Effect of low‐dose factor VIII prophylaxis therapy on bone mineral density and 25(OH) vitamin D level in children with severe haemophilia A

Abstract

Background Decreased bone mineral density (BMD) is a significant morbidity in haemophilia. Vitamin D is important for the bone health of people with haemophilia. Regular factor VIII prophylaxis can prevent bleeding and arthropathy. Aim To determine the 25(OH) vitamin D level in severe haemophilia A patients and correlate it to their Hemophilia Joint Health Score (HJHS) and dual‐energy X‐ray absorptiometry (DEXA). We also compared the 25(OH) vitamin D and DEXA in haemophilia A and healthy children and in haemophilia A children on prophylaxis versus on‐demand therapy. Methods Fifty severe haemophilia A patients were compared to 50 age‐matched healthy boys. Patients were recruited from the Pediatric Hematology Clinic, Ain Shams University from May 2017 to April 2018. Full medical history was taken with emphasis on frequency of bleeding episodes, duration and amplitude of pain assessed by the pain score. Weight, height, body mass index and HJHS were assessed. 25(OH) vit‐D3, calcium, phosphorus and alkaline phosphatase were measured. BMD was assessed using Lunar DEXA, paediatric software. Results People with haemophilia had significantly lower 25(OH) vit‐D3 (P < .001) and DEXA z‐score (P < .001) than controls. Seventy per cent of patients were on factor VIII prophylaxis twice weekly (15U/kg/dose). Significant difference was found regarding DEXA z‐score (P = .012), 25(OH) vit‐D3 (P = .033) and HJHS (P = .022) among patients on prophylaxis and on‐demand therapy. Conclusion Severe haemophilia A patients showed significantly lower 25(OH) vit‐D3 and DEXA than controls. Hence, vitamin D deficiency should be tested in all people with haemophilia for early diagnosis and treatment. Low‐dose prophylaxis in severe haemophilia preserves BMD and increases vitamin D. Further studies are required to evaluate the effect of different prophylaxis protocols on BMD and haemophilic arthropathy.

Low bone mass and hypovitaminosis D in haemophilia: A single‐centre study in patients with severe and moderate haemophilia A and B

“…The pathogenesis is multifactorial and includes reduced physical activity due to fear of trauma and bleeding, the presence of haemophilic arthropathy 10,14 and lack of weight‐bearing exercise during childhood and adolescence which is associated with a deficient peak bone mass 15 . Other factors such as hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infections and their treatment may be independently associated with decreased bone mineral density (BMD), as well the extremely widespread vitamin D deficiency across all age groups and geographic areas 9,16‐18 …”

Factor VIII replacement prophylaxis in patients with hemophilia A transitioning to adults: a systematic literature review

“…To overcome this, Hua et al and Li et al studied the effects of low-dose prophylaxis and suggested that even low-dose prophylaxis can reduce ABR and improve the quality of life compared with episodic treatment [ 42 , 44 ]. A study by Andrawes et al reported that low-dose prophylaxis in severe hemophilia preserves bone mineral density (BMD), increases vitamin D levels, and decreases hemophilia joint health score (HJHS) [ 59 ]. Kavakli et al conducted a study on low- and high-dose prophylaxis; the results of the first 6 months indicated lower ABRs with high doses, but ABRs with both doses were comparable in the next 6 months [ 26 ].…”

Asymptomatic Joint Bleeding and Joint Health in Hemophilia: A Review of Variables, Methods, and Biomarkers

“…89 Low vitamin D levels have also been associated with decreased BMD, physical activity, quality of life and poor joint health. [90][91][92] These studies suggest that routine assessment of serum levels of vitamin D could guide early diagnosis of joint damage and treatment in patients with hemophilia, particularly in children. In patients with hemophilia, prevention of poor bone health should include primary prophylaxis, a diet rich in calcium and vitamin D, physiotherapy, and weight-bearing physical activities.…”

“…In patients with hemophilia, prevention of poor bone health should include primary prophylaxis, a diet rich in calcium and vitamin D, physiotherapy, and weight-bearing physical activities. 52,[89][90][91]…”