Recombinant Factor VIIA in the Treatment of Bleeding

Madhu V. Midathada, MD; Paulette Mehta, MD; Milton Waner, MD; Louis M. Fink, MD


Am J Clin Pathol. 2004;121(1) 

In This Article

Renal Failure and Nonhemophilic Bleeding Disorders

Renal Failure

Acute renal failure is associated with uremic platelet dysfunction and leads to impaired primary hemostasis. Bleeding associated with uremia is treated with dialysis, transfusion of cryoprecipitate, desmopressin, and correction of the underlying cause. rFVIIa has been effective short-term symptomatic treatment for controlling the bleeding associated with uremic platelet dysfunction, thrombocytopenia, or both.[72] There has been a report of prompt control of bleeding in a 12-year-old patient with end-stage renal insufficiency.[73]

Nonhemophilic Bleeding Disorders

rFVIIa has been used investigationally in patients with hereditary bleeding disorders other than hemophilia, eg, factor VII deficiency, antibody to other clotting factors, and platelet disorders such as Glanzmann thrombasthenia.

Factor VII deficiency is a rare autosomal bleeding disorder that can cause severe bleeding when levels are below 1%. Treatment consists of FFP, PCCs, or factor VII concentrates. rFVIIa is a useful alternative and seems to be a safe and effective treatment modality. Mariani et al[74] described 17 patients treated for 27 spontaneous bleeding episodes and 7 major and 13 minor surgical interventions. Hemostasis was secured in the 7 major and 13 minor surgical interventions. There were no side effects and no evidence of thrombotic tendency. All bleeding episodes were controlled effectively.[74]

Continuous infusion might be better because repeated doses have to be given because of the short half-life of factor VII.[58,75] Jimenez-Yuste et al[76] describe a 30-year-old woman with moderate factor VII deficiency and HIV infection who underwent cesarean delivery. She had a history of frequent bleeding episodes during childhood, including recurrent epistaxis, bleeding following dental extraction, and melena treated with FFP. She was treated with a bolus dose of rFVIIa before the cesarean section followed by continuous infusion of rFVIIa and did not have any bleeding complications. Wong et al[77] describe an infant with severe factor VII deficiency (factor VII protein, 0% [0.00]) and massive intracranial hemorrhage who was treated successfully with rFVIIa. rFVIIa was well tolerated, hemostasis was effective, and there was a good clinical outcome and no evidence of hypercoagulation.[77] There has been a case report on use of rFVIIa for short-term oral surgery prophylaxis in patients with severe congenital factor VII deficiency.[78] rFVIIa, when used with endometrial ablation, reportedly controlled bleeding in a patient with intractable menorrhagia secondary to factor VII deficiency.[79]

A dose kinetic study with rFVIIa was performed in 5 patients with severe congenital deficiency of factor VII to evaluate the true kinetic parameters of rFVIIa without the interference of factor VII.[80] No differences were observed between the dosages with respect to total body clearance, volume of distribution area, or mean residence time. These findings suggest that the pharmacokinetics of rFVIIa are dose-dependent.

There was another case report on the use of rFVIIa in factor XI deficiency, which could be hereditary or acquired. The patient was a 75-year-old woman with chronic myelomonocytic leukemia and an acquired factor XI deficiency (factor XI level, 5% [0.05]) related to factor XI inhibitor (38 Bethesda units) who needed therapeutic drainage of a pleural effusion. Small doses of rFVIIa were used to achieve hemostasis, and the procedure was done successfully with no adverse effects.[81]

Two siblings affected by type III vWD with precipitating alloantibodies against von Willebrand factor (vWF) were treated effectively with rFVIIa for oral surgery.[82] Grossmann et al[83] reported continuous infusion of rFVIIa in the treatment of a patient with type III vWD and alloantibodies against vWF. A 51-year-old man with type III vWD (factor VIII level, 1% [0.01]; vWF level, <1%; vWF/ristocetin cofactor, <1%) sought care because of recurrent nosebleeds. He was treated with an rFVIIa-based treatment protocol with an initially good response, but subsequently he had a poor response that was managed effectively with a factor VIII—vWF scheme. He was readmitted with another bleeding episode that did not respond to continuous infusion of rFVIIa combined with tranexamic acid.

Another patient with vWD and recurrent gastrointestinal bleeding due to angiodysplasia had inadequate responses to vWF replacement and medical and endoscopic treatment, including resection of the affected bowel and frequent blood transfusions. Therapy with rFVIIa was started at home, and bleeding was controlled rapidly without the need for blood transfusions.[84] An elderly man with life-threatening hematuria and gastrointestinal bleeding due to acquired vWD associated with monoclonal gammopathy of undetermined significance was treated successfully with rFVIIa.[85] There are other case reports supporting the use of rFVIIa in patients with acquired vWD for bleeding or prophylactically during surgery.[86,87]

Bleeding associated with amyloid-associated factor X deficiency might be difficult to control with plasma or PCC. Splenectomy ameliorates factor X deficiency. Administration of rFVIIa achieved hemostasis and made splenectomy feasible in a 63-year-old woman with amyloid-associated factor X deficiency.[88]


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