Focusing on haemophilia B: prophylaxis in Spanish patients

Abstract

observed in the cases mutated for INV22 inversion. This discrepancy could be attributed to the low number of patients who have so far proven positive for intron 1 inversion. Among our 9 patients who were positive for this inversion, two developed inhibitors with the titres of 8.96BU and 6.72BU. These two patients received pdFVIII only for the treatment of severe bleeding episodes. In China, the majority of HA patients receive little replacement therapies as result of the financial constraints and shortage of the plasma. Most patients were exposed to limited amount and restricted types of intermediate-purity FVIII other than high-purity FVIII or rFVIII. The overall prevalence of inhibitors in Chinese HA patients was 3.9% and the prevalence of severe haemophiliacs was 4.3% [5], much lower than that reported in the Western countries. The limited types of treatment regimens and limited exposure days may contribute to low inhibitor rate in Chinese HA patients. In this study, the frequency of the inhibitor developed in the patients with INV1 is 22.22%, much higher than the inhibitor rate in the Chinese population as a whole and agrees well with that found among INV22 carriers (21.5-34.5%; [4]). Based on less therapyrelated risk factors of inhibitor development in China, it seems that the genetic factors may contribute more to the inhibitor development. As estimating the risk of developing inhibitors has relevant implications for the clinical management strategy, these preliminary data need further support in a much larger series of patients.In summary, it seems that the frequency of the intron 1 inversion is lower and the risk of inhibitor development higher than that reported in most previous studies. Nevertheless, this mutation remains the second most frequent molecular cause of HA after the intron 22 inversion. As it is easy and fast to analyse, we recommend this test as the second step in a mutation-screening programme after exclusion of the intron 22 inversion and before screening of the entire gene. DisclosuresThe authors stated that they had no interests which might be perceived as posing a conflict or bias. References1 Keeney S, Mitchell M, Goodeve A. The molecular analysis of haemophilia A: a guideline from the UK haemophilia centre doctors organization haemophilia genetics laboratory network. Haemophilia 2005; 11: 387-97. 2 Brinke A, Tagliavacca L, Naylor J et al. Two chimeric transcription units result from an inversion breaking intron 1 of the factor VIII gene and a region reportedly affected by reciprocal translocations in T-cell leukaemia. Hum Mol Genet 1996; 5: 1945-51. 3 Schroder J, El-Maarri O, Schwaab R et al. Factor VIII intron-1 inversion: frequency and inhibitor prevalence.The results of the first epidemiological study carried out in Spain in 51 haemophilia treatment centres throughout the country (85% of them) were published in 2009 [1]. On the basis of this study, we aimed to achieve knowledge of the real current situation of primary (PP) and secondary prophylactic (SP) treatments provided to hae...

Multicentre, randomized, open‐label study of on‐demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects

“…Prevention and treatment of bleeding episodes in patients with haemophilia B is based upon prophylactic or on-demand replacement of the deficient FIX with plasma-derived or recombinant FIX products. However, only 21-55% of haemophilia B patients receive prophylaxis therapy [5][6][7][8]. Primary prophylaxis is initiated in the absence of documented osteochondral joint disease (determined by physical examination and/or imaging studies), before the second clinically evident large joint bleed, at 3 years of age; secondary prophylaxis begins after two or more bleeds into large joints, before the onset of documented joint disease [4].…”

“…Primary prophylaxis is initiated in the absence of documented osteochondral joint disease (determined by physical examination and/or imaging studies), before the second clinically evident large joint bleed, at 3 years of age; secondary prophylaxis begins after two or more bleeds into large joints, before the onset of documented joint disease [4]. However, only 21-55% of haemophilia B patients receive prophylaxis therapy [5][6][7][8]. Underutilization of prophylaxis therapy is even more evident in haemophilia A patients.…”

Point-of-care Ultrasonography in Orthopedic Management of Hemophilia: Multiple Uses of an Effective Tool

“…In patients with hemophilia, POC-US is also a valid and sensitive tool for continuous monitoring of joints [11, 28, 31, 37, 43] and of treatment response [4, 28]. Some expert groups have recommended sonographic follow-up of acute joint lesions using the HEAD-US system, repeating the exam every one or two weeks until resolution [15].…”

Haemophilia in a real‐world setting: the value of clinical experience in data collection

“…Due to longer the half‐life of FIX, less frequent replacement factor infusions are required in haemophilia B compared with haemophilia A. The recommended regimen for prophylaxis in haemophilia B is twice‐weekly doses of rFIX (15–30 IU/kg) , but is underutilised with only 21%–55% of patients receiving regular prophylaxis . Maintenance of FIX levels >1 IU/dL (lowest level before next dose) has been the target of prophylaxis, although the putative relationship between the factor level and bleeding frequency has not been confirmed in clinical trials in haemophilia B .…”