Bleeding risks associated with inheritance of the Quebec platelet disorder

Abstract

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with increased urokinase-type plasminogen activator in platelets and ␣-granule protein degradation. To determine bleeding risks and common manifestations of QPD, a history questionnaire was developed and administered to 127 relatives in a family with QPD. Data entry was done blinded to affected and unaffected status, determined by assays for platelet urokinase-type plasminogen activator (u-PA) and fibrinogen degradation. Odds ratios (ORs), with 95% confidence intervals (CIs), were determined for items queried. Summative bleeding scores for each individual were calculated using items with OR more than 1. Mean ages (34 years; range, 1-89 years) were similar for affected (n ‫؍‬ 23) and unaffected (n ‫؍‬ 104) family members. Affected individuals had higher mean bleeding scores (P < .0001) and a much higher likelihood (OR > 20) of having bleeding that led to lifestyle changes, bruises that spread lower or as large or larger than an orange or both, joint bleeds, bleeding longer than 24 hours after dental extractions or deep cuts, and received or been recommended other treatments (fibrinolytic inhibitors) for bleeding. Individuals with QPD and exposure(s) to hemostatic challenges had experienced excessive bleeding only when fibrinolytic inhibitors had not been used. These data illustrate that QPD is associated with increased risks of bleeding that can be modified by fibrinolytic inhibitors.

Clinical phenotype in heterozygote and biallelic Bernard‐Soulier syndrome—A case control study

“…The questionnaire, previously developed for study of bleeding symptoms in the general Icelandic public [12], was designed to identify defects in primary hemostasis (mucocutaneous symptoms), secondary hemostasis (hemarthrosis, muscle bleeding), bleeding with surgery or tooth extraction or abnormal gynecological bleeding. In an attempt to quantify symptoms further, some adaptations were made to the questionnaire based on our experience and others [13]. The questionnaire is available as Supporting Information Appendix.…”

Thrombopoietin levels in Quebec platelet disorder—Implications for the mechanism of thrombocytopenia

“…In QPD, platelet morphology (by light and electron microscopy), size,3 and dense granule release are normal, and secondary platelet aggregation is absent with epinephrine, with or without reduced maximal aggregation with collagen, adenosine diphosphate, and/or thromboxane analog U46619 10. Many persons with QPD have thrombocytopenia as platelet counts in this disorder are typically about 50% lower than the platelet counts of unaffected relatives (reported range: ~120‐245 × 10 9 /L11). The reduction in platelet counts in QPD is clinically significant as lower platelet counts are associated with wound healing problems 11…”

Diagnosis and Management of Mild Bleeding Disorders

“…13 For women, the bleeding history needs to include questions about bleeding with menstrual periods and abnormal bleeding of childbirth, although both can reflect other problems (e.g., fibroids, uterine atony postpartum). 12,13,15 Queries about bruises and nosebleeds are often included in a bleeding history.…”

“…13 For women, the bleeding history needs to include questions about bleeding with menstrual periods and abnormal bleeding of childbirth, although both can reflect other problems (e.g., fibroids, uterine atony postpartum). 12,13,15 Queries about bruises and nosebleeds are often included in a bleeding history. [12][13][14] Like heavy menstrual periods, these symptoms are more prevalent among individuals with bleeding problems but are commonly reported by individuals without recognized bleeding disorders (Table 1).…”

“…12,13,15 Queries about bruises and nosebleeds are often included in a bleeding history. [12][13][14] Like heavy menstrual periods, these symptoms are more prevalent among individuals with bleeding problems but are commonly reported by individuals without recognized bleeding disorders (Table 1). 4,13,16,17 Questions about some types of bleeding (e.g., gum, urinary tract) tend to be less useful, although there are exceptions.…”