Prenatal diagnosis of haemophilia: our experience of 44 cases

Federica Zarrilli, Veronica Sanna, Rosaria Ingino, Rita Santamaria 3 , Angiola Rocino 4 , Antonio Coppola 5 , Giovanni Di Minno 5 ,  and Giuseppe Castaldo
  • 1 CEINGE-Biotecnologie Avanzate, Naples, Italy
  • 2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy
  • 3 Dipartimento di Farmacia, Università di Napoli Federico II, Naples, Italy
  • 4 Centro Emofilia e Trombosi, Ospedale S.G. Bosco, Naples, Italy
  • 5 Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, Naples, Italy
Federica Zarrilli, Veronica Sanna, Rosaria Ingino, Rita Santamaria, Angiola Rocino, Antonio Coppola, Giovanni Di Minno and Giuseppe Castaldo


Background: Haemophilia A and B (HA, HB) are the most frequent X-linked bleeding diseases; two-thirds of cases are severe.

Methods: We counselled 51 couples for prenatal diagnosis (PD) of haemophilia. In 7/51 (13.7%) cases, the couple decided not to undergo PD because counselling revealed that they were carriers of a mild form of the disease, while we performed 44 PD for severe HA (36 cases) or HB (8 cases). The indication for PD was a haemophilic child (30/44, 68.2%) or an affected family member (12/44, 27.3%); in two cases the non-carrier mother of isolated haemophilic patients requested PD because of the risk of mosaicism.

Results: We completed PD in 43/44 cases; in one case, the prenatal sample was contaminated by maternal DNA; however, molecular analysis revealed the female sex of the foetus. We performed PD for 16 of the 36 couples at risk of HA (44.4%) by analysing the intron (IVS)22 inversion; in 1/36 cases (2.8%) the mother had the IVS1 inversion, and in 8/36 (22.2%) the family mutation was identified by sequencing; in 11/36 (30.6%) cases the family mutation was unknown, and PD was performed by linkage (no recombination nor uninformative cases occurred). For HB, in 6/8 (75.0%) cases, PD was performed by DHPLC or by sequencing; in 2/8 cases we tested intragenic markers (again with no cases of recombination or uninformative families).

Conclusions: PD in well-equipped laboratories, and multidisciplinary counselling are an aid to planning reproductive and early therapeutic strategies in families with severe haemophilia.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.