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

Human plasma prekallikrein (Fletcher factor) clotting activity and antigen levels have been examined in various clinical conditions. Prekallikrein antigen was measured by a newly developed, specific, and sensitive radioimmunoassay. The assay had no demonstrable cross-reactivity with human urinary kallikrein nor, in the species tested, animal plasma prekallikrein. This assay was able to measure plasma kallikrein after its biological functions had been inactivated by plasma inhibitors. Normal human pooled plasma contained approximately 50 microgram/ml prekallikrein. Quantitative measurement of plasma prekallikrein was possible for concentrations as low as 0.3% of that of normal pooled plasma. A good correlation (correlation coefficient = 0.71) existed between titers of plasma prekallikrein measured by Fletcher factor clotting assays and radioimmunoassays among 40 normal subjects. Both prekallikrein clotting activity and antigen were significantly reduced in plasmas of patients with advanced hepatic cirrhosis or DIC. Prekallikrein activity and antigen were mildly decreased in plasmas or serums of patients with chronic renal failure and nephrotic syndrome but were normal in those of patients under treatment with warfarin or suffering from SLE, rheumatoid arthritis, sarcoidosis, or HANE. Human cord serum contained a lower titer of prekallikrein antigen than adult serum. Strenuous physical exercise did not significantly change plasma prekallikrein levels.
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PMID:Human plasma prekallikrein (Fletcher factor) clotting activity and antigen in health and disease. 65 66

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

C1-Inhibitor (Berinert, C1 INH), a 104 kDa protein, inhibits complement components (C1 esterase) as well as enzymes of the contact phase of coagulation (Factor XII, Factor XI) and kallikrein, thus regulating kinin generation. C1 INH is used for the treatment of the hereditary angioneurotic edema. This paper will give a survey about the evidence in recent literature concerning the potential efficacy of the compound on other diseases associated with shock, capillary leakage and inflammation as well. In our own experiments we evaluated whether the compound could influence acute inflammatory reactions or the severe systemic inflammatory response syndrome (SIRS) as a consequence of an experimental septic shock. To prevent the sepsis-induced DIC we co-infused the thrombin inhibitors AT III or rec. hirudin in combination with C1 INH. Coinfusion of C1-inhibitor (50-200 U/kg x h) with either rec. hirudin or AT III significantly improved survival rate compared to thrombin inhibitor alone.
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PMID:Influence of C1-inhibitor on inflammation, edema and shock. 817 80

Localized edema of the larynx and pharynx leading to death from asphyxia has long been recognized as a characteristic symptom of hereditary angioneurotic edema (HANE). Long-term follow-up of younger HANE patients has revealed that transient localized acute attacks of edema affect tissues where the microcirculation maintains the blood supply. However, with aging, HANE attacks precipitate disseminated intravascular coagulation (DIC) or multiple organ failure (MOF). Substitution with a C1-inhibitor (C1-INH) has resulted in a fulminant lethal end with a rapid and profound decrease in antithrombin-III (AT-III) activity. A possible mechanism is as follows: Exogenous stimuli activate plasma proteinase systems with the generation of plasma kallikrein that activates the tissue factor pathway (TF) and liberates bradykinin (BK). In younger patients, BK enhances vascular permeability. In the elderly, activated TF is controlled by tissue factor pathway inhibitor (TFPI) and generates thrombin, which is the target enzyme of AT-III and precipitates DIC or MOF. In elderly patients, the characteristic symptom of HANE is hypercoagulation by age-related changes in the biosynthesis of AT-III or TFPI.
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PMID:Hereditary angioneurotic edema and thromboembolic diseases: I: How symptoms of acute attacks change with aging. 965 97

The plasma kallikrein-kinin system (KKS) participates in the pathogenesis of inflammatory reactions involved in cellular injury, coagulation, fibrinolysis, kinin formation, complement activation, cytokine secretion and release of proteases. It has been shown that KKS activation in the systemic inflammatory response syndrome results in decrease of its component plasma proteins. Similar changes have been documented in diabetes, sepsis, children with vasculitis, allograft rejection, disseminated intravascular coagulation, patients with recurrent pregnancy losses, hereditary angioedema, adult respiratory distress syndrome and coronary artery disease. Direct involvement of the KKS in the pathogenesis of experimental acute arthritis and acute and chronic enterocolitis has been documented by previous studies from our laboratory using experimental animal models. It has been found that in HK deficient Lewis rats, experimental IBD was much less severe. We showed a genetic difference in kininogen structure between resistant Buffalo and susceptible Lewis rats, which results in accelerated cleavage of HK and it is responsible for the susceptibility to the inflammatory process in the Lewis rats. It has been demostrated that therapy with a specific plasma kallikrein inhibitor (P8720) modulated the experimental enterocolitis, arthritis and systemic inflammation. Furthermore, it has been shown that a bradykinin 2 receptor (B2R) antagonist attenuates the inflammatory changes in the same animal model. We have showed that a monoclonal antibody targeting HK decreases angiogenesis and arrests tumor growth in a syngeneic animal model. In summary, these results indicate that the plasma KKS plays a central role in the pathogenesis of chronic intestinal inflammation, arthritis and angiogenesis.
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PMID:[High molecular weight kininogen in inflammation and angiogenesis: a review of its properties and therapeutic applications]. 1670 6