Immune‐Mediated Coagulopathy: A Case Report

Abstract

Surgical hemostasis may be achieved by using a number of physical, chemical, or biologic methods. One such method is with topical thrombin; however, one member of that class of drugs, bovine-derived thrombin, is associated with potentially serious consequences such as development of immune-mediated coagulopathy. This case report describes a 61-year-old man with peripheral artery disease who presented with a nonhealing ulcer between his toes. Previous exposure to bovine thrombin was unknown but was considered likely because of his extensive surgical history that included procedures in which topical thrombin is commonly used. The patient was admitted and underwent lower extremity revascularization during which he received his first documented exposure to bovine-derived thrombin. By postoperative day 9, he developed a 2.7-cm retroperitoneal hematoma that had progressed to 9.6 cm by postoperative day 13. Evacuation of the hematoma was performed, during which the patient received his second known exposure to topical bovine thrombin. Based on a plasma mixing study on postoperative day 25, presence of factor V and thrombin inhibitors was suspected. A hematology consultation determined that the patient had developed an immune-mediated coagulopathy manifested as exaggerated laboratory coagulation values that continued even after discontinuation of oral anticoagulation, treatment with multiple transfusions of fresh frozen plasma, and intravenous vitamin K administration. The patient was discharged, after no further bleeding episodes had occurred, on postoperative day 29. Although determining previous exposure to bovine-derived thrombin or presence of antibodies can be difficult, a surgeon's index of suspicion should be raised in patients experiencing coagulopathy if they have previously undergone vascular, cardiac, or spinal procedures in which they were most likely exposed to topical thrombin.

Topical thrombin preparations and their use in cardiac surgery

“…35,56 Cases of IMC and bleeding events have been reported in a wide range of surgical cases including neurosurgery, obstetrics, and vascular surgery. 33,36,47,49,51,52,55,56,63 A significant number of adverse events have been reported in cardiac surgery patients following exposure to bovine thrombin (Table 1). [29][30][31][32][33][34][35][37][38][39][41][42][43][44][45][46][47][48]50,53,54,58,59,61,62 Table 1 addresses the summary of reported experiences related to the use of topical bovine thrombin in cardiac surgery patients.…”

“…19,22,69,72 Documentation of use of these products in the medical record is often very difficult to verify making it problematic to document a history of exposure to bovine thrombin. 18,63,78 In addition, there are no commercially available tests to screen for the presence of antibodies to bovine thrombin further complicating this issue. 17,18,77,78 Attempts at estimating the incidence of bleeding with IMC have been addressed in a few studies.…”

“…53 Clinicians need to maintain a high level of suspicion for IMC especially in higher risk populations like cardiac, vascular, and neurosurgical populations where previous exposure to bovine thrombin may be high. 53,63,80 The course of events surrounding the potential risk involved with the use of bovine thrombin led the FDA in 1996 to issue a boxed warning for bovine thrombin cautioning about possibility for development of potentially serious coagulopathies related to its use and that patients with antibodies to bovine thrombin should not be re-exposed. 64 Since that time, Thrombin-JMI ® has modified its purification process to further reduce factor V in the bovine product in an attempt to further reduce the antigenicity of the product, however, the potential advantages of this reduction remain unknown and the most recent package labeling continues to carry the warning.…”

“…84 Often, the initial indication for IMC secondary to bovine thrombin exposure is alteration in coagulation parameters (eg, PT, aPTT, INR, TT) in the presence or absence of bleeding. 16,53,63,80 A comparison of these coagulation parameters against values obtained prior to bovine thrombin exposure may indicate the presence of an acquired coagulopathy and may support the diagnosis of bovine thrombin induced IMC. 62,63,80 However, other causes of acquired coagulopathies, all which may be present in this population including therapeutic anticoagulation (eg, warfarin, heparin), hypothermia, acidosis, hemodilution, sepsis, disseminated intravascular coagulation, liver disease, and vitamin K deficiency need to be ruled out.…”

“…16,53,63,80 A comparison of these coagulation parameters against values obtained prior to bovine thrombin exposure may indicate the presence of an acquired coagulopathy and may support the diagnosis of bovine thrombin induced IMC. 62,63,80 However, other causes of acquired coagulopathies, all which may be present in this population including therapeutic anticoagulation (eg, warfarin, heparin), hypothermia, acidosis, hemodilution, sepsis, disseminated intravascular coagulation, liver disease, and vitamin K deficiency need to be ruled out. 21,80 Correction of above abnormalities and administration of fresh frozen plasma (FFP) ± vitamin K should allow for correction for acquired coagulopathy.…”