OMIA 001001-9615 : Thrombocytopenia in Canis lupus familiaris

In other species: domestic cat , horse , cattle

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 155100 (trait) , 141000 (trait) , 188000 (trait) , 188020 (trait) , 188025 (trait) , 188030 (trait) , 273900 (trait) , 274000 (trait) , 313900 (trait) , 613112 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2008

Cross-species summary: Includes macrothrombocytopenia

Inheritance: From segregation analysis of 16 families of Cavalier King Charles Spaniels [CKCS] in which this disorder was segregating, Pedersen et al. (2002) concluded that " idiopathic, asymptomatic thrombocytopenia in CKCS is inherited in an autosomal recessive manner. The condition most likely constitutes an inherited macrothrombocytopenia in dogs".

Molecular basis: Being aware of an earlier unpublished discovery by M.K. Boudreaux of a missense mutation in the TUBB1 gene (encoding beta1-tubulin) in several King Charles Cavalier Spaniels (CKCS) with macrothrombocytopenia, Davis et al. (2008) genotyped for this mutation in 100 CKCS dogs and 52 dogs from other breeds, for most of which platelet numbers and volume were recorded. They confirmed that a "missense mutation (c.745 G>A) in the gene encoding beta1-tubulin, predicted to result in the substitution of an asparagine for aspartic acid (D249N), correlated with the macrothrombocytopenia observed" (with thanks to Dr. Mario Van Poucke for identifying an error in an earlier version of this entry). Only one of the dogs from other breeds (a Labrador Retriever) had the same mutation (as a heterozygote).

Gelain et al. (2014) reported a different missense mutation (c.5G>A; p.R2H) in the same gene (TUBB1) as the likely cause of a very similar disorder in Norfolk and Cairn Terriers.

Clinical features: This disorder occurs in many different forms, many of which are not inherited. As summarised by Żmigrodzka et al. (2014), "Thrombocytopenia (low platelet count) can occur as a result of a megacaryocyte disorder, disturbance of platelet production as well as their premature destruction. Platelet count can be also decreased due to sequestration of platelets in the tissues . . . . Myeloproliferative bone marrow disorders as well as certain drugs (e.g. oestrogens and chloramphenicol) can alter platelet production in the bone marrow . . . . The most frequent cause of thrombocytopenia is premature platelet destruction due to an abnormal immune response; when no underlying disease is found and aetiological agent remains undetermined IMT is described as primary. Secondary disease can develop in neoplastic conditions (e.g. mammary gland tumour, haemangiosarcoma, and lymphoma), infectious diseases (e.g. babesiosis, leptospirosis, and other bacterial, viral, and parasitic infections), after vaccination with live attenuated viruses (e.g. canine distemper virus), or after drug treatment (e.g. chloramphenicol, cephalosporin, sulphonamides, and gold salts). Rapid platelet consumption is often observed in acute haemorrhage, disseminated intravascular coagulation, or inflammation. Destruction and consumption of platelets are also enhanced in microangiopathies . . . . Common causes of platelet sequestration are splenomegaly, splenic torsion, and sepsis . . . ."

Breeds: Cairn Terrier, Cavalier King Charles Spaniel, Norfolk Terrier.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TUBB1 tubulin, beta 1 class VI Canis lupus familiaris 24 NC_051828.1 (44625242..44634669) TUBB1 Homologene, Ensembl, NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Norfolk Terrier Thrombocytopaenia TUBB1 missense 24 c.5G>A p.(R2H) 2014 25060661
King Charles Spaniel Thrombocytopaenia TUBB1 missense 24 c.745G>A p.(D249N) 2008 18466252


