Monitoring Recombinant Factor VIIa Treatment: Efficacy Depends on High Levels of Fibrinogen in a Model of Severe Dilutional Coagulopathy

Objectives: Recombinant activated factor VII (rFVIIa) is increasingly being given to treat massive bleeding. However, there is no clear guidance on which patients are suitable for treatment and how the effects of treatment should be monitored. The aim of this in vitro study was to assess the coagulation status of severely hemodiluted blood samples before and after treatment with therapeutic doses of rFVIIa and/or fibrinogen with 2 viscoelastic point-of-care coagulation analyzers: ROTEM (Pentapharm GmbH, Munich, Germany) and Sonoclot (Sienco Inc, Arvada, CO).

Design: Laboratory study.

Setting: Research coagulation laboratory.

Participants: Ten healthy male volunteers without hereditary or acquired coagulation disorders.

Interventions: Blood samples were obtained. After severe hemodilution with albumin 5%, therapeutic doses of rFVIIa and/or fibrinogen were added, and the coagulation status was assessed with new 1:1,000 diluted tissue factor–activated tests from ROTEM and Sonoclot.

Measurements and Main Results: The administration of therapeutic doses of rFVIIa to hemodiluted samples shortened the initiation phase of coagulation only. Isolated fibrinogen administration to physiologic levels improved both the initiation of coagulation as well as clot formation and strength. Combined fibrinogen and rFVIIa administration further improved both effects.

Conclusions: ROTEM and Sonoclot were able to monitor the effects of rFVIIa and fibrinogen administration with 1:1,000 diluted tissue factor–activated tests. The efficacy of rFVIIa was largely dependent on the presence of high levels of fibrinogen in reversing this severe dilutional coagulopathy.

Key Words: recombinant activated factor VII, fibrinogen concentrate, hemodilution, dilutional coagulopathy, thromboelastography, thromboelastometry, ROTEM, Sonoclot analyzer