K Vepsäläinen1, R Lassila2, M Arola3, P Huttunen4, S Koskinen5, R Ljung6, P Lähteenmäki7, M Möttönen8, P Riikonen9. 1. Department of Paediatrics, Kuopio University Hospital, Kuopio, Finland. kaisa.vepsalainen@kuh.fi. 2. Coagulation Disorders Unit, Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. 3. Department of Paediatrics, Tampere University Central Hospital, Tampere, Finland. 4. Children's Hospital, Helsinki University Hospital, Helsinki, Finland. 5. Finnish Red Cross Blood Transfusion Service, Helsinki, Finland. 6. Department of Clinical Sciences - Paediatrics and Paediatric Clinic and Malmö Centre for Thrombosis and Haemostasis, Skånes Universitetssjukhus, Lund University, Lund, Sweden. 7. Department of Paediatrics and Adolescent Medicine, Turku University Hospital and Turku University, Turku, Finland. 8. Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology, University Hospital of Oulu, Oulu, Finland. 9. Department of Paediatrics, Kuopio University Hospital, Kuopio, Finland.
Abstract
INTRODUCTION: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. AIM: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL(-1) ). METHODS: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. RESULTS: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2-13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. CONCLUSION: The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.
INTRODUCTION: Currently the most serious treatment complication of haemophilia is the inhibitor development (ID), i.e. neutralizing antibody development. AIM: This nationwide multicentre study in Finland evaluated the incidence and risk factors of ID in previously untreated patients (PUPs) with severe haemophilia A (FVIII:C < 0.01 IU mL(-1) ). METHODS: We enrolled all PUPs (N = 62) born between June 1994 and May 2013 with at least 75 exposure days (EDs) to screen ID during follow-up extending to September 2013. RESULTS: Thirteen ID (21% of 62) occurred; 10 (16% of 62) with high titre. Fifty-one patients (82%) were on primary prophylaxis (regular prophylaxis before the age of 2 and before the first joint bleed) from the median age of 11.4 months, 90% via a central venous access device. The initial product was rFVIII in 63% and pd-FVIII in 37%, moreover in 24% pd-FVIII was switched to rFVIII concentrate during the 75 EDs. Non-transient inhibitors developed in 9/51 (17.6%; 13.7% high titre) children with primary and in 4/11 (36.4%; 27.3% high titre) patients with secondary prophylaxis (P = 0.24). Overall, 74% had a high-risk genotype similarly distributed among the prophylaxis groups. The history of a major bleed enhanced ID (aHR, 4.0; 95% CI, 1.2-13.7), whereas FVIII treatment intensity or source and early implantation of ports did not increase ID risk. CONCLUSION: The cumulative incidence of ID was low notwithstanding prevalent high-risk mutations. Despite patient-related risk factors, our management involving early intensive primary prophylaxis via ports helps to prevent bleeds and lower the incidence of inhibitors.
Authors: Christine Keipert; Ursula Drechsel-Bäuerle; Doris Oberle; Mirco Müller-Olling; Anneliese Hilger Journal: Int J Environ Res Public Health Date: 2020-12-30 Impact factor: 3.390