Regular ArticlePlasma ADAMTS13, von Willebrand Factor (VWF) and VWF Propeptide Profiles in Patients with DIC and Related Diseases
Introduction
Fig. 2, Fig. 4
ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type I motifs 13) is a metalloproteinase that specifically cleaves the multimeric von Willebrand factor (VWF) [1], [2], [3], [4], [5]. A severe deficiency in the ADAMTS13 activity is caused by either a mutation of the ADAMTS13 gene [2], [6] or by the presence of inhibitory antibodies against ADAMTS13 [7]. Unusually large VWF multimers (UL-VWFMs) produced and released from the injured vascular endothelial cells to the plasma of patients with familial and nonfamilial thrombotic thrombocytopenic purpura (TTP) [8], [9].
The pre-pro VWF, which is synthesized in endothelial cells and megakaryocytes, undergoes intracellular modifications including signal peptide cleavage, C-terminal dimerization, glycosylation, sulfation, and N-terminal multimerization [10]. Then proteolysis occurs in the trans-Golgi where the VWF propeptide (VWFpp) is cleaved but remains stored together with mature VWF in alpha-granules (megakaryocytes) and Weibel-Palade bodies (endothelial cells). After the secretion of VWFpp and VWF into plasma from endothelial cells in response to several physiological or pathological stimuli, VWFpp dissociates from VWF [11], [12]. An elevated plasma level of VWFpp has been reported in patients with thrombotic microangiopathy (TMA) [13]. Disseminated intravascular coagulation (DIC) is a life-threatening disease that is often associated with severe organ failure and a bleeding tendency [14]. DIC is diagnosed based on the clinically laboratory coagulation tests but are not sensitive for the early phase of DIC. Thus, a new marker is required for the diagnosis of DIC [14]. Decreased ADAMTS13 levels were previously reported in the patients with septic DIC [15], [16].
In this study, we measured the ADAMTS13 activity, and the VWFpp and VWF antigens in the plasma from 69 patients with DIC, 143 with non-DIC, 21 with TTP and 23 with atypical hemolytic uremic syndrome (aHUS) to evaluate usefulness in diagnosing DIC.
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Materials And Methods
The ADAMTS13 activity, VWF antigen and VWF propeptide (VWFpp) were measured in 50 healthy volunteers, 69 patients with DIC, 143 without DIC (non-DIC), 21 with TTP and 23 with aHUS. The DIC patients and non-DIC patients were continuously selected from the patients with a platelet count < 100,000/μl from January 1, 2010 until December 31, 2010 at the Mie University Hospital. The patients were classified into three groups: patients with infectious diseases (25 with DIC and 30 with non-DIC), with
Results
The plasma ADAMTS13 activities were significantly decreased in any of patients with DIC, non-DIC, TTP and aHUS compared with those in healthy volunteers (Fig. 1-A and Table 1). Although the plasma ADAMTS13 activity in patients with DIC was significantly lower than in those with non-DIC, however, it is still significantly higher than that of TTP. The plasma levels of VWF and VWFpp antigens were significantly elevated in patients with DIC, non-DIC, TTP and aHUS compared with that of healthy
Discussion
In the present study, the plasma ADAMTS13 activities in patients with DIC were significantly lower than those with non-DIC, but were significantly higher than in those with TTP. Decrease of ADAMTS13 activity was reported in patients with sepsis-induced DIC [15] and severe DIC [16]. The number of DIC patients with infections was higher in this study (n = 25) than that described in Dr Hyun's report (n = 5)[16] and the cut-off value of fibrin related markers in the diagnostic criteria for overt-DIC
Conflict of interests statement
All authors have no conflict interest.
Acknowledgments
This work was supported in part by Grant-in-Aid for Blood Coagulation Abnormalities from the Ministry Health, Labor and Welfare of Japan.
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