Clinical significance of plasma D-dimer and von Willebrand factor levels in patients with ulcer colitis

Abstract

AIM: To investigate the levels of D-dimer (DD) and von Willebrand factor (vWF) and the relationship between DD and vWF in ulcerative colitis (UC) patients.

METHODS: A total of 29 plasma specimens were obtained from patients with ulcerative colitis (male 13, female 16), aged 21-47 years (33 ± 11). Disease activity was assessed by Truelove-Writeria. Patients with a score of above 5 were regarded as having active colitis. Twenty healthy people (male 12, female 8), aged 19-53 years (31 ± 14), served as normal controls. Blood samples were taken from an antecubital vein puncture. Blood (1.8 mL) was injected into the tubes containing sodium citrate (0.13 mmol/L). The plasma was obtained by centrifugation at 3000 r·min^-1 for 10 min, and stored at -80 °C until assayed by ELISA.

RESULTS: The mean plasma levels of DD and vWF in active UC patients were significantly higher than those of the controls (0.69 ± 0.41 vs 0.27 ± 0.11, P < 0.01; 143 ± 46 vs 103 ± 35, P < 0.01). The mean plasma levels of DD in the patients with active disease were higher than those with inactive disease (0.69 ± 0.41 vs 0.48 ± 0.29, P < 0.05). The levels of vWF were not different between active and inactive patients. DD levels were positively related to vWF levels (r = 0.574, P < 0.01). There was no significant difference between levels of DD and vWF and the scope of disease and sex of the patients.

CONCLUSION: vWF is an important feature and a good marker of UC; intravascular thrombus and endothelial cell dysfunction were found in UC patients; and the combined test of DD and vWF is helpful to distinguish the activity of the UC patients.

Key Words: $[Keywords]

INTRODUCTION

The pathogenesis of ulcerative colitis (UC) is still unknown[1,2]. Some studies suggested that intestinal vascular injury caused by intramural vascular thrombosis or vasculitis was considered as a potential pathogenetic mechanism of inflammatory bowel disease. The D-Dimer (DD) is known to be a special fibrin degradation product, which is used as anindex of fibrin turnover and intravascular thrombogenesis[3]. von willebrand factor (vWF) is released from endothelial cells, which is used as a marker for endothelial damage[4]. In this study, we investigated the change of DD and vWF levels in UC patients and the relationship between these two markers.

MATERIALS AND METHODS

Patients

A group of 29 patients (male 13, female 16), aged 21-47 years (33 ± 11), were diagnosed by routine clinical, radiologic, endoscopic and histologic means (excluding heart and brain vessel diseases, diabetes and other diseases that affect blood coagulation). Disease activity was assessed by Truelove-Writeria. Patients with a score of above 5 were regarded as having active colitis. Meanwhile 20 healthy people (male 12, female 8), aged 19-53 years (31 ± 14), served as normal controls.

Measurement of plasma DD and vWF levels

Blood samples were taken from an antecubital vein puncture. Blood (1.8 mL) was injected into the tubes containing sodium citrate (0.13 mmol/L). The plasma was obtained by centrifugation at 3000 r·min^-1 for 10 min, and stored at -80 °C until assayed by ELISA (The Sun Biotechnology Company, Fujian, China).

Statistical analysis

Statistical analysis of mean value of DD and vWF levels were made by Student’s t test and Student-Newman-keuls’s test. P < 0.05 was considered to be significant.

RESULTS

DD and vWF levels in patients with UC

The mean plasma levels of DD and vWF in active UC patients were significantly higher than those of the controls (P < 0.01, Table 1). The mean plasma levels of DD in the patients with active disease were higher than that of inactive disease (P < 0.05). The levels of vWF had no difference between active and inactive patients. DD levels was positively related to vWF levels (r = 0.574, P < 0.01).

