Linear relationship between ADAMTS13 activity and platelet dynamics even before severe thrombocytopenia

Abstract

Von Willebrand factor (VWF) cleaving metalloprotease, ADAMTS13, known for its causative relation to thrombotic thrombocytopenic purpura (TTP), also decreases to variable degree in other clinical conditions associated with thrombocytopenia, indicating a possible contribution of moderate deficiency of ADAMTS13 to platelet dynamics. We measured ADAMTS13 activity along with VWF activity, collagen binding activity (VWF:CB), and thrombin/antithrombin complex (TAT) in plasma drawn from patients with consumptive coagulopathy, in whom the platelet count was closely followed. ADAMTS13 activity was significantly but variably decreased in the patients, and VWF activity and VWF:CB were markedly increased as expected. The platelet count itself was not correlated with ADAMTS13 activity, VWF activity, or VWF:CB. However, the rate of decline of log-scaled platelet count (DeltaLnPLT/day) correlated well with ADAMTS13 activity and VWF:CB. ADADMTS13 activity showed inverse correlation with VWF:CB. Moreover, the correlation between ADAMTS13 and DeltaLnPLT/day was preserved even after VWF:CB was controlled. Multiple regression analysis showed that ADAMTS13 activity was the sole factor explaining DeltaLnPLT/day among ADAMTS13, VWF:CB, TAT, prothrombin time, d-dimer, and fibrinogen. TAT level and d-dimer as indicators of systemic fibrinolytic activity did not correlate with ADAMTS13 activity. In conclusion, we found that the decrease of ADADMTS13 activity in consumptive coagulopathy has stronger relationship to platelet dynamics than has generally been recognized.