Abstract
Introduction: Severe infections often lead to hemostatic abnormalities such as disseminated intravascular coagulation (DIC). However, the causes of thrombocytopenia and organ failure in severe infections remain largely unclear. ADAMTS13 (a disintegrin-like and metallo-protease with thrombospondin type 1 motif, member 13) is a plasma metalloproteinase that cleaves von Willebrand factor (VWF) in a shear-dependent manner to control platelet adhesion and aggregation. While ADAMTS13 is suspected in assuming a pivotal role in thrombocytopenia and organ failure, a consensus has failed to be reached regarding the activities of ADAMTS13 in DIC. To date, a number of Japanese studies on the relationship between ADAMTS13 and various severity scores (SIRS [systemic inflammatory response syndrome] score, DIC score, and SOFA [sequential organ failure assessment] score) have been carried out.
Design and Methods: Twenty-three patients were admitted to our facility between February 2009 and August 2010 for treatment of severe infection with an antithrombinIII<60%. In the present study we determined 1) time-dependent changes in ADAMTS13 activity, severity scores, platelet counts, serum creatinine, and protein C; 2) correlation between ADAMTS13 activities and the severity scores, platelet count, and levels of serum creatinine and protein C; 3) differences between groups with higher and lower levels of ADAMTS13 activity; 4) differences in 28-day outcomes between groups with higher and lower levels of first-day ADAMTS13 activity.
Results: ADAMTS13 activity was observed in 9.1% of the patients in one group (accounting for <10% of activities), and in 41% in another group (accounting for <30%). ADAMTS13 activity, in addition to platelet count and protein C, increased with time, while severity scores and serum creatinine levels demonstrated a discernible chronological reduction. ADAMTS13 activity correlated negatively with DIC and SOFA scores, and creatinine, but positively with protein C. The group with lower levels of ADAMTS13 activity demonstrated higher severity scores and serum creatinine levels, but lower platelets and protein C levels. The 28-day mortality rates were 55.6% (5/9) and 7.7% (1/13) for the lower and higher activity groups, respectively, representing a significant difference (Log Rank test. p<0.05).
Conclusion: We assayed ADAMTS13 activities in patients presenting with severe infections in Japan. 9.1% of patients showed less than 10% of ADAMTS13 activity. Severity scores and ADAMTS13 activities showed good to excellent correlations. Some cases presenting with a severe deficiency in ADAMTS13 activity may possess clinical conditions mimicking thrombotic microangiopathy. This study paves the path for similar studies focusing on life-threatening hemostatic abnormalities such as DIC.
