Quebec Platelet Disorder (QPD) is a rare, autosomal dominant bleeding disorder described in a family from the province of Quebec in Canada.

Pathophysiology

The disorder is characterized by large amounts of the fibrinolytic enzyme urokinase

Urokinase

Urokinase , also called urokinase-type plasminogen activator , is a serine protease . Urokinase was originally isolated from human urine, but is present in several physiological locations, such as blood stream and the extracellular matrix...

-type plasminogen activator (u-PA) in platelets . Consequently, stored platelet plasminogen is converted to plasmin

Plasmin

Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notably, fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.- Function :...

, which is thought to play a role in degrading a number of proteins stored in platelet α-granules . These proteins include platelet factor V, Von Willebrand factor, fibrinogen, thrombospondin-1, and osteonectin

Osteonectin

Osteonectin also known as secreted protein acidic and rich in cysteine or basement-membrane protein 40 is a protein that in humans is encoded by the SPARC gene....

 . There is also a quantitative deficiency in the platelet protein multimerin 1 (MMRN1

MMRN1

Multimerin-1 is a protein that in humans is encoded by the MMRN1 gene.-Further reading:...

). 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).

Presentation

Individuals with QPD are at risk for experiencing a number of bleeding symptoms, including joint bleeds, hematuria, and large brusing . In 2010, the genetic cause of QPD has been determined as a mutation

Mutation

In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

 involving an extra copy of the uPA (urokinase plasminogen activator) gene http://bloodjournal.hematologylibrary.org/content/115/6/1264.long. The mutation causes overproduction of an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that accelerates blood clot breakdown.

History

The discovery was found by a team of doctors at McMaster University

McMaster University

McMaster University is a public research university whose main campus is located in Hamilton, Ontario, Canada. The main campus is located on of land in the residential neighbourhood of Westdale, adjacent to Hamilton's Royal Botanical Gardens...

, led by Dr. Catherine Hayward, a hematologist.