Hemostatic activation in a chemically induced rat model of severe hemolysis and thrombosis.

INTRODUCTION: In hemolytic diseases such as sickle cell disease and beta-thalassemia, the mechanisms of thrombosis are poorly understood, however erythrocyte/endothelium interactions are thought to play an important role. Appropriate animal models would increase our understanding of the pathophysiology of thrombosis and aid in the development of new therapeutic strategies. We previously reported that rats exposed to 2-butoxyethanol (2-BE) develop hemolysis and enhanced adherence of erythrocytes to the extracellular matrix, possibly secondary to the recruitment of cellular adhesion molecules at the erythrocyte/endothelium interface. METHODS: We exposed rats to 250 mg/kg/day of 2-BE for 4 days, and collected blood for coagulation markers on each day. RESULTS: As previously observed, erythrocytes dropped precipitously (8.0 to 1.8x10(6)/microl in 48 h), and diffuse microvascular thrombosis developed in the heart, lungs, liver, bones and eyes. Prothrombin times, activated partial thromboplastin times, fibrinogen, and antithrombin-III were unchanged between treated and control rats, indicating that hemostasis is largely unperturbed. However the thrombin-antithrombin III levels in the 2-BE treated rats for all days were 3-7 times greater than the control rats. The plasma intercellular adhesion molecule-1 (ICAM-1) levels of 2-BE treated animals were approximately twice that of the controls on days 2 and 3 and 1.5 times the controls on day 4 (P<0.05). CONCLUSION: Our findings are consistent with the observations of increased erythrocyte aggregation, increased erythrocyte/endothelium interaction, and increased plasma ICAM-1 levels observed in sickle cell disease and beta-thalassemia patients. This model may be useful for studying therapeutic agents that disrupt erythrocyte/endothelium interactions.

Antihuman factor V antibodies after use of relatively pure bovine thrombin.

Although bovine thrombin is commonly used in the operating room, there is evidence that exposure to bovine thrombin can result in the development of autoimmune antibodies, usually against factor V, which can lead to a profound coagulopathy. It is thought that impurities in bovine thrombin preparations are responsible for the adverse reactions in patients. Here we describe a case in which exposure to a relatively pure bovine thrombin preparation resulted in the development of an antihuman factor V antibody-associated coagulopathy. This report calls into question the safety of even relatively pure bovine thrombin.