Thrombin Products: Economic Impact of Immune‐Mediated Coagulopathies and Practical Formulary Considerations

Abstract

Thrombin has demonstrated utility in aiding surgical hemostasis since its introduction more than 60 years ago. It is used across a wide variety of surgical procedures by virtually every specialty. Only recently have new equally effective and safe products entered the market, causing decision makers to evaluate formulary selection among products with otherwise modest differences. This evaluation includes identifying costs beyond those of acquisition and storage, as well as indirect factors such as monitoring or specialized distribution requirements. One factor to consider specifically in selection of topical thrombin products is the potential for patients to develop an immune-mediated coagulopathy (IMC) after exposure to bovine-derived thrombin. Costs due to adverse drug events fall into the category of indirect costs and, in some instances, can be substantial if bleeding due to IMC occurs.

Optimizing Hemostatic Practices: Matching the Appropriate Hemostat to the Clinical Situation

“…Other clinical consequences associated with transfusion include the risk of mistransfusion (ie, one of every 12,000 to 19,000 units transfused) and viral infection (eg, less than one of every one million units transfused) 2 . Additional clinical risks include transfusion‐related immunomodulation, circulatory overload, and complications associated with use of red blood cells stored for longer than 28 days (eg, limitation of oxygen delivery, multiple organ system failure, increased mortality) 2,8 …”

“…Given the similar efficacy between thrombin products, further consideration of their differences may help health care providers select the most appropriate agent for a clinical situation. For instance, although all three thrombin products have been found to have similar safety profiles in clinical trials, postmarketing surveillance has shown that bovine thrombin has been associated with antibody formation that can lead to immune‐mediated coagulopathy and death, which is why this product carries a black box warning 8,21 . As such, repeated use of bovine thrombin is not recommended because the immunologic reaction may not be evident until a subsequent re‐exposure to the product 21…”

Topical thrombin preparations and their use in cardiac surgery

“…18, In these cases, the spectrum of disease ranges from asymptomatic alterations in laboratory coagulation tests (eg, prothrombin time [PT], activated partial thromboplastin time [aPTT], international normalized ratio [INR] and thrombin time [TT]) to severe bleeding events and death. [16][17][18]77,78,82,83 Bleeding events associated with IMC may even occur several months after exposure to bovine thrombin. 35,56 Cases of IMC and bleeding events have been reported in a wide range of surgical cases including neurosurgery, obstetrics, and vascular surgery.…”

“…63,80 There is no standard treatment protocol established at this time for the treatment of IMC secondary to bovine thrombin inhibitors. 39,53,80,83 What information that does exist for the treatment of this disease is derived from various case reports and case series. 39,53,80,83 Treatment strategies have usually been driven based on severity of clinical manifestation.…”

“…39,53,80,83 What information that does exist for the treatment of this disease is derived from various case reports and case series. 39,53,80,83 Treatment strategies have usually been driven based on severity of clinical manifestation. 53,62,80 Patients who present with abnormal coagulation test without bleeding require no treatment other than careful monitoring and follow-up with serial testing.…”