Differential Prevalence of Anti-Heparin-Platelet Factor 4 Antibodies In Elderly Patients with Acute Hip Fracture Undergoing Orthopaedic Surgery and Anticoagulated with Unfractionated Heparin and Enoxaparin

Abstract 4217

Orthopaedic surgical interventions pose a high risk of thrombosis (up to 50%) and require prophylactic anticoagulation. Conventionally, UFH and LMWH (enoxaparin) are used for the prophylactic anticoagulation. Both of these agents are capable of generating anti-heparin-platelet factor 4 antibodies. However, the exact prevalence with their use in elderly patients is not known. The purpose of this study was to determine the prevalence of the generation of anti-heparin-platelet factor 4 antibodies in this population with reference to the differences between UFH and LMWH. This study was conducted as a sub-study of PK532, in which 341 patients were recruited with acute hip fracture requiring orthopaedic surgical intervention. Patients were randomized into two groups and received either UFH 5000 units BID or enoxaparin 40 mg OD. Blood samples were drawn the day prior to surgery and on post-op days 1, 3, 5, and 7. Citrated plasma samples were kept frozen at -70 degrees Celsius and were batch analyzed for the presence of anti-heparin platelet factor 4 antibodies using GTI (Milwaukee, Wisconsin) and Aniara (Paris, France) methods. The sub-study was carried out on 94 patients representing 42 enoxaparin and 51 heparin anticoagulation. The prevalence of anti-heparin platelet factor 4 antibody was expressed in terms of antibody titer by measuring optical density in the ELISA method and by determining the positive patients using the criterions established by each kit. Of the 94 patients recruited in this study, both methods showed a progressive increase in optical density starting on post-op day 3 suggesting the generation of anti-heparin platelet factor 4 antibodies. The relative absorbance was lower in the Aniara method. Overall, across all study days, the prevalence of anti-heparin platelet factor 4 antibodies was found to be 18.09% and 10.64% in all patients using the GTI and Aniara methods, respectively. The heparin treated group showed a much higher prevalence (29.41% and 19.61% using GTI and Aniara, respectively) whereas the enoxaparin treated group exhibited a much lower prevalence (2.33% and 0% using the GTI and Aniara methods, respectively). The highest prevalence was found to be on post-op day 7. On post-op day 7, the heparin treated group exhibited 27.59% prevalence using the GTI method and 13.79% prevalence of anti-heparin platelet factor 4 antibodies using the Aniara method (p<0.05). The results of both GTI and Aniara methods correlated well, especially on post-op day 5 and 7. These results suggest that both UFH and enoxaparin are capable of generating anti-heparin platelet factor 4 antibodies, which are more detectable on post-op days 5 and 7. The prevalence of these antibodies is found to be higher in the UFH group compared to the enoxaparin group. However, there are differences in the two methods. The GTI method has a higher sensitivity in detecting these antibodies in contrast to the Aniara method. Based on these results, the GTI method appears to be a more suitable global screening of patients suspected of having anti-heparin platelet factor 4 antibodies.