Soluble Endothelial Protein C Receptor (sEPCR) IN Haemodialysis Patients: A Potential Marker for Thrombosis

Abstract

SUMMARY AND CONCLUSION C hronic kidney disease (CKD) is a growing global health problem, which is typically associated with a prothrombotic tendency in the early stages of the disease, where as in its more advanced stage, that is, end-stage renal disease, thrombotic events are common and play significant role in cardiovascular events, the main cause of mortality in this patient group, also they lead to the development of stroke and vascular access thrombosis, which is one of the main causes of HD patients hospitalization. The protein C pathway is a physiologically important mechanism for regulating coagulation. Protein C/EPCR interaction stimulates protein C activation. A soluble form of this receptor (sEPCR) circulates in plasma and inhibits both protein C and activated protein C (APC) anticoagulant activity. Increased sEPCR levels may be prothrombotic and may be associated with an increased risk of venous thrombosis and thromboemolic manifestations by acting as a procoagulant agent by reducing the antithrombotic and anti-inflammatory effects of APC. Several studies suggested that sEPCR may be a marker for hypercoagulable state in HD patients, in this regard ,our study aimed to measure the level of sEPCR in haemodialysis patients, to correlate its level with other parameters that are possible risk factors for thrombotic events (i.e, demographic features, dialysis duration, body mass index, and various laboratory parameters such as whole blood count and serum levels of albumin, calcium, phosphorus, uric acid, ferritin, parathyroid hormone (PTH), fibrinogen and D –dimer) and correlate its level with the occurrence of thrombotic events. This study was carried out on 50 HD patients, divided into 2 groups; group I with no history of thrombosis and group II with history of thrombosis. Patients with increased tendency toward thrombotic events (diabetic patients, malignancy patients, smokers) and patients on oral anti coagulant therapy were excluded. A control group of 10 age and sex matched healthy subjects was also included in the study sEPCR level was measured using ELISA technique (HCUSABio® (sEPCR) ELISA kit. Catalog No. CSB-E09901h) Our results showed, a statistically significant higher serum levels of sEPCR in both groups of HD patients compared to the healthy control group. Also on comparing serum sEPCR levels among HD patients with thrombosis (group II) and HD patients without thrombosis (group I), we found that group II patients had statistically significant higher sEPCR level compared to group I. Also, group II patients had statistically significant higher PTH, fibrinogen and ferritin levels compared to group I patients. On performing a Receiver Operating Curve (ROC curve) analysis to assess the diagnostic and prognostic performance of sEPCR, a cut-off value of 32 ng/mL for sEPCR was able to differentiate between patients and control group with a diagnostic accuracy of 100%. While, the best cutoff level for sEPCR to differentiate between HD patients with and without thrombotic manifestations was 200 ng/ml which had a prognostic accuracy of 90.31%. We also attempted to classify the 50 HD patients into 3 tertiles according to sEPCR level where we found that the rate of thrombosis development increased with the increased level of sEPCR. In conclusion, our study showed increased sEPCR in patients with Haemodialysis especially those with thrombotic complications. Increased sEPCR could be implicated in the heamostatic derangement in these patients and could be used as a marker for a hypercoagulable state in these patient groups.