Table 1 Changes of DD and vWF levels in patients with UC (^-x±s).

	n	DD (mg/l)	vWF (%)
controls	20	0.27 ± 0.11	102.75 ± 34.91
UC
active	17	0.69 ± 0.41ab	142.71 ± 45.96a
Inactive	12	0.48 ± 0.29a	135.00 ± 26.25a

^aP < 0.01, vs control;

^bP < 0.05, vs inactive

DD and vWF levels in gender of disease and scope of disease

DD and vWF levels seemed to be increased with the scope of disease gradually, but differences were not significant with different scope of disease. There was no statistical difference between males and females (Table 2).

Table 2 The levels of DD and vWF in different sex and scope of disease (^-x±s).

	n	DD (mg/l)	vWF (%)
Sex
Male	13	0.58 ± 0.11	142.84 ± 42.85
Female	16	0.55 ± 0.15	138.75 ± 36.75
Scope of disease
Rectum-sigmoid	15	0.58 ± 0.27	137.11 ± 36.87
Left-side	9	0.59 ± 0.26	138.78 ± 42.22
Colon	5	0.63 ± 0.41	143.60 ± 51.60

DISCUSSION

Von willebrand factor (vWF) is a high molecular weight multimeric glycoprotein, synthesized and released by vascular endothelial cells and megakaryocytes. It has two functions: firstly, this glycoprotein carries factor VIII in the circulation and is required for factor VIII stability in the plasma. Serving as the carrier for factor VIII, vWF may also coordinate formation of the fibrin rich thrombus at the site of endothelial cell injury; secondly, this glycoprotein may mediate initial platelet adhesion to the subendothelium by linking to specific platelet membrane receptors and to constituents of subendothelial connective tissues. This is pertinent to the damage of the vascular endothelium[5]. Most of plasma vWF is derived from endothelial cells rather than from platelets under normal circumstances, suggesting that vWF is a good marker of endothelial dysfunction[6,7]. Clinically, in vitro and animal studies support the concept that increased levels of circulating vWF reflect endothelial cell damage or injury[8]. Elevated vWF levels have been demonstrated in the patients with inflammatory vascular disease and associated disorders, including rheumatoid arthritis, systemic sclerosis, systematic lupus erythematosus, Felty’s syndrome, giant cell arteritis and polyarteritis nodosa. Intestinal vascular injury caused by intramural vascular thrombosis or vasculitis is considered as a potential pathogenetic mechanism of inflammatory bowel disease. We investigated the role of vascular injury in the pathogenesis of UC by examining the levels of plasma vWF. The results showed that vWF levels were more significantly raised in the active or inactive patients with UC, as compared with the controls. The levels of vWF were unrelated to the scope of the disease, and there was no statistical difference between males and females. Our results confirmed and extended those of other investigators[9], showing that concentration of circulation vWF is elevated in UC patients. Our results supported the hypothesis that intestinal endothelial cell damage was an important feature of UC and proved that vWF was a good marker of UC.

It is well known that DD is a marker of ongoing intravascular thrombogenesis. In the previous researches, DD test was established as a useful aid in the diagnosis of the deep-vein thrombosis of the lower limbs and pulmonary embolism[10]. Some reports showed higher DD levels in patients with coronary artery disease, Sickle cell disease, systemic lupus erythematosus, several sorts of neoplasms[11,12] and acute pancreatitis[13]. Weber’s results showed that DD levels were higher in patients with UC[14]. Our results showed significantly higher DD levels in patients with UC, both in active and inactive patients, as compared with the controls. It confirmed the presence of intravascular thrombus in UC patients. Thus anticoagulant treatment, with either warfarin or heparin, may have a positive influence on UC.

Several reports indicated that DD is used as a marker of inflammation. Elevated level is a well-established marker of acute-phase reaction and may reflect the presence of inflammation[12,15]. Our results showed that DD levels were significantly higher in patients with active UC than those with inactive UC, but there was no statistical difference in vWF levels between active and inactive UC patients. There was positive correlation between vWF and DD, we therefore, proposed that the combined test of DD and vWF is helpful to distinguish the activity of the UC patients.