Abstract：
BACKGROUND: Predicting the bleeding risk in hemophilia A and B carriers (HAC, HBC) is challenging.
OBJECTIVE: The objectives of this study were to describe the bleeding phenotype in HAC and HBC using the standardized Tosetto bleeding score (BS); to determine whether the BS correlates better with factor levels measured with a chromogenic assay than with factor levels measured with chronometric and thrombin generation assays; and to compare the results in HAC and HBC.
METHODS: This ambispective, noninterventional study included obligate and sporadic HAC and HBC followed at a hemophilia treatment center between 1995 and 2019.
CONCLUSIONS: The median BS (3, range 0-21 vs. 3.5, range 0-15, P = ns, respectively) and the abnormal BS rate (35.6% vs. 38.2%, P = ns) were not significantly different in 104 HAC and 34 HBC (mean age: 38 years, 6-80 years). However, some differences were identified. The risk of factor deficiency was higher in HBC than HAC. Specifically, Factor VIII activity (FVIII):C/Factor IX activity (FIX):C level was low (<40 IU/dl) in 18.3% (chronometric assay) and 17.5% (chromogenic assay) of HAC and in 47% and 72.2% of HBC ( P < 0.001). Moreover, the FIX:C level thresholds of 39.5 IU/dl (chronometric assay) and of 33.5 IU/dl (chromogenic assay) were associated with very good sensitivity (92% and 100%, respectively) and specificity (80% for both) for bleeding risk prediction in HBC. Conversely, no FVIII:C level threshold could be identified for HAC, probably due to FVIII:C level variations throughout life.
OBJECTIVE: The objectives of this study were to describe the bleeding phenotype in HAC and HBC using the standardized Tosetto bleeding score (BS); to determine whether the BS correlates better with factor levels measured with a chromogenic assay than with factor levels measured with chronometric and thrombin generation assays; and to compare the results in HAC and HBC.
METHODS: This ambispective, noninterventional study included obligate and sporadic HAC and HBC followed at a hemophilia treatment center between 1995 and 2019.
CONCLUSIONS: The median BS (3, range 0-21 vs. 3.5, range 0-15, P = ns, respectively) and the abnormal BS rate (35.6% vs. 38.2%, P = ns) were not significantly different in 104 HAC and 34 HBC (mean age: 38 years, 6-80 years). However, some differences were identified. The risk of factor deficiency was higher in HBC than HAC. Specifically, Factor VIII activity (FVIII):C/Factor IX activity (FIX):C level was low (<40 IU/dl) in 18.3% (chronometric assay) and 17.5% (chromogenic assay) of HAC and in 47% and 72.2% of HBC ( P < 0.001). Moreover, the FIX:C level thresholds of 39.5 IU/dl (chronometric assay) and of 33.5 IU/dl (chromogenic assay) were associated with very good sensitivity (92% and 100%, respectively) and specificity (80% for both) for bleeding risk prediction in HBC. Conversely, no FVIII:C level threshold could be identified for HAC, probably due to FVIII:C level variations throughout life.
摘要：
背景：预测血友病A和B携带者的出血风险（HAC，HBC）具有挑战性。
目的：本研究的目的是使用标准化的托塞托出血评分（BS）描述HAC和HBC的出血表型；确定BS与显色测定法测得的因子水平的相关性是否比与计时和凝血酶生成测定法测得的因子水平的相关性更好；并比较HAC和HBC的结果。
方法：这种综合，非干预性研究包括1995年至2019年在血友病治疗中心随访的专性和散发性HAC和HBC.
结论：中位数BS（3，范围0-21vs.3.5，范围0-15，P=ns，分别）和BS异常率（35.6%与38.2%,P=ns）在104HAC和34HBC中没有显着差异（平均年龄：38岁，6-80岁）。然而,确定了一些差异。HBC因子缺乏的风险高于HAC。具体来说,因子VIII活性(FVIII):C/因子IX活性(FIX):在18.3%(计时测定)和17.5%(显色测定)的HAC中以及在47%和72.2%的HBC中C水平低(<40IU/dl)(P<0.001)。此外，FIX：39.5IU/dl（计时测定）和33.5IU/dl（显色测定）的C水平阈值与非常好的灵敏度（92％和100％，分别）和HBC出血风险预测的特异性（两者均为80％）。相反，没有FVIII：可以确定HAC的C水平阈值，可能是由于整个生命周期中的FVIII：C水平变化。
目的：本研究的目的是使用标准化的托塞托出血评分（BS）描述HAC和HBC的出血表型；确定BS与显色测定法测得的因子水平的相关性是否比与计时和凝血酶生成测定法测得的因子水平的相关性更好；并比较HAC和HBC的结果。
方法：这种综合，非干预性研究包括1995年至2019年在血友病治疗中心随访的专性和散发性HAC和HBC.
结论：中位数BS（3，范围0-21vs.3.5，范围0-15，P=ns，分别）和BS异常率（35.6%与38.2%,P=ns）在104HAC和34HBC中没有显着差异（平均年龄：38岁，6-80岁）。然而,确定了一些差异。HBC因子缺乏的风险高于HAC。具体来说,因子VIII活性(FVIII):C/因子IX活性(FIX):在18.3%(计时测定)和17.5%(显色测定)的HAC中以及在47%和72.2%的HBC中C水平低(<40IU/dl)(P<0.001)。此外，FIX：39.5IU/dl（计时测定）和33.5IU/dl（显色测定）的C水平阈值与非常好的灵敏度（92％和100％，分别）和HBC出血风险预测的特异性（两者均为80％）。相反，没有FVIII：可以确定HAC的C水平阈值，可能是由于整个生命周期中的FVIII：C水平变化。
