Factor concentrates for rare congenital coagulation disorders: where are we now?

Abstract

Introduction: Current treatments of rare coagulation disorders (RCD) include fresh frozen plasma, cryoprecipitates, prothrombin complex concentrates, plasma-derived concentrates and recombinant products. Single-factor concentrates are the therapy of choice since they allow administration of only the defective protein and reduce the risk of transfusion adverse effects. Specific legislation has been developed to stimulate the development of drugs for such rare diseases, the so-called “orphan drugs.”

Areas covered: The focus of this review is on single factor plasma-derived and recombinant concentrates administered in patients with rare congenital coagulation deficiencies. Based on the results of pharmacokinetics, safety and efficacy studies, the pros and cons of each single-factor concentrate in selected RCD are discussed. Factor concentrates currently under development are also reviewed.

Expert opinion: The development of single-factor concentrates for the management of RCD is challenging. These diseases are often poorly classified, misdiagnosed and the evidence based for their management is weak. Reaching the high number of subjects required by some authorities to achieve studies is difficult in such low-prevalence diseases. Alternative therapies such as monoclonal antibodies inhibiting anticoagulant pathway factors, engineered modified factors, peptides inhibitors and DNA or RNA aptamers are promising.

Keywords:

• afibrinogenemia
• coagulation factor deficiency
• dysfibrinogenemia
• hemorrhage
• hypofibrinogenemia
• plasma-derived factor concentrate
• rare coagulation disorders
• recombinant factor concentrate
• thrombosis

Article highlights.

• Single-factor concentrates are the therapy of choice for rare coagulation disorders since they allow infusing only the defective protein and reduce the risk of transfusion adverse effects.

• Fibrinogen concentrates are effective for treating bleeding episodes, but their efficacy and safety of preventing bleeding in patients with fibrinogen deficiency should be confirmed, or at least better individualized for potential selected cases to decrease the risk of related thrombosis.

• Factor X and especially factor V concentrates are eagerly awaited to improve management of such diseases.

• Recombinant FVIIa and FXIII-A are safe and effective in preventing and treating bleeding in patients with FVII and FXIII deficiency; however, their cost remains an issue.

• Factor XI concentrates should be carefully used in view of the infusion-related risk of thrombosis.

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