Q2. What are the common hemorrhagic manifestations of hemophilia?
The most common hemorrhagic manifestations of hemophilia are recurrent hemarthroses, mainly in elbows, knees and ankles, which lead to a progressive joint destruction, irreversible crippling arthropathy and chronic pain [1].
Q3. How many children with hemophilia A have been randomized to prophylaxis?
Forty-five children with severe hemophilia A, aged 1–7 years (median 4), with negative clinical-radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factorVIII (25 IU kg)1 3 ·week) or episodic therapy with ‡25 IU kg)1 every 12–24 h until complete clinical bleeding resolution.
Q4. What are the main strengths of this study?
Strengths of this study are the randomized controlled design, the intention-to treat analysis, the pragmatic approach, with a relatively broad range of patients with different ages at study entry and with modalities of treatment that reflect the common practise, an approach that provides information that can be extrapolated to all children with hemophilia, and the longest follow-up so far.
Q5. What is the word for the phrase prophylaxis?
The long-term, regular, continuous administration of concentrates, based upon two to three or more weekly infusions, is the most effective method to forestall bleeding and bleeding-related complications [3], and therefore it was described as prophylaxis.
Q6. How many patients were evaluated for eligibility?
Seventy-two patients were assessed for eligibility in a2011 International Society on Thrombosis and Haemostasisconsecutive and competitive fashion (Milan, 14; Rome, 10; Bari, 9; Naples, 7; Bolzano, 5; Genoa, 5; Castelfranco V., 4; Catania, 4; Florence, 4; Palermo, 4; Parma, 3; Vicenza, 3).
Q7. How many patients were excluded from the study?
Of these, 17 were excluded because of unmet inclusion criteria (nine parents refused randomization, three patients had suffered from more than two bleeding episodes in the same joints, three patients had not bled in the previous 6 months, one child had radiologic signs of arthropathy, and one child belonged to an unreliable (dysfunctional) family).
Q8. What are the barriers to prophylaxis in children with hemophilia?
There are barriers to early and long-term prophylaxis in children with hemophilia, mainly related to cumbersome venous access leading to inadequate patient/family compliance with the prescribed treatment.
Q9. What percentage of children on episodic treatment felt that their parents had often or always to limit their?
Twenty per cent of children and adoles-cents on episodic treatment perceived that their parents had often or always to limit their time at work or leisure because of their hemophilia compared with none in the prophylaxis group, where only 10% of children perceived that their parents had only sometimes their work or leisure time limited.
Q10. How was the coagulant activity measured in the patients randomized to prophylaxis?
In patients randomized to prophylaxis, plasma levels of FVIII coagulant activity were obtained every 6 months immediately prior to one of the regularly scheduled infusions, in order to determine if trough levels were above 1%.
Q11. What was the protocol for a bleed?
The protocol allowed early change of the assigned treatment when it was deemed inadequate by the supervisor, owing to one of the following reasons: a high frequency of bleeding episodes (defined as 3 monthly bleeds or more), development of a target joint (defined as three bleeds in the same joint in a 6-month time period), life-threatening hemorrhage; or bone or cartilage damage on joint imaging.
Q12. How many patients were randomized to prophylaxis?
The image-proven evidence of arthropathy was observed in three-quarters of the patients randomized to episodic therapy, compared with only one-quarter of those randomized to prophylaxis.
Q13. What is the cost of prophylaxis in children with severe hemophilia?
it confirms that early prophylaxis is more efficaciousthan delayed prophylaxis, even though the latter still generates substantial benefits to these patients.
Q14. How many bleeds did the patients who started prophylaxis earlier have?
None of the patients who started prophylaxis at the age of 3 years or earlier had on averagemore than three bleeds per year, compared with 5 of 13 patients who started prophylaxis later (38%).
Q15. What is the bleeding distribution in the two treatment groups?
Figure 2 shows the bleeding distribution in the two treatment groups: 11 of 21 patients (52%) in the prophylaxis group had on average<1 hemarthrosis per year, whereas only 4 of 19 patients in the episodic therapy group (21%) had the same low frequency of bleeding (P < 0.05).
Q16. Why did the JOS study find a higher percentage of patients with radiologic evidence of joint?
Compared with the JOS findings, their study found a higher percentage of patients with radiologic evidence of joint damage, due to the older population recruited and perhaps also to the much longer follow-up.