BackgroundPlatelet function disorders (PFDs) have emerged as an important etiology of heavy menstrual bleeding (HMB) in adolescents. However, neither clinical nor laboratory data have been methodically analyzed in this population subset. The objective of this study was to evaluate these parameters in order to distinguish characteristics of the disorder that in turn will lead to earlier diagnosis and therapy initiation.MethodsRetrospective review of medical records from postmenarcheal adolescents with documented PFDs referred to a hemophilia treatment center and university faculty practices for bleeding diatheses with their clinical and laboratory data evaluated.ResultsOf 63 teens with documented PFDs, HMB was the most common clinical manifestation of PFD (43; 68.3%). Of these, 37 (86%) were diagnosed with PFD either at or after menarche with the diagnosis based on HMB symptoms alone. Only 6 (14%) were diagnosed with a PFD prior to menarche, based on associated bleeding, i.e., epistaxis, ecchymosis, and all developed HMB after menstruation onset. Interestingly, 20 girls were diagnosed with a PFD prior to menarche and of these, only 6 (30%) went on to develop HMB after pubertal transition, while the majority (14; 70%) did not. The average age-at-PFD diagnosis was 14.5yrs, significantly differing from the 10.9yrs average age-at-PFD diagnosis in their counterparts that, after menarche, did not develop HMB (P<.01) Blood type O occurred significantly more frequently (76%) than national norms (P <.037). Incidence of δ-Storage Pool deficiency (δ-SPD) was significantly higher (74%) than their non-HMB cohorts (45%) (P <.007). Coagulation and von Willebrand factor studies were all normal. Abnormal closure times and aggregation studies were observed in 42% and 60%, respectively, of tested girls. In 25.6% for whom standard platelet studies were normal, electron microscopy detected reduced platelet δ-granules numbers (δ-SPD).ConclusionsAdolescents with PFDs and HMB appear to be clinically distinct from their non-HMB counterparts. This group of girls is characterized by HMB the major bleeding symptom, significantly high incidences of blood group O and the δ-SPD with a PFD diagnosed well after menarche. High false negative standard platelet function study results indicate additional diagnostic strategies, particularly for δ-SPD, should be considered.

The purpose of this study was to examine patterns of use for oral contraceptive and desmopressin acetate nasal spray, both used in managing menorrhagia in adolescents with von Willebrand disease (vWD). Hospital records of adolescents with documented vWD and menorrhagia were reviewed retrospectively. Subjects with vWD type 1 (n = 36) administered either oral contraceptives (OC) or intranasal desmopressin acetate (DDAVP) and followed from 6 months to 4 years were selected for inclusion. Treatment outcomes were examined with respect to effectiveness and safety. Assessing menstrual blood loss using PBAC scores from pretreatment and treatment periods determined effectiveness. Safety was evaluated by monitoring reported adverse events. No significant differences were identified in treatment effectiveness for controlling menorrhagia in vWD adolescents in the OC and intranasal DDAVP group comparisons: 86% versus 77% (P > 0.05), respectively. When combining both treatment groups, the majority of vWD adolescents, 81% (P > 0.05), experienced alleviation of menorrhagia symptoms. Treatment failures were attributed to either the inability of a regimen to control bleeding or to adverse events, including severe headaches and flushing with DDAVP. Safety outcomes were not significantly greater in vWD patients with menorrhagia when OC were compared with intranasal DDAVP. Both medical approaches, OC and DDAVP nasal spray, used in managing menorrhagia in adolescents with documented type I vWD were well tolerated and showed equivalent effectiveness, and no serious adverse events were reported.

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Objective: To evaluate whether computer-based learning (CBL) improves newly acquired knowledge and is an effective strategy for teaching prenatal ultrasound diagnostic skills to third-year medical students when compared with instruction by traditional paper-based methods (PBM). Study Design: We conducted a randomized, prospective study involving volunteer junior (3 rd year) medical students consecutively rotating through the Obstetrics and Gynecology clerkship during six months of the 2005-2006 academic year. The students were randomly assigned to permuted blocks and divided into two groups. Half of the participants received instruction in prenatal ultrasound diagnostics using an interactive CBL program; the other half received instruction using equivalent material by the traditional PBM. Outcomes were evaluated by comparing changes in pre-tutorial and post instruction examination scores. Results: All 36 potential participants (100%) completed the study curriculum. Students were divided equally between the CBL (n=18) and PBM (n=18) groups. Pre-tutorial exam scores (mean ± s.d.) were 44% ± 11.1% for the CBL group and 44% ± 10.8% for the PBL cohort, indicating no statistically significant differences (p > 0.05) between the two groups. After instruction, posttutorial exam scores (mean ± s.d.) were increased from the pre-tutorial scores, 74% ± 11% and 67% ± 12%, for students in the CBL and the PBM groups, respectively. The improvement in post-tutorial exam scores from the pre-test scores was considered significant (p < 0.05). When post-test scores for the tutorial groups were compared, the CBL subjects achieved a score that was, on average, 7 percentage points higher than their PBM counterparts, a statistically significant difference (p < 0.05). Conclusion: Instruction by either CBL or PBM strategies is associated with improvements in newly acquired knowledge as reflected by increased post-tutorial examination scores. Students that received CBL had significantlyhigher post-tutorial exam scores than those in the PBM group, indicating that CBL is an effective instruction strategy in this setting.

Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs). The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs) has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs). In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29) and negative hematopoietic stem cell markers (CD45 and CD34) expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin (TPO) for 18 days. The MK differentiation was analyzed by flow cytometry and confocal microscopy. The differentiation medium was collected for PLT production analysis by flow cytometry, transmission electron microscopy and functional measurements. Our results show: 1) MKs were successfully generated from hESSCs as identified by expression of specific markers (CD41a: 1±0.09% and 39±3.0%; CD42b: 1.2±0.06% and 28±2.0%, control vs. differentiation) accompanied with reduction of pluripotent transcription factors (Oct4 and Sox2) expression; 2) The level of PLTs in the differentiation medium was 16±1 number/µl as determined by size (2–4 µm) and CD41a expression (CD41a: 1±0.4% and 90±2.0%, control vs. differentiation); 3) Generated PLTs were functional as evidenced by the up-regulation of CD62p expression and fibrinogen binding following thrombin stimulation; 4) Released PLTs showed similar ultra-structure characteristics (alpha granules, vacuoles and dense tubular system) as PLTs from peripheral blood determined by electron microscopic analysis. Data demonstrate the feasibility of generating MKs from hESSCs, and that the generated MKs release functional PLTs. Therefore, hESSCs could be a potential new stem cell source for in vitro MK/PLT production.