The long-term course of factor VIII inhibitors in patients with congenital haemophilia A without immune tolerance induction.
The development of alloantibodies that inhibit or neutralise the function of factor VIII is considered the most serious complication of the treatment of congenital haemophilia A. In order to describe their course without immune tolerance induction (ITI), we documented data on all performed inhibitor tests with dates as well as on clotting factor infusions of all consecutive patients who were treated in our centre between 1993 and 2006. Patients were tested every 7.1 months (95% confidence interval [CI], 6.6-7.8). A 'sustained negative inhibitor status' was defined as consistent non-positive inhibitor measurements for two years or longer. A total of 60/486 (12%) patients tested had a positive inhibitor titre in two or more occasions. Most of the patients (56%) with a maximum inhibitor titre of < 5 Bethesda unit (BU)/ml (named "low titre inhibitor") developed a sustained negative inhibitor status. Among patients with high (5-9.9 BU/ml) and very high (≥ 10 BU/ml) inhibitor titres, the proportions were 50% and 3%, respectively. Our findings suggest that ITI might not be needed for all patients with non-transient inhibitors, especially when their maximum inhibitor titre is below 10 BU/ml. Further studies in countries where ITI is not available are needed to examine predictors of the natural sustained negative inhibitor status.
Grupo de Estudo a Hemostasia e Trombose -- GETHe/UFMG, Belo Horizonte, Brazil.
Camila
C
Caram
Roberta Grazielle
RG
de Souza
Júlio Carepa
JC
de Sousa
Tatiana
T
Araújo Pereira
Ana Maria
AM
do Amaral Cerqueira
Johanna G
JG
van der Bom
Suely Meireles
SM
Rezende
D000293:Adolescent; D000328:Adult; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000276:immunology*; D006467:Hemophilia A / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D007518:Isoantibodies / Q000097:blood*; D008137:Longitudinal Studies; D019370:Observation; D012189:Retrospective Studies; D013995:Time; D017186:Titrimetry; D055815:Young Adult
D001779:Blood Coagulation Factors; D007518:Isoantibodies; D005169:Factor VIII