| Abstract |
ASSOCIATION BETWEEN ENHANCED SOLUBLE CD40 LIGAND AND PROTHROMBOTIC STATE IN INFLAMMATORY BOWEL DISEASE
Inflammatory bowel disease (IBD) is associated with an increased incidence of thromboembolic complications. Thromboembolic disease is a significant cause of morbidity and mortality in patients with IBD. There is evidence from several reports that a hypercoagulable state exists in IBD which involves all components of the clotting system and has been suggested to be linked to the disease pathogenesis.
The CD40/CD40L system has been demonstrated on a range of cell types and it has an important role in adaptive immunity and inflammation. CD40L also displays prothrombotic properties.
The aim of this study was to assess the plasma levels of sCD40L in patients with IBD (ulcerative colitis and Crohn’s disease) in comparison with non IBD inflammation and healthy controls, as well as the association of sCD40L with established hypercoagulable state indexes (thrombocytosis, levels of F1+2 and TAT) and platelets activation as it is expressed with plasma levels of P-selectin.
Methods : Plasma levels of sCD40L, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex and soluble P-selectin were measured in 104 inflammatory bowel disease patients (54 ulcerative colitis and 50 Crohn’s disease), in 18 cases with other causes of intestinal inflammation and in 80 healthy controls using commercially available enzyme-linked immunosorbent assays. Plasma levels of sCD40L were correlated with disease activity, type, localization and treatment as well as with the measured thrombophilic parameters.
Results : CD patients had significantly higher sCD40L levels than both groups of controls (CD vs. HC p<0.001; CD vs. non-IBD p<0.05). UC patients had higher but not significantly different sCD40L levels compared to controls. Both UC and CD patients with active disease had significantly higher sCD40L levels in comparison with patients with inactive disease. Plasma levels of sCD40L were correlated with platelet count (r=0.27 p=0.001) with prothrombin F1+2 (r=0.16 p=0.01), TAT (r=0.15 p=0.04) and with p-selectin (r=0.19 p=0.01).
Conclusions : The increased sCD40L plasma levels may represent at least in some degree, a molecular link between inflammatory bowel disease and the procoagulant state.
ROLE OF ACQUIRED AND HEREDITARY THROMBOTIC RISK FACTORS IN COLON ISCHEMIA OF AMBULATORY PATIENTS
Reversible colon ischemia represents the most common form of gastrointestinal ischemia. It usually occurs in old people in association with serious illnesses such as shock, colon cancer, or the period after surgical intervention in the aorta or the mesenteric vessels. It may also spontaneously appear in apparently healthy individuals. Although several risk factors have been proposed associated with colon ischemia, such as various medications, oral contraceptives, cocaine use, sickle cell disease or vasculitis, its pathogenesis remains obscure. The role of hereditary or acquired thrombotic risk factors in the disease pathogenesis has not been extensively investigated.
Aim of this study was to investigate the role of hereditary and acquired thrombotic risk factors in patients with definite diagnosis of colon ischemia.
Methods: We undertook a retrospective review of all patients with non-occlusive colon ischemia who were non-surgically treated at the University Hospital of Heraklion from January 1995 to December 2000. In 36 patients (23 males, 13 females, mean age 64.8 ετών) who included in the study the frequency of antiphospholipid antibodies, protein C, protein S and antithrombin deficiencies, factor V Leiden, prothrombin gene mutation G20210GA and methylentetrahydrofolate reductase C677T were measured. They were compared to 18 patients with diverticulitis and 52 healthy controls age and gender matched.
Results: The prevalence of antiphospholipid antibodies were significantly higher in patients with colon ischemia compared to inflammatory and healthy controls (19.4% vs. 0% & 1.9%). Among genetic factors only factor V Leiden, was significantly associated with colon ischemia (22.2% vs. 0% & 3.8%). A combination of thrombophilic disorders was found in 25% of the cases. Overall, one or several prothrombotic abnormalities were present in 26 patients (72%).
Conclusions: A comprehensive thrombophilic screening in colon ischemia reveals a congenital or acquired thrombophilic state in 72% of patients. Hereditary and acquired thrombotic risk factors may play an important role in the disease pathogenesis. Moreover, an interaction between acquired and hereditary thrombotic risk factors may be important since multiple thrombotic risk factors were present in 25% of patients in our study.
LOW PLASMA PROTEIN Z LEVELS IN PATIENTS WITH ISCHEMIC COLITIS
Hypercoagulable states have been suggested to play an important role in the pathogenesis of ischemic colitis. Protein Z is, as recently demonstrated, important in the regulation of coagulation. The protein Z dependent inhibitor complex is a factor Xa inhibitor. Patients representing with FVL mutation and low protein Z levels show earlier onset and higher frequency of thromboembolic events than do patients presenting with factor V Leiden mutation and normal protein Z levels. Low plasma protein Z levels have also been found in patients with APL antibodies. Protein Z deficiencies have also been described in patients with ischemic stroke. The role of protein Z in ischemic colitis has not been investigated.
Aim of this study was to assess the serum levels of protein Z in ambulatory patients with definite ischemic colitis in connection to established hypercoagulable states such as FVL mutation and APL antibodies.
Methods: All patients with non-occlusive colon ischemia who were non-surgically treated at the University Hospital of Heraklion from January 1997 to December 2002 were included in the study. The plasma levels of protein Z were measured using a commercially available enzyme-linked immunosorbent assay in 33 patients with ischemic colitis (21 males, 12 females, mean age 63.9 years), 13 patients with diverticulitis (mean age 62.8 years) and 33 healthy controls (mean age 61.9 years). In all patients and controls the levels of APL antibodies and FVL mutation were also measured.
Results : Mean plasma protein Z levels were 1.38+/-0.52 μg/ml in patients with ischemic colitis and were significantly lower compared to healthy controls (1.86+/-0.49 μg/ml) and patients with diverticulitis (1.72+/-0.53 μg/ml) (Ρ=0.001). Protein Z deficiency was found in 6 patients cases with ischemic colitis (18.2%) compared to one with diverticulitis (7.7%) and one healthy control (3.0%). Mean plasma protein Z levels in the IC cases with FVL mutation (1.25+/-0.55 μg/ml) and in cases with raised APL antibodies (1.27+/-0.35 μg/ml)
were lower, but not statistically significant, compared to those without these thrombophilic abnormalities (1.45+/-0.53 μg/ml) (P=0.57).
Conclusions: Our results showed significantly lower protein Z levels in patients with ischemic colitis compared to inflammatory and healthy controls. The high frequency of protein Z deficiency in IC patients indicates that it may play a role in the disease development. Since recent studies have shown a relationship between protein Z deficiency and arterial (ischemic strokes, unstable angina) but not venous thrombosis, we could suggest that protein Z deficiency may be involved in the development of the disease in a subgroup of patients by causing thrombosis in small mesenteric arteries. The absence of association between protein Z deficiency and FVL as well as APL antibodies also supports this suggestion.
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Παράγοντες φλεγμονής και θρόμβωσης επί ιδιοπαθούς φλεγμονώδους εντεροπάθειεας (ΙΦΕΝ) και ισχαιμικής κολίτιδας (ΙΚ)
