Prevalence of Cross Reactive Epitopes to Bovine Factor Va Light Chain Fragments in Normal and Patients Plasma.

Abstract

Several reports have described the presence of antibodies to bovine coagulation factors, such as factor V, prothrombin and factor X in plasma samples obtained from patients exposed to topical bovine thrombin. Other reports have also demonstrated the presence of anti-bovine coagulation factors in patients who have not been exposed to bovine thrombins, suggesting that anti-bovine protein antibodies can be generated in normal individuals. It has been suggested that surgical patients treated with topical bovine thrombin develop specific antibodies to bovine factor V which may be responsible for the bleeding and thrombotic complications. However, there is no definitive clinical study demonstrating a relationship between the apparent hemostatic defects and the presence of bovine factor Va antibodies. It was hypothesized that bovine factor Va antibodies are usually present in patients plasma because of the exposure to dietary bovine products. To test this hypothesis plasma samples from patients with end state renal disease (ESRD)(n=80), acute coronary syndrome (ACS)(n=160), burns (n=40) and healthy normal volunteers (n=140) were profiled for the presence of human factor V antigen (HFVA), bovine FVa antigen as measured by using a modified Elisa method and western blotting methods where bovine factor Va light chain fragment is used as a probe. In contrast to the normals (89±12%), the factor V antigen levels were found to be increased in the ESRD (148±30%), ACS (164±41%) and burn (145±27%) patients. Thus, there appears to be an up regulation of factor V antigen in these patients. All of the groups tested for the presence of immunoreactive material to the bovine factor Va light chain exhibited 2–3 ug/ml levels which were not significantly different. However, in the western blotting studies all groups exhibited cross reactivity with the factor Va light epitopes. There were bands present in the molecular weight range of 22, 36, 45 and 97 Kda in both the ESRD and burn patients. In the ACS patients there was an additional band observed at 166 Kda. These observations underscore the notion that bovine antifactor Va antibodies are non-specific and highly prevalent in both the surgical/interventional patients and normal population. A possible explanation for the presence of these antibodies is that most normal individual and patients problem are exposed to bovine proteins. Moreover, the higher prevalence of these antibodies in the ESRD and ACS patients may be due to additional exposure to heparin and aprotonin.