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Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care

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The Coagulation Cascade: rFVIIa Mechanism of Action

rFVIIa is a form of human factor VII produced by recombinant technology. The molecule is 406 amino acids in length and has a molecular weight of 50 kDa. As a protein-based therapy, it must be given intravenously to facilitate coagulation at sites of bleeding and has a half-life of 2.5 hours. This intravenously delivered product works as a potent procoagulant by effectively bypassing parts of the clotting process normally required for clotting. rFVIIa helps to promote clotting in two ways:

  1. At physiologic levels and in association with tissue factor (e.g., on damaged tissue), it activates factors IX and X to initiate the clotting leading to formation of a thrombin plug, which allows for clot stability. This normal physiological mechanism suggests that rFVIIa activity is targeted to areas of tissue damage.

  2. In pharmacological doses, it also binds to activated platelets and drives the process of thrombin clot formation forward via factor X activation, even in the absence of tissue factor. This mechanism is relatively specific to areas of tissue damage.

These mechanisms effectively bypass portions of the clotting process that are normally required for clotting to occur. Thus, clotting can occur despite factor deficiencies (in factors VII, VIII, IX, and XI) or when the number or function of platelets is reduced. It can facilitate control of bleeding in situations where standard human blood product transfusions have failed.

While mainly used for hemophilia and related conditions, off-label use of rFVIIa has increased in the hospital setting. Practice patterns have outstripped available evidence as rFVIIa off-label use has transitioned from extraordinarily infrequent use to more common application.