piperidines and Disseminated-Intravascular-Coagulation

To investigate the characteristic differences between disseminated intravascular coagulation (DIC) found in surgical sepsis (septic DIC) and those found in patients with advanced gastrointestinal cancer (cancer DIC), we focused on two substances, endotoxin and platelet- activating factor (PAF).. Coagulation test values were determined in 36 patients with DIC, and endotoxin and PAF concentrations in 13 of these patients. Seven septic patients were given a PAF antagonist to evaluate its usefulness in treating thrombocytopenia.. Blood PAF and endotoxin concentrations were higher in patients with septic DIC, but they were almost normal in those with cancer DIC. Blood PAF concentrations showed a strong positive relationship to endotoxin only in septic DIC. There was a negative correlation between PAF concentrations and platelet counts in septic patients; platelet counts gradually increased after the administration of a PAF antagonist.. PAF is inversely associated with platelet counts in patients with septic DIC. A PAF antagonist showed marked inhibitory effects on the characteristic changes of septic DIC, especially thrombocytopenia.

Topics: Carcinoma, Hepatocellular; Data Interpretation, Statistical; Disseminated Intravascular Coagulation; Endotoxins; Gastrointestinal Neoplasms; Humans; Liver Neoplasms; Piperidines; Platelet Activating Factor; Pyridinium Compounds; Sepsis; Surgical Procedures, Operative

Lung cancer complicated with Trousseau syndrome (TS) or disseminated intravascular coagulation (DIC) has a severe prognosis. We herein report an elderly lung cancer patient who presented with a critically ill condition due to concomitant TS and DIC and responded dramatically to alectinib. There are no rules regarding treatment indications based on the age or severity of critically ill patients. If the patient's cancer cells are positive for anaplastic lymphoma kinase rearrangement, alectinib is worthwhile to administer, even in a critically ill condition. In our patient, anticoagulation failed to suppress the TS complications. We also report how to prevent the recurrence of TS.

Topics: Adenocarcinoma of Lung; Aged; Carbazoles; Critical Illness; Disseminated Intravascular Coagulation; Humans; Lung Neoplasms; Piperidines

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Antineoplastic Agents; Delayed Diagnosis; Disease Susceptibility; Disseminated Intravascular Coagulation; Fatal Outcome; Humans; Immunocompromised Host; Lymphoma, Mantle-Cell; Male; Meningitis, Bacterial; Neoplasm Proteins; Piperidines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; Receptors, Antigen, B-Cell; Risk Factors; Shock, Septic

Topics: Carbazoles; Crizotinib; Disseminated Intravascular Coagulation; Drug Resistance, Neoplasm; Gene Amplification; Humans; Liver Neoplasms; Piperidines; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Pyrazoles; Pyridines

Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Contraindications; Delivery, Obstetric; Disseminated Intravascular Coagulation; Female; Fetal Death; Fetus; Humans; Infusions, Intravenous; Labor, Induced; Misoprostol; Oxytocics; Piperidines; Pregnancy; Remifentanil

We examined whether JTV-803, a specific activated factor X inhibitor independent of antithrombin III (ATIII), is effective against disseminated intravascular coagulation (DIC) in rat models induced by tissue factor (TF) or lipopolysaccharides (LPS). In male Wistar rats, DIC was induced by a 4 h infusion of thromboplastin (3.75 U/kg) or LPS (50 mg/kg). The rats were given JTV-803 (0.3 or 3 mg/kg, bolus intravenously) (JTV-803 groups) or low molecular weight heparin (LMWH groups) (200 U/kg, bolus intravenously) prior to an injection of TF or LPS. The results showed that JTV-803 was dose-dependently effective against DIC in both TF-induced and LPS-induced rat models. This anti-DIC effect of JTV-803 at higher doses was almost equivalent to that of LMWH in both types of DIC. Plasma ATIII activity was more prominent in the group treated with JTV-803 than in that treated with LMWH. None of rats died in the TF-induced DIC model with or without drug administration. On the contrary, seven of 22 rats died (mortality rate, 31.8%) in the LPS-induced DIC model without drug administration. Although the mortality rate of rats induced with LPS and treated with LMWH was quite high (6/16, 37.5%), none of the LPS-induced rats treated with JTV-803 died. These findings suggested that JTV-803 can treat both TF-induced and LPS-induced DIC models, and that this drug has greater potential in preserving ATIII and in improving the prognosis of DIC.

