Severe reduction of ADAMTS13 activity or high titers of ADAMTS13 autoantibody levels have been implicated as causative factors in Thrombotic Thrombocytopenia Purpura (TTP). Ultralarge von Willebrand factor (UL-VWF) has been shown to mediate the binding of platelets and sickle red blood cells to the endothelium. Thus, ADAMTS13, which cleaves UL-VWF, may play a role in thrombotic events in patients with sickle cell disease (SCD). In this preliminary study, patients with SCD were compared with normal donors for plasma levels of ADAMTS13 antigen, activity, autoantibody, and ADAMTS13/fXI complex. ADAMTS13 antigen was measured using IMUBIND® ADAMTS13 ELISA, ADAMTS13 activity using the ACTIFLUOR™ ADAMTS13 FRET, ADAMTS13 autoantibody titers using IMUBIND® ADAMTS13 Autoantibody ELISA, and complex using IMUBIND ADAMTS13/fXI. Patients with SCD included in this study (n=10) exhibit a number of thrombotic symptoms including deep vein thrombosis, pulmonary embolism, and pulmonary hypertension. Some were found to have autoantibodies to Protein S or alloantibodies to red blood cell proteins. Patients were treated with hydroxyurea, coumadin, as well as various pain medications. Patients in a crisis stage of SCD were included in this study. The four ADAMTS13-related markers were found to be abnormal in patients with SCD compared with normal donors. Cutoff levels for each of the markers, determined based upon normal donor plasmas, were found to be as follows: for ADAMTS13 activity, values lower than 510 ng/ml were considered below normal; for ADAMTS13/fXI complex, values exceeding 360% of the normal were considered to be elevated; for ADAMTS13 autoantibody, values above 14.8 AU/ml were considered above normal. Using these cutoff levels, none of the normal donors (n=47) had abnormal activity or complex levels. One normal donor (2.1%) had elevated autoantibody levels. In comparison, for patients with SCD, 7/10 (70%) had reduced activity levels, 8/10 (80%) had elevated levels of ADAMTS13/fXI complex, and autoantibody was detected in 6/10 (60%) of the patients. These data suggest that ADAMTS13 may play a role in thrombotic complications associated with SCD. ADAMTS13-related biomarkers measured herein may aid in the diagnosis of patients with SCD and may prove useful in monitoring the treatment of SCD.

Author notes

Disclosure:Employment: Four of the authors are employed by the company whose products are being used in the presentation.