Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Influence of the protein C activator from snake venom on blood coagulation was studied. Incubation of different concentrations of the activator with rat blood plasma resulted in a dose-dependent prolongation of the activated partial thromboplastin time (APTT). Cleavage of the protein C to the active form was detected by electrophoresis. Intravenous administration of the activator (100 mg/kg) into rats led to prolongation of APTT to 242 +/- 80%, to increase in the plasminogen activator level to 145 +/- 29% and to decrease in the factor V activity to 57 +/- 14%. When thrombosis was induced by means of administration of the thromboplastin lethal dose, pretreatment with the activator prevented animal death in 90% of cases. The effects of the activator observed appear to occur via transformation of the endogenous protein C into its active form.
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PMID:[Antithrombotic effect of protein C activator from a snake venom]. 261 27

There is uncertainty as to which preoperative examinations are necessary before performing regional anesthesia. Therefore an interdisciplinary consensus conference was established to obtain recommendations on some of the open questions related to this topic. Preoperative laboratory examinations are not necessary prior to peripheral nerve blocks near large vessels if these are easy to compress. In patients on anticoagulant therapy direct puncture of the vessel should be avoided. Prior to spinal or epidural anesthesia, no preoperative laboratory examinations are necessary if no anamnestic or clinical evidence of coagulation disorders exists. Otherwise the following examinations are useful: clotting time, prothrombin time, partial thromboplastin time (PTT), and thrombocyte count. Low-dose heparin prophylaxis is no contraindication to spinal or epidural anesthesia. However, in patients at increased risk of bleeding or with low body weight, PTT and thrombocyte count are necessary. Since at present no definite data exist as to the bleeding risk in patients treated with low-molecular-weight heparin prophylaxis, spinal/epidural anesthesia should be performed in controlled studies only under these conditions. This particular precaution seems to be necessary because low-molecular-weight heparin increases levels of plasminogen activators (t-PA) and therefore has fibrinolytic activity. If plasma expanders are administered perioperatively, the highest bleeding risk exists after dextran infusions. There is also an increased bleeding risk if nonsteroidal anti-inflammatory drugs, especially acetylsalicylic acid, are administered repeatedly within 5 days prior to spinal/epidural anesthesia. In these patients preoperative determination of the clotting time appears necessary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hemostatic requirements for the performance of regional anesthesia. Workshop on hemostatic problems in regional anesthesia]. 268 21

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.
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PMID:Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy. 275

Coagulation disorders have been noted during orthotopic liver transplantation (OLT) especially just after reperfusion of the grafted liver. This study was undertaken to clarify the coagulation disorders following reperfusion of the liver graft. OLT was carried out in adult mongrel dogs using a cuff technique. Fresh and 24-hour preserved livers were grafted. Platelet count (P1), activated partial thromboplastin time (A-PTT), prothrombin time (PT) and plasma fibrinogen levels (Fng) were measured before and after OLT. Next perfusate obtained from fresh livers or preserved livers for 24-hours or 48-hours was determined for their ability of inducing coagulation disorders when infused in untreated dogs, and was also tested for their activity of platelet aggregation, tissue thromboplastin (F-III), and plasminogen activator (PA). All dogs which received preserved livers showed a marked coagulation disorders including a decrease in P1 and Fng, and prolongation of A-PTT and PT, but the dogs with fresh liver grafts did not. Infusion of the perfusate collected from a perfusion of the preserved liver induced similar coagulation disorders in untreated dogs. The perfusate obtained from the preserved liver showed significant increased F-III activity as compared with that from fresh liver. On the other hand, neither direct platelet aggregation activity nor PA activity was seen or very low if any. These results indicate that F-III liberated from a damaged liver is responsible for the coagulation disorders after reperfusion of the graft in liver transplantation.
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PMID:[Coagulation disorders during orthotopic liver transplantation]. 279 56

