Glanzmann's Thrombasthenia

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Glanzmann's Thrombasthenia is an autosomal-recessive genetic immune-mediated disease of the Great Pyrenees and Otterhound breeds characterized by hemophilia[1].

A similar unrelated thrombopathia has been reported in the Finnish Spitz and Basset Hound[2] but has different molecular markers when screening dogs with this condition[3][4].

This genetic defect results in molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Because αIIbβ3 is the major receptor for the adhesive ligand fibrinogen, inherited molecular defects of αIIbβ3 prevent platelets from aggregating at the site of a vascular injury to repair damaged blood vessels, leading to platelet dysfunction and poor clot formation[5].

Dogs with this inherited condition frequently present from 6 months of age with spontaneous bruises, epistaxis, buccal bleeding during tooth eruption, melena and prolonged clotting times post-operatively[6].

Bleeding tendencies in affected individuals ranged from mild to severe, with males and females being equally affected[7].

In affected dogs, transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets[8].

Blood tests reveal normal platelet numbers but lack of platelet aggregation in response to all agonists and severely impaired clot retraction. Coagulation screening tests and von Willebrand factor antigen levels should be performed to exclude more common causes of coagulopathy.

Diagnosis requires coagulation screening test and DNA testing to isolate the genomic DNA from blood and amplification of exon 13 and intron 13 of the gene encoding for platelet glycoprotein subunit alphaIIb[9].

A differential diagnosis would include more common causes of bleeding such as Von Willebrand's disease, anticoagulant rodenticides, aplastic pancytopenia, hemangiosarcoma and Waldenström's macroglobulinemia[10].

In some canine patients, the disorder may lessen in severity as they mature but may develop severe thrombocytopenia and life-threatening hemolytic anemia after administration of an annual vaccination.

Life-long vitamin K supplementation may assist survival in these patients and use of pre-operative use of platelet-rich plasma is recommended during any surgical procedure to minimize blood loss.

Bone marrow transplantation has been shown to be effective in some patients but risks may outweigh use of this therapeutic modality[11].

References

  1. Boudreaux MK & Catalfamo JL (2001) Molecular and genetic basis for thrombasthenic thrombopathia in otterhounds. Am J Vet Res 62(11):1797-1804
  2. Boudreaux MK et al (2007) Calcium diacylglycerol guanine nucleotide exchange factor I (CalDAG-GEFI) gene mutations in a thrombopathic Simmental calf. Vet Pathol 44(6):932-935
  3. Johnstone IB & Lotz F (1979) An inherited platelet function defect in basset hounds. Can Vet J 20:211–215
  4. Brooks M & Catalfamo J (1993) Buccal mucosa bleeding time is prolonged in canine models of primary hemostatic disorders. Thromb Haemost 70(5):777-780
  5. Coller BS & Shattil SJ (2008) The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: A technology-driven saga of a receptor with twists, turns, and even a bend. Blood 112:3011–3025
  6. Dodds WJ (1967) Familial canine thrombocytopathy. Thromb Diath Haemorrh Suppl 26:241–248
  7. Boudreaux MK et al (1996) Type I Glanzmann’s thrombasthenia in a Great Pyrenees dog. Vet Pathol 33:503–511
  8. Fang J et al (2011) Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs. Proc Natl Acad Sci U S A 108(23):9583-9588
  9. Brdecka DJ et al (2004) Successful ovariectomy in a dog with Glanzmann thrombasthenia. J Am Vet Med Assoc 224(11):1796-1798
  10. Callan MB & Giger U (2001) Assessment of a point-of-care instrument for identification of primary hemostatic disorders in dogs. Am J Vet Res 62(5):652-658
  11. Niemeyer GP et al (2003) Correction of a large animal model of type I Glanzmann's thrombasthenia by nonmyeloablative bone marrow transplantation. Exp Hematol 31(12):1357-1362