Thrombin use in surgery: an evidence-based review of its clinical use

Abstract

When surgical ligation of bleeding fails, or is not possible, surgeons rely on a number of hemostatic aids, including thrombin. This review discusses the history, pharmacology and clinical application of thrombin as a surgical hemostat. The initial thrombin was bovine in origin, but its use has been complicated by the formation of antibodies that cross-react with human coagulation factors. This has been associated with life-threatening bleeding and in some circumstances anaphylaxis and death. Human thrombin, isolated from pooled plasma of donors, was developed in an effort to minimize these risks, but its downsides are its limited availability and the potential for transmitting blood-borne pathogens. Recently a recombinant thrombin has been developed, and approved for use by the FDA. It has the advantage of being minimally antigenic and devoid of the risk of viral transmission. Thrombin is often used in conjunction with other hemostatic aids, including absorbable agents such as Gelfoam, and with fibrinogen in fibrin glues. The last part of this review will discuss these agents in detail, and review their clinical applications.

Keywords: antibodies; antigenicity; bovine; food drug administration (FDA); human; recombinant; thrombin.

Figure 1

Diagram of coagulation cascade. Blue boxes and arrows include various hemostatic agents with their mechanism of actions. (*) these agents affect the entire coagulation cascade by concentration and by creating a matrix for coagulation factors at the bleeding site. Red arrows indicate the inhibition caused by bovine generated antibodies to thrombin, factor V, and platelet antiphospholipids.