Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-eight patients with hepatic malignancy (47 with hepatocellular carcinoma, one with metastatic colon carcinoma), who underwent transcatheter arterial embolization (TAE) for treatment of hepatic neoplasms, were investigated to determine the effects of TAE on coagulation and fibrinolysis. TAE was followed by a significant decrease in the platelet count (P less than .001); a prolongation of prothrombin time (P less than .001); an early increase in levels of fibrinopeptide A (P less than .01), fibrinopeptide B beta-15-42 (P less than .001), and fibrin(ogen) degradation products (P less than .001); and a delayed increase in the fibrinogen level (P less than .001), without a significant prolongation of the activated partial thromboplastin time. In the three patients who developed disseminated intravascular coagulation (DIC) after TAE, a reduction of both the platelet count and fibrinogen level occurred significantly earlier and in a more severe form than in the other patients without DIC; this reduction preceded the onset of the characteristic symptoms of DIC. Data suggested that close monitoring of platelet count and fibrinogen level is important for early detection of DIC following TAE.
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PMID:Hepatic neoplasms: effects of transcatheter arterial embolization on coagulation and fibrinolysis. 215 36

Platelet function following inoculation of chemically induced carcinoma was evaluated in the rat. The original line of tumor (NGW1) was obtained using N-methyl-N-nitrosoguanidine. After trypsin homogenation a cell suspension of 0.3 X 10(6) viable tumor cells was injected subserosally in the cecum of each animal. Controls received injections of equal volumes of 0.9% NaCl solution or trypsin. The animals were subjected to laparotomy 2, 4, and 6 weeks after inoculation. Platelet function was assessed in vivo by measuring bleeding time and blood loss during mesenteric vessel transection or liver resection upon laparotomy. Hemoglobin, hematocrit, platelet count, activated partial thromboplastin time, platelet aggregation, thromboxane B2, platelet factor 4, and fibrinogen levels were evaluated after sacrifice by exsanguination. Significant decrease in bleeding time and blood loss was observed in animals with local primary tumors as well as in rats with lymph node metastases. Hemoglobin and hematocrit were decreased in the presence of metastases. Platelet count was not changed. Activated partial thromboplastin time was not affected by the presence of tumor. Platelet aggregation in vitro was accelerated in the presence of primary tumor or lymph node metastases, as well as following addition of tumor cells to platelet suspensions. No changes in thromboxane B2 or platelet factor 4 could be registered. Fibrinogen levels were decreased in the presence of liver metastases. Enhancement of primary hemostasis and platelet function in the presence of colon carcinoma in the rat was demonstrated both in vivo and in vitro. Direct or indirect interaction of the tumor cell with thrombocytes may play a role in determining the metastatic potential of the neoplasm.
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PMID:Hemostasis following inoculation and during spreading of colon carcinoma in the rat. 375 13

Peptidomimetic thrombin inhibitors (TI), derived from L-Asp-D-Phe were examined in confluent monolayers of a human colon carcinoma cell line (Caco-2) to elucidate their transepithelial transport properties. Effect availabilities, based on activated partial thromboplastin time (aPTT) measurements in rats, after peroral administration of five TI correlated reasonably well with permeability coefficients obtained from in vitro transport studies in Caco-2 monolayers, whereas physicochemical properties, such as molecular mass, solubilities, pKa and octanol-buffer partition coefficients failed to yield meaningful relationships. Substitution of the beta-carboxylic group of L-Asp leads to analogues which are mainly transported by passive diffusion, while an unsubstituted carboxylic group favours carrier-mediated active transport. The effects of concentration, temperature, competitive inhibitors and direction dependence on in vitro transport were investigated. The results obtained are compatible with a saturable carrier-mediated transport, operating parallel to a passive paracellular route. The Michaelis-Menten parameters for the active transport component (Km = 1.67 mM, Vmax = 26.5 pmol min-1 mg protein-1) indicate an involvement of the intestinal di/tripeptide transport system for one of the TI. The Caco-2 transport model may be helpful for the design of perorally active peptidomimetics.
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PMID:Transepithelial transport properties of peptidomimetic thrombin inhibitors in monolayers of a human intestinal cell line (Caco-2) and their correlation to in vivo data. 761 21

Bleeding complications are one of the major risks during oral anticoagulation. If further anticoagulation is indicated, low-molecular-weight heparin (LMWH) may offer an alternative treatment in those patients. In a prospective, nonrandomized study, 120 patients have been switched from oral anticoagulants to LMWH because of bleeding complications or other severe side effects during treatment with vitamin K antagonists. Indication for further anticoagulation was prophylaxis of recurrent thromboembolism, artificial heart valve replacement, atrial fibrillation with embolism and cardiomyopathy. The treatment period ranged from 2 months to 10.8 years. No fatal embolism occurred. One major but not severe episode of gastrointestinal bleeding occurred in a patient with an as yet unknown colon carcinoma. The cumulative treatment period amounts to 250 years. No drop in platelet count occurred in any patient. No other side effects were observed. LMWH was injected subcutaneously at doses ranging from 2500 to 15,000 anti-factor Xa units per day by the patient himself. The dose was adjusted on the basis of body weight, bleeding risk and thromboembolic risk. The results indicate that LMWH may be effectively and safely used as alternative anticoagulant regimen in patients with side effects or other complications on oral anticoagulants.
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PMID:Long-term anticoagulation of outpatients with adverse events to oral anticoagulants using low-molecular-weight heparin. 920 Mar 42