The long-term course of factor VIII inhibitors in patients with congenital haemophilia A without immune tolerance induction

Camila Caram; Roberta Grazielle de Souza; Júlio Carepa de Sousa; Tatiana Araújo Pereira; Ana Maria do Amaral Cerqueira; Johanna G. van Der Bom; Suely Meireles Rezende

doi:10.1160/TH10-04-0231

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(01): 59-65
DOI: 10.1160/TH10-04-0231

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

The long-term course of factor VIII inhibitors in patients with congenital haemophilia A without immune tolerance induction

Authors

Camila Caram

¹Grupo de Estudo da Hemostasia e Trombose – GETHe/UFMG, Belo Horizonte, Brazil
Roberta Grazielle de Souza

²Prefeitura de Pará de Minas, Pará de Minas, Brazil
Júlio Carepa de Sousa

³Target M&E Consultoria, Belo Horizonte, Brazil
Tatiana Araújo Pereira

⁴Sulamérica, São Paulo, Brazil
Ana Maria do Amaral Cerqueira

⁵Fundação HEMOMINAS, Belo Horizonte, Brazil
Johanna G. van Der Bom

⁶Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
Suely Meireles Rezende

⁷Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

Abstract

Summary

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.

Keywords

Haemophilia - inhibitor - alloantibody - factor VIII - natural history

Full Text

References

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