Recombinant activated factor VII (rFVIIa) as a hemostatic agent in liver disease: A break from convention in need of controlled trials
✍ Scribed by Stephen H. Caldwell; Charissa Chang; B. Gail Macik
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 256 KB
- Volume
- 39
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
The management of coagulopathy in patients with acute and chronic liver disease has undergone little change in many years despite advances in our understanding of the pathogenesis of this problem. In general, deficiency of clotting factors as a result of poor hepatic synthetic function accounts for most of the coagulopathy. However, other processes such as disseminated intravascular coagulation (DIC), hyperfibrinolysis, dysfibrinogenemia, hemolysis, and a decrease in number or function of platelets may be present and thus add to the complexity of the problem. Coexisting portal hypertension and the associated risks of volume expansion, renal failure, and endothelial dysfunction add even more difficulty to the management of these patients. The clinician's despair is only exacerbated by uncertainty regarding the significance of laboratory indices of coagulation and the lack of agreement between health care providers regarding how to use these indices. Simple, conventional interventions such as vitamin K or plasma administration often produce only limited amelioration, and the latter carries the potential disadvantage of volume overexpansion as well as the risk of infection and transfusion reactions. Into this complex and uncertain clinical situation has arrived the antihemophilic agent recombinant activated factor VII (rFVIIa). Its development has led to a fundamental re-evaluation of the classic understanding of the normal clotting cascade. Moreover, use of this product in liver disease patients is increasing despite the lack of definitive studies or literature to guide therapy. Herein we review the mechanism of action of this agent, report the clinical applications in patients with liver disease, address the limitations and risks associated with the drug, and discuss the issue of its cost-effectiveness. (HEPATOLOGY 2004;39:592-598.)
Recombinant Activated Factor VII and Changing Concepts of the Clotting Cascade
Recombinant activated factor VII (rFVIIa) is one of the unusual types of scientific advances whose existence caused a re-evaluation of the general conceptual milieu from which it sprang. 4 Its development brought with it a new appreciation of the integration of the traditional intrinsic and extrinsic clotting pathways with the humoral and cellular components of the clotting cascade (Fig. 1). Typical clot formation occurs through the interaction of a Abbreviations: DIC, disseminated intravascular coagulation; rFVIIa, recombinant activated factor VII; FVIIa, activated factor VII; TF, tissue factor; ICP, intracranial pressure.