Thrombopathia Newfoundland Type (TBP)

54.90 € inc. Vat

Acronyms: TBP
Gene: RAS-GRP2
Mutation: Point mutation
Mode of inheritance: Autosomal recessive
Breeds: Landseer, Newfoundland

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Product Description

Thrombopathia Newfoundland Type

Thrombopathia Newfoundland type is an inherited blood clotting disorder affecting Newfoundland dog breed. The disorder is characterized by blood clotting malfunction, and as such causes increased bleeding. Until now, thrombopathia has been reported among three dog breeds: Basset, Newfoundland and American Eskimo dog, and they differ among each other by three distinct causative disorders.

Platelets are also known as thrombocytes, and they have a key role in bleeding prevention through clumping of blood vessel injuries. At a site of vascular injury, platelets are exposed to surface which is not from blood vessel, and they initiate to aggregate to each other, which results in formation of a hemostatic plug that will seal the defect. Key role in platelet aggregation has the platelet integrin alphaIIb-beta3, also known as the platelet glycoprotein complex IIb-IIIa. This platelet integrin has high affinity for fibrin, which in the formation of the blood clot has a role as its stabilizer. In inactivated platelets, the integrin is in its form that has low affinity for the fibrin, disabling formation of the blood clot. Agents that can induce affinity of the integrin for fibrinogen are ADP, collagen, thromboxane, and thrombin. Unfortunately, in case of thrombopathia, these agents do not have an effect on improved platelet aggregation.

Characteristics and Symptoms

Thrombopathia Newfoundland Type is an inherent platelet defects type hemorrhagia. Another type of hemorrhagia, or excessive bleeding is extrinsic type, caused due to external factors. Affected dogs platelets are defective and are unable to form blood clot. The defect in the platelets of the Landseer dogs is suspected to be related to a structural or functional deficiency glycoprotein complex IIb-IIIa, similar as has been reported in humans with Glanzmann’s disease and Bernard-Soulier syndrome, human bleeding disorders.

Symptoms of canine thrombopathia are spontaneous bleeding. Bleeding occurs as nose bleeding, also known as epistaxis, and from other mucosal surfaces, such as mouth, gums, etc. Excessive bleeding inside the mouth may be especially present during change of puppy teeth with permanent teeth. Platelet number, von Willebrand factor, clot retraction and coagulation are normal, whereas bleeding time is prolonged.


Thrombopathia Newfoundland type is caused by a point mutation in the RASGRP1 gene that causes a shift in the reading frame responsible for expression of the Rap 1 protein. This shift in the reading frame causes a truncated protein. In healthy dog, Rap 1 protein is highly expressed in platelets, but also in neutrophils and in the brain. In platelets variant of Rap 1, protein Rap1b is present in high levels and it has a role in integrin activation. In case of mutation in the RASGRP1 gene, defected protein will not be able to induce integrin activation, which causes improper platelet aggregation and blood clotting.

The disorder is inherited in an autosomal recessive manner.  Healthy parents of an affected puppy are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the Thrombopathia Landseer type. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.


Boudreaux, M. K., Catalfamo, J. L., & Klok, M. (2007). Calcium-diacylglycerol guanine nucleotide exchange factor I gene mutations associated with loss of function in canine platelets. Translational Research, 150(2), 81-92.