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Multicenter Study
. 2022 Jul 26;6(14):4256-4265.
doi: 10.1182/bloodadvances.2022007620.

The bleeding phenotype in people with nonsevere hemophilia

Fabienne R Kloosterman  1 , Anne-Fleur Zwagemaker  1 , Catherine N Bagot  2 , Erik A M Beckers  3 , Giancarlo Castaman  4 , Marjon H Cnossen  5 , Peter W Collins  6 , Charles Hay  7 , Michel Hof  8 , Britta Laros-van Gorkom  9 , Frank W G Leebeek  10 , Christoph Male  11 , Karina Meijer  12 , Ingrid Pabinger  13 , Susan Shapiro  14   15 , Michiel Coppens  16 , Karin Fijnvandraat  1   17 , Samantha C Gouw  1
Affiliations
Multicenter Study

The bleeding phenotype in people with nonsevere hemophilia

Fabienne R Kloosterman et al. Blood Adv. .

Abstract

Detailed information on the onset, frequency, and severity of bleeding in nonsevere hemophilia is limited. We aimed to assess the bleeding phenotype of persons with nonsevere hemophilia and to analyze the association between baseline factor VIII/IX (FVIII/IX) levels and the joint bleeding rate. In the DYNAMO (Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B) study, an international multicenter cohort, we included males with nonsevere hemophilia (FVIII/IX, 0.02-0.35 IU/mL) aged 12 to 55 years. Information on age at first treated (joint) bleed, annual bleeding rates (ABRs), and annual joint bleeding rates (AJBRs) was collected from the medical files. The association between baseline FVIII/IX levels and the joint bleeding rate was assessed by using a frailty model for recurrent events. In total, 304 persons (70 with moderate hemophilia and 234 with mild hemophilia) were included. The median age was 38 years (interquartile range [IQR], 25-49 years), and the median baseline FVIII/IX level was 0.12 IU/mL (IQR, 0.05-0.21 IU/mL). In total, 245 (81%) persons had experienced at least 1 bleed, and 156 (51%) had experienced at least 1 joint bleed. The median age at first bleed and first joint bleed was 8 and 10 years, respectively. The median ABR and AJBR was 0.2 (IQR, 0.1-0.5) and 0.0 (IQR, 0.0-0.2). From baseline FVIII/IX levels 0.02 to 0.05 IU/mL to >0.25 IU/mL, the median ABR decreased from 0.6 (IQR, 0.2-1.4) to 0.1 (IQR, 0.0-0.2) and the AJBR from 0.2 (IQR, 0.0-0.4) to 0.0 (IQR, 0.0-0.0). Baseline FVIII/IX was inversely associated with the joint bleeding rate (P < .001). Low bleeding rates were observed in persons with nonsevere hemophilia. However, one-half of all adolescents and adults had experienced a joint bleed.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Kaplan-Meier analysis: age at first bleed. Analysis was conducted according to hemophilia severity (A) and categories within mild hemophilia (B). The line represents the cumulative incidence. The shaded area in panel A represents the 95% CI. Crosses represent right-censored patients.
Figure 2.
Figure 2.
Kaplan-Meier analysis: age at first joint bleed. Analysis was conducted according to hemophilia severity (A) and categories within mild hemophilia (B). The line represents the cumulative incidence. The shaded area in panel A represents the 95% CI. Crosses represent right-censored patients.
Figure 3.
Figure 3.
Scatterplots of the ABR and AJBR according to baseline FVIII/IX levels. Analysis was presented for ABR (A) and AJBR (B). A smoothed local polynomial line of fit is shown. Dots represent the individual participants. In the ABR graph, one outlier (ABR = 10.9) was omitted to allow detailed scaling.
See this image and copyright information in PMC

References

    1. Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A; Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis . Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014;12(11):1935-1939. - PubMed
    1. Srivastava A, Santagostino E, Dougall A, et al. ; WFH Guidelines for the Management of Hemophilia panelists and co-authors . WFH Guidelines for the Management of Hemophilia, 3rd edition [published correction appears in Haemophilia. 2021;27(4):699]. Haemophilia. 2020;26(suppl 6): 1-158. - PubMed
    1. Peyvandi F, Tavakkoli F, Frame D, et al. . Burden of mild haemophilia A: systematic literature review. Haemophilia. 2019;25(5):755-763. - PMC - PubMed
    1. Soucie JM, Monahan PE, Kulkarni R, Konkle BA, Mazepa MA; US Hemophilia Treatment Center Network . The frequency of joint hemorrhages and procedures in nonsevere hemophilia A vs B. Blood Adv. 2018;2(16):2136-2144. - PMC - PubMed
    1. Måseide RJ, Berntorp E, Astermark J, et al. . Joint health and treatment modalities in Nordic patients with moderate haemophilia A and B—the MoHem study. Haemophilia. 2020;26(5):891-897. - PubMed

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