Electronic Physician (ISSN: 2008-5842) http://www.ephysician.ir
September 2015, Volume: 7, Issue: 5, Pages: 1270-1276, DOI: 10.14661/1270
Corresponding author:
Amna Ahmed Metwaly, Intensive Care Department, Theodor Bilharz Research Institute, Cairo, Egypt.
E-mail: amnametwaly@hotmail.com
Received: June 14, 2015, Accepted: July 21, 2015, Published: September 16, 2015
iThenticate screening: July 18, 2015, English editing: August 04, 2015, Quality control: August 12, 2015
© 2015 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-
NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is
non-commercial and no modifications or adaptations are made.
Page 1270
The Role of Hemostatic Factors in Atherosclerosis in Patients with Chronic Renal Disease
Manal Zahran
1
, Fatma Mohammed Nasr
2
, Amna Ahmed Metwaly
2
, Noha El- Sheikh
3
, Nevine Sherif Ali Khalil
3
,
Tarek Harba
3
1
Clinical Chemistry Department, Theodor Bilharz Research Institute, Cairo, Egypt
2
Intensive Care Department, Theodor Bilharz Research Institute, Cairo, Egypt
3
Nephrology Department, Theodor Bilharz Research Institute, Cairo, Egypt
Type of article: Original
Abstract
Introduction: Atherosclerotic cardiovascular disease remains the leading cause of increased morbidity and
mortality observed in chronic kidney disease (CKD) patients. Endothelial dysfunction (ED) is thought to be a key
initial event in the development of atherosclerosis. The aim of this study was to evaluate the potential role of
hemostatic factors in atherosclerosis, thrombosis and cardiovascular complications in patients suffering from
chronic renal disease.
Methods: The study was conducted on 50 renal patients divided into two groups of equal size. Group 1 consisted
of 25 patients with end-stage renal disease (ESRD) on regular hemodialysis. Group 2 consisted of 25 chronic
renal disease patients on conservative treatment. Twenty age- and sex-matched healthy subjects were included in
the study to serve as a control group. Thrombomodulin (TM), von Willebrand factor (vWF), tissue plasminogen
activator (t-PA), plasminogen activator inhibitor (PAI-1) and hsCRP were assessed. High-resolution B-mode
ultrasonography of both the common and internal carotid arteries to measure carotid intima media thickness
(CIMT) was performed on all subjects.
Results: There were highly significant increases in hsCRP, TM, vWF, tPA and PAI-1 in both patient groups
compared to the control group (P<0.01 for all except for TM between group 2 and 3 P<0.05) with significant
increase in group 1 compared to group 2 (P<0.01). In addition, there was a highly significant increase in CIMT in
both patient groups compared to the control group (P<0.01) with a significant increase in group 1 compared to
group 2 (P<0.05). The study revealed significant positive correlation of hemostatic factors (TM, vWf, PAI-1 & t-
PA) with creatinine, urea, hsCRP & CIMT.
Conclusion: CKD patients have increased risk of atherosclerosis as measured by CIMT, which is used as a
surrogate marker of early atherosclerosis and has been shown to be a strong predictor of future myocardial
infarction and stroke. They have high levels of TM, vWF, tPA, PAI-1 that correlate with kidney function, hsCRP
and CIMT. Therefore, these abnormalities in hemostasis may account for the increased risk of atherothrombosis
in these patients. The elevated hsCRP levels and their correlation to hemostatic factors and CIMT might provide
an important clue to link a systemic marker of inflammation to atherosclerosis. Further research is required to
better understand the procoagulant state in patients with CKD.
Keywords: Chronic kidney disease (CKD), hemodialysis (HD), atherosclerosis, carotid intima media thickness
(CIMT), TM, vWf, t-PA, PAI-1
1. Introduction
Atherosclerotic cardiovascular disease (CVD) remains the leading cause of increased morbidity and mortality
observed in chronic kidney disease (CKD) patients (1). Endothelial cells form a natural barrier between circulating
blood and the surrounding tissue. Along with this barrier function, the cells generate several anti-thrombotic factors
that prevent hemostasis in the circulation. When damaged, endothelial cells lose their anti-thrombotic capacity and