title: Parallel use of by-passing agents in haemophilia with inhibitors: a critical review.
abstract: In the absence of new outbreaks of transfusion-related infections, the occurrence of neutralizing antibodies currently remains the most prominent complication in haemophilia. Coagulation factor products that may circumvent the inadequate activation of factor X in classical haemophilia, often referred to as bypassing agents, have demonstrated a high degree of efficacy. A smaller number of patients have been described in whom either bypassing agent, or both, demonstrate diminished efficacy. In those cases, the use of both bypassing agents in parallel was attempted, either using simultaneous (combined) or alternating (sequential) infusion of the two drugs, reportedly with successful haemostasis. We speculated whether such treatment might cause thromboembolism. A thorough literature search disclosed 17 reports regarding the parallel use of bypassing agents in the same bleeding episode in 49 patients; reporting nine patients with acquired haemophilia and forty patients with congenital haemophilia with inhibitors. Notable incidences of thromboembolic manifestations were observed: in nine patients with acquired haemophilia, five and in 40 patients with congenital haemophilia five suffered from significant thrombotic complications, and overall four cases were fatal. Although efficacy of parallel treatment was reported excellent in most cases, thromboembolism is rare in haemophilia and parallel treatment with activated prothrombin complex concentrate and activated recombinant human factor VII appears to increase the risk of thrombosis in these patients.
authors: Centre for Haemophilia and Thrombosis, University Hospital Skejby/Aarhus, University of Aarhus, Aarhus, Denmark. Ingerslev@ki.au.dk
authors: Jørgen
authors: J
authors: Ingerslev
authors: Benny
authors: B
authors: Sørensen
mesh_terms: D001779:Blood Coagulation Factors / Q000009:adverse effects / Q000627:therapeutic use*; D005164:Factor IX / Q000276:immunology; D005169:Factor VIII / Q000276:immunology; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced / Q000453:epidemiology; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D007518:Isoantibodies; D011994:Recombinant Proteins; C036309:fibrin fragment D; D005169:Factor VIII; D005164:Factor IX; C103587:recombinant FVIIa; C065655:anti-inhibitor coagulant complex; D015942:Factor VIIa