Differential clot stabilising effects of rFVIIa and rFXIII‐A2 in whole blood from thrombocytopenic patients and healthy volunteers

• Published in: British journal of haematology 2008-11, Vol.143 (4), p.559-569
• Main Authors: Johansson, Pär I., Jacobsen, Niels, Viuff, Dorthe, Olsen, Eva H. N., Rojkjaer, Rasmus, Andersen, Søren, Petersen, Lars C., Kjalke, Marianne
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Cell Count; Blood Coagulation - drug effects; Dose-Response Relationship, Drug; factor VIIa; Factor VIIa - pharmacology; factor XIII; Factor XIIIa - pharmacology; Fibrinolysis - drug effects; Hematologic and hematopoietic diseases; Humans; Medical sciences; Platelet diseases and coagulopathies; Recombinant Proteins - pharmacology; Stem Cell Transplantation; thrombelastography; Thrombelastography - methods; thrombocytopenia; Thrombocytopenia - blood; Thrombocytopenia - therapy
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2008.07379.x

Summary 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 of rFVIIa 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 and rFXIII‐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 μg/ml). rFVIIa only modestly improved anti‐fibrinolysis, whereas rFXIII‐A2 (0–20 μg/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.