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

Abstract

IntroductionIn countries with restricted access to clotting factor concentrates, early implementation of low‐dose prophylaxis is recommended over episodic treatment. ObjectiveThe 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. MethodsBoys 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. ResultsThirty‐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. ConclusionA 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.