The frequency of joint hemorrhages and procedures in nonsevere hemophilia A vs B

Abstract

Key Points• Joint hemorrhages and orthopedic procedures are more frequent in patients with hemophilia A than in those with hemophilia B.• FA levels of 20% may be required to prevent all joint hemorrhages.Data are needed on minimal factor activity (FA) levels required to prevent bleeding in hemophilia. We aimed to evaluate associations between hemophilia type and FA level and joint bleeding and orthopedic procedures using longitudinal data. Data were collected over an 11-year period on males with nonsevere hemophilia A or B without inhibitors who were receiving on-demand factor replacement therapy. Data on the number of joint bleeds in the previous 6 months and data on procedures from clinical records were analyzed using regression models. Data were collected on 4771 patients (hemophilia A, 3315; hemophilia B, 1456) from 19 979 clinic visits. Ages ranged from 2 to 91 years and baseline FA level ranged from 1% to 49% with a mean of 9.4%. Joint bleeding rates were heterogeneous across the FA range and were highest among men age 25 to 44 years. Adjusted for FA level, the mean number of joint bleeds per 6 months was 1.4 and 0.7 for patients with hemophilia A and B, respectively (P , .001). Regression models predicted 1.4 and 0.6 bleeds per year for hemophilia A and B patients, respectively, at an FA level of 15%. Patients with hemophilia B were 30% less likely than those with hemophilia A to have undergone an orthopedic procedure. We conclude that joint bleed rates for any given FA level were higher among hemophilia A than hemophilia B patients, and target FA levels of 15% are unlikely to prevent all joint bleeding in US males with hemophilia.

The 1st WFH Gene Therapy Round Table: Understanding the landscape and challenges of gene therapy for haemophilia around the world

“…These genes encode proteins that work in concert to contribute to clot formation at a break in a blood vessel wall, and their absence results in prolonged bleeding. Clinical manifestations include severe arthropathy from repeated bleeding into joints, and increased mortality if untreated . An estimated 1 in 5000 males are affected by haemophilia; however, identification of these patients is a challenge, which disproportionately affects developing countries.…”

Hemophilia trials in the twenty‐first century: Defining patient important outcomes

“…den Uijl et al assembled observational data showing that a baseline level >12% FA would make non‐traumatic bleeding very unlikely . In another study, Soucie et al found more inter‐individual variability, but found similar results in that individuals with levels above 15% FA had minimal joint bleeding . Therefore, if gene therapy results in high and sustained hemostatic factor activity, as preliminary trials suggest, we would not expect spontaneous bleeding in patients with levels over 15% FA.…”

“…89 In another study, Soucie et al found more inter-individual variability, but found similar results in that individuals with levels above 15% FA had minimal joint bleeding. 90 Therefore, if gene therapy results in high and sustained hemostatic factor activity, as preliminary trials suggest, we would not expect spontaneous bleeding in patients with levels over 15% FA. On the other hand, we cannot really predict how many traumatic bleeds one would observe; first, because published data are scanty; second, because traumatic bleeds depend on level and intensity of physical activity, which may vary a lot patient to patient.…”

Hemophilia management: Huge impact of a tiny difference

“…When we focus on the annual joint bleeding rate (AJBR), a rate of 0.08 (SD ± 0.26) is seen in the cohort study of Tagliaferri et al In contrast, a recent study performed in the United States by Soucie et al, demonstrated a higher AJBR of 0.97 in patients with mild hemophilia A. However, for this latter study the data on joint bleeds were collected through patient‐reported forms, and this may have potentially led to an overestimation of the AJBR due to misclassification of bleeds by patients …”

“…However, for this latter study the data on joint bleeds were collected through patient-reported forms, and this may have potentially led to an overestimation of the AJBR due to misclassification of bleeds by patients. 30 The first detailed study to investigate the association between baseline FVIII levels and the bleeding phenotype was a single-center study from the Netherlands including 377 patients. 31 This study found that the age at first FVIII treatment increased with a higher FVIII level, as the median age at first treatment with FVIII concentrate was 2.9 and 5.5 years in the moderate and mild hemophilia A groups, respectively.…”