern Med 2008;22:540–545 p. 5426 Kelley J, Sharkey LC, Christopherson PW, Rendahl A. Platelet count and plateletcrit in Cavalier King Charles Spaniels and Greyhounds using the Advia 120 and 2120. Vet Clin Pathol 2014; 43(1):43-49 7 Data on File. TI-04255 and TI-04614, Zoetis Inc.8 Tvedten H. Hemostatic Abnormalities [Chapter 5]. Small Animal Clinical Diagnosis by Laboratory Methods. 2012: 97.

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Inherited Macrothrombocytopenia on the VETSCAN® HM57Macrothrombocytes will not break into fragments when exposed to lyse solution, and may cause inaccurate counts and/or instrument errors, particularly in analyzers that use impedance technology as the primary measurement method. When such samples are analyzed on the VETSCAN HM5 hematology analyzer, an “L” fl ag will often be displayed. While an “L” fl ag could suggest a potential lyse resistant red blood cell anomaly or a problem with lyse delivery, in this case, the analyzer is reporting the macroplatelets as non-lysed red blood cells.

A CBC from the VETSCAN HM5 for a patient with inherited macrothrombocytopenia will typically show an elevated LYM and a warning “L” fl ag. There will not be a signifi cant PLT peak and the PLT count will be reported as very low. The MPV may also be reported as normal. Please see an example of macrothrombocytopenia on the HM5 to the right.

Note: not every CKCS has macrothrombocytopenia. Those individuals with normally-sized platelets will not show the features mentioned above.

Blood Film Evaluation The medical recommendation for patient samples with any cell count outside of the reference range is to always evaluate a blood fi lm. A quick method for estimation of platelet numbers can be determined from a blood fi lm at high power (100x, immersion oil) in the monolayer region of the slide using the following method:

Estimated Platelet Number = the average number of platelets in 10 fi elds x 15,000-20,000platelets/uL8

If a true low platelet count is observed with high numbers of macrothrombocytes, macrothrombocytopenia should be considered based on the patient’s breed and history.