Pathophysiology of disseminated intravascular coagulation (DIC) progresses at a different rate in tissue factor-induced and lipopolysaccharide-induced DIC models in rats

Abstract

Tissue factor (TF) and lipopolysaccharide (LPS) are frequently used to induce disseminated intravascular coagulation (DIC) in experimental animal models. Although the pathophysiology of DIC may differ depending on which agent is used for induction, previous studies on models of DIC have not distinguished which DIC-inducing agent was used. In the present paper, we evaluate the characteristics of TF-induced and LPS-induced DIC using two types of DIC models, with special reference to selected hemostatic parameters and pathological findings within the kidney. Male Wistar rats were administered TF (3.75 U/kg; sustained infusion for 4 h) or LPS (30 mg/kg; sustained infusion for 4 h) via the tail vein, and blood sampling was performed at 0, 1, 3, 4, 5, 7, 9, 11, and 28 h. Judging from changes in the levels of thrombin-antithrombin complex, fibrinogen levels, and platelet counts, it is reasonable to conclude that the severity of both types of experimental DIC is similar with regard to hemostatic activation and consumption coagulopathy. A marked elevation in the level of D-dimer was noted without any organ dysfunction or much fibrin deposition in the kidney upon administration of TF. However, a markedly prolonged period of elevation in plasminogen activator inhibitor activity, a prolonged depression in antithrombin III activity, severe organ failure, and a markedly prolonged period of fibrin deposition in the kidney was observed following LPS administration. A modest number of the rats from the TF-induced DIC model died during the experimental period, whereas a large number of rats died during LPS-induced DIC, especially after 9 h. Since the time course of the pathophysiology differed remarkably among the TF-induced and LPS-induced DIC models in rats, we recommend that TF-induced and LPS-induced DIC be approached as distinct models in order to determine the implications of their experimental and clinical use.

Heat Stroke

“…Coagulopathy may worsen during the first few days after cooling and result in bleeding diathesis (11,78,238). Bleeding diathesis (also known as consumptive coagulation) is characterized by excessive blood loss as the consumption of platelets and coagulation proteins outpaces production (20,28). Heat stroke patients may experience hemorrhagic complications such as prolonged bleeding from venipuncture sites or other areas, including the gums (183).…”

Heat stroke: Role of the systemic inflammatory response

“…Early in heat stroke, widespread activation of coagulation stimulates excess deposition of fibrin in the arterioles and capillaries along with platelet aggregation that leads to microvascular thrombosis. Although rapid cooling of the heat stroke patient may normalize fibrinolysis, coagulation often persists until platelets and coagulation proteins are consumed at a faster rate than they are produced (2,4). Consumptive coagulation may lead to excessive, prolonged bleeding from multiple tissue sites (e.g., venipuncture sites, gums) and is associated with fatal outcome (46).…”

No interplay between the pathways mediating coagulation and inflammation in tissue factor-induced disseminated intravascular coagulation in rats

“…This profibrinolytic response is almost immediately followed by suppression of fibrinolytic activity. This is caused by a sustained increase in the plasma level of plasminogen activator inhibitor in LPS-induced DIC (1)(2)(3)(4)(5). Activation of coagulation and impairment of fibrinolysis is mediated by cytokines, such as TNF, IL-1, and IL-6, in LPS-induced DIC (1-4).…”

“…which clinically resembles DIC due to sepsis. The other is a TF-induced model of DIC, which clinically resembles DIC in the setting of acute leukemia (5,21,22). The following features were common to both models examined in this study: Markedly increased plasma TAT levels were observed, as were significantly depressed plasma fibrinogen levels and platelet counts.…”

“…Considerable differences exist with regard to the pathophysiology of tissuefactor (TF)-and lipopolysaccharide (LPS)-induced DIC in rats (the former clinically resembles the DIC of acute leukemia, whereas the latter shares features with sepsis-associated DIC) (5). Briefly, a marked elevation of D-dimer is observed in the absence of organ dysfunction or notable fibrin deposition in the kidney on administration of TF.…”