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A modified thrombin generation test for investigating very low levels of factor VIII activity in hemophilia A.
Int J Hematol. 2009 Dec; 90(5):576-582.IJ

Abstract

Discrepancies between low levels of FVIII:C and clinical symptoms in severe hemophilia A are well-known. We have recently demonstrated that levels of FVIII:C < 0.2 IU/dl were consistent with clinical phenotype by clot waveform analysis, suggesting that precise measurement of very low levels of FVIII:C was clinically important. Thrombin generation tests (TGTs) triggered by tissue factor (TF) have been recently utilized to monitor coagulation function in hemophilia A. We examined whether TGT was useful for evaluating hemophilia A patients with very low levels of FVIII:C. TGTs in 40 hemophilia A plasmas with FVIII:C < 0.2-17 IU/dl (measured by clot waveform analysis using MDA-II) were performed using TF and/or ellagic acid (ELG). The lagtime in ELG-TGT at very low levels of FVIII:C was shortened dose-dependently, whilst this parameter in TF-TGT was not significantly affected. Other parameters (endogenous thrombin potential, peak thrombin, time to peak) correlated with FVIII:C levels to some extent in both assays (r = 0.4-0.7). Using a TF/ELG mixture in TGT, however, the correlation coefficients increased to ~0.85. TGT parameters correlated well with levels of FVIII:C > 0.2 IU/dl, although the lagtime was not especially informative. We conclude that modified TGT, using a TF/ELG mixture as the trigger, is useful for monitoring coagulation function at very low levels of FVIII:C in hemophilia A.

Authors+Show Affiliations

Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. roc-noga@naramed-u.ac.jp.Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.

Pub Type(s)

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

Language

eng

PubMed ID

19937483

Citation

Matsumoto, Tomoko, et al. "A Modified Thrombin Generation Test for Investigating Very Low Levels of Factor VIII Activity in Hemophilia A." International Journal of Hematology, vol. 90, no. 5, 2009, pp. 576-582.
Matsumoto T, Nogami K, Ogiwara K, et al. A modified thrombin generation test for investigating very low levels of factor VIII activity in hemophilia A. Int J Hematol. 2009;90(5):576-582.
Matsumoto, T., Nogami, K., Ogiwara, K., & Shima, M. (2009). A modified thrombin generation test for investigating very low levels of factor VIII activity in hemophilia A. International Journal of Hematology, 90(5), 576-582. https://doi.org/10.1007/s12185-009-0450-y
Matsumoto T, et al. A Modified Thrombin Generation Test for Investigating Very Low Levels of Factor VIII Activity in Hemophilia A. Int J Hematol. 2009;90(5):576-582. PubMed PMID: 19937483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A modified thrombin generation test for investigating very low levels of factor VIII activity in hemophilia A. AU - Matsumoto,Tomoko, AU - Nogami,Keiji, AU - Ogiwara,Kenichi, AU - Shima,Midori, Y1 - 2009/11/25/ PY - 2009/09/04/received PY - 2009/11/03/accepted PY - 2009/10/19/revised PY - 2009/11/26/entrez PY - 2009/11/26/pubmed PY - 2010/3/20/medline SP - 576 EP - 582 JF - International journal of hematology JO - Int J Hematol VL - 90 IS - 5 N2 - Discrepancies between low levels of FVIII:C and clinical symptoms in severe hemophilia A are well-known. We have recently demonstrated that levels of FVIII:C < 0.2 IU/dl were consistent with clinical phenotype by clot waveform analysis, suggesting that precise measurement of very low levels of FVIII:C was clinically important. Thrombin generation tests (TGTs) triggered by tissue factor (TF) have been recently utilized to monitor coagulation function in hemophilia A. We examined whether TGT was useful for evaluating hemophilia A patients with very low levels of FVIII:C. TGTs in 40 hemophilia A plasmas with FVIII:C < 0.2-17 IU/dl (measured by clot waveform analysis using MDA-II) were performed using TF and/or ellagic acid (ELG). The lagtime in ELG-TGT at very low levels of FVIII:C was shortened dose-dependently, whilst this parameter in TF-TGT was not significantly affected. Other parameters (endogenous thrombin potential, peak thrombin, time to peak) correlated with FVIII:C levels to some extent in both assays (r = 0.4-0.7). Using a TF/ELG mixture in TGT, however, the correlation coefficients increased to ~0.85. TGT parameters correlated well with levels of FVIII:C > 0.2 IU/dl, although the lagtime was not especially informative. We conclude that modified TGT, using a TF/ELG mixture as the trigger, is useful for monitoring coagulation function at very low levels of FVIII:C in hemophilia A. SN - 1865-3774 UR - https://www.unboundmedicine.com/medline/citation/19937483/A_modified_thrombin_generation_test_for_investigating_very_low_levels_of_factor_VIII_activity_in_hemophilia_A_ L2 - https://dx.doi.org/10.1007/s12185-009-0450-y DB - PRIME DP - Unbound Medicine ER -