title: Combined treatment with APCC (FEIBA®) and tranexamic acid in patients with haemophilia A with inhibitors and in patients with acquired haemophilia A--a two-centre experience.
abstract: The management of bleeding in haemophilia patients with inhibitors can be challenging when using monotherapy with either activated prothrombin complex concentrate (APCC) or recombinant activated FVII (rFVIIa) fail. The antifibrinolytic agent tranexamic acid (TXA) increases clot stability and is used concomitantly with coagulation factor replacement to improve haemostasis in haemophilia patients without inhibitors in many countries in Europe. Combined treatment with TXA and rFVIIa is not contraindicated in haemophilia patients with inhibitors. However, the combined approach of TXA and APCC has not been investigated due to safety concerns of increased risk of thrombosis or disseminated intravasal coagulation (DIC). The aim of this study is to report our experience of concomitant use of APCC and TXA in haemophilia A patients with inhibitor and in patients with acquired haemophilia A with respect to safety and efficacy. Seven (n = 6) haemophilia A patients with inhibitors and one (n = 1) with acquired haemophilia A from Oslo (Norway) and Stockholm (Sweden) were included in the study. The APCC was given at doses consistent to the manufacturers' recommendation. TXA was administered concomitantly either 10 mg kg(-1) every 6-8 h intravenously or 20 mg kg(-1) every 6-8 h orally. Haemostatic response was assessed by thromboelastography (TEG) and thrombin generation assay (TGA) in three of the patients. A total number of three bleeding episodes and two minor and six major surgical procedures were performed under the coverage with APCC and TXA. Haemostatic outcome was rated excellent or good in 10 of 11 (91%) treatment episodes. One episode was rated with poor effect. No episodes of arterial, venous thrombosis or DIC occurred during or after the treatment. Data from TEG and TGA analysis showed no signs of hypercoagulability following the combined treatment. This report demonstrates that, in a limited number of patients, combined treatment with APCC and TXA seemed to be safe, tolerated and relatively effective in management of bleeding episodes and in preventing haemorrhage during surgery in haemophilia patients with inhibitors and in a patient with acquired haemophilia A. Further studies should be performed to confirm these data.
authors.affiliation: Coagulation Unit, Hematology Centre Karolinska University Hospital, Stockholm, Sweden. margareta.holmstrom@karolinska.se
authors.forename: M
authors.initials: M
authors.lastname: Holmström
authors.forename: H T T
authors.initials: HT
authors.lastname: Tran
authors.forename: P A
authors.initials: PA
authors.lastname: Holme
mesh_terms: D000328:Adult; D000368:Aged; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood; D001779:Blood Coagulation Factors / Q000494:pharmacology / Q000627:therapeutic use*; D003029:Coagulants / Q000494:pharmacology / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013916:Thrombelastography / Q000187:drug effects; D013917:Thrombin / Q000187:drug effects; D014148:Tranexamic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D003029:Coagulants; D014148:Tranexamic Acid; C065655:anti-inhibitor coagulant complex; D013917:Thrombin