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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 in Canada. The disorder is characterized by large amounts of the fibrinolytic enzyme
urokinase Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally i ...
-type plasminogen activator (uPA) in
platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
. This causes accelerated
fibrinolysis Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other c ...
(
blood clot A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
breakdown) which can result in bleeding.


Presentation

Individuals with QPD are at risk for experiencing a number of bleeding symptoms, including joint bleeds,
hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
, and large bruising.


Pathophysiology

The disorder is characterized by large amounts of uPA in
platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
.Kahr, 2001 Consequently, stored platelet plasminogen is converted to
plasmin Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encoded ...
, which is thought to play a role in degrading a number of proteins stored in platelet α-granules. These proteins include platelet
factor V Factor V (pronounced factor five) is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor. Deficienc ...
,
von Willebrand factor Von Willebrand factor (VWF) () is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytopen ...
,
fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clo ...
,
thrombospondin-1 Thrombospondin 1, abbreviated as THBS1, is a protein that in humans is encoded by the ''THBS1'' gene. Thrombospondin 1 is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and ...
, and
osteonectin Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the ''SPARC'' gene. Osteonectin is a glycoprotein in the bone that binds calciu ...
. There is also a quantitative deficiency in the platelet protein multimerin 1 (
MMRN1 Multimerin 1, also known as elastin microfibril interfacer 4 (EMILIN-4), is a protein that, in humans, is encoded by the ''MMRN1'' gene. Multimerin is a massive, soluble protein found in platelets and in the endothelium of blood vessels. It is co ...
). 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). In 2010, the genetic cause of QPD was determined as a
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
involving an extra copy of the gene encoding uPA. The mutation causes overproduction of uPA, an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that accelerates
blood clot A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
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 The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
or
Southern blotting A Southern blot is a method used in molecular biology for detection of a specific DNA sequence in DNA samples. Southern blotting combines transfer of electrophoresis-separated DNA fragments to a filter membrane and subsequent fragment detecti ...
for the genetic sequence, or assays for platelet uPA levels or platelet granules.


Treatment

Bleeding episodes are treated using antifibrinolytic medication, particularly
tranexamic acid Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken eith ...
, to prevent
fibrinolysis Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other c ...
.


History

The discovery was made by a team of doctors at
McMaster University McMaster University (McMaster or Mac) is a public research university in Hamilton, Ontario, Canada. The main McMaster campus is on of land near the residential neighbourhoods of Ainslie Wood and Westdale, adjacent to the Royal Botanical Ga ...
led by Dr. Catherine Hayward, a
hematologist Hematology (American and British English spelling differences#ae and oe, always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to ...
.


References


External links

{{Medical resources , DiseasesDB = , ICD10 = D69.1 , ICD9 = , ICDO = , OMIM = 601709 , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = C536260 , GeneReviewsName = , Orphanet = 220436 Genetic disorders with OMIM but no gene Coagulopathies