Quebec platelet disorder
{{Infobox medical condition
| synonyms = Factor V Quebec
| name = Quebec platelet disorder
| image = Autosomal dominant - en.svg
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| caption = Autosomal dominant is the manner of inheritance of this condition
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Quebec platelet disorder (QPD) is a rare autosomal dominant bleeding disorder first described in a family from the province of Quebec, Canada.{{cite journal | vauthors = Hayward CP, Rivard GE, Kane WH, Drouin J, Zheng S, Moore JC, Kelton JG | year = 1996 | title = 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 | journal = Blood | volume = 87 | issue = 12| pages = 4967–78 | pmid = 8652809 | doi = 10.1182/blood.V87.12.4967.bloodjournal87124967 | doi-access = free }}{{cite journal | vauthors = Diamandis M, Veljkovic DK, Maurer-Spurej E, Rivard GE, ((Hayward CPM)) | year = 2008 | title = Quebec platelet disorder: features, pathogenesis and treatment | journal = Blood Coagulation and Fibrinolysis | volume = 19 | issue = 2| pages = 109–119 | doi=10.1097/mbc.0b013e3282f41e3e| pmid = 18277131 | s2cid = 23559737 }} The disorder is characterized by large amounts of the fibrinolytic enzyme urokinase-type plasminogen activator (uPA) in platelets. This causes accelerated fibrinolysis (blood clot breakdown) which can result in bleeding.
Signs and symptoms
Individuals with QPD are at risk for experiencing a number of bleeding symptoms, including joint bleeds, hematuria, and large bruising.McKay & Haq, 2004
Pathophysiology
The disorder is characterized by large amounts of uPA in platelets.Kahr, 2001 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.Sheth, 2003 These proteins include platelet factor V, von Willebrand factor, fibrinogen, thrombospondin-1, and osteonectin. There is also a quantitative deficiency in the platelet protein multimerin 1 (MMRN1). Furthermore, upon QPD platelet activation, uPA can be released into forming clots and accelerate clot lysis, resulting in delayed-onset bleeding (12-24hrs after injury).Diamandis & Adam, 2006
In 2010, the genetic cause of QPD was determined as a mutation involving an extra copy of the gene encoding uPA.{{cite journal|vauthors=Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP|date=Feb 2010|title=Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene|journal=Blood|volume=115|issue=6|pages=1264–6|doi=10.1182/blood-2009-07-233965|pmid=20007542|doi-access=free}} The mutation causes overproduction of uPA, an enzyme that accelerates blood clot breakdown.
Diagnosis
Genetic testing is the only way to definitively diagnose QPD, as most other tests cannot confirm this diagnosis. Methods include polymerase chain reaction or Southern blotting for the genetic sequence, or assays for platelet uPA levels or platelet granules.
Treatment
Bleeding episodes are treated using antifibrinolytic medication, particularly tranexamic acid, to prevent fibrinolysis.{{Cite journal|last1=Blavignac|first1=Jessica|last2=Bunimov|first2=Natalia|last3=Rivard|first3=Georges|last4=Hayward|first4=Catherine P.M.|date=September 2011|title=Quebec Platelet Disorder: Update on Pathogenesis, Diagnosis, and Treatment|url=http://www.thieme-connect.de/DOI/DOI?10.1055/s-0031-1291382|journal=Seminars in Thrombosis and Hemostasis|language=en|volume=37|issue=6|pages=713–720|doi=10.1055/s-0031-1291382|pmid=22102275 |issn=0094-6176}}
History
The discovery was made by a team of doctors at McMaster University led by Dr. Catherine Hayward, a hematologist.{{Cite web |url=http://www.ctvnews.ca/gene-that-causes-rare-bleeding-disorder-identified-1.488779 |title=Gene that causes rare bleeding disorder identified |date=4 March 2010 |publisher=CTV.ca |access-date=2010-03-04 |url-status=live |archive-url=https://web.archive.org/web/20100306002208/http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20100304/qpd_100304/20100304?hub=TopStoriesV2 |archive-date=2010-03-06 }}
References
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External links
{{Medical resources
| DiseasesDB =
| ICD10 = D69.1
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| OMIM = 601709
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| MeshID = C536260
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| Orphanet = 220436
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