title: Sequential therapy with activated prothrombin complex concentrates and recombinant FVIIa in patients with severe haemophilia and inhibitors: update of our previous experience.
abstract: Haemophilia patients with inhibitors can develop bleeding episodes, which are refractory to monotherapy with either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrates (APCC). Management of such bleeds is often difficult. We previously reported the safety of using a combination of rFVIIa and APCC given in sequential fashion. In this report, we update our experience with sequential therapy. A retrospective review of medical records was conducted including all reports of sequential therapy defined as receiving both rFVIIa and APCC within 6 h. Data extracted included demographic data, treatment prior to and following hospital admission, clinical data including type and location of bleed, response to therapy, physical examination and laboratory data. In addition, for some patients, thromboelastography was performed to document the effect of sequential therapy on clot formation characteristics. Four patients comprising 35 admissions, 209 hospital days and 115 days of sequential therapy were included in the updated dataset. No patient developed thrombosis or overt disseminated intravascular coagulation (DIC) although elevations in the D-dimer above 5 microg mL(-1) were noted in 42% of the courses that lasted >3 days. Efficacy is suggested by the fact that patients had resolution of their bleeds after a median of 3 days of sequential therapy after failing to respond to a median of 3 days of monotherapy. Thromboelastography demonstrated an additive effect. Sequential therapy is a safe, potentially efficacious approach in the management of refractory bleeding episodes in patients with haemophilia and inhibitors.
authors.affiliation: Department of Pediatric Hematology, Children's Hospital of Orange County, Orange, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Schneiderman
authors.forename: E
authors.initials: E
authors.lastname: Rubin
authors.forename: D J
authors.initials: DJ
authors.lastname: Nugent
authors.forename: G
authors.initials: G
authors.lastname: Young
mesh_terms: D004359:Drug Therapy, Combination; D005164:Factor IX / Q000037:antagonists & inhibitors*; D005165:Factor V / Q000627:therapeutic use*; D005167:Factor VII / Q000627:therapeutic use*; D015942:Factor VIIa; D015951:Factor Xa / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; C022475:prothrombinase complex; D005165:Factor V; D005167:Factor VII; D005164:Factor IX; C103587:recombinant FVIIa; D015942:Factor VIIa; D015951:Factor Xa