Novel Applications of Recombinant Factor VIIa for the Management of Pediatric Coagulopathic Diseases

Abstract

Recombinant factor VIIa (rFVIIa) was envisioned for the treatment of bleeding in hemophilia patients with inhibitors. In response to tissue factor expressed upon vessel wall injury, rFVIIa amplifies the thrombin burst primarily on membrane surfaces, including activated platelets. Because it is functional at a key point in the clotting cascade, rFVIIa shows promise as a therapeutic option for various bleeding situations. The prothrombin time (PT) is often used as a surrogate to monitor rFVIIa therapy. Using laboratory and clinical measures of outcome, the use of rVIIa as a therapeutic option in treating several different pediatric coagulopathic conditions is described.

The use of recombinant activated factor VII in pediatric coagulation disorders

“…No toxicity or adverse events were reported with the use of rFVIIa 86 . The author’s experience with the use of rFVIIa in non‐hemophilia situations have been previously reported 44,87 …”

“…Advantages to the use of rFVIIa include the rapid onset of action of rFVIIa (about 10 minutes), the low risk of thrombogenicity in this population, the low‐volume dosing leading to rapid administration without risk of fluid overload, especially in the postoperative setting and in preterm infants, and the recombinant nature of the product that alleviates infectious disease issues compared with FFP and other blood products 3,83,87,88 . Limitations to the use of rFVIIa exist, and include its substantial cost, the risk of thrombosis, the variability of current dose and dosing intervals especially in the non‐hemophilia bleeding situations, a short plasma half‐life in children that translates to frequent dosing, limited or no randomized trials on efficacy in non‐hemophilia situations, and limited safety data and data on dosing outside of the hemophilia arena.…”

Successful Treatment of Acute Lymphoblastic Leukemia With L-Asparaginase-Induced Intracranial Hemorrhage to Activated Recombinant Factor Viia in a Child

“…In recent years, recombinant factor VIIa has been shown to be effective in managing severe life-threatening bleeding in nonhemophilia patients [13][14][15][16][17], with no significant adverse events being reported. Mortality was reported as high as 30-40% in intracranial bleedings [18] and anticoagulant and antiplatelet drugs have been used in the prevention of thromboembolic events, with the trade-off of bleeding side effects.…”

Unlabeled uses of factor VIIa (recombinant) in pediatric patients

“…25 No patient had complete cessation of bleeding after the first dose, but all had reduced blood product requirements. Eleven case reports and case series involving 33 patients with coagulopathies have been published, [27][28][29][30][31][32][33][34][35][36][37] with the most common coagulopathy being Glanzmann thrombasthenia, a rare congenital disorder of platelet function. Almeida et al 33 studied 7 patients age 2.5-11 years with inherited platelet disorders, 5 of whom were diagnosed with Glanzmann thrombasthenia.…”

“…Thirteen other bleeding episodes occurred; 11 were rated as having excellent responses. A case series by Mathew et al 37 included 5 patients, age eight days to 15 years, given factor VIIa (recombinant) at a dose of 25-100 µg/kg for up to five days for the prevention or treatment of bleeding after surgery. All patients received additional therapies, including FFP, PRBCs, cryoprecipitate, phytonadione, or aminocaproic acid, and all had an excellent recovery.…”