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A. Zia et al.
Table 2. Types of bleeding disorders in the whole group and according to menstrual bleeding pattern.
All patients Anovulatory HMB Ovulatory HMB (N=200) (N=100) (N=100)
n(%) n(%) n(%)
Low
vWF
Type 1
Type 2
Qualitative platelet dysfunction
Clotting factor deficiencies
Symptomatic hemophilia carrier
vWF: von Willebrand factor; vWD: von Willebrand disease.
38 (19)
17 (8.5)
13 (6.5)
4 (2)
9 (2) 2 (1.5) 1 (0.5)
14 (14)
12 (12)
5(5)
3(3) 5 (5) 2(2) 1(1)
24 (24)
5 (5)
8(8)
1(1) 4(4) - -
AB
Figure 2. Kaplan-Meier curves showing time from the first bleeding event to bleeding disorder diagnosis. (A) Time until diagnosis for the entire group. (B) Time according to the menstrual bleeding group. The number of patients diagnosed according to the group is shown at the bottom of the graphic, on the x-axis.
four years after menarche because of a brother with FVIII deficiency, was diagnosed to be a symptomatic hemophil- ia carrier (FVIII: 124%; positive for a pathogenic type 1 intron 22 inversion mutation (F8 c.6429+?_6430-? inv.). None of the participants showed evidence of systemic hyperfibrinolysis based on our testing protocol, though specific testing for plasminogen activator inhibitor or antiplasmin deficiency were not performed (Table 2 and Online Supplementary Tables S3 and S4). Of those diag- nosed with BD, 29 (43%) had HMB as the sole complaint, 21 (31%) had one additional, 12 (18%) had two, four (6%) had three, and one participant had five additional bleeding symptoms. Of those without BD, 118 (88%) had HMB as the sole complaint; 12 (9%) had one, and 3 (2%) had two additional bleeding symptoms in addition to HMB (Online Supplementary Table S5).
Predictors of bleeding disorders
The results of the univariable logistic regression of potential predictors of BD are shown in Table 3. The final model (multivariable, stepwise logistic regression) includ- ed four predictors: younger age at first bleeding event, Hispanic ethnicity, non-presentation to ED, and ISTH BAT score of ≥4.
Time to diagnosis
Kaplan-Meier curves showed that the median time from the first bleed to BD diagnosis was four years (range 2-5) in the entire cohort, two years (range 1-3) in the anovula- tory group, and six years (range 4-9) in the ovulatory group. There was a significant difference in time to diag- nosis across groups (log-rank test, P<0.0001) (Figure 2).
Concomitant non-hemostatic disorders
Twenty-three participants with BD were diagnosed with additional disorders: three (1.5%) with polycystic ovarian syndrome, and four with uterine structural abnor- malities (three with endometriosis and one with uterine polyps). Four participants without BD were diagnosed with vWF exon 28 polymorphism p.D1472H (suspected based on isolated decreased vWF:RCo) (Table 4). Only 100 participants underwent a joint exam for benign joint hypermobility (BJH); of those, 20 met criteria for BJH.
Discussion
Our study systematically investigated adolescents with HMB and showed that 33% had a BD. Almost 80% of
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haematologica | 2020; 105(7)