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Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by the use of clot waveform analysis.
J Thromb Haemost. 2014; 12(3):355-62.JT

Abstract

BACKGROUND

Assays to determine the optimal hemostatic effects of bypass therapy in hemophilia A (HA) patients with inhibitors are difficult to compare. Clot waveform analysis (CWA), based on the continuous monitoring of routine coagulation parameters (prothrombin time/activated partial thromboplastin time), offers a useful method for assessing global clotting function.

OBJECTIVES

To investigate the technique of CWA for the hemostatic monitoring of bypass therapy in HA patients with inhibitors.

METHODS AND RESULTS

Ellagic acid (Elg), tissue factor (TF) or both (Elg/TF) were used as trigger reagents in CWA. The standard parameters - clot time (CT), maximum coagulation velocity (|min1|), and acceleration (|min2|) - were recorded. Optimal monitoring was defined as: (i) a significant difference in these parameters between plasma from HA patients with inhibitors and normal plasmas; and (ii) a significant improvement in these indices in HA patients with inhibitors after bypass therapy. Experiments in vitro demonstrated that there were significant differences between plasma from HA patients with inhibitors and normal plasma with various triggers, in the order Elg > Elg/TF >> TF. Addition of therapeutically achievable concentrations of bypassing agents, however, showed significant improvements in the different parameters only with Elg/TF, suggesting that this reagent provided the most appropriate assay. A total of 20 plasmas from HA patients with inhibitors in which bypassing agents were infused were evaluated ex vivo by Elg/TF CWA. The postinfusion parameters CT and |min2| reflected clinical effects, and were close to normal levels. Furthermore, Elg/TF CWA facilitated quantitative evaluation of perioperative hemostatic management of bypass therapy in HA patients with inhibitors.

CONCLUSIONS

CWA is a promising method for the quantitative monitoring of bypass therapy during routine automated clotting assays with a modified trigger reagent comprising a well-balanced mixture of Elg and TF.

Authors+Show Affiliations

Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.No 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

24354697

Citation

Haku, J, et al. "Optimal Monitoring of Bypass Therapy in Hemophilia a Patients With Inhibitors By the Use of Clot Waveform Analysis." Journal of Thrombosis and Haemostasis : JTH, vol. 12, no. 3, 2014, pp. 355-62.
Haku J, Nogami K, Matsumoto T, et al. Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by the use of clot waveform analysis. J Thromb Haemost. 2014;12(3):355-62.
Haku, J., Nogami, K., Matsumoto, T., Ogiwara, K., & Shima, M. (2014). Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by the use of clot waveform analysis. Journal of Thrombosis and Haemostasis : JTH, 12(3), 355-62. https://doi.org/10.1111/jth.12488
Haku J, et al. Optimal Monitoring of Bypass Therapy in Hemophilia a Patients With Inhibitors By the Use of Clot Waveform Analysis. J Thromb Haemost. 2014;12(3):355-62. PubMed PMID: 24354697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by the use of clot waveform analysis. AU - Haku,J, AU - Nogami,K, AU - Matsumoto,T, AU - Ogiwara,K, AU - Shima,M, PY - 2013/08/21/received PY - 2013/12/21/entrez PY - 2013/12/21/pubmed PY - 2014/11/15/medline KW - blood coagulation factor inhibitors KW - clinical laboratory techniques KW - factor VIII KW - hemophilia A KW - hemostatic techniques SP - 355 EP - 62 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 12 IS - 3 N2 - BACKGROUND: Assays to determine the optimal hemostatic effects of bypass therapy in hemophilia A (HA) patients with inhibitors are difficult to compare. Clot waveform analysis (CWA), based on the continuous monitoring of routine coagulation parameters (prothrombin time/activated partial thromboplastin time), offers a useful method for assessing global clotting function. OBJECTIVES: To investigate the technique of CWA for the hemostatic monitoring of bypass therapy in HA patients with inhibitors. METHODS AND RESULTS: Ellagic acid (Elg), tissue factor (TF) or both (Elg/TF) were used as trigger reagents in CWA. The standard parameters - clot time (CT), maximum coagulation velocity (|min1|), and acceleration (|min2|) - were recorded. Optimal monitoring was defined as: (i) a significant difference in these parameters between plasma from HA patients with inhibitors and normal plasmas; and (ii) a significant improvement in these indices in HA patients with inhibitors after bypass therapy. Experiments in vitro demonstrated that there were significant differences between plasma from HA patients with inhibitors and normal plasma with various triggers, in the order Elg > Elg/TF >> TF. Addition of therapeutically achievable concentrations of bypassing agents, however, showed significant improvements in the different parameters only with Elg/TF, suggesting that this reagent provided the most appropriate assay. A total of 20 plasmas from HA patients with inhibitors in which bypassing agents were infused were evaluated ex vivo by Elg/TF CWA. The postinfusion parameters CT and |min2| reflected clinical effects, and were close to normal levels. Furthermore, Elg/TF CWA facilitated quantitative evaluation of perioperative hemostatic management of bypass therapy in HA patients with inhibitors. CONCLUSIONS: CWA is a promising method for the quantitative monitoring of bypass therapy during routine automated clotting assays with a modified trigger reagent comprising a well-balanced mixture of Elg and TF. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/24354697/Optimal_monitoring_of_bypass_therapy_in_hemophilia_A_patients_with_inhibitors_by_the_use_of_clot_waveform_analysis_ L2 - https://doi.org/10.1111/jth.12488 DB - PRIME DP - Unbound Medicine ER -