Significant reduction in hemarthrosis in boys with severe hemophilia A: The China hemophilia individualized low-dose secondary prophylaxis study

Runhui Wu; Xiaojing Li; Wanru Yao; Qing Zhang; Min Zhou; Ningning Zhang; Sheng Yang; Zhenping Chen; Yan Wang; Yangying Kuang; Ling Tang; Yingzi Zhen; Audrey Abad; Andrea S Doria; Pamela Hilliard; Danial M Ignas; Prasad Mathew; Derek Stephens; Victor S Blanchette; Koon-Hung Luke

doi:10.1002/rth2.12552

Significant reduction in hemarthrosis in boys with severe hemophilia A: The China hemophilia individualized low-dose secondary prophylaxis study

Res Pract Thromb Haemost. 2021 Sep 18;5(6):e12552. doi: 10.1002/rth2.12552. eCollection 2021 Aug.

Authors

Runhui Wu¹, Xiaojing Li^{2

3}, Wanru Yao¹, Qing Zhang², Min Zhou², Ningning Zhang⁴, Sheng Yang⁵, Zhenping Chen¹, Yan Wang⁶, Yangying Kuang⁷, Ling Tang¹, Yingzi Zhen¹, Audrey Abad⁸, Andrea S Doria^{9

10}, Pamela Hilliard⁸, Danial M Ignas⁸, Prasad Mathew¹¹, Derek Stephens¹⁰, Victor S Blanchette¹², Koon-Hung Luke¹³

Affiliations

¹ Hemophilia Comprehensive Care Center Hematology Department Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
² Hemophilia Diagnosis and Treatment Center Department of Hematology and Oncology Chengdu Women's and Children's Central Hospital School of Medicine University of Electronic Science and Technology of China Chengdu China.
³ Hemophilia Treatment Center Department of Pediatrics New Century Women's and Children's Hospital Chengdu China.
⁴ Hemophilia Comprehensive Care Center, Radiology Center Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
⁵ Hemophilia and Diagnosis Treatment Center Department of Ultrasound Chengdu Women's and Children's Central Hospital School of Medicine University of Electronic Science and Technology of China Chengdu China.
⁶ Hemophilia Comprehensive Care Center, Rehabilitation Department Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
⁷ Hemophilia Diagnosis and Treatment Center Department of Radiology Chengdu Women's and Children's Central Hospital School of Medicine University of Electronic Science and Technology of China Chengdu China.
⁸ Child Health Evaluative Sciences, Research Institute The Hospital for Sick Children Toronto ON Canada.
⁹ Department of Diagnostic Imaging Medical Imaging Department The Hospital for Sick Children University of Toronto Toronto Canada.
¹⁰ The Hospital for Sick Children Research Institute University of Toronto Toronto ON Canada.
¹¹ Division of Pediatric Hematology/Oncology Presbyterian Health Services Hospital Albuquerque NM USA.
¹² Division of Hematology/Oncology The Hospital for Sick Children and Department of Pediatrics University of Toronto Toronto ON Canada.
¹³ Department of Pediatrics Laboratory Medicine and Pathology Division of Hematology and Oncology University of Ottawa Children Hospital of Eastern Ontario Ottawa ON Canada.

Abstract

Introduction: In countries with restricted access to clotting factor concentrates, early implementation of low-dose prophylaxis is recommended over episodic treatment.

Objective: The objective of this 1-year prospective secondary prophylaxis study was to evaluate the efficacy of a dose/frequency escalating protocol in young boys with hemophilia A in China.

Methods: Boys were started on a low-dose protocol (minimum 10-15 IU/kg of factor VIII [FVIII] twice weekly). Escalation was based on index joint bleeding, swelling/persistent joint swelling, and serial ultrasound (gray scale and color Doppler) examinations of index joints.

Results: Thirty-three boys, median age 4.8 years (interquartile range, 3.8-6.1) were enrolled in a 3-month observation period that preceded a 1-year prophylaxis phase. A significant reduction in total bleeding events (43.0%, P = .001), index joint bleeds (53.2%, P = .002), and target index joint bleeds (70.0%, P = 0.02) was observed during the prophylaxis phase. During the prophylaxis period, 40% of target joints resolved. The percentage of boys with zero index joint bleeds increased significantly (P = .004) from 51.5% during the observation phase to 81.8% in last quarter of the prophylaxis phase (months 10-12). There was no progression of arthropathy based on physical examination (Hemophilia Joint Health Score), X-ray, and ultrasound obtained at entry into the prophylaxis phase and at study exit. The median FVIII consumption over the prophylaxis phase was 1786 IU/kg/y.

Conclusion: A low-dose, individualized prophylaxis protocol, guided by individual bleeding profiles and serial assessment of joint status, enables escalation of treatment intensity in boys with severe hemophilia A, leading to a significant reduction in bleeding events and reduction in target joint bleeding.

Keywords: China; health care; hemarthrosis; hemophilia A; outcome assessment; prophylaxis studies; ultrasonography.