Quebec platelet disorder
| Quebec platelet disorder | |
|---|---|
| Classification and external resources | |
| OMIM | 601709 |
Quebec Platelet Disorder (QPD) is a rare, autosomal dominant bleeding disorder described in a family from the province of Quebec in Canada.[1][2]
Pathophysiology
The disorder is characterized by large amounts of the fibrinolytic enzyme urokinase-type plasminogen activator (u-PA) in platelets.[3] Consequently, stored platelet plasminogen is converted to plasmin, which is thought to play a role in degrading a number of proteins stored in platelet α-granules.[4] These proteins include platelet factor V, Von Willebrand factor, fibrinogen, thrombospondin-1, and osteonectin.[3] There is also a quantitative deficiency in the platelet protein multimerin 1 (MMRN1). Furthermore, upon QPD platelet activation, u-PA can be released into forming clots and accelerate clot lysis, resulting in delayed-onset bleeding (12-24hrs after injury).[5]
Presentation
Individuals with QPD are at risk for experiencing a number of bleeding symptoms, including joint bleeds, hematuria, and large bruising.[6] In 2010, the genetic cause of QPD has been determined as a mutation involving an extra copy of the uPA (urokinase plasminogen activator) gene [7] http://bloodjournal.hematologylibrary.org/content/115/6/1264.long. The mutation causes overproduction of an enzyme that accelerates blood clot breakdown.
History
The discovery was found by a team of doctors at McMaster University, led by Dr. Catherine Hayward, a hematologist.[8]
References
- ↑ Hayward CP, Rivard GE, Kane WH, Drouin J, Zheng S, Moore JC, Kelton JG (1996). "An autosomal dominant, qualitative platelet disorder associated with multimerin deficiency, abnormalities in platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen and an epinephrine aggregation defect". Blood 87: 4967–78.
- ↑ Diamandis M, Veljkovic DK, Maurer-Spurej E, Rivard GE, Hayward CPM (2008). "Quebec platelet disorder: features, pathogenesis and treatment". Blood Coagulation and Fibrinolysis 19 (2): 109–119. doi:10.1097/mbc.0b013e3282f41e3e.
- 1 2 Kahr, 2001
- ↑ Sheth, 2003
- ↑ Diamandis & Adam, 2006
- ↑ McKay & Haq, 2004
- ↑ Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP (Feb 2010). "Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene". Blood 115 (6): 1264–6. doi:10.1182/blood-2009-07-233965.
- ↑ "Gene that causes rare bleeding disorder identified". CTV.ca. Retrieved 2010-03-04.