Topical thrombin and acquired coagulation factor inhibitors: Clinical spectrum and laboratory diagnosis

Abstract

Topical bovine thrombin preparations are used extensively in cardiovascular, neurosurgical, and otolaryngologic procedures. Patients who are treated with these topical thrombin preparations may develop antibodies to bovine coagulation factors that may cross-react with the endogenous human clotting proteins. We have identified four patients with acquired factor inhibitors following exposure to topical thrombin at Duke University Medical Center and summarize these cases in addition to 13 patients previously reported in the literature. In most cases, the inhibitor developed following a second (or subsequent) exposure to topical thrombin. The clinical course was extremely variable, ranging from totally asymptomatic to life-threatening hemorrhage. The most consistent laboratory abnormality was a prolonged bovine thrombin clotting time, which corrected, at least partially, when human thrombin was substituted for bovine thrombin. Some of these patients also developed factor V inhibitors with prolonged prothrombin and activated partial thromboplastin times. Although these patients have prolonged clotting times, they should not be considered "autoanticoagulated," since thromboembolic complications can still occur. Therapeutic intervention is largely empirical and depends on the clinical manifestations of the individual patient.

Factor VLeiden

“…However, the overlapping APC resistance results between controls and patients makes it difficult to apply this concept to individual patient care [41]. Patients have been reported to develop autoantibodies against factor V after exposure to bovine thrombin leading to APC resistance, with subsequent thrombosis of unclear etiology [42][43][44]. One study has also observed APC resistance (as measured by endogenous thrombin potential without dilution into factor V-deficient plasma) in unselected patients with untreated hematological malignancies, which may contribute to the increased risk of venous thrombosis observed in these patients [45].…”

Transient FV inhibitor of unknown origin in difficult clinical situation

“…[9] Three other patients presented serious bleeding and received a specific treatment without anticoagulant. [10][11][12] All of these 4 patients evolved favorably. The remaining six patients were treated with heparin (LMWH or unfractionated heparin) during the initial phase followed by anti-vitamin K or oral anticoagulants.…”

A surgeon, a rabbi and a lawyer walk in to an OR… Absorbable haemostatic agents and the dangers of product evolution – clinical, religious and legal implications

“…[5][6][7] Granulomatous foreign body reactions and excessive fibrotic reactions may lead to catastrophic sequelae, particularly when the agents have been used within the abdominal cavity. Cases of appendicitis, 8 small bowel obstruction 9 and caseating peritoneal granulomas 10 have been described.…”