Successful outcome of DIC and life-threatening bleeding in a toddler with neuroblastoma treated with recombinant activated factor VII

Abstract

Bleeding in disseminated intravascular coagulation (DIC) associated with advanced or metastatic tumors is often difficult to control by conventional methods [1]. The standard treatment includes red blood cells, (RBC), fresh frozen plasma (FFP), cryoprecipitate, and platelet concentrates. However, such replacement therapy is associated with increased risks of morbidity and mortality [2]. Sallah et al. [1] reported the use of rFVIIa in 18 patients with cancer and bleeding secondary to DIC; 15 of them responded to the treatment with improvement in coagulation laboratory data and arrest in bleeding. Here we report on the use of rFVIIa in a 16-month-old boy with metastatic bilateral neuroblastoma and massive bleeding secondary to DIC. The boy presented with pallor and abdominal distension, due to a large palpable mass. Image studies revealed an unresectable extending bilaterally tumor with lymph node involvement and bone marrow infiltration. Fine-needle biopsy confirmed the diagnosis of neuroblastoma; chemotherapy with the Rapid-COJEC protocol (vincristine, carboplatin, etoposide, dexamethasone) was proceeded. On day 7, bleeding (petechiae, ecchymoses) suggested the DIC diagnosis, confirmed by laboratory data (see Table 1). Treatment with RBC, PLT, and FFP was started. On day 10, since worsening of the haemorrhagic picture had occurred, replacement therapy with antithrombin concentrate and cryoprecipitates were administered. The patient despite concurrent treatment of the underlying malignancy over a 5-day period did not respond to the treatment. Life threatening bleeding with severe coagulopathy forced us to use rFVIIa, at a dose of 60 lg/kg per day. Bleeding stopped and the coagulation parameters improved over a 48-h period. Treatment with rFVIIa lasted for 8 days. Prothrombin time, activated thromboplastin time, and fibrinogen levels normalized shortly, while D-dimer levels normalized 10 days later. The patient successfully completed the chemotherapy protocol. Activated recombinant factor VII (rFVIIa/Novoseven , Novo Nordisk, Bagsvaerd, Denmark) is a novel hemostatic agent with a potential role in treatment of bleeding with congenital and acquired coagulopathies [3]. Since the first report in 1999, the use of rFVIIa in an exsanguinating trauma patient [4], an increasing number of case series and reports described its efficacy in a broad spectrum of clinical situations with bleeding, including patients without prior coagulopathy [5–9]. In some of these cases, cessation of bleeding has been dramatic. The hemostatic efficacy of rFVIIa is thought to be as the result of activated platelets binding to the surface with subsequent activation of factor X and generation of thrombin leading to the formation of a haemostatic plug. The action of rFVIIa is localized to the area of vascular injury, where tissue factor (TF) is expressed and activated platelets are found [10]. Administration of a high dose of rFVIIa results in huge increase in VIIa level, causing faster and higher thrombin generation. In addition to the pharmacological concentrations, rFVIIa binds to the phospholipid membrane of activated platelets, FX, and FIX even without the presence of TF which further augments the coagulation process [11]. The localized E. S. Hatzipantelis V. Sidi E. Papakonstantinou D. E. Koliouskas Paediatric Oncology Department, ‘‘Hippokration’’ General Hospital of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece