Activated recombinant factor VII in management of bleeding in patients with thrombocytopenia

The presented study evaluates the feasibility of recombinant activated factor VII (rFVIIa) (NovoSeven) to control bleeding in 28 patients with thrombocytopenia of different etiology (idiopathic thrombocytopenic purpura – 4/28, acute myelocytic leukemia – 10/28, acute lymphoblastic leukemia – 2/28, non-Hodgkin's lymphoma – 8/28, aplastic anemia – 2/28, chronic hepatitis C – 2/28) complicated with hemorrhagic syndrome. The platelet count in the selected group of patients varied from 3 × 10⁹/l to 80 × 10⁹/l (mean 31 × 10⁹/l). Some of the patients suffered from coagulopathy (associated with hepatitis – five cases, associated with sepsis – 10 cases, and associated with bleeding – six cases). All patients experienced severe bleeds: postoperative – eight cases, CNS – seven cases, epistaxis – four cases, gastrointestinal – three cases, pulmonary hemorrhage – one case, after central line placement or other invasive manipulation – five cases. The majority received supportive treatment with FFP and/or PLT and RBC transfusions, which was unsuccessful. A mean dose of 86 mg/kg rFVIIa (range 41–114 mg/kg) was administered as an intravenous bolus injection. Fifteen patients received the treatment once, 11 patients were given a second dose of rFVIIa, and two patients received three doses.

Laboratory haemostatic tests revealed a reduction of the PT of 1.5–2 times compared with the levels before administration of rFVIIa (Table 1). Thromboelastography (TEG) was performed in 18 patients. Before administration of rFVIIa the reaction time (R) was within the normal range, but the kinetic time (K) was prolonged and the maximum amplitude (MA) decreased, both results indicating a low platelet count. After administration of rFVIIa, eight patients appeared to have improved TEG parameters, in seven cases these parameters worsened, and in three cases the TEG parameters remained unchanged (Table 2). In 16 cases bleeding stopped 10–30 min following the injection, and decreased dramatically in six cases. Six patients did not achieve effective hemostasis after administration of rFVIIa. Bleeding reoccurred in seven cases after 6 hours and more following infusion of rFVIIa. In 25 cases no adverse events were reported; two patients developed high temperature (38.7°C and 39.0°C) within 15 min after the injection of rFVIIa. The described observations suggest efficiency of rFVIIa in controlling the postoperative and spontaneous bleeding in patients with various types of thrombocytopenia. Nevertheless, the laboratory tests do not always correlate with clinical efficiency of this treatment.

Table 1

Table 2