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)

The sick neonate may develop spontaneous or catheter-related thromboses, which must in part reflect poor regulation of the formation and activities of the coagulation enzyme, thrombin. We hypothesized that the balance between the generation and inhibition of thrombin may differ in sick neonates compared with healthy neonates. Fifty neonates with respiratory failure requiring mechanical ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had normal coagulation screening tests and a platelet count greater than 150 x 10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth weight, and health status were prepared. Eight plasma pools from 40 healthy neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of GA less than 30 wk were studied. Thrombin generation was measured by amidolysis of a chromogenic substrate, S2238, after defibrination, contact activation, and recalcification of the test plasmas. The contributions of antithrombin III, heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin were quantitated by SDS-PAGE followed by autoradiography and densitometry. Thrombin generation was similar for both healthy and sick neonates of GA 30-38 wk. However, the inhibition of thrombin was impaired in plasma from sick neonates of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/- 0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombin inhibition is impaired in plasma of sick neonates. 137 86

To estimate the degree of coagulopathy in abdominal sepsis, we measured the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme-linked immunosorbent assay in 38 patients with disseminated intravascular coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml, respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1 + 2, TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III levels in DIC due to sepsis were lower than those in DIC due to malignancy, the levels of F1 + 2, TAT and PIC in the former were not significantly more increased than those in the latter. The plasma levels of F1 + 2 were positively correlated with TAT and PIC in DIC patients with malignancy; however, there was no correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis. In addition, the levels of serum albumin in the two groups were similar. These results suggest that activation of coagulation and fibrinolytic systems may not be so prominent in cases of DIC due to abdominal sepsis, compared to related events in DIC due to malignancy. It is also suggested that the depletion of AT III in cases of sepsis is not only caused by a consumption related to intravascular coagulation or to an alternate distribution of protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis: determination of prothrombin fragment 1 + 2 and other markers. 138 63

1. North American poisonous snakes have a wide spectrum of complex venoms. 2. Venom, especially that of the rattlesnakes, may cause a variety of hemostatic abnormalities by directly, yet only partially, cleaving fibrinogen, activating the fibrinolytic system, or activating and clearing platelets through the action of proteolytic enzymes. 3. Because these venoms do not result in the generation of thrombin, the syndrome is distinct from true DIC. Bleeding or thrombosis is rare. 4. As thrombin generation remains intact, hemostasis is largely preserved despite dramatic changes in hemostatic tests. 5. Therapy with heparin, blood, or blood products is rarely indicated. 6. Therapy with antivenin in selected cases is logical and efficacious.
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PMID:Hemostatic aspects of envenomation by North American snakes. 140 81

We measured plasma heparin cofactor II (HC II) activity in patients with disseminated intravascular coagulation (DIC) due to various underlying diseases together with the levels of antithrombin III (AT III), pseudocholinesterase (a marker of hepatic synthesis), and various haemostatic molecular markers. Both HC II and AT III were decreased in DIC secondary to all the underlying diseases studied, except acute promyelocytic leukemia (APL), when compared with healthy subjects. The lowest HC II and AT III levels was observed in coagulopathy secondary to liver disease, the HC II level in sepsis was the second lowest. In DIC due to APL, the decrease in HC II was not accompanied by a decrease in AT III. Thus, we divided all 124 samples tested into APL and non-APL groups. The HC II level correlated positively with fibrinogen and plasminogen in both the APL and non-APL groups. In the APL group, the HC II level had a significant negative correlation with the thrombin-AT III complex (TAT), fibrinogen/fibrin degradation products, and D-dimer levels as well as the prothrombin time, while AT III showed no correlations with any of the haemostatic parameters. These results suggest that HC II may be consumed preferentially by thrombin in APL patients with DIC, and thus may spare the consumption of AT III. Accordingly, HC II seems to be a superior indicator of DIC than AT III in APL patients. Moreover, replacement therapy with HC II instead of AT III may be useful to treat DIC associated with APL. In the non-APL group, the HC II levels were positively correlated with the levels of AT III and pseudocholinesterase activity. This indicates that plasma HC II levels are closely related not only to consumption coagulopathy but also to hepatic synthetic activity, as is the case for plasma AT III.
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PMID:Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyelocytic leukemia. 141 8

