Mendoza Ana, Rivas Isabel, Hidalgo Olga Benítez, Cid Ana Rosa, Olivieri Martin, Ranta Susanna, Labarque Veerle, Andersson Nadine G, de Kovel Marloes, Álvarez-Román María Teresa
Hematology Department, Hospital Universitario La Paz, Madrid, Spain.
Hematology Department, Hospital Universitari Vall d'Hebron, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Haemophilia. 2025 Jul;31(4):679-686. doi: 10.1111/hae.70018. Epub 2025 May 30.
Patients with severe haemophilia A (HA) with no family history of haemophilia will be diagnosed upon their first bleeding event.
Herein, we studied the effects of lack of family history in HA and the subsequent delay of diagnosis on bleeding pattern and early treatment, as well as on the risk of inhibitor development. For this purpose, data on 1237 severe HA patients with known family history ("positive" or "negative"), born between 2000 and 2022, were collected in 29 participating centres.
At diagnosis, 45.9% (554/1208) of patients had a positive family history of HA and 54.1% (654/1208) had a negative family history. A positive family history significantly shortened the time to diagnosis (8 months) and the treatment initiation (2 months). Prophylaxis was more frequently the first treatment in those with a positive family history compared to the negative family history group (21% vs. 13%). Bleeding was the main reason for first exposure day (ED) in both groups, but less frequently in the family history group than in those without a family history (67% vs. 80%). Positive family history was associated with fewer peak treatments at first five EDs (12% vs. 16%). In non-inhibitor patients, bleeding occurred earlier in those with positive family history (9.2 months vs. 10.6 months). The inhibitor incidence was similar in both groups (33% vs. 30%), and a positive family history was associated with earlier inhibitor development (13 months vs. 15 months).
The majority of patients presented without a family history of HA which led to a delayed diagnosis and treatment initiation.
无血友病家族史的重度甲型血友病（HA）患者将在首次出血事件时被诊断出来。
在此，我们研究了HA患者缺乏家族史以及随后诊断延迟对出血模式、早期治疗以及抑制剂形成风险的影响。为此，在29个参与中心收集了2000年至2022年出生的1237例有已知家族史（“阳性”或“阴性”）的重度HA患者的数据。
在诊断时，45.9%（554/1208）的患者有HA家族史阳性，54.1%（654/1208）有家族史阴性。家族史阳性显著缩短了诊断时间（8个月）和开始治疗时间（2个月）。与家族史阴性组相比，家族史阳性的患者更常将预防治疗作为首次治疗（21%对13%）。两组中出血都是首次暴露日（ED）的主要原因，但家族史组的频率低于无家族史组（67%对80%）。家族史阳性与前五个ED时的峰值治疗次数较少相关（12%对16%）。在无抑制剂的患者中，家族史阳性的患者出血更早（9.2个月对10.6个月）。两组的抑制剂发生率相似（33%对30%），家族史阳性与抑制剂形成更早相关（13个月对15个月）。
大多数患者就诊时无HA家族史，这导致了诊断和治疗开始的延迟。
