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)

In vitro effects of S-2441, H-D-Pro-Phe-Arg-NH-Heptyl, include potent anti-bradykinin activity and broad-spectrum inhibition of serine proteases involved in the coagulation cascade. In this study, rats infused with 7.8 X 10(8) viable Escherichia coli were treated either with saline (group A) or with intravenous (0.1 mg) and intraperitoneal (0.4 mg) doses of S-2441 (group B). Survival rates for groups A and B were 68% and 98%, at 12 hours (P less than 0.001), and 37% and 73% at 24 hours (P less than 0.001), respectively. Hematologic studies revealed that S-2441 significantly inhibited E. coli-induced prolongation of prothrombin time and partial thromboplastin time as well as a rapid decrease in the values of factor X, anti-thrombin III, and fibrinogen. In addition, S-2441 attenuated E. coli-induced hypoglycemia and a marked reduction of serum complement level. Ultrastructural evaluation of the liver demonstrated that S-2441 prevented the development of extensive sinusosoidal microthrombosis and hepatocellular necrosis. The results indicate that S-2441 affords protection in lethal gram-negative bacteremia owing in part to attenuation of disseminated intravascular coagulation and complement-mediated reactions. The findings are consistent with the concept that S-2441 and related oligopeptides modulate serine protease-mediated responses involving inhibition of active enzymes with competitive antagonism of pharmcologically active products formed during the activation of coagulation, fibrinolytic, kallikrein, and complement systems.
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PMID:Efficacy of S-2441, a synthetic oligopeptide, in a rat model for gram-negative bacteremia. 388 74

Plasma fibronectin (Fn), a glucoprotein of suggested importance in host defence during infections also seems to be involved in blood coagulation and to be consumed during clot formation. Low Fn concentrations have been found in patients with DIC, but also in patients with infections without signs of overt DIC. In a randomized trial of Fn supplementation 28 patients with moderately severe infections, hospitalized in the Department for Infectious Diseases, were scheduled to receive either cryoprecipitate from 30 donors (n = 14) or 250-300 ml of stored plasma (n = 14). To elucidate the relationship between Fn plasma levels, Fn-rich cryoprecipitate infusion, and possible low-grade DIC in these patients, we measured platelet count, prothrombin complex (NT), fibrinogen, F V, F VIIIR:Ag, F VIII:C, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin III (AT), kallikrein-inhibiting activity (KI) and spontaneous proteolytic activity (SPA). Compared to healthy controls, high initial values (p less than .001) were found for fibrinogen, F VIIIR:Ag, F VIII:C and SPA. Most values for platelets, F V, Plg, AP and KI were within the reference range. Low levels (p less than .001) were found for Fn, NT, F XII, AT and for the ratio F VIII:C/F CIIIR:Ag. A significant correlation was found between F XII, Plg and AT. Fn correlated poorly to the other variables. Cryoprecipitate infusion normalized the Fn concentration, but had no influence on other measured variables. Thus, although no patient had clinically overt DIC, and all survived, we observed a distinct pattern indicating activation of the coagulation system. Fn levels were low, but were not specifically related to this activation.
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PMID:Fibronectin and other DIC-related variables in patients with moderately severe infections receiving cryoprecipitate. 393 19

In a controlled study of fibronectin supplementation in sepsis, 11 ICU patients in septic shock were scheduled to receive either cryoprecipitate from 20-40 donors (n = 6) or 250-300 ml of stored plasma (n = 5) (two infusions over 24 h). We wanted to: compare some "conventional" DIC variables in the ICU (platelet count, prothrombin complex = NT, FDP) to additional variables: Fibronectin (Fn), fibrinogen (Fg), F V, FVIII R:Ag, F VIII:C activity, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin (AT), kallikrein inhibiting activity (KI) and spontaneous proteolytic activity (SPA): study the effects of cryoprecipitate or plasma infusion on three variables. Samples were taken before the first infusion, and 24 and 48 h after. At onset, high levels (p less than .001 when compared to blood donors) of Fg, VIIIR:Ag and VIII:C were seen. KI levels were within the normal range. F V was low (p less than .05). Fn, NT, XII, Plg, AP and AT were markedly low (p less than .001). SPA showed great variation. When compared to 28 patients with severe infections, but not in septic shock, the ICU group had higher VIIIR:Ag (p less than .05) and VIII:C (p less than .01), and lower XII, Plg, AP and AT (p less than .001). FDP was elevated in all ICU patients. Five patients were thrombocytopenic, and in these a pattern with low levels of Plg and AT was observed. Fn did not correlate well to the other variables measured. These results indicate a marked activation of coagulation and fibrinolysis in these severely ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibronectin and other DIC-related variables in septic ICU patients receiving cryoprecipitate. 393 20