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2016 Cooper, S.A., Huang, A.A., Raskin, R.E., Weng, H.Y., Scott-Moncrieff, J.C. :
Clinical data, clinicopathologic findings and outcome in dogs with amegakaryocytic thrombocytopenia and primary immune-mediated thrombocytopenia. J Small Anim Pract 57:142-7, 2016. Pubmed reference: 26799165. DOI: 10.1111/jsap.12441.
2014 Gelain, M.E., Bertazzolo, W., Tutino, G., Pogliani, E., Cian, F., Boudreaux, M.K. :
A novel point mutation in the β1-tubulin gene in asymptomatic macrothrombocytopenic Norfolk and Cairn Terriers. Vet Clin Pathol 43:317-21, 2014. Pubmed reference: 25060661. DOI: 10.1111/vcp.12168.
Schwartz, D., Sharkey, L., Armstrong, P.J., Knudson, C., Kelley, J. :
Platelet Volume and Plateletcrit in Dogs with Presumed Primary Immune-Mediated Thrombocytopenia. J Vet Intern Med :, 2014. Pubmed reference: 25056453. DOI: 10.1111/jvim.12405.
Zmigrodzka, M., Guzera, M., Winnicka, A. :
Evaluation of reticulated platelets in dogs with breed-related thrombocytopenia. Pol J Vet Sci 17:137-42, 2014. Pubmed reference: 24724481.
2013 Collicutt, N.B., Garner, B. :
Erythrocyte dysplasia in peripheral blood smears from 5 thrombocytopenic dogs treated with vincristine sulfate. Vet Clin Pathol :, 2013. Pubmed reference: 24138476. DOI: 10.1111/vcp.12089.
2011 Bodié, K., Gagne, G.D., Sramek, M.K., Desmond, D.J., Abel, S.J., Fagerland, J.A. :
Asymptomatic macrothrombocytopenia in a young pure-bred beagle dog: a case report. Toxicol Pathol 39:980-7, 2011. Pubmed reference: 21859886. DOI: 10.1177/0192623311416261.
2010 Gelain, M.E., Tutino, G.F., Pogliani, E., Bertazzolo, W. :
Macrothrombocytopenia in a group of related Norfolk terriers. Vet Rec 167:493-4, 2010. Pubmed reference: 20871084. DOI: 10.1136/vr.c4782.
2009 Botsch, V., Küchenhoff, H., Hartmann, K., Hirschberger, J. :
Retrospective study of 871 dogs with thrombocytopenia. Vet Rec 164:647-51, 2009. Pubmed reference: 19465753.
Shelah-Goraly, M., Aroch, I., Kass, P.H., Bruchim, Y., Ofri, R. :
A prospective study of the association of anemia and thrombocytopenia with ocular lesions in dogs. Vet J 182:187-92, 2009. Pubmed reference: 18664411. DOI: 10.1016/j.tvjl.2008.05.027.
2008 Bommer, N.X., Shaw, D.J., Milne, E.M., Ridyard, A.E. :
Platelet distribution width and mean platelet volume in the interpretation of thrombocytopenia in dogs. J Small Anim Pract 49:518-24, 2008. Pubmed reference: 18793252. DOI: 10.1111/j.1748-5827.2008.00636.x.
Davis, B., Toivio-Kinnucan, M., Schuller, S., Boudreaux, MK. :
Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels. J Vet Intern Med 22:540-5, 2008. Pubmed reference: 18466252. DOI: 10.1111/j.1939-1676.2008.0085.x.
Putsche, J.C., Kohn, B. :
Primary immune-mediated thrombocytopenia in 30 dogs (1997-2003). J Am Anim Hosp Assoc 44:250-7, 2008. Pubmed reference: 18762561. DOI: 10.5326/0440250.
2005 Middleton, SM. :
Immune-mediated thrombocytopenia in a 4-month-old German shepherd dog. Can Vet J 46:443-5, 2005. Pubmed reference: 16018567.
Singh, MK., Lamb, WA. :
Idiopathic thrombocytopenia in Cavalier King Charles Spaniels. Aust Vet J 83:700-3, 2005. Pubmed reference: 16315671.
2004 Cowan, SM., Bartges, JW., Gompf, RE., Hayes, JR., Moyers, TD., Snider, CC., Gerard, DA., Craft, RM., Muenchen, RA., Carroll, RC. :
Giant platelet disorder in the Cavalier King Charles Spaniel. Exp Hematol 32:344-50, 2004. Pubmed reference: 15050744. DOI: 10.1016/j.exphem.2004.01.008.
Olsen, L.H., Kristensen, A.T., Qvortrup, K., Pedersen, H.D. :
Comparison of manual and automated methods for determining platelet counts in dogs with macrothrombocytopenia. J Vet Diagn Invest 16:167-70, 2004. Pubmed reference: 15053372.
2002 Pedersen, H.D., Haggstrom, J., Olsen, L.H., Christensen, K., Selin, A., Burmeister, M.L., Larsen, H. :
Idiopathic asymptomatic thrombocytopenia in Cavalier King Charles Spaniels is an autosomal recessive trait Journal of Veterinary Internal Medicine 16:169-173, 2002. Pubmed reference: 11899033.
Rozanski, E.A., Callan, M.B., Hughes, D., Sanders, N., Giger, U. :
Comparison of platelet count recovery with use of vincristine and prednisone or prednisone alone for treatment for severe immune-mediated thrombocytopenia in dogs Journal of the American Veterinary Medical Association 220:477-481, 2002. Pubmed reference: 11860242.
2000 LeGrange, S.N., Fossum, T.W., Lemire, T., Storts, R.W., Thomas, J.S. :
Thrombosis of the caudal vena cava presenting as an unusual cause of an abdominal mass and thrombocytopenia in a dog Journal of the American Animal Hospital Association 36:143-151, 2000. Pubmed reference: 10730625.
1998 Mischke, R., Adamik, A. :
Sensitivity of resonance thrombography in thrombocytopenia in dogs [German] Berliner und Munchener Tierarztliche Wochenschrift 111:302-305, 1998. Pubmed reference: 9741188.
1997 Smedile, L.E., Houston, D.M., Taylor, S.M., Post, K., Searcy, G.P. :
Idiopathic, asymptomatic thrombocytopenia in cavalier king charles spaniels - 11 cases (1983-1993) Journal of the American Animal Hospital Association 33:411-415, 1997. Pubmed reference: 9278116.
1995 Mackin, A. :
Canine immune-mediated thrombocytopenia .1. Compendium on Continuing Education for the Practicing Veterinarian 17:353, 1995.
Mackin, A. :
Canine immune-mediated thrombocytopenia .3. Compendium on Continuing Education for the Practicing Veterinarian 17:515, 1995.
1994 Eksell, P., Haggstrom, J., Kvart, C., Karlsson, A. :
Thrombocytopenia in the Cavalier King Charles Spaniel Journal of Small Animal Practice 35:153-155, 1994.
Kristensen, A.T., Weiss, D.J., Klausner, J.S., Laber, J., Christie, D.J. :
Comparison of microscopic and flow cytometric detection of platelet antibody in dogs suspected of having immune-mediated thrombocytopenia American Journal of Veterinary Research 55:1111-1114, 1994. Pubmed reference: 7978651.

Edit History

  • Created by Frank Nicholas on 03 Nov 2010
  • Changed by Frank Nicholas on 29 Sep 2011
  • Changed by Frank Nicholas on 18 Feb 2012
  • Changed by Frank Nicholas on 15 Sep 2014
  • Changed by Frank Nicholas on 22 Apr 2016