Page 338 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
the IPFD participants, 12 (35%) had aspirin-like defect, one (3%) had Bernard Soulier, and in the remaining 20 (59%), the identified defect was non-specific (reduced aggregation and/or secretion to ≥1 agonist).
Annualized bleeding rate was calculated by dividing the number of clinically significant episodes one year before the first evaluation by history and/or emergency department, doctor’s surgery, or hospital visits for bleeding. Median ABR was 12 (IQR: 2-13) for IPFD, 12 (IQR: 4.5-14) for vWD-1, and 12 (IQR: 1-13) for controls (P=0.13) (Figure 1A). The most fre- quent bleeding event in all groups was HMB (N=96, 48.2%). The subsequent most frequent bleeding event in the IPFD cohort was surgical bleeding, while in vWD-1 and controls, it was epistaxis (Online Supplementary Figure S1A).
Severe bleeding events, defined as any bleeding event re- quiring medical or surgical interventions including high-dose oral hormonal therapy every 6 or 8 hours/day for several days, intravenous estrogen, blood transfusion, and surgical interventions to stop bleeding, occurred in 18 (53%) IPFD, 20 (43%) vWD-1, and 50 (44%) control participants. The median number of bleeds requiring treatment was 2 (IQR: 1-12) for IPFD, 12 (IQR: 1-13) for vWD-1, and 3 (IQR 0-12) for controls (P=0.16) (Figure 1B). Receipt of treatment was defined as any bleeding requiring systemic therapy or surgical intervention for bleeding symptoms, but excluding topical agents (i.e., oxymetazoline for epistaxis). Hormonal therapy was the most utilized treatment in vWD-1 (N=26; 43%) and controls (N=56; 48%), whereas surgical therapy, including packing, suturing, and cauterization, was highest in IPFD (N=14; 33%) (Online Supplementary Figure S1B).
Median BS was 3 (IQR: 2.75-4) in the IPFD group, 4 (IQR: 3-5) in vWD-1, and 3 (IQR: 3-4) in controls (Figure 1C). BS between the vWD-1 and control groups varied significantly (P=0.012), while no significant difference was found between IPFD and vWD-1 or controls. Clinically significant bleeding events were defined as bleeding involving all sites but ex-
cluding bleeding lasting <10 minutes, events not requiring intervention, and all cutaneous bleeding except for wound bleeds lasting >10 minutes. In all study groups, median BS was significantly higher in those with clinically significant bleeding events than in those without (P<0.05) (Figure 2). A BS >4 in IPFD (area under the curve [AUC]=0.85) and vWD-1 (AUC=0.85) groups predicted clinically significant bleeding events with very good accuracy (Online Supplementary Figure S2A). For bleeding events requiring treatment, a BS >3 in the IPFD group (AUC=0.95) predicted treatment with excellent accuracy, while a BS >2 in the vWD-1 group (AUC = 0.71) predicted treatment with good accuracy (Online Supplementary Figure S2B). Severe bleeding events were predicted at BS >7 in the IPFD group (AUC=0.89) with very good accuracy and BS >5 in the vWD-1 group (AUC=0.62) with sufficient accuracy (Online Supplementary Figure S2C). The likelihood of clinically significant bleeding events, bleeds requiring treatment, and severe bleeding events were sig- nificantly higher in the IPFD and vWD-1 groups when the BS was above the respective identified cut-off values, except for severe bleeding in vWD (Online Supplementary Figure S3). We show that IPFD is common among pediatric patients re- ferred to a tertiary care center, with 18% of our participants diagnosed with IPFD. Varying incidence seen in other studies, such as 5% by Bidlingmaier et al.10 and 21% by Adler et al.,11 can be explained by differences in sample size, prospective nature, and different methods of testing platelet function. We demonstrate high ABR in IPFD participants that were not significantly different than those with vWD-1. Gresele et al.12 found higher bleeding rates in IPFD than vWD patients, but once patients with Glanzmann thrombasthenia and Bernard Soulier were removed, similar to our study popula- tion, no significant differences remained. A higher proportion (20%) of IPFD participants suffered surgical bleeding events compared to vWD-1 and required more invasive interven- tions, such as surgery. This is in stark contrast to the data
ABC
Figure 1. International Society of Thrombosis and Hemostasis Bleeding Assessment Tool Bleeding Score, annual bleeding rate, and bleeds requiring treatment among study population. (A) Annual bleeding rate (ABR), (B) bleeding events requiring treatment, and (C) International Society of Thrombosis and Hemostasis Bleeding Assessment Tools Bleeding Score between study group participants. Data are presented as medians and interquartile ranges. **P<0.01. vWD: von Willebrand disease; IPFD: inherited platelet function disorder; yr: years. Controls had a bleeding phenotype but no identifiable bleeding disorder on comprehensive laboratory evaluation.
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