Topics: Animals; Anticoagulants; Antithrombin III; Biomarkers; Blood Proteins; Dalteparin; Disseminated Intravascular Coagulation; Dose-Response Relationship, Drug; Drug Design; Drug Evaluation, Preclinical; Factor X; Hemostasis; Isoquinolines; Kidney Glomerulus; Lipopolysaccharides; Male; Piperidines; Pyridines; Rats; Rats, Wistar; Tetrahydroisoquinolines; Thromboplastin

The new thrombin inhibitor CRC 220 was characterized in vivo for its antithrombotic effects. CRC 220 led to a dose-dependent prolongation of clotting parameters as determined in rats, rabbits, dogs, sheeps, pigs and monkeys. We evaluated the efficacy of CRC 220 to prevent thrombus formation in arteries and in the microcirculation in different animal models. In a rabbit model of tissue factor-induced coagulation activation, infusion of 0.5 mg/kg x h CRC 220 (3 hours) led to a significant prevention of fibrinogen decrease. In a rat model of lethal LPS-induced DIC CRC 220 significantly prevented the mortality rate after a 4h-infusion of 0.75 mg/kg x h. Thrombin-induced platelet aggregation in rat lungs could be prevented by the i.v. bolus injection of CRC 220. A dose of 0.3 mg/kg leads to a reduction of more than 80% of platelet deposition in the lung, significant inhibition was still observed 90 minutes after CRC 220 administration; at this time the inhibitor had already been cleared from plasma. Arterial thrombosis was induced in rabbits by squeezing and stenosis of the A. carotis. The i.v. bolus administration of CRC 220 dose-dependently prevented thrombus formation, an ED50 of 0.03 mg/kg was calculated. This dose was associated with only a minor prolongation of aPTT.

Topics: Animals; Antithrombins; Blood Coagulation; Dipeptides; Disseminated Intravascular Coagulation; Dogs; Dose-Response Relationship, Drug; Female; Macaca fascicularis; Male; Mice; Piperidines; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Rats; Rats, Sprague-Dawley; Sheep; Swine; Thrombosis

A possible role of platelet-activating factor (PAF) in the occurrence of the two septic complications, i.e., disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) was investigated, employing a rabbit model and a novel PAF antagonist E5880. By an instillation of fecal suspension into the common bile duct of the rabbit, manifestations of DIC and MOF were observed with high reproducibility by 9 hours after the septic insult. E5880 was intravenously administered to 12 rabbits for 1 hour after the septic insult at dose of 1 mg/kg (n = 6) or 3mg/kg (n = 6). All the rabbits were subjected to observation of vital signs and serial determination of laboratory tests for 9 hours and then lung, liver and kidney were removed for histological examination. Blood endotoxin level increased significantly by 9 hours after the septic insult. Although administration of E5880 did not affect the endotoxemia, the antagonist attenuated in a dose related manner laboratory manifestation of DIC such as thrombocytopenia and prolonged prothrombin time as well as that of MOF such as increase in serum bilirubin and creatinine level. The beneficial effect of E5880 on MOF was also confirmed by the histological evaluation. These observations indicated that PAF is deeply involved in the occurrence of DIC and MOF due to sepsis and E5880 may be one of the modalities to treat or prevent these two major septic complications.

Topics: Alanine Transaminase; Animals; Bacterial Infections; Blood Cell Count; Blood Urea Nitrogen; Cholangitis; Common Bile Duct; Disseminated Intravascular Coagulation; Endotoxins; Fibrinogen; Hematocrit; Liver; Male; Multiple Organ Failure; Partial Thromboplastin Time; Piperidines; Platelet Activating Factor; Pyridinium Compounds; Rabbits

The effect of heparin, hirudin, and a synthetic thrombin inhibitor on antithrombin III, fibrinogen and platelets was studied in a rat model of disseminated intravascular coagulation (DIC) induced by thrombin infusion. Antithrombin III is consumed during thrombin infusion to a limited degree. Simultaneous administration of exogenous thrombin inhibitors ameliorates the consumption of fibrinogen and platelets. At high thrombin doses, tolerated only during additional administration of thrombin inhibitors, heparin leads to increased consumption of antithrombin III, whereas hirudin and the synthetic inhibitor do not. In every case, the thrombin effect on fibrinogen and platelets is inhibited.

Topics: Animals; Antithrombin III; Dipeptides; Disseminated Intravascular Coagulation; Female; Fibrinogen; Heparin; Hirudins; Male; Piperidines; Platelet Count; Rats; Rats, Inbred Strains; Thrombin