Hemophilia

Treatment for bleeding episodes consists of replacing the missing clotting factor by intravenous infusion of FVIII (or FIX). There are both human plasma-derived FVIII and FIX concentrates and recombinant DNA-derived FVIII and FIX concentrates. The useful life for both proteins (FVIII and FIX) once infused is relatively short (on average, half is degraded within twelve hours for FVIII and within eighteen hours for FIX). Thus for serious bleeding episodes or surgery, frequent repeat dosing (or continuous infusion) is often necessary.

Prophylaxis is also used, particularly in persons with severe hemophilia A or B. This consists of giving FVIII three times weekly, and FIX twice weekly (in view of its longer half-life, once infused). The aim of prophylaxis (which is often begun between age one and three) is to prevent joint bleeding (and the resulting increase in joint destruction and disability).

Persons with mild hemophilia A can often be treated with the synthetic agent DDAVP (1-deamino-8-D-arginine vasopressin). This analogue of the naturally occurring antidiuretic hormone vasopressin results in a rapid release of whatever FVIII (and another large plasma glycoprotein, von Willebrand factor) is in the individual's body storage sites. Thus, following intravenously administered DDAVP, FVIII (and von Willebrand factor) increase (two-to tenfold), but then fall back to baseline within approximately twelve to fifteen hours. This drug comes in several formulations, for intravenous, subcutaneous, and intranasal use.

It is hoped that gene therapy for persons with severe hemophilia may eventually become a realistic option. In early 2002 there were several ongoing phase-one trials (very early research studies) in human subjects with severe hemophilia, using different vectors and different techniques. However, formidable challenges remain.