Plasma concentration of thrombin-antithrombin III complex (TAT), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-2, D-dimer complex and urokinase-plasminogen activator (u-PA) activity were studied in 30 patients with acute nonlymphoblastic leukemia (ANLL), before and during antileukemic therapy. Fifteen patients showed signs of disseminated intravascular coagulation (DIC), 10 of them classified as M3, 2 as M2 and 3 as M5 subtypes. The initial levels of TAT complex were elevated in all ANLL patients. This increase was more pronounced in patients with DIC (p less than 0.05). TAT increased significantly during the treatment period in all cases. u-PA and PAI-1 levels were elevated but there were no statistically significant differences between patients with and without DIC. PAI-2 levels were below the limit of detection in controls and in patients. However, the initially elevated D-dimer complex levels were significantly higher in DIC cases (p less than 0.01) and they increased during the treatment period. A significant and positive correlation between D-dimer and TAT complex values was found in DIC patients (r = 0.68, p less than 0.001). The high TAT complex and D-dimer levels further increased during chemotherapy treatment strongly suggest a hypercoagulable state with secondary activation of fibrinolysis not severe enough to manifest itself as clinically evident DIC in the majority of cases.
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PMID:Increase in the D-dimer levels during treatment in patients with acute myelogenous leukemia. 142 55

Plasma levels of von Willebrand factor (vWf) are frequently elevated in patients with disseminated intravascular coagulation (DIC). To investigate the qualitative abnormalities of vWf and the possibility of its ex vivo modification in DIC, we analysed the multimeric composition of vWf in citrated plasma from 15 patients with DIC in the presence or absence of serine protease inhibitors (aprotinin and soybean trypsin inhibitor) and/or cysteine protease inhibitors (leupeptin, N-ethylmaleimide and EDTA). The proportion of large vWf multimers in plasma prepared in the presence of cysteine protease inhibitors was higher than those without such inhibitors. The addition of serine protease inhibitors during the preparation of plasma had no effect on the relative amounts of large multimers. The relative proportion of large multimers in plasma prepared without inhibitors and the difference between plasmas prepared with and without cysteine protease inhibitors correlated with plasma plasmin-alpha 2-plasmin inhibitor complex values, but not with other plasma or serum markers of DIC (platelet count, fibrinogen, FDP, D-dimer or thrombin-antithrombin III complex). We conclude that ex vivo proteolysis of plasma vWf occurs frequently in patients with DIC and cysteine protease inhibitors can protect this degradation.
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PMID:Enhanced ex vivo proteolysis of plasma von Willebrand factor in disseminated intravascular coagulation. 145 Mar 24

We investigated the imbalance between thrombin and plasmin activity in vivo with various grades of severity of disseminated intravascular coagulation (DIC) in relation to the underlying diseases. Plasma thrombin-antithrombin-III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) levels were measured in 133 blood samples obtained from patients with DIC. The TAT/PAP ratio was higher in patients with sepsis or solid cancer than in those with hematologic malignancies. In acute promyelocytic leukemia (APL), the TAT levels were the highest, but the PAP levels were even higher and the TAT/PAP ratio was the lowest. As for the severity of DIC, in mild DIC, both thrombin and plasmin activities were increased. In moderate DIC, the TAT/PAP ratio increased, and thrombin activity was much more predominant. However, in severe DIC, the ratio decreased, and plasmin activity became excessive. In 3 patients with acute myeloblastic leukemia, APL and pancreatic cancer, respectively, the PAP level remained high during heparin therapy although the TAT level was decreased. When tranexamic acid was given, the PAP level was selectively reduced, and the TAT/PAP ratio was markedly decreased along with clinical improvement. These results indicate that monitoring of the TAT/PAP ratio may contribute to decisions regarding the institution and performance of combination therapy for DIC using anticoagulants and antifibrinolytic agents.
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PMID:Imbalance between thrombin and plasmin activity in disseminated intravascular coagulation. Assessment by the thrombin-antithrombin-III complex/plasmin-alpha-2-antiplasmin complex ratio. 146 20

