Safety of topical thrombins: the ongoing debate

Christopher Lomax

doi:10.1186/1754-9493-3-21

Abstract

Until recently, only bovine-derived thrombin was available for use as a stand-alone topical hemostat or as a component of other hemostatic devices. Concerns over a number of case reports of immune-mediated coagulopathies associated with the use of bovine-derived thrombin resulted in a United States Food and Drug Administration warning letter being issued in 1996 and the later addition of a boxed warning ("Black Box Warning") to all bovine-derived thrombin products. Since 2007, both a human-pooled plasma thrombin product and a recombinant thrombin have entered the market.With the addition of these two products to the topical thrombin class, a unique situation has developed in which only a single member (bovine-derived thrombin) within the class carries the Food and Drug Administration's strongest cautionary language about possible adverse events related to an agent's use. Neither the human-pooled plasma thrombin nor the recombinant thrombin products have a boxed warning; although, the human-pooled plasma product does include a precaution/warning about infectious agent transmission - a warning common to products derived from human sources. This report will address this unique situation and the impact, clinical and non-clinical, that thrombin choice may have. Since alternatives are now available, institutions may need to revisit their formulary choice of thrombin preparation, taking into consideration the potential risks associated with bovine-derived products.

Highlights

Between 370,000 and 500,000 patients in the United States are exposed to topical bovine thrombin for surgical hemostasis [1]
1990, the first description of bThrombin antibodies with cross-reactivity to native coagulation factors was reported, resulting in an Food and Drug Administration (FDA) warning letter regarding occasional hemostatic abnormalities and the inclusion of a boxed warning in the package insert of bThrombin [2]
[2] A search of PubMed and Medline databases for English-language reviews and case reports has demonstrated that new cases of immunemediated coagulopathies (IMC) have continued to

Summary

Introduction

Between 370,000 and 500,000 patients in the United States are exposed to topical bovine thrombin (bThrombin) for surgical hemostasis [1]. Over 100 cases of bThrombin-associated acquired factor V and thrombin (factor IIa) antibodies have been reported in the literature and have been associated with various adverse events.

Results

Conclusion