Can Intravesical Instillation of Recombinant Activated Factor VII (rFVIIa) and Aminocaproic Acid (AA) Stop Bleeding in Hemorrhagic Cystitis?

Hemorrhagic cystitis (HC) is a serious complication of hematopoietic stem cell transplant (HSCT) caused by toxic effects of the conditioning regimen and/or viral reactivation. Treatment of HC is supportive and most interventions result in only transient hemostasis. rFVIIa is a potent procoagulant and is FDA approved for use in patients with Hemophilia. Intravenous rFVIIa has been used off-label to establish hemostasis in multiple conditions. Intravenous rFVIIa in patients with HC has been shown to briefly stop the bleeding. We successfully used intravesical installation of rFVIIa to stop bleeding in patients with post-transplant HC. Pediatric patients with post-transplant HC were treated with intravesical rFVIIa. The bladder was irrigated by normal saline (NS) until clear outflow was achieved; then rFVIIa (~ 50mcg/kg) was instilled in 50-100 ml of NS and dwelled for 1-2 hours. The intravesical instillation of rFVIIa resulted in hemostasis, however it took several days for the bleeding to completely stop. To enhance hemostasis, we instilled 4 gm of AA in 50-100 ml of NS immediately after the rFVIIa was drained and dwelled AA for 1-2 hours. The addition of AA lead to effective hemostasis and development of intravesical clot. Intravesical instillation and dwelling of rFVIIa followed by instillation and dwelling of AA safely and effectively stops HC post HSCT. Based on this experience we are developing a standardized protocol to treat post-transplant HC in the early stages of its development.