In order to elucidate the activation of the coagulation cascade in patients with malignant neoplasms, we measured the levels of plasma prothrombin fragment F1 + 2, which is liberated in the process of thrombin generation. Twenty healthy adults (Group A), 29 patients with malignancies not complicated with DIC (Group B) and 4 patients with DIC (Group C) were evaluated. The values of F1 + 2 in Group C (2.38 +/- 0.55 nmol/l) were significantly higher (p < 0.01) than those in Group A (0.52 +/- 0.19 nmol/l) and B (0.86 +/- 0.68 nmol/l). Many patients in Group B showed higher levels of F1 + 2 compared to normal subjects, however, no significant differences were found between Group A and B. With respect to other coagulation molecular markers such as TAT, D-Dimer and PIC, F1 + 2 levels revealed positive correlation to those levels. Concerning the clinical course of DIC, elevated levels of F1 + 2 normalized much rapidly than those of TAT and D-Dimer by continuous administration of heparin. In conclusion, the measurement of plasma F1 + 2 is important in monitoring the activation of coagulation system in patients with malignancies, especially with respect to early detection and treatment of DIC.
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PMID:[Evaluation of hypercoagulable state in patients with malignancies by using prothrombin fragment F1 + 2]. 146 81

We had a sixty-five year old male patient who suddenly complained of dyspnea and fever with pulmonary tuberculosis, severe respiratory failure, disseminated intravascular coagulation (DIC) and intractable bilateral pneumothoraces. From the first hospital day severe hypoxemia which did not respond to conventional oxygen therapy developed with a diffuse ill-defined reticulo-nodular shadow in the plain chest x-ray film. On the 2nd hospital day mechanical ventilation with 2cmH2O PEEP was introduced. Antituberculous agents as well as corticosteroids were started suspecting acute interstitial pneumonia with pulmonary tuberculosis and adult respiratory distress syndrome (ARDS). Medication was followed by the treatment of Gabexate mesilate and heparin against DIC on laboratory data. Though clinical findings and pulmonary infiltrate on chest x-ray film transiently improved, right pneumothorax occurred suddenly on the 6th day followed with left pneumothorax on the 36th day. Tube drainage of both pleural spaces and repeated instillation of thrombin-rich oxycel cotton via bronchofiberscope failed to stop air leakage. He ultimately expired on 49th hospital day. At postmortem lung had multiple bilateral bulla several of which ruptured to the pleural site and caseating necrotic area containing bacilli positively stained with Ziehl-Nielsen stain in the bilateral upper lobe. No typical caseating necrotic lesion, however, was found in the other lung tissue. Therefore, it seemed to show a chronic phase of diffuse alveolar damage (DAD).
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PMID:[A case of pulmonary tuberculosis associated with severe respiratory failure, DIC and intractable bilateral pneumothoraces]. 148 64

A sandwich enzyme-linked immunosorbent assay (ELISA) has been developed to measure plasma levels of thrombin-antithrombin complex (TAT). The assay is performed in a microtitre plate using polyclonal antibodies specific for antigenic determinants on prothrombin and antithrombin. Antibody to prothrombin was immobilized on a solid phase, using a titre predetermined to optimize capture of TAT. The performance of the microtitre plate ELISA for TAT has been extensively investigated and compared with the performance characteristics of a tube-based ELISA for TAT which is available commercially (Enzygnost-TAT, from Behringwerke, Marburg, Germany). Studies with plasma containing various levels of prothrombin showed that the zymogen competed with TAT for capture antibody in both assays. Variations in prothrombin levels between plasma samples present a potential source of artifact, but one which does not critically affect the performance of either assay in detecting large elevations in TAT. A high correlation (r = 0.88) was established between the results of plasma samples assayed by both assays, whether citrate or EDTA anticoagulant was used to prepare plasma. High correlations (r > 0.90) were also established for each assay between the results of plasma prepared with EDTA as compared to citrate anticoagulant. Both assays were able to discriminate completely between a group of 16 normal controls and a group of 31 patients with disseminated intravascular coagulation (DIC).
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PMID:A microtitre plate ELISA to measure thrombin-antithrombin complex using pan-specific antibodies. 148 1


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