The effects on the fibrinolytic system after a single s.c. bolus injection (at 9 a.m.) of either 5000 IU conventional heparin or 5000 anti-Xa U of a fractionated low molecular weight heparin (Fragmin, KabiVitrum, Sweden) were investigated in 9 healthy volunteers. The effects were compared to those of an injection of normal saline in 6 volunteers. Samples for biochemical analyses were taken regularily during 6 hours after drug or placebo administration. In the coagulation system the following parameters were measured: Activated partial thromboplastin time (APTT), anti-Xa activity, thrombin time and fibrinogen. The fibrinolytic system was monitored by analysing: plasminogen, alpha 2-antiplasmin, fibrin(ogen) degradation products (FDP), euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI) activity. Injection of the 2 drugs was followed by elevations in APTT and anti-Xa activity, and were more pronounced for Fragmin than heparin. The fibrinolytic system exhibited a diurnal variation with decreasing PAI activity and increasing t-PA activity during the day. Volunteers receiving normal saline (placebo) showed a similar pattern. The results were unrelated to heparin. It is concluded from this study that neither heparin nor Fragmin had any significant effect on the fibrinolytic parameters when measured after a single s.c. bolus injection since the observed variations were within the diurnal range.
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PMID:Heparin and fibrinolysis--comparison of subcutaneous administration of unfractionated and low molecular weight heparin. 283 26

Recombinant tissue-type plasminogen activator (t-PA) is a DNA-synthesized thrombolytic agent recently approved for clinical trials. We present the results of t-PA infusions in 18 patients with thrombosed peripheral arteries (12 patients) and peripheral bypass grafts (six patients). The duration of occlusion ranged from 1 to 21 days (mean, 6.8 days). Infusions of t-PA were done by way of an intra-arterial approach at a dose of 0.1 mg/kg/hr. All patients demonstrated thrombus lysis angiographically. Fifteen of 18 (83%) had clinical as well as angiographic improvement. Secondary procedures to maintain patency of the arterial segment were required in seven patients. No complications occurred that were related to the t-PA infusion. No significant prolongation of the prothrombin, thrombin, or activated partial thromboplastin times occurred. At the end of t-PA infusion, the mean circulating fibrinogen level was 59% of the starting value. The therapeutic use of t-PA is still in its preliminary stages and the efficacy and safety of this promising agent need to be further established. From our early experience with t-PA, it appears to be safe as well as effective.
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PMID:Peripheral artery and bypass graft thrombolysis with recombinant human tissue-type plasminogen activator. 307 38

Vasopressin infusions in normal volunteers that produce concentrations in plasma comparable to those seen during stress, cause an increase in plasma factor VIII and shortening of the euglobulin clot lysis time (ECLT). We have investigated the relationship between endogenous vasopressin (aVP) release and haemostatic function in 7 patients undergoing major abdominal surgery. Blood samples were taken at nine intervals during the operative procedure. Plasma aVP levels peaked at median values of 51 pg/ml during bowel manipulation and remained elevated on the first post-operative day. Following, and in close temporal relationship with the rise in aVP there were increases in factor VIII coagulant activity, the ristocetin co-factor, von Willebrand antigen, plasminogen activator activity (10(6)/ECLT2) and fibrinopeptide A concentrations with shortening of the activated partial thromboplastin time. The relationship was similar to that seen following infusion of aVP in human volunteers. The results are consistent with the hypothesis that aVP is an important mediator of changes in haemostatic function which accompany stress and might contribute to the thrombotic risk associated with surgical operations.
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PMID:Intra-operative activation of coagulation--a stimulus to thrombosis mediated by vasopressin? 308 60

