title: Use of prothrombin complex concentrates and activated prothrombin complex concentrates as prophylactic therapy in haemophilia patients with inhibitors.
abstract: Haemophilia patients with inhibitors are treated for acute bleeding with prothrombin complex concentrates (PCCs) or activated prothrombin complex concentrates (aPCCs). Despite this therapy, patients with high-level inhibitors are at increased risk of developing devastating joint disease. This paper examines available information that supports the study of PCCs and/or aPCCs as prophylactic therapy for haemophilia patients with inhibitors. This strategy would require that PCCs or aPCCs be administered repetitively in a dose that is sufficient to prevent haemarthrosis without causing thrombogenic events, or causing anamnestic response in inhibitor titre. PCC doses ranging from 30 to 50 U kg-1 every other day for up to 8 months have resulted in subjective improvement both in bleeding associated with target joints and in the management of chronic joint inflammation. aPCC doses as low as 50-100 U kg-1 every other day have been useful in postsurgical prophylaxis. The risk of developing a myocardial infarction or clinically relevant disseminated intravascular coagulation is linked to total dosages of either PCCs or aPCCs greater than 200 U kg-1 day-1. It is uncertain what anamnestic response would result from prophylaxis, but with typical therapy the aPCCs cause such a response in only a small percentage of patients. Based on these findings, a clinical trial of these products used in doses of 50-100 U kg-1 every other day would appear to be warranted in patients who have permanent inhibitors and frequent joint bleeding.
authors.affiliation: Tulane University School of Medicine, Section of Hematology/Medical Oncology, New Orleans, LA 70122, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Leissinger
mesh_terms: D001779:Blood Coagulation Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006395:Hemarthrosis / Q000517:prevention & control*; D006467:Hemophilia A / Q000517:prevention & control* / Q000628:therapy*; D006801:Humans; D007518:Isoantibodies / Q000009:adverse effects*; D013927:Thrombosis / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D001779:Blood Coagulation Factors; D007518:Isoantibodies; C025667:prothrombin complex concentrates