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Platelet-dependent coagulation assays for factor VIII efficacy measurement after substitution therapy in patients with haemophilia A.
Platelets. 2006 Sep; 17(6):378-84.P

Abstract

FVIII therapy for haemophilia A is safe and effective, with the problem of individually sufficient efficacy unsettled. Routine one-stage clotting assays and tests employing chromogenic substrates poorly detect individual haemostatic effects of FVIII due to artificial test conditions. In particular, the use of cell-free and diluted plasma samples neglect the crucial role of platelets for thrombin and fibrin formation. To optimize FVIII substitution therapy, we measured in 40 patients with severe to mild haemophilia A before and after FVIII substitution the FVIII activity in cell-free plasma samples using a one-stage clotting assay as well a chromogenic substrate assay and compared the data with those obtained with cell-based coagulation tests, i.e. thrombin generation in platelet-rich plasma (PRP) and thromboelastography (TEG) in samples of citrated whole blood (WB). To determine the maximum ex vivo haemostatic effect we added 1 unit/ml of FVIII to samples of PRP and WB and measured the maximum thrombin generation in the thrombin generation test (TGT) and the maximum clot firmness (MCF) in TEG. After FVIII substitution we observed a nearly linear relation between the individual FVIII activities administered to the patients and the activities measured in the plasma samples. However, data obtained with TGT and TEG revealed a high inter-individual variation and a very poor correlation to the administered FVIII activity. Actually, it could be shown that FVIII substitution yielding in a FVIII plasma activity of about 30% is sufficient to get an ex vivo haemostatic effect of more that 90% as measured by maximum thrombin generation and MCF. FVIII substitution up to a plasma activity of more than 90% did not further enhance the haemostatic effect. Our data clearly demonstrate that the haemostatic effect of FVIII is not only dependent on the activity that is measured in plasma but also depends on the interplay between coagulation and blood cells, in particular with platelets. The use of cell-based coagulation tests such us TGT or TEG may help to optimize FVIII therapy by determining the individual FVIII dosage that produces a maximum haemostatic effect.

Authors+Show Affiliations

GFF/Deutsche Klinik für Diagnostik, Section Haemostasis, Wiesbaden, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

16973498

Citation

Bassus, S, et al. "Platelet-dependent Coagulation Assays for Factor VIII Efficacy Measurement After Substitution Therapy in Patients With Haemophilia A." Platelets, vol. 17, no. 6, 2006, pp. 378-84.
Bassus S, Wegert W, Krause M, et al. Platelet-dependent coagulation assays for factor VIII efficacy measurement after substitution therapy in patients with haemophilia A. Platelets. 2006;17(6):378-84.
Bassus, S., Wegert, W., Krause, M., Escuriola-Ettinghausen, C., Siegemund, A., Petros, S., Scholz, T., Scharrer, I., Kreuz, W., Engelmann, L., & Kirchmaier, C. M. (2006). Platelet-dependent coagulation assays for factor VIII efficacy measurement after substitution therapy in patients with haemophilia A. Platelets, 17(6), 378-84.
Bassus S, et al. Platelet-dependent Coagulation Assays for Factor VIII Efficacy Measurement After Substitution Therapy in Patients With Haemophilia A. Platelets. 2006;17(6):378-84. PubMed PMID: 16973498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Platelet-dependent coagulation assays for factor VIII efficacy measurement after substitution therapy in patients with haemophilia A. AU - Bassus,S, AU - Wegert,W, AU - Krause,M, AU - Escuriola-Ettinghausen,C, AU - Siegemund,A, AU - Petros,S, AU - Scholz,T, AU - Scharrer,I, AU - Kreuz,W, AU - Engelmann,L, AU - Kirchmaier,C M, PY - 2006/9/16/pubmed PY - 2006/12/21/medline PY - 2006/9/16/entrez SP - 378 EP - 84 JF - Platelets JO - Platelets VL - 17 IS - 6 N2 - FVIII therapy for haemophilia A is safe and effective, with the problem of individually sufficient efficacy unsettled. Routine one-stage clotting assays and tests employing chromogenic substrates poorly detect individual haemostatic effects of FVIII due to artificial test conditions. In particular, the use of cell-free and diluted plasma samples neglect the crucial role of platelets for thrombin and fibrin formation. To optimize FVIII substitution therapy, we measured in 40 patients with severe to mild haemophilia A before and after FVIII substitution the FVIII activity in cell-free plasma samples using a one-stage clotting assay as well a chromogenic substrate assay and compared the data with those obtained with cell-based coagulation tests, i.e. thrombin generation in platelet-rich plasma (PRP) and thromboelastography (TEG) in samples of citrated whole blood (WB). To determine the maximum ex vivo haemostatic effect we added 1 unit/ml of FVIII to samples of PRP and WB and measured the maximum thrombin generation in the thrombin generation test (TGT) and the maximum clot firmness (MCF) in TEG. After FVIII substitution we observed a nearly linear relation between the individual FVIII activities administered to the patients and the activities measured in the plasma samples. However, data obtained with TGT and TEG revealed a high inter-individual variation and a very poor correlation to the administered FVIII activity. Actually, it could be shown that FVIII substitution yielding in a FVIII plasma activity of about 30% is sufficient to get an ex vivo haemostatic effect of more that 90% as measured by maximum thrombin generation and MCF. FVIII substitution up to a plasma activity of more than 90% did not further enhance the haemostatic effect. Our data clearly demonstrate that the haemostatic effect of FVIII is not only dependent on the activity that is measured in plasma but also depends on the interplay between coagulation and blood cells, in particular with platelets. The use of cell-based coagulation tests such us TGT or TEG may help to optimize FVIII therapy by determining the individual FVIII dosage that produces a maximum haemostatic effect. SN - 0953-7104 UR - https://www.unboundmedicine.com/medline/citation/16973498/Platelet_dependent_coagulation_assays_for_factor_VIII_efficacy_measurement_after_substitution_therapy_in_patients_with_haemophilia_A_ L2 - https://www.tandfonline.com/doi/full/10.1080/09537100600757448 DB - PRIME DP - Unbound Medicine ER -