Abstract
Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~ 2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 116-122 |
| Number of pages | 7 |
| Journal | Thrombosis Research |
| Volume | 132 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2013 |
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Keywords
- Factor VII
- Factor VII deficiency
- Factor VIIa
- Plasmin generation
- Rare Bleeding Disorder
- Thrombin generation
ASJC Scopus subject areas
- Hematology
Cite this
Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients. / Van Geffen, Mark; Mathijssen, Natascha C J; Holme, Pål A.; Laros-Van Gorkom, Britta A P; Van Kraaij, Marian G J; Masereeuw, Roselinde; Peyvandi, Flora; Van Heerde, Waander L.
In: Thrombosis Research, Vol. 132, No. 1, 07.2013, p. 116-122.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients
AU - Van Geffen, Mark
AU - Mathijssen, Natascha C J
AU - Holme, Pål A.
AU - Laros-Van Gorkom, Britta A P
AU - Van Kraaij, Marian G J
AU - Masereeuw, Roselinde
AU - Peyvandi, Flora
AU - Van Heerde, Waander L.
PY - 2013/7
Y1 - 2013/7
N2 - Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~ 2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy.
AB - Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~ 2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy.
KW - Factor VII
KW - Factor VII deficiency
KW - Factor VIIa
KW - Plasmin generation
KW - Rare Bleeding Disorder
KW - Thrombin generation
UR - http://www.scopus.com/inward/record.url?scp=84881310127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881310127&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2013.04.021
DO - 10.1016/j.thromres.2013.04.021
M3 - Article
C2 - 23731565
AN - SCOPUS:84881310127
VL - 132
SP - 116
EP - 122
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 1
ER -