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(Stroke. 2009;40:2882.)
© 2009 American Heart Association, Inc.

Research Letters

Tissue Factor in Brain Is Not Saturated With Factor VIIa

Implications for Factor VIIa Dosing in Intracerebral Hemorrhage

Maureane Hoffman, MD, PhD Dougald M. Monroe, PhD

From the Pathology & Laboratory Medicine Service, Durham VA Medical Center, Durham, NC; and the Division of Hematology/Oncology, University of North Carolina, Chapel Hill.

Correspondence to Dr Maureane Hoffman, Pathology & Laboratory Medicine Service (113), Durham VA Medical Center, 508 Fulton St, Durham, NC 27705. E-mail maureane.hoffman@med.va.gov

Key Words: hemorrhage • stroke • histology • blood coagulation • factor VIIa

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The recent commentary by Dr Torbey on "Intracerebral Hemorrhage: What’s Next?"¹ has prompted us to share some data and thoughts on the use of activated factor VII (FVIIa, NovoSeven, Novo Nordisk A/S) in the management of intracerebral hemorrhage. FVIIa is approved to promote hemostasis in hemophiliacs with inhibitors. Studies have also suggested that it promotes hemostasis in nonhemophilic patients with bleeding attributable to trauma² or with intracranial hemorrhage.³

The commercial FVIIa product is the activated form of the naturally occurring human protein. The precursor, FVII, is readily activated by a number of coagulation and noncoagulation proteases once it has bound to its cofactor, tissue factor (TF). FVIIa has little proteolytic activity in solution. Binding to a suitable phospholipid surface enhances its activity somewhat, but binding to TF greatly enhances proteolytic activity toward its substrates, FIX and FX. Plasma levels of FVIIa are normally around 100 pmol/L.⁴ Because of the very low activity exhibited by FVIIa in the absence of TF and the very high affinity of TF for FVII, it is thought that FVIIa only exhibits significant activity in vivo when complexed to TF. Exogenous FVIIa was originally thought to enhance hemostasis by increasing activation of FX by the TF pathway. However, very high levels of FVIIa are required to promote hemostasis in hemophilia: up to 1000x the normal plasma level and much more than should be needed to saturate the available TF. Evidence has now accumulated from in vitro, ex vivo, and animal studies to suggest that at . . . [Full Text of this Article]