Clinical and laboratory characteristics of adolescents with platelet function disorders and heavy menstrual bleeding

Abstract

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.

Pathophysiology of Heavy Menstrual Bleeding

“…Endometrial polyps are the commonest endometrial pathology associated with tamoxifen treatment, with an incidence rate of 8-36% [26]; this frequency is much higher compared with the incidence of 0-11% which is seen in untreated women [27]. Compared with women not taking tamoxifen, these polyps are likely to be larger, more fibrotic and to more frequently show mucinous metaplasia.…”

“…Women with PFDs and HMB have been reported to be a clinically distinctive subgroup of women with HMB, with significantly high incidences of blood group O and the δ-storage pool deficiency with a PFD diagnosed well after menarche. High false negative standard platelet function study results are reported therefore additional diagnostic strategies, such as electron microscopy to detect significantly reduced platelet δ-granule numbers should be considered [27].…”

“…Other conditions such as disorders of deficiency in clotting factors (inherited or acquired hemophilia A and B, chronic liver disease, vitamin K deficiency and factor VIII inhibitor); disorders of fibrinolysis and thrombocytopenic disorders can in theory cause HMB but are extremely rare [9]. Platelet function disorders (PFDs), a heterogeneous group of inherited, qualitative platelet defects have emerged as an important cause of HMB, particularly in adolescents [27]. Women with PFDs and HMB have been reported to be a clinically distinctive subgroup of women with HMB, with significantly high incidences of blood group O and the δ-storage pool deficiency with a PFD diagnosed well after menarche.…”

“…In addition, genetic mutations and the overexpression of endometrial aromatase, which increases the local estrogenic signal, are also thought to be involved in the formation of endometrial polyps [24,25]. Small (<1 cm) benign endometrial polyps often regress but larger lesions are likely to persist [23,24].Endometrial polyps are the commonest endometrial pathology associated with tamoxifen treatment, with an incidence rate of 8-36% [26]; this frequency is much higher compared with the incidence of 0-11% which is seen in untreated women [27]. Compared with women not taking tamoxifen, these polyps are likely to be larger, more fibrotic and to more frequently show mucinous metaplasia.…”

Weak correlation of bleeding scores to platelet electron microscopy: A retrospective chart review of pediatric patients with delta‐storage pool disorder

“…However, a larger portion of patients who do not have identifiable genetic mutations are diagnosed with δ‐SPD via qualitative and quantitative platelet evaluations . δ‐SPD is a relatively rare platelet function disorder with only few studies describing laboratory and clinical findings in the pediatric population …”