Differential clot stabilising effects of rFVIIa and rFXIII-A2 in whole blood from thrombocytopenic patients and healthy volunteers
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
The haemostatic effect of recombinant activated factor VII (rFVIIa;NovoSeven) in thrombocytopenic patients has been a matter of controversy. Haemostasis by rFVIIa occurs via FVIIa-mediated thrombin generation in a platelet-dependent manner and may therefore be suboptimal in patients without functional platelets. Under such conditions, a clot-stabilizing agent, such as factor XIII (FXIII), may supplement the effect ofrFVIIa and improve haemostasis. Recombinant factor XIII (rFXIII-A2) is produced as an A2 homodimer of the FXIII A subunit and is equivalent to cellular FXIII normally found in platelets. The combined effects of rFVIIa andrFXIII-A2 were evaluated in clot lysis assays using factor XIII-deficient plasma and by whole blood thrombelastography (TEG) analysis from normal donors and thrombocytopenic stem cell transplantation patients. Clotting time was shortened by rFVIIa (0.6-10 microg/ml). rFVIIa only modestly improved anti-fibrinolysis,whereas rFXIII-A2 (0-20 microg/ml) enhanced anti-fibrinolysis without effect on clotting time. TEG analysis showed rFVIIa shortened the clotting time, and enhanced clot development, maximal mechanical strength and resistance to fibrinolysis, whereas, rFXIII-A2 enhanced clot development,maximal mechanical strength and markedly enhanced resistance to fibrinolysis. These data illustrate that rFVIIa and rFXIII-A2 contribute to clot formation and stability by different mechanisms suggesting enhanced haemostatic efficacy by combining these agents
Udgivelsesdato: 2008/11
Udgivelsesdato: 2008/11
Originalsprog | Engelsk |
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Tidsskrift | British Journal of Haematology |
Vol/bind | 143 |
Udgave nummer | 4 |
Sider (fra-til) | 559-569 |
Antal sider | 10 |
ISSN | 0007-1048 |
Status | Udgivet - 2008 |
ID: 10906442