For decades, the monogenetic bleeding disorders hemophilia A and B (coagulation factor VIII and IX deficiency) have been treated with systemic protein replacement therapy.
Forty-five patients were enrolled in each group; 71 % of PBWD had a severe form of the bleeding disorder (FVIII/IX activity < 1 % or VWD type 3), and 60 % of all PWBD were treated on-demand.
Forty-five patients were enrolled in each group; 71 % of PBWD had a severe form of the bleeding disorder (FVIII/IX activity < 1 % or VWD type 3), and 60 % of all PWBD were treated on-demand.
How well a patient's whole blood clotting deficiency is corrected after a dose of FVIII may be an indicator of subsequent bleeding tendency in patients with otherwise equivalent FVIII peak and trough levels.
Although patients with severe hemophilia (i.e., with FVIII:C and FIX:C levels <1IU/dL) are generally those with the most severe bleeding phenotype, it is common experience that a variable proportion of them experiences a milder bleeding tendency.
The immune response against therapeutic clotting factors VIII and IX (FVIII and FIX) is a major adverse event that can effectively thwart their effectiveness in correcting bleeding disorders.
Combined deficiency of factor V (FV) and FVIII (F5F8D) is an autosomal recessive bleeding disorder characterized by simultaneous decreases of both coagulation factors.
The larger size of rats relative to mice and the presence of this coagulation defect in both sexes provide a unique model, well-suited to the development of novel therapies for acquired and hereditary FVIII deficiencies.
F5F8D is characterized by concomitantly low levels (usually between 5% and 20%) of both FV and FVIII, and is associated with a mild to moderate bleeding tendency.
Deficiencies of coagulation factors other than factor VIII and factor IX (afibrinogenemia, FII, FV, FV+FVIII, FVII, FX, FXI, FXIII) that cause bleeding disorders (RBDs) are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500,000 and 1 in 2 million for the homozygous forms.
Adeno-associated viral (AAV) gene transfer of coagulation factor VIII and IX to skeletal muscle and liver of murine and canine models of hemophilia A and B have resulted in sustained systemic expression and, in several studies, in complete cure of the bleeding disorder.
von Willebrand disease (vWD) is one of the most common inherited human bleeding disorders, which is caused by quantitative or qualitative defects of von Willebrand factor (vWF). vWF is a highly multimerized glycoprotein that promotes platelet adhesion and aggregation at a high shear rate, while also acting as a carrier of coagulation factor VIII. vWD has been subdivided into three categories, which reflect their pathophysiology.
The coagulation factor VIII is required for normal haemostasis, because deficiency or genetic defects in this molecule cause a life-threatening coagulation disorder known as hemophilia A.
Gene therapy for haemophilia A would represent a significant improvement over the current treatment by providing prophylactic expression of FVIII and correction of the coagulation defect.
Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder in which the levels of both coagulation factor V and coagulation factor VIII are diminished.