The effect of Norplant subdermal implants on 22 different hemostatic variables was determined in 100 women attending the Fertility Control Clinic of the Singapore National University Hospital before and after 6 and 12 months of use. The factors analyzed were: hematocrit, hemoglobin (Hb), prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, fibrinogen, coagulation factor II, Factor V,Factor VII, Factor VIII, Factor VIIIR:Ag, Factor X, plasminogen activator, FDP, plasminogen (imm), antithrombin III (functional), antithrombin (antigen), protein C, alpha2-antiplasmin, alpha2-macroglobulin, alpha2-antitrypsin, platelet count, platelet aggregation (ADP), and platelet aggregation (collagen). The factors that differed significantly after 12 months were: Hb,PT,APTT, Factors II,V,VII, and VIIIR:Ag, Plasminogen (imm), antithrombin III(antigen), alpha2-antiplasmin, platelet count, and platelet aggregation. Most of these differences, while significant, were still within the normal range, except for PT,APTT, and platelet count. The subjects were considered to be in an enhanced risk for hypercoagulation and thrombosis.
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PMID:The effects of Norplant-2 rods on clinical chemistry in Singaporean acceptors after 1 year of use: haemostatic changes. 314 69

Tissue fibrin deposition may be an important component of inflammatory reactions. Current evidence suggests that intraalveolar procoagulant (PC) and plasminogen activator (PA) activities may be important determinants of local fibrin turnover in lung injury. In this study, we measured the PC and PA activities in cell-free bronchoalveolar lavage fluid (BALF) obtained from 17 patients with pulmonary sarcoidosis and 12 normal volunteers. Procoagulant activity was assayed by timing clot formation in a one-stage coagulation assay, and plasminogen activator activity was determined by measuring plasminogen-dependent lysis of [125I]fibrin. Mean PC activity in the sarcoidosis group was significantly elevated (102 +/- 25 versus 31.5 +/- 8.1 tissue thromboplastin units/ml; p less than 0.002), with 6 of 17 patient values beyond the 95% confidence limits of normals. These differences were not seen when PC activity was corrected for total protein in BAL. In contrast, PA activity tended to be lower in the sarcoidosis group (0.54 +/- 0.094 versus 0.643 +/- 0.106 Plough units/ml, p less than 0.3), and this difference became significant when PA was normalized to total protein (p less than 0.001). The ratio of procoagulant activity compared to plasminogen activator (PC/PA) was greater in the patients with sarcoidosis than normals (258 +/- 54 versus 40.3 +/- 6.4; p less than 0.001). The PC/PA ratios in 14 of 17 patients exceeded the 95% confidence limits of normals. In the sarcoidosis group, the PC/PA ratio correlated weakly with the number and percentage of lymphocytes retrieved by BAL. The plasminogen activator was a urokinase by molecular weight (53 kDa) and by comparing neutralization of PA activity by antibodies against urokinase and tissue plasminogen activator. The procoagulant was particulate and functioned as a factor X activator comprised of tissue thromboplastin and factor VII. We conclude that in pulmonary sarcoidosis, abnormal expression of procoagulant and plasminogen activator activities in alveolar fluid may favor accumulation of fibrin matrix at inflammatory foci.
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PMID:Procoagulant and plasminogen activator activities of bronchoalveolar fluid in patients with pulmonary sarcoidosis. 337 Dec 78

We have analyzed the CM of 20 human tumor cell lines for the presence of PA, PA-I and PC. Most of the cell lines expressed PA activity as measured by a radioiodinated fibrin plate assay. The urinary type and tissue-type PA activities were specifically quantified by means of purified inhibitory antibodies. U-PA and/or t-PA antigen, as measured by radioimmunoassays, were detected in all but 4 of the CM and were generally 10 times more concentrated than PA activity, indicating the presence of specific PA-Is. Analysis of CM by electrophoresis followed by fibrin-agarose zymography demonstrated the presence not only of free but also of inhibitor-complexed PA. Affinity purification demonstrated that 8/20 cell lines expressed detectable PA-I activity. The PA-I1 and PA-I2 inhibitors were most frequently observed, while PN was recovered only from CM of the HT1080 fibrosarcoma cell line. PC activity, as measured by the plasma recalcification time method, was found in 9/20 CM. It was of the thromboplastin tissue factor type since most of its activity was lost when assayed with a Factor VII-deficient plasma.
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PMID:Plasminogen activators, plasminogen activator inhibitors and procoagulant analyzed in twenty human tumor cell lines. 349 Apr 46


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