It has been shown that the development in animals of disseminated intravascular coagulation (DIC) caused by long-term intravenous infusion of thrombin was accompanied by appreciable activation of the kallikrein-kinin system, being characteristic of acute pathological processes. In the initial stages of the process development, prekallikrein and kallikrein inhibitor were observed to be secreted from the lungs to arterial blood. Further development of DIC led to the depletion of the reserves of the kinin system. Pretreatment with a single low dose of acetylsalicylic acid considerably reduced the total animals' lethality and postponed blood kinin system activation determined by the development of DIC.
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PMID:[Activation of the blood kallikrein-kinin system in disseminated intravascular coagulation in rats. The significance of the pulmonary component and an attempt at correction with aspirin]. 633 54

Levels of prekallikrein and HMW kininogen that had increased during pregnancy decreased with start of labor. The role of the kinin-forming system with oxytocin in the mechanism of labor was suggested from the results of decreased prekallikrein and HMW kininogen, appearance of a free kallikrein-like enzyme during labor, and from the case of arrested labor in which both prekallikrein and HMW kininogen were markedly decreased. Prekallikrein was markedly decreased in patients with acute obstetrical DIC and severe toxemia of pregnancy. The excessive activation of prekallikrein in DIC seemed to be of help for understanding such clinical signs as shock, abnormal labor, and increased permeability in obstetrical DIC.
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PMID:The kinin-forming enzyme system in pregnancy and obstetrical DIC. 642 Dec 72

In a search for new variables, for the diagnosis of disseminated intravascular coagulation (DIC) and for guidelines of therapy in such conditions, 22 severely ill patients were studied. The diagnosis of DIC was based on determinations of platelet counts, prothrombin complex (Normotest), antithrombin (AT), fibrinogen degradation products and fibrinogen. Nine patients were diagnosed as having DIC, eight patients were referred to a suspected DIC group and five to a group of no DIC. The laboratory findings were found to agree with the clinical status. In addition several new parameters were investigated: factor XII, prekallikrein, Simplastin A--another prothrombin complex factor method, factor X, plasminogen (PLG), antiplasmin (AP) and kallikrein inhibitors (KI). Platelet counts, prothrombin complex and antithrombin were mostly pathological in DIC-patients. Of the alternative tests prothrombin complex, fibrinopeptide A and the kallikrein inhibitor as well as the two tests for fibrinolysis (PLG and AP) were significantly altered in DIC-patients. The inhibitor capacity (AT, APV and KI) was lower in patients who died than in survivors and decreased still further in those of the non-survivors who had DIC. Thus the inhibitors can be used as predictors of outcome and hopefully for guiding therapy. To establish the diagnosis of DIC we suggest measurement of platelet count, prothrombin complex, plasminogen as well as of the inhibitors.
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PMID:Blood coagulation and fibrinolytic factors and their inhibitors in critically ill patients. 655 31

