Bleeding Disorder, Platelet-Type, 8

A number sign (#) is used with this entry because of evidence that platelet-type bleeding disorder-8 (BDPLT8) is caused by compound heterozygous mutation in the P2RY12 gene (600515) on chromosome 3q25.

Description

Platelet-type bleeding disorder-8 is an autosomal recessive condition characterized by mild to moderate mucocutaneous bleeding and excessive bleeding after surgery or trauma. The defect is due to the inability of ADP to induce platelet aggregation (review by Cattaneo, 2011).

Clinical Features

Cattaneo et al. (1992) reported a patient with a congenital defect of platelet function characterized by severe impairment of platelet response to ADP.

Nurden et al. (1995) studied a family in which ADP induced a small and rapidly reversible platelet aggregation even at high doses. This was associated with a markedly reduced binding of ADP to platelets and a failure of ADP to lower the content of cAMP of platelets preincubated with prostaglandin E1. Electron microscopy showed that the ADP-induced aggregates of platelets in the proband were composed of loosely bound shape-changed platelets with few contact points. Thus, this receptor defect had a direct influence on the capacity of platelets to bind to each other in response to ADP. The proband in the family reported by Nurden et al. (1995) was a 61-year-old Caucasian man with a history of episodes of excessive bleeding. The first severe episode occurred at the age of 17 when, after a minor accident, he developed a subretinal hemorrhage that led to the loss of an eye. A second major episode occurred during surgery performed when he was 28 years old. The third episode occurred during middle age when pulmonary bleeding led to hemoptysis. Other affected family members included a father, who died from bleeding after a motor accident, an uncle who died as a result of severe epistaxis, and a sister. The parents of the proband were cousins; there was no information on the mother, who died during the proband's early childhood. The only offspring of the proband appeared normal.

Cattaneo et al. (2003) reported a 60-year-old white man with a lifelong history of easy bruising and excessive posttraumatic and postsurgical blood loss. A daughter and son had never suffered abnormal bleeding episodes.

Molecular Genetics

In a patient with a bleeding disorder reported by Nurden et al. (1995), Hollopeter et al. (2001) identified a mutation in the P2RY12 gene (600515.0001).

In a patient with a congenital bleeding disorder, Cattaneo et al. (2003) identified compound heterozygosity for 2 mutations in the P2RY12 gene (600515.0002; 600515.0003). His unaffected children were both heterozygous for 1 of the mutations.