QPD is a functional disorder caused by autosomal dominant duplication of the PLAU gene located on chromosome 10. PLAU codes for platelet urokinase (urinary plasminogen activator, uPA), and the duplication somehow raises uPA activity 100-fold in platelet alpha granules but not in plasma or urine. The elevated uPA activity metabolizes alpha granule proteins such as factor V and fibronectin. Affected platelets break down clots and bleeding resembles typical platelet disorders with trauma-induced hematomas, epistaxis, and menorrhagia, but is delayed 12 hours to 4 days after a hemostatic challenge. Joint bleeds are documented in 50% of QPD sufferers, and many experience spontaneous gross hematuria in the absence of infection. Bleeding may appear as a mild response to hemostatic challenge or may be spontaneous and severe. Because the condition is autosomal dominant, symptoms appear in the affected parent and about half of their offspring. Plasma, clotting factors, and platelet concentrate are ineffective; the only effective therapy is an antifibrinolytic such as tranexamic acid (Cyclokapron) or aminocaproic acid (Amicar). Most hemostasis laboratory results are normal except light transmittance aggregometry where the responses to the agonists epinephrine and ADP are often, but not consistently, reduced or absent. The condition is diagnosed by the molecular detection of the duplicated gene.
Dr. Elman’s patient’s condition resembles QPD because of the delayed bleeding that is managed with Amicar, however she reports no characteristic childhood or adult bleeding symptoms and no first-degree relatives with symptoms. Nevertheless, our experts recommend molecular testing for the PLAU duplication, perhaps to merely rule out the diagnosis.
- Hayward CPM, Liang M, Tasneem S, Soomro A, Waye JS, Paterson AD, et al. (2017) The duplication mutation of Quebec platelet disorder dysregulates PLAU, but not C10orf55, selectively increasing production of normal PLAU transcripts by megakaryocytes but not granulocytes. PLoS ONE 12(3): e0173991. https:// doi.org/10.1371/journal.pone.0173991
- Blavignac J, Bunimov N, Rivard GE, Hayward CPM. Quebec platelet disorder: Update on pathogenesis, diagnosis, and treatment. Semin Thrombos Haemostas 2011; 37: 713–19.
- Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, et al. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood 2010; 115: 1264–6.