Plasma kallikrein acts as a chemical mediator of microcirculation and as a contracting agent of smooth muscle by liberating bradykinin from high molecular weight kininogen. In addition, prekallikrein relates to coagulation process of blood. It is, therefore, a intriguous problem to know the behavior of prekallikrein in obstetrics, especially as to the mechanisms of labor, edema of toxemia and DIC. The following results were obtained: 1) Plasma prekallikrein determined by chromogenic tripeptide substrate was increased with advance of gestational ages, and reached maximum (213.5 +/- 31.1%) at the term. At the beginning of labor, the prekallikrein level was suddenly decreased, and remained low during labor. Rapidly lowered plasma prekallikrein during labor seems to be result from consumption of prekallikrein due to conversion to kallikrein. The kallikrein probably relates to uterine contraction by forming bradykinin. 2) A lowered plasma prekallikrein level was observed in 29 cases of toxemia, especially in edema type. In toxemic cases, kallikrein may play an important role in producing edema by bradykinin. 3) In 16 cases of DIC, prekallikrein was significantly low (p less than 0.001) especially in cases of endotoxic shock, suggesting consumption of prekallikrein as in other various coagulation fibrinolysis factors in DIC.
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PMID:[Physiological and pathological significance of plasma prekallikrein in obstetrics]. 692 84

Thromboembolism of minor vessels in the lungs is almost constantly seen in posttraumtic lung insufficiency. Many investigators consider it as the primary factor in the pathogenesis of this condition. The present paper deals with screening of the coagulation system as part of a more extended project also investigating changes in the fibrinolytic system and the kallikrein-kinin system. The data are also to be compared with morphological findings during the development of experimental posttraumatic lung insufficiency. The experimental syndrome was evoked in Labrador retriever dogs by haemorrhagic hypotension combined with clamping of the portal triad. The surgical procedure was extended to additional thoracotomy in one group of dogs. Group I, without thoracotomy, were followed for 12 hours. Group II, with thoracotomy, were followed until they succumbed (3-14 hours). Thrombotest (TT) showed a steady prolongation of clotting time in both groups, whereas Cephotest did not reveal any alterations, except for a significant prolongation in group II just before collapse. Fibrinogen was markedly reduced in both groups. Platelets and leucocytes were significantly reduced, but only in group II. It is concluded that the present data are indicative of disseminated intravascular coagulation. The involvement of the intrinsic coagulation system is questioned.
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PMID:Blood cells and coagulation during experimental lung insufficiency in dogs. 693 93

From the viewpoint of fetal distress related disseminated intravascular coagulation (DIC), the Hageman Factor, kinin-kallikrein system were investigated and on the other hand the adaptation of the normal newborn to extrauterine life was also evaluated. (1) The Kininogen volume of the cord venous blood was approximately 1/2-1/3 or there abouts and was remarkable in serious cases of asphyxiated newborn. (2) In a similar manner the Hageman factor decreases in asphyxiated newborn. On the other hand, SFMC increases in aspyxiation as well as FDP. According to these results, there seems to be a coagulation obstruction due to consumption. Or it may be interpreted as an inhibition of kinin separation. In any event it may be considered as a rational contribution to the living body. (3) Based on the above, in cases of serious asphyxiation, DIC may possibly play a role and in these cases and the kininkallikrein system may be one of the mediators.
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PMID:A biochemical study on the kinetics of kininogen in asphyxiated newborn. 706 58

The hypotension and disseminated intravascular coagulation (DIC) in bacteremia is thought to be mediated by the combined actions of cytokines, prostaglandins, and complement. The contact system, via the release of bradykinin and the activation of Factor XI, has been postulated to be contributing to the observed hypotension and DIC. Using a mAb to Factor XII (C6B7), we blocked the activation of the contact system in an established experimental baboon model in which Escherichia coli was infused to produce lethal bacteremia with hypotension. The untreated group (n = 5) displayed contact activation, manifested by a significant decrease in high molecular weight kininogen (HK) and a significant increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-Kal). The C6B7-treated group (n = 5) showed an inactivation of Factor XII and the changes in HK and alpha 2M-Kal complexes were prevented. Both groups developed DIC manifested by a decrease in platelet, fibrinogen, and Factor V levels. The untreated group developed irreversible hypotension. The treated group experienced an initial hypotension that was reversed and extended the life of the animals. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system, and specific antibody therapy can modulate both the pathophysiological and biochemical changes.
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PMID:The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. 767 10


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