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Abstract: Introduction: Dense granule (DG) deficiency (DGD) is a feature of some platelet function disorders (PFD) with a prevalence similar to von Willebrand disease. Most laboratories assess for DGD using whole mount platelet preparations and electron microscopy (EM). We evaluated our experiences with this test and associations between DGD and bleeding. Methods: Dense granule EM records for 2006‐2017 were examined for patients and simultaneously tested controls, and for an overlapping PFD study cohort to evaluate findings and their relationship to bleeding. Results: More patient than control samples had reduced DG counts (6.5% vs 0.3%, P < .01). DG counts showed no relationship to age or mean platelet volume and had acceptable within‐subject variability that was higher for DGD than control participants (28% vs 12%). Repeat tests confirmed DGD in all persons with initial DG counts <4.0/platelet, but not in those with less severe reductions (4.0‐4.8 DG/platelet) or normal DG counts (≥4.9 DG/platelet). Aggregometry and adenosine triphosphate release tests, respectively, had only ~52% and 70% sensitivity for DGD. Confirmed DGD by EM was associated with higher bleeding scores and a bleeding disorder. Conclusion: Whole mount EM is useful for the evaluation of suspected PFD due to DGD and detects abnormalities associated with bleeding. [ABSTRACT FROM AUTHOR]

Introduction Inherited defects in RUNX1 are important causes of platelet function disorders. Aim Our goals were to evaluate RUNX1-related platelet disorders among individuals evaluated for uncharacterized, inherited platelet function disorders and test a proof of concept that bleeding risks could be quantitatively estimated for typical families with an inherited platelet function disorder. Methods Index cases with an uncharacterized inherited platelet function disorder were subjected to exome sequencing with confirmation of RUNX1 mutations by Sanger sequencing. Laboratory findings were obtained from medical records and persistence of platelet non-muscle myosin heavy chain IIB ( MYH10), a biomarker of RUNX1 defects, was assessed by Western blotting. Bleeding histories were assessed using standardized assessment tools. Bleeding risks were estimated as odds ratios ( OR) using questionnaire data for affected individuals compared to controls. Results Among 12 index cases who had their exomes sequenced, one individual from a family with eight study participants had a c.583dup in RUNX1 that segregated with the disease and was predicted to cause a frameshift and RUNX1 haploinsufficiency. Unlike unaffected family members ( n = 2), affected family members ( n = 6) had increased bleeding scores and abnormal platelet aggregation and dense granule release responses to agonists but only some had thrombocytopenia and/or dense granule deficiency. This family's mutation was associated with persistence of MYH10 in platelets and increased risks ( OR 11-440) for wound healing problems and mild bleeding symptoms, including bleeding interfering with lifestyle in women. Conclusion Inherited platelet dysfunction due to a RUNX1 haploinsufficiency mutation significantly increases bleeding risks. [ABSTRACT FROM AUTHOR]

Introduction Lumi-aggregometry quantification of platelet dense granule adenosine triphosphate ( ATP) release is commonly used for diagnosing platelet function disorders. As the test findings show considerable variability for healthy controls, we postulated that patient findings might also be variable and investigated patients who were assessed for dense granule ATP release defects more than once. Methods Analyses were performed on prospectively collected data for first and second tests for subjects tested for dense granule ATP release defects more than once by the Hamilton Regional Laboratory Program ( HRLMP) between January 2007 and June 2013 (cohort I). Similar analyses were performed for subjects who were recruited to a platelet disorder study (cohort II) and were assessed for ATP release defects more than once before October 2015. Results A total of 150 unique subjects had multiple ATP release tests. Results with individual agonists were variable for many subjects. While normal findings with all tested agonists were often confirmed by the second test (cohort I: 83%; cohort II: 100%), impaired release with multiple agonists was confirmed in only some subjects (cohort I: 34%; cohort II: 54%). Inconsistent findings were common (cohort I: 36%; cohort II: 39%). ISTH bleeding scores showed no relationship to the test findings. The finding of impaired ATP release with 2 or more agonists on both tests was not associated with an increased likelihood of a definite bleeding disorder. Conclusion The variability in platelet dense granule ATP release findings amongst patients assessed for diagnostic purposes suggests that the test has limited value for diagnosing platelet disorders. [ABSTRACT FROM AUTHOR]

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Background: Pelvic floor dysfunction (PFD) is the most common complication of childbirth. Assumptions have been made that perineal trauma increases the risk of PFD compared to an intact perineum, however the evidence for this is lacking. The aim of this study was to explore the relationship between perineal outcome and postpartum PFD., Materials and Methods: Prospective cohort study design, with a self-reported quality of life (QOL) questionnaire mailed to all primiparous women with a non-instrumental delivery at The Townsville Hospital between 2011 and 2012 (n = 766). ANOVA was used to compare how the symptoms of PFD affect QOL in women with an intact perineum, episiotomy or spontaneous tear., Results: Seventy-nine percent of the population had perineal injury; 60% had a spontaneous tear and 19% had an episiotomy. Ninety-seven percent of women who completed the questionnaire (n = 196) complained of PFD symptoms. Women with episiotomy had the best QOL, reporting the lowest levels of urinary dysfunction (statistically significant). No differences between the groups were found for symptoms of bowel, prolapse or sexual dysfunction., Conclusions: This study shows a relationship between perineal outcome and PFD and suggests that an episiotomy is associated with the least morbidity due to symptoms of urinary incontinence. Additional large-scale prospective research is required to further investigate and delineate the impact of childbirth on PFD., (© 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objectives: The Perigee™ transobturator cystocoele repair system (AMS) was designed and first used in Townsville, Australia. In this study, we are reporting our five-year experience with the Perigee™ system in the management of cystocoele stage III and above., Methods: Women who underwent surgery with the Perigee™ system between March 2004 and June 2008 were reviewed. Women who consecutively presented to our clinic with a stage III cystocoele or above were given information regarding the Perigee™ mesh surgery. Those who consented were included in our study. The study involved a POPQ assessment pre- and post-operatively at six weeks, three months, six months, 12 months and subsequently biannually., Results: A total of 376 women underwent surgery with the Perigee™ system between March 2004 and June 2008, of which 26 were lost to follow-up. The anatomical success rate for the device was 94.3%, and there were no life-threatening complications with the procedure. 39 (11.1%) of women were found to have small mesh extrusion through the vagina, and 20 (5.7%) had recurrence of stage II cystocoele. Of the subset of women analysed, 45.1% reported no sexual dysfunction, 40.9% reported improvement in sexual function, while 4.1% reported worsening of dyspareunia., Conclusion: In this five-year experience, the Perigee™ system is deemed safe with an acceptable recurrence risk rate and complication rate. Further randomised controlled trials comparing Perigee™ system with traditional anterior colporrhaphy should be performed to evaluate mesh-based surgery safety and efficacy for level one evidence., (© 2011 The Authors. ANZJOG © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)