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We describe a case in which uncontrolled chronic disseminated intravascular coagulation (DIC) caused by an aortic aneurysm that was exacerbated by chemotherapy for lung cancer, showed dramatic improvement when warfarin, which was being administered for atrial fibrillation, was replaced by rivaroxaban, a direct oral anticoagulant (DOAC). The present case is interesting because a DOAC was effective in treating DIC due to an aortic aneurysm, whereas warfarin, another oral anticoagulant, was ineffective. In controlling DIC, it is important to inhibit activated coagulation factors such as thrombin and activated factor X, rather than the coagulation factors, which act as substrates.

Objective: Previous reports have suggested an interplay between the pathways mediating coagulation and inflammation in endotoxemia and sepsis. The present study was designed to examine whether cross-signaling between the pathways mediating coagulation and inflammation occurs, as suggested by the pattern of cytokine production observed following tissue-factor (TF)-induced disseminated intravascular coagulation (DIC)., Design: Prospective, comparative, experimental study., Setting: Laboratory at a university hospital., Subjects: Male Wistar rats, aged 6-7 wks, and weighing 160-170 g., Interventions: Male Wistar rats were administered TF (3.75 units/kg every 4 hrs), TF, and tranexamic acid (TA; 50 mg/kg every 4.5 hrs) or lipopolysaccharide (30 mg/kg every 4 hrs) via the tail vein, and blood was sampled at 0, 4, 8 and 12 hrs., Measurements and Main Results: Subsequent alterations in thrombin-antithrombin complex and fibrinogen levels, as well as platelet counts, indicated that the severity of both types of experimental DIC (TF-induced and lipopolysaccharide-induced) was similar with respect to hemostatic activation and development of consumption coagulopathy. In lipopolysaccharide-induced DIC, a sharp increase in plasma tumor necrosis factor levels was observed at 4 hrs, after which a sharp decline was noted. Plasma levels of interleukin-6 were markedly increased at 4 hrs, after which a sustained elevation was observed for the duration of the experimental period (tumor necrosis factor, 1270 +/- 280, 180 +/- 40, and 120 +/- 30 pg/mL at 4, 8 and 12 hrs, respectively; interleukin-6, 5810 +/- 1320, 4850 +/- 730, and 5230 +/- 1280 pg/mL at 4, 8 and 12 hrs, respectively). On the other hand, tumor necrosis factor and interleukin-6 were not detected following TF-induced DIC (0 +/- 0 at 4, 8, and 12 hrs for both tumor necrosis factor and interleukin-6). In the TF+TA group, significant increases in tumor necrosis factor and interleukin-6 were observed, compared with the TF group., Conclusions: There is no overt interplay between the pathways mediating coagulation and inflammation in TF-induced DIC, as observed in lipopolysaccharide-induced DIC.

Objective: We attempted to clarify the effect of immunoglobulin concentrates on the rat lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) model., Design: Prospective, comparative, experimental study., Setting: Laboratory at a university hospital., Subjects: Male Wistar rats, aged 6 to 7 wks and weighing 160 to 170 g., Interventions: Two kinds of experiments were performed. In the first, experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 hrs via the tail vein, and two doses of immunoglobulin (25 or 100 mg/kg/4.5 hrs) were administered to rats 30 mins before infusion of LPS, after which immunoglobulin infusion was continued for a further 4 hrs. In the second, experimental DIC was induced by sustained infusion (5 mg/kg/1 hr) of LPS for 1 hr, and one dose of immunoglobulin (100 mg/kg/4 hrs) was administered to rats after LPS induction. The parameters were estimated at 4 hrs and 8 hrs in the first experiment and at 1, 5, and 10 hrs in the second one., Measurement and Main Results: Similar results were observed in the two experiments. Consumption coagulopathy and hemostatic activation were attenuated, especially when immunoglobulin was administered before LPS infusion. Plasma levels of creatinine and alanine aminotransferase were significantly depressed by coadministration of immunoglobulin. Marked glomerular fibrin deposition was observed in the LPS-induced DIC model, but this deposition was reduced by immunoglobulin. In the first stage of the experiment, plasma levels of tumor necrosis factor (TNF) and interleukin (IL)-6 were suppressed by coadministration of immunoglobulin. In the second, plasma levels of IL-6 were significantly suppressed by immunoglobulin., Conclusion: It was concluded that plasma levels of TNF and IL-6 could be significantly suppressed by immunoglobulin in the LPS-induced DIC model. Moreover, hemostatic abnormality, organ dysfunction, and glomerular fibrin deposition in this model were all ameliorated by immunoglobulin.

Chronic disseminated intravascular coagulation (DIC) is a well-known complication of aortic aneurysm. A 63-year-old man with bleeding tendency and a large palpable abdominal aortic aneurysm (AAA) was diagnosed as having fibrinolysis dominant DIC by the excessive activation of both coagulation and fibrinolysis (plasmin -alpha2 plasmin inhibitor complex concentration is usually >4 microg/ml). Although several treatments were tried, DIC could not be controlled until the patient was given combined therapy of danaparoid (1,250 U/12 h, bolus IV) and tranexamic acid (0.5 g x 3/day, oral administration). This therapy may be beneficial when control for bleeding is required without restricting the ambulatory movement of patients by continuous drip.

In a rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC), we used urokinase (UK) in an attempt to clarify the role of fibrinolysis and to investigate changes in plasma endothelin levels. Two kinds of experiment were performed. The first one: experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 h via the tail vein, and two doses of UK (2.0 or 10.0 IU/g/4.5 h) were administered to rats 30 min before infusion of LPS, after which UK infusion was continued for a further 4 h. The second one: experimental DIC was induced by sustained infusion of 1 mg/kg/10 min LPS for 10 min, and two doses of UK (2.0 or 10.0 IU/g/4 h) were administered to rats at 30 min after LPS infusion. The parameters described below were determined at 4 h in the first experiment, at 4 h and 8 h in the second one. The similar results were observed in both kinds of experiment. There were no significant differences in plasma thrombin-antithrombin complex, fibrinogen or platelet number among the three DIC groups, in both kinds of experiment. Plasma levels of D-dimer were significantly increased in the LPS + higher dose of UK group when compared with the LPS group. The increased plasma plasminogen activator inhibitor (PAI) activity seen in the LPS group was significantly suppressed in the groups receiving UK (especially higher dose of UK). In addition, the increased plasma levels of creatinine and alanine aminotransferase seen in the LPS group were significantly suppressed in the groups receiving UK (especially higher dose of UK). Plasma levels of endothelin, known to be a potent vasoconstrictive agent, were markedly elevated by LPS infusion, and were significantly suppressed in the groups receiving UK of both kinds of experiment, in a dose-dependent fashion compared with LPS group. Glomerular fibrin deposition was significantly suppressed in the groups receiving UK when compared with the LPS group. No manifestations of bleeding were observed in any of the groups. Enhanced fibrinolysis and depressed endothelin induced by UK thus appear to play an important role in preventing the development of organ failure in the LPS-induced DIC model.