Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 36-year-old woman with disseminated intravascular coagulation syndrome (DIC) was admitted to the Third Department of Internal Medicine of the National Defense Medical College Hospital. Even after she recovered from DIC, she had a low level of C1-inactivator. Her past history, family history and family study revealed that she and her family showed hereditary angioneurotic edema (HANE). There have been no reports of HANE associated with DIC. She had two HANE attacks after discharge. We used nafamostat mesilate, a strong inhibitor of activated first complement component, to treat the attacks. She obtained subjective relief and her serological data were improved. Nafamostat mesilate was considered effective for HANE attack.
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PMID:[Hereditary angioneurotic edema associated with DIC and treated effectively by nafamostat mesilate]. 154 13

Nafamostat mesilate (NM), a synthetic protease inhibitor, is frequently used for the treatment of disseminated intravascular coagulation (DIC) in Japan. NM inhibits several proteases which may be importantly involved in the pathophysiology of DIC. Since tissue factor (TF) plays a critical role in DIC associated with septicemia, inhibition of the extrinsic pathway of coagulation by coagulation inhibitors may be useful for the treatment of DIC. NM inhibited extrinsic pathway activity (TF-F.VIIa mediated-F.Xa generation) in a concentration dependent manner; the IC50 was 1.0 x 10(-7) M. F.Xa was not inhibited by NM at the concentrations used in the experiment, suggesting that NM might inhibit TF-F.VIIa complex activity. When incubated with TF-F.VIIa complex, NM inhibited the complex activity with an IC50 of 1.5 x 10(-7) M, the same value that found for inhibition of extrinsic pathway activity. A Lineweaver-Bulk's plot of the inhibition demonstrated that NM inhibited TF-F.VIIa complex in a competitive fashion, with an inhibition constant (Ki) of 2.0 x 10(-7) M. These findings suggested that NM may be a potent inhibitor of TF-F.VIIa complex and the therapeutic effect of NM in DIC patients could be partly explained by inhibition of the extrinsic pathway of the coagulation system.
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PMID:Effect of nafamostat mesilate, a synthetic protease inhibitor, on tissue factor-factor VIIa complex activity. 802 16

1. Nafamostat mesilate (NM) is a novel serine-protease inhibitor used for the treatment of acute pancreatitis and disseminated intravascular coagulation. Recently, NM has been reported to cause hyperkalemia due to reduced urinary excretion of potassium (K). 2. This review briefly summarizes the roles of the cortical collecting duct (CCD) in the renal K excretion. 3. In vitro microperfusion technique was applied to examine whether NM, and its two metabolites, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol, directly act on the CCD. 4. It was demonstrated that these compounds act mainly on the apical membrane of the collecting duct cell in the CCD and inhibit the amiloride-sensitive sodium (Na) conductance, resulting in an inhibition of K secretion. PGBA had the most potent action. 5. This direct action of these two metabolites, rather than NM, could contribute to the NM-induced hyperkalemia.
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PMID:Mechanisms of hyperkalemia caused by nafamostat mesilate. 874 49

Nafamostat mesilate (FUT) was first reported by Fujii et al, in 1981 as a synthetic protease inhibitor. FUT has been reported as a drug for the treatments of DIC (disseminated intravascular coagulation) and acute pancreatitis and as an anticoagulant in extracorporeal circulation. FUT has a structure of ester conjugate of p-guanidinobenzoic acid and 6-amidino-2-naphthol. In in vivo, this ester site was found as the reaction center as well as the site for the catabolic changes. Plasma half life (t1/2 beta) of FUT was about 23.1 min, compared to about 55 seconds of the related compound, FOY. The inhibitory activity of FUT on the protease was found to be due to the mis-reading of serine protease in vivo.
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PMID:[Pharmacokinetics studies of nafamostat mesilate (FUT), a synthetic protease inhibitor, which has been used for the treatments of DIC and acute pancreatitis, and as an anticoagulant in extracorporeal circulation]. 1083 50

A 65-year-old man with chronic aortic dissection experienced two massive subcutaneous hemorrhages. Laboratory data indicated disseminated intravascular coagulation, whereas a contrast computed tomographic scan revealed a dilatated aortic arch with a partial thrombosis at the false lumen. Because disseminated intravascular coagulation can be caused by chronic aortic dissection, and the aortic arch was 6 cm in diameter, we performed graft replacement from the ascending to the descending aorta in a single stage. Before graft replacement, nafamostat mesilate, a protease inhibitor, was administered and the disseminated intravascular coagulation improved. Nafamostat mesilate may be useful for managing disseminated intravascular coagulation associated with chronic aortic dissection.
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PMID:Effects of nafamostat mesilate on coagulopathy with chronic aortic dissection. 1976 34

Nafamostat mesylate, an apparent soi-disant panacea of sorts, is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass, mitigate the inflammatory response in patients diagnosed with acute pancreatitis, and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East. The serine protease inhibitor nafamostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia. Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases, neuroinflammatory signaling cascades, and the endoplasmic reticulum stress responses, downregulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents, modulating the activity of intracellular signal transduction pathways, and supporting neuronal survival (brain-derived neurotrophic factor/TrkB/ERK1/2/CREB, nuclear factor kappa B. The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture. Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in patients undergoing cardiac, hepatic, renal, or intestinal transplant, preventing allograft rejection, and treating solid organ malignancies. Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.
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PMID:Nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia. 3259 33

Nafamostat mesylate (NM) is a synthetic serine protease inhibitor that can be used as an anticoagulant during blood purification in critically ill patients, as well as a treatment for disseminated intravascular coagulation. Although NM has been reported to reduce the risk of bleeding during blood purification, its effect on survival outcomes of patients who received blood purification treatments is unclear. We hypothesized that administration of NM during blood purification can reduce mortality in patients with sepsis. A post hoc analysis was conducted on a nationwide retrospective registry that included data from 3195 sepsis patients registered at 42 intensive care units throughout Japan. We evaluated the effect of NM on hospital mortality and bleeding complications using propensity score matching in 1216 sepsis patients who underwent blood purification in the intensive care unit (ICU). Two-hundred-and-sixty-eight pairs of propensity score-matched patients who received NM and conventional therapy were compared. Hospital and ICU mortality rates in the NM group were significantly lower than those in the conventional therapy group. However, rates of bleeding complications did not differ significantly between the two groups. These data suggest that administration of NM improved the survival outcomes of sepsis patients who underwent blood purification in the ICU.
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PMID:Nafamostat Mesylate Improved Survival Outcomes of Sepsis Patients Who Underwent Blood Purification: A Nationwide Registry Study in Japan. 3282 37