ADAMTS-13 contents in therapeutic plasma products

Abstract

Background ADAMTS-13 is a zinc-containing metalloprotease enzyme that cleaves the von Willebrand factor (VWF). In human beings, changes in ADAMTS-13 levels have been observed in a number of diseases. The determination of ADAMTS-13 levels and those of its substrate will help to elucidate therapeutic strategies including ADAMTS-13 supplementation for these diseases. Successful treatment has been reported with both fresh-frozen plasma and cryoprecipitate poor plasma (CPP) as replacement fluids. This study aimed to investigate ADAMTS-13 and some coagulation factors in the different plasma products commonly used to increase ADAMTS-13 levels. Materials and methods A total of 180 U of whole blood (WB) were collected from healthy young male blood donors, their ages ranging from 20 to 32 years. Sixty donors were of blood type O+, 50 were A+, 50 were B+, and 20 were AB+. All blood donors included in this study underwent tests for assessment of their liver and kidney functions, and they were declared free from any disease. Plasma from the blood samples was extracted either on the day of collection (the platelet-rich plasma method) or after an overnight hold of WB (the Buffy coat method). Factor VIII (FVIII) activity was measured and levels of fibrinogen, VWF, and human ADAMTS-13 in plasma were quantitatively determined. Results There was no difference in the mean concentrations of ADAMTS-13 in plasma products obtained using the two different methods. Blood group O showed a higher concentration compared with other ABO blood groups. The concentration of ADAMTS-13 was higher in cryoprecipitate than in plasma and CPP. The mean values of FVIII activity were lower in many plasma and cryoprecipitate units prepared by overnight holding of WB for close to 24 h. In addition, the mean values of FVIII activities and VWF levels were lower in plasma and cryoprecipitate units prepared from blood group O compared with those prepared from other ABO blood groups. No differences were detected in the mean values of fibrinogen and VWF in the plasma products when different methods were used for preparation. Conclusion The observation that the concentration of ADAMTS-13 is higher in cryoprecipitate than in plasma and CPP suggests that cryoprecipitate may be a reasonable source of ADAMTS-13 in clinical settings when volume is an issue. In addition, in our study, the use of cryoprecipitate from blood group O in clinical settings yielded higher concentrations of ADAMTS-13 with less VWF. Although the use of cryoprecipitate instead of plasma or CPP could potentially double the amount of ADAMTS-13 infused, further studies from multiple centers are needed to validate the results.