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Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors.
Haemophilia. 2014 Jan; 20(1):e7-14.H

Abstract

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.

Authors+Show Affiliations

CUCEI, Universidad de Guadalajara, Guadalajara, Jalisco, México; Doctorado en Genética Humana, CUCS, Universidad de Guadalajara, Guadalajara, Jalisco, México.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24354488

Citation

Luna-Záizar, H, et al. "Thrombin Generation as Objective Parameter of Treatment Response in Patients With Severe Haemophilia a and High-titre Inhibitors." Haemophilia : the Official Journal of the World Federation of Hemophilia, vol. 20, no. 1, 2014, pp. e7-14.
Luna-Záizar H, Beltrán-Miranda CP, Esparza-Flores MA, et al. Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors. Haemophilia. 2014;20(1):e7-14.
Luna-Záizar, H., Beltrán-Miranda, C. P., Esparza-Flores, M. A., Soto-Padilla, J., Bergés-García, A., Rodríguez-Zepeda, M. D., Pompa-Garza, M. T., & Jaloma-Cruz, A. R. (2014). Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors. Haemophilia : the Official Journal of the World Federation of Hemophilia, 20(1), e7-14. https://doi.org/10.1111/hae.12309
Luna-Záizar H, et al. Thrombin Generation as Objective Parameter of Treatment Response in Patients With Severe Haemophilia a and High-titre Inhibitors. Haemophilia. 2014;20(1):e7-14. PubMed PMID: 24354488.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thrombin generation as objective parameter of treatment response in patients with severe haemophilia A and high-titre inhibitors. AU - Luna-Záizar,H, AU - Beltrán-Miranda,C P, AU - Esparza-Flores,M A, AU - Soto-Padilla,J, AU - Bergés-García,A, AU - Rodríguez-Zepeda,M D C, AU - Pompa-Garza,M T, AU - Jaloma-Cruz,A R, PY - 2013/10/07/accepted PY - 2013/12/21/entrez PY - 2013/12/21/pubmed PY - 2014/8/13/medline KW - bypass therapy KW - inhibitor kinetics KW - inhibitor therapy KW - severe haemophilia A KW - thrombin generation assay KW - treatment response SP - e7 EP - 14 JF - Haemophilia : the official journal of the World Federation of Hemophilia JO - Haemophilia VL - 20 IS - 1 N2 - 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. SN - 1365-2516 UR - https://www.unboundmedicine.com/medline/citation/24354488/Thrombin_generation_as_objective_parameter_of_treatment_response_in_patients_with_severe_haemophilia_A_and_high_titre_inhibitors_ L2 - https://doi.org/10.1111/hae.12309 DB - PRIME DP - Unbound Medicine ER -