Clinical Experience with Recombinant Factor VIla in Patients with Thrombocytopenia

Abstract

Platelets play a central role in primary hemostasis. The role of the coagulation mechanism during early stages of hemostasis is less clear, although increasing evidence is emerging indicating the ultimate importance of the factor VII (FVII)-tissue factor-dependent coagulation system in providing the first thrombin molecules necessary for the platelet activation to occur. Supporting this, early fibrin formation has been reported to occur within the bleeding time wound and infusion of recombinant FVIIa (rFIIa) has been shown to shorten the bleeding time in rabbits. We have investigated whether infusion of rFVIIa would enhance fibrin formation in bleeding time wounds in patients with thrombocytopenia as reflected by a shortening of the bleeding time. A reduction of the bleeding time was found in 55/105 cases (52%). The decrease was significantly more pronounced when the platelet count exceeded 20 × 10⁹/l. With the exception of an anaphylactoid reaction in 1 patient, no major adverse reactions related to the study drug were observed. Nine infusions of rFVIIa were given to 8 thrombocytopenic patients with overt bleeding. One patient received two infusions. Bleeding decreased in all patients and stopped in 6 patients.

Experiences with recombinant FVIIa in the emergency treatment of patients with autoimmune thrombocytopenia: a review of the literature

“…Thus, the effect observed in all responsive patients and cases can not be solely attributed to rFVIIa. On the other hand, there are a number of reports describing the successful use of rFVIIa to stop bleeding in patients with nonimmune thrombocytopenia [20,27,28,42]. These studies indicate that rFVIIa is effective in the treatment of bleeding in patients with thrombocytopenia and/or thrombocytopathy, without a combination with other hemostatic agents.…”

Effective hemostasis with rFVIIa treatment in two patients with severe thrombocytopenia and life‐threatening hemorrhage

“…It has also been successfully used for the treatment of bleeding in patients with congenital or acquired thrombocytopathies [5À8]. A preliminary phase I/II study demonstrated that rFVIIa reduced the bleeding time in 55 out of 105 patients with thrombocytopenia of various causes [9]. Furthermore administration of rFVIIa to a small cohort of 8 patients with thrombocytopenia and active bleeding resulted in eective hemostasis without any adverse eect [9].…”

Acquired factor VII deficiency in hematopoietic stem cell transplant recipients

“…Novel therapies such as rFVIIa, perhaps combined with antifibrinolytic agents, may result in improved outcomes, particularly in view of recent data documenting the efficacy of rFVIIa in both FVII-deficient and thrombocytopenic patients. [30][31][32] In conclusion, we describe an uncommon form of acquired coagulopathy arising as a complication of highdose chemotherapy and SCT, which contributed to the early demise of several patients undergoing this therapy. Further studies are needed to clearly elucidate the mechanism of this coagulopathy and whether patients with associated bleeding might be candidates for therapy with novel hemostatic agents.…”