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Bleeding disorders in heavy menstrual bleeding
Table 4. Prevalence of non-hemostatic disorders and concomitant disorders.
Anovulatory HMB Ovulatory HMB
BD NoBD BD NoBD
(n=31) (n=69) (n=36) (n=64)
PCOS 3300
BJH** 3764
Uterine structural ab. 1@ 1^ 3@@ 0
Systemic disorders 6* 10! 1# 4&
Exon28polym. 0 1 0 3
ab: abnormalities; BD: bleeding disorder; PCOS: polycystic ovarian syndrome; BJH: benign joint hypermobility; polym: polymorphism. **BJH assessment was performed only on 100 participants. Systemic or medical disorders: *depression (n=4), remote history of cancer (n=1), and hypothyroidism (n=1); ! depression (n=3), asthma requiring medica- tions (n=3), remote history of cancer (n=3), hypothyroidism (n=1); #one had juvenile rheumatoid arthritis; &depression (n=1), diabetes mellitus (n=2); celiac disease (n=1). Uterine structural abnormalities; @one had endometriosis; ^one had erosive vaginitis from tampon use; @@two were diagnosed with endometriosis, and one was diagnosed with uterine polyps.
from the average delay of 16 years previously reported in women with BD,33 it highlights the importance of hema- tologists in the care of adolescents with HMB. For primary care practitioners, the relatively high prevalence of vWD in adolescent HMB is a reminder to test for vWD. A recent retrospective analysis of a large national claims database of 23,888 post-pubertal girls and adolescents with HMB observed a very low rate of screening for vWD of only 8% in those with HMB and 16% in those with severe HMB.34
The strengths of our study include the largest powered adolescent cohort ever prospectively examined. Participants underwent a uniform, protocolized evalua- tion for BD compared to “tiered” testing based on suspi- cion of a BD. Another finding of interest is an overall lower prevalence of QPD than that previously reported in the literature, where initial abnormal platelet aggregation was not repeated for confirmation. We diagnosed QPD based on reproducible findings, an approach that had been not undertaken in previous studies, leading to the overes- timation of QPD (Online Supplementary Table S4 and Online Supplementary Figure S1).
Our study has some limitations. Although we consecu- tively enrolled unselected adolescents with HMB, they had, in effect, already been selected by their referring providers. This referral bias probably led to a higher fre- quency of BD in our center compared to primary care set- tings. This bias, however, is inherent to all studies carried out in tertiary care centers. The overall frequency of BD in our cohort is lower than that in previously reported data from other multidisciplinary clinics (33% vs. <60%) and is reflective of the stringent criteria used to diagnose BD. We also excluded patients referred for abnormal coagulation profiles, including initial abnormal vWF analysis, which may have under-estimated the prevalence of BD in our cohort.
We did not exclude participants on hormonal suppres- sion for HMB. Even though PBAC scores were calculated for pre-hormonal cycles, it may have impacted PBAC scores and its predictive ability due to recall bias. Moreover, PBAC has not been validated for retrospective use or without using standardized brand pads and tam- pons. Because our study was conducted in large academic centers with dedicated Young Women’s Blood Disorders clinics, our results are unlikely to apply to settings with a low prevalence of BD. Our time to diagnosis is subject to length bias; adolescents with severe bleeding phenotypes were likely referred earlier, leading to differences in time to diagnosis.
Our study will stimulate further research; the pediatric cut-off for an abnormal ISTH BAT score needs to be revis- ited for the adolescent age group. Even though we showed no difference in the frequency of BD according to HMB pattern, follow-up studies are in order on whether the efficacy of hemostatic-based therapies are equivalent. Finally, future studies are needed to assess the cost-effec- tiveness of selective testing in multidisciplinary clinics compared with universal screening across the population where the sole bleeding complaint could be HMB. Our predictive model also needs to be validated internally and externally in a larger population.
In summary, a high awareness, irrespective of the type of menstrual bleeding, is paramount to identify adoles- cents with BD.
Funding
AZ is supported by a grant from the National Institutes of Health (1K23HL132054-01). The funding source was not involved in the study design, analysis and interpretation of data; in the writing of the report or the decision to submit the article for publication.
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