The factor VIII/von Willebrand factor complex: basic and clinical issues.

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Federici AB

The factor VIII/von Willebrand factor complex: basic and clinical issues.

Haematologica. 2003 Jun;88(6):EREP02.

PubMed ID

12826528 [ View in PubMed

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Abstract

Factor VIIII (FVIII) and von Willebrand factor (VWF) are two distinct but related glycoproteins that circulate in plasma as a tightly bound complex (FVIII/VWF). Their deficiencies or structural defects are responsible for the most common inherited bleeding disorders, namely hemophilia A (HA) and von Willebrand's disease (VWD). The VWF has a dual role in hemostasis: first it promotes platelet adhesion to thrombogenic surfaces as well as platelet-to-platelet cohesion during thrombus formation; second, it is the carrier for FVIII in plasma. FVIII acts as a co-factor to accelerate the activation of factor X by activated factor IX in the coagulation cascade. After many years of investigations, the molecular mechanisms of FVIII/VWF interactions are now well known and recent biochemical investigations have confirmed that VWF is a key partner for FVIII, playing significant roles in FVIII function, its production and its stabilization, in its conformation and immunogenicity. FVIII and VWF are both present in most plasma-derived FVIII/VWF concentrates used in clinical practice. FVIII/VWF concentrates can be classified into three main categories according to the degree of their purification. Intermediate-high purity plasma-derived concentrates containing FVIII/VWF currently in use since 1987 carry a low risk of transmitting blood-borne infections. Concentrate safety depends on the interaction of two factors: the decrease of viral plasma load and the increase of viral inactivation. These FVIII/VWF concentrates are currently used in type 3 VWD and in type 1 or 2 VWD patients who are unresponsive to desmopressin (DDAVP). More recently the presence of the physiologic FVIII/VWF complex has been considered to play an important role also in replacement therapy for patients with HA. The correct use of FVIII/VWF concentrates in VWD and HA have been reported in several national and international guidelines.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Coagulation Factor IX (Recombinant)	Coagulation factor VIII	Protein	Humans	Yes	Cofactor	Details
Coagulation Factor IX Human	Coagulation factor VIII	Protein	Humans	Yes	Cofactor	Details