Antibodies Against the Fibrin β-Chain Amino-Terminus Detect Active Canine Venous Thrombi

Abstract
Background This study was performed to determine whether antibodies against the amino-terminus of the β-chain of fibrin (anti-β) could noninvasively distinguish actively enlarging thrombi from thrombi stabilized with anticoagulants. Methods and Results Dogs with unilateral femoral vein thrombi were allocated into three groups: (1) no anticoagulation, (2) intravenous heparin maintained in the “therapeutic” range (0.2 to 0.5 U/mL plasma), and (3) “excess” heparin, maintained at >1.0 U/mL plasma. Thrombolysis was suppressed with tranexamic acid. 111 In-labeled anti-β was infused, and gamma scans of the legs were performed at regular intervals for 24 hours. Scans were interpreted in a blinded fashion. In addition, for each scan, the number of gamma counts from the femoral area on the thrombosed side was compared with the contralateral side. Clot/blood isotope density was determined postmortem. Leg thrombi in the no-anticoagulation group were 100% detectable, mean (±SD) relative count in the thrombosed femoral area was 186% (±30%) of the contralateral side, and clot/blood ratio was 14.7 (±2.0). Thrombi in the therapeutic heparin group were only 75% detectable, relative counts in the thrombosed femoral areas decreased to 125% (±20%), and clot/blood ratio declined to 11.3 (±3.5). In the “excess heparin” group, leg thrombi were only 50% detectable, the thrombosed femoral area had relative counts of 118%±17%, and the clot/blood ratio fell to 7.8±1.9. Conclusions Radiolabeled anti-β noninvasively distinguishes propagating thrombi from those stabilized by anticoagulants. They may be useful for detecting thrombosis clinically as well as for monitoring the efficacy of anticoagulation.