Low Molecular Weight Heparin Treatment in Steroid Refractory Ulcerative Colitis: Clinical Outcome and Influence on Mucosal Capillary Thrombi

Abstract

Vrij AA, Jansen JM, Schoon EJ, de Bruṏne A, Hemker HC, Stockbrügger RW. Low molecular weight heparin treatment in steroid refractory ulcerative colitis: clinical outcome and influence on mucosal capillary thrombi. Scand J Gastroenterol 2001;36 Suppl 234:41-47. Background: In ulcerative colitis, a state of hypercoagulation has frequently been observed. Unfractionated heparin has shown bene cial effects as an adjuvant treatment of steroid refractory ulcerative colitis in open trials and in one placebo-controlled trial. Low molecular weight heparin (LMWH) offers advantages in the method of administration, but it has not been evaluated in severe ulcerative colitis. We therefore assessed the tolerability, safety and potential therapeutical effects of LMWH in hospitalized patients with steroid refractory ulcerative colitis. Methods: Twenty-ve patients with severely active ulcerative colitis were included in an open-labelled trial. All patients had a are-up of disease under glucocorticosteroid treatment. Nadroparine calcium 5.700 IE anti-Xa/0.6 mL s.c. was self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events, and changes in clinical symptoms and in laboratory, endoscopical and histological results were analysed. Results: Tolerability and compliance were excellent and no serious adverse events occurred. In 20 of 25 patients, a good clinical and laboratory response was observed. Also, the endoscopic and histological signs of in ammation were found to be signi cantly improved. However, this was not accompanied by a signi cant reduction in the number of mucosal microvascular thrombi after 8 weeks of LMWH treatment. Conclusion: LMWH may be a safe adjuvant therapy for patients with active, glucocorticosteroid refractory ulcerative colitis.

Thrombin generation in mesalazine refractory ulcerative colitis and the influence of low molecular weight heparin

“…With the reviparin doses used we observed a temporary rise in the liver ALT level, a known side effect of heparin treatment [35], also reported in a previous study on LMWH in UC [15]. Fortunately, as in other studies [15,34], no serious bleeding complications were encountered, suggesting that LMWH is a relatively safe drug in this patient group with tendency for mucosal bleeding.…”

“…This is in contrast with the positive results found in a previous but open study done with nadroparin, in corticosteroid-resistant UC patients [15]. It suggests that LMWH, in combination with aminosalicylates but in the absence of corticosteroids, does not have any therapeutic advantage above a placebo, as was recently also shown by other investigators [34].…”

“…3 Box-whisker plots of TAT (lg/ml; normal upper limit 1.90 lg/ml) and F1.2 (nmol/l; normal upper limit 1.45 nmol/l) during 8 weeks of follow-up in patients with UC, treated with mesalazine and reviparin reduced thrombin generation has any influence with respect to the HDA score. However, the combination of LMWH and corticosteroids did reduce the HDA score significantly within 8 weeks of therapy in a previous study [15].…”

“…However, ''fibrinoid'' mucosal capillary thrombi have been detected in rectal biopsies of patients with UC [14]. As the micro-vascular thrombi were found without a clear relationship to the degree of surrounding inflammation, they might represent an association with underlying pathophysiological mechanisms [14,15]. The finding of raised levels of plasma coagulation and fibrinolysis end-products indirectly reflects a state of hypercoagulation in patients with IBD [16].…”

Efficacy of Intracolonic Administration of Low-Molecular-Weight Heparin CB-01-05, Compared to Other Low-Molecular-Weight Heparins and Unfractionated Heparin, in Experimentally Induced Colitis in Rat

“…Current medical treatment of IBD, titrated according to the severity of the disease and to the individual response, includes 5-aminosalicylic acid (ASA) derivatives, corticosteroids, immunosuppressants, and most recently biologic agents mainly targeted against tumor necrosis factor (TNF)-a. Among the emerging treatments for ulcerative colitis, the parenteral administration of low-molecular-weight heparins (LMWHs), i.e., dalteparin, enoxaparin, nadroparine, reviparin, deligoparin, and tinzaparin, was judged clinically useful by some authors [1][2][3], but questioned by others [4][5][6][7][8]. The administration of LMWHs by oral route has recently been attempted, resulting safe and effective in corticosteroid-resistant UC patients [9].…”