Abstract

Thrombosis is a recognized complication of inflammatory bowel disease (IBD). In contrast disseminated intravascular coagulation (DIC) has rarely been described with IBD, and then only during periods of intense disease activity or during colectomy. However, we recently encountered a young woman with a 3-year history of ulcerative colitis (UC) and a 10-year history of recurrent thrombosis who presented with DIC when her disease appeared to be well controlled. For the previous two months she had been forced to discontinue her usual warfarin because of extreme over anticoagulation and extensive ecchymoses. Otherwise she felt well and was working full time. When she presented to us, the following laboratory data were obtained: pro time 18.7s, aPTT 43.6s, fibrinogen 56 mg/dL, D-dimer 8–16 μg/mL, platelet count 123K/μL, thrombin-antithrombin complexes 47 μg/mL (nl, 1.3–4.0), plasma endotoxin 6.3 EU/mL (control 0.1), positive prothrombin G20210A heterozygosity, negative FVLeiden, but positive APC resistance. Antithrombin, protein C, protein S, and homocysteine were within normal limits. Extensive imaging studies failed to reveal evidence of malignancy or venous malformations. The patient was treated with 1 mg/kg/d enoxaparin with resolution of her ecchymoses and normalization of her laboratory values. Subsequently we exposed cultured human umbilical vein endothelial cells (HUVECs) to our patient’s serum and assayed HUVEC lysates for tissue factor. After a 2 hour incubation a 20% dilution of her serum increased the tissue factor in the HUVECs to a level twice that observed with serum from a normal donor. Furthermore, the effect of her serum was negated by the addition of 1 μg/mL polymyxin-B, which specifically inhibits endotoxin.

Discussion: Prothrombin G20210A, APC resistance, and UC are individually associated with an increase risk of thrombosis. However, the combination of all 3 factors in our patient apparently led to an intense degree of hypercoagulability that provoked not only recurrent thrombosis but DIC. Furthermore, the contribution of UC to her hypercoagulability may have been mediated by endotoxin diffusing from her inflamed bowel and upregulating tissue factor in her endothelium and/or monocytes. Because this patient’s recurrent thromboses predated her diagnosis of UC by 7 years, we suggest that occult IBD should be considered in the evaluation of idiopathic thrombophilia.

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