Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors
| Autor: | M. D. C. Rodríguez-Zepeda, M. A. Esparza-Flores, Janet Soto-Padilla, Hilda Luna-Záizar, A. R. Jaloma-Cruz, A. Berges-Garcia, M. T. Pompa-Garza, Claudia Patricia Beltrán-Miranda |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Serial dilution Adolescent Haemophilia A Pharmacology Hemophilia A Thrombin generation Young Adult Thrombin Isoantibodies hemic and lymphatic diseases Medicine Humans In patient Child Blood Coagulation Genetics (clinical) Factor VIII biology business.industry Infant Hematology General Medicine Middle Aged medicine.disease Prognosis In vitro Treatment Outcome Child Preschool Immunology biology.protein Analysis of variance Blood Coagulation Tests Antibody business medicine.drug |
| Zdroj: | Haemophilia : the official journal of the World Federation of Hemophilia. 20(1) |
| ISSN: | 1365-2516 |
| Popis: | Summary In Mexico, 15% of haemophilia A (HA) patients develop inhibitory alloantibodies in response to replacement therapy with factor VIII (FVIII), requiring bypass therapy such as activated prothrombin complex concentrate (APCC). Because bypass therapy has not been broadly available in Mexico even in recent years, this study aimed to evaluate the thrombin generation assay (TGA) in assessing the response to FVIII or APCC treatment in patients with severe HA positive to inhibitors. We studied 189 patients with severe HA. Clinical severity was verified by one-stage APTT-based clotting assay. Inhibitors to FVIII were investigated by the Nijmegen–Bethesda (N–B) method, and type of inhibition was assessed through serial plasma dilutions. Thrombin generation was measured with the calibrated automated thrombogram in inhibitor-positive plasmas previously spiked and incubated with FVIII or APCC. Data were analysed using anova, Student or Fisher's exact tests. We detected 47 (24.9%) subjects with high-titre (5–1700 N–B U mL−1) and 25 (13.2%) subjects with low-titre inhibitor antibodies (0.6–4.7 N–B U mL−1). We found an association between kinetic behaviour and clinical response to FVIII (P = 0.0049) or vs. FVIII response evaluated with TGA (P = 0.0007). Global concordance between clinical and in vitro response was 70%. By evaluating the capacity of thrombin formation in a plasma sample, TGA predicts the response to FVIII or APCC therapy and allows individual optimization of resources in patients with severe HA and high-titre inhibitors. The inhibition pattern of the antibodies to FVIII:C correlated with the TGA parameters and showed an association with the clinical response to FVIII. |
| Databáze: | OpenAIRE |
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