Regular Article
Plasma ADAMTS13, von Willebrand Factor (VWF) and VWF Propeptide Profiles in Patients with DIC and Related Diseases

https://doi.org/10.1016/j.thromres.2011.10.011Get rights and content

Abstract

ADAMTS13, endothelial von Willebrand factor (VWF) and related proteins are involved in the pathogenesis of some life threatening systemic thrombotic coagulopathies. Changes of plasma ADAMTS13 activity in thrombotic thrombocytopenic purpura (TTP) is well known but is also involved in septic disseminated intravascular coagulation (DIC). Here we investigated the ADAMTS13 activity, VWF and VWF propeptide (VWFpp) antigens in 69 patients with DIC, 143 with non-DIC, 21 with thrombotic thrombocytopenic purpura (TTP) and 23 with atypical hemolytic uremic syndrome (aHUS) for diagnosis of DIC.

The plasma ADAMTS13 activity was significantly low in patients with DIC, and the plasma levels of VWF and VWFpp antigens, were the highest in these patients, but there were no significant differences in the plasma VWFpp levels between the patients with DIC and those with aHUS. The difference in the plasma ADAMTS13 activity, the VWF and VWFpp antigens between DIC and non-DIC cases was significant in those with infectious and malignant diseases, but the difference in the VWFpp/ VWF ratio were significant only in subjects with infectious diseases. As an indicator for prognosis, the plasma levels of VWFpp were significantly higher in non-survivors than in survivors. Then, VWFpp/ VWF ratio and VWFpp/ADAMATS13 ratio will be potent informative indicators in DIC.

These findings suggest that ADAMTS13/VWF profiles may have important roles in the pathogenesis of DIC, and that ADAMTS13 and VWFpp are useful indicators for the diagnosis and prognosis of DIC.

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.

Section snippets

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.

References (22)

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