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. RESULTS AND CONCLUSION: The median BS (3, range 0-21 vs. 3.5, range 0-15, P â=âns, respectively) and the abnormal BS rate (35.6% vs. 38.2%, P â=âns) were not significantly different in 104 HAC and 34 HBC (mean age: 38âyears, 6-80âyears). 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 (<40âIU/dl) in 18.3% (chronometric assay) and 17.5% (chromogenic assay) of HAC and in 47% and 72.2% of HBC ( P â<â0.001). Moreover, the FIX:C level thresholds of 39.5âIU/dl (chronometric assay) and of 33.5âIU/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.
Subject(s)
Hemophilia A , Hemophilia B , Hemorrhage , Humans , Hemophilia A/blood , Hemophilia A/complications , Hemophilia B/blood , Hemophilia B/complications , Adult , Adolescent , Child , Middle Aged , Hemorrhage/etiology , Hemorrhage/blood , Hemorrhage/diagnosis , Young Adult , Aged , Male , Aged, 80 and over , Female , Factor IX/analysis , Factor IX/metabolism , Blood Coagulation Tests/methods , Factor VIII/analysisSubject(s)
Factor V/antagonists & inhibitors , Databases, Factual , Female , France , Humans , Iatrogenic Disease , Middle Aged , PharmacovigilanceABSTRACT
BACKGROUND: Physical performance measured by gait speed is being recognized as a major instrument for clinical evaluation in older adults, because it predicts physical frailty, loss of autonomy, hospitalization and decreased survival. Low-grade chronic inflammation and oxidative stress, mediated partly by the superoxide anion produced by NADPH oxidase, are closely linked and could be involved in age-related physical decline. OBJECTIVE: To determine whether slow gait speed is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation. DESIGN AND SETTING: Observational study among the 280 elderly of an ambulatory geriatric care unit (191 women, 89 men, 79.9 ± 6.1 years old). METHODS: Gait speed was evaluated by walking at self-chosen usual pace. Usual gait speed < 0.8 m/s was defined as slow gait speed. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method. Inflammation was evaluated by CRP, fibrinogen and leukocyte count. RESULTS: Among the 280 participants, 179 (63.9%) walked with a gait speed < 0.8 m/s (slow walkers) and 101 (36.1%) with a gait speed ≥ 0.8 m/s. Superoxide production and inflammation markers, such as fibrinogen, were more important in slow walkers (p = 0.004 and p = 0.006, respectively). In multivariate analysis, superoxide anion overproduction and fibrinogen were independently associated with physical frailty assessed by slow gait speed (p = 0.028 and p = 0.007, respectively). CONCLUSION: Physical frailty in older people is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation.
