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)

We tested the response of the fibrinolytic activity and factor VIII-antigen levels to infusion of DDAVP in healthy volunteers and we studied the influence of propranolol and aspirin on this response. After DDAVP, 0.4 microgram/kg in 10 min i.v., the fibrinolytic activity of redissolved euglobulins rose from 179 to 452 mm2 (lysis area of fibrin plates); after pretreatment with propranolol, 320 mg per day during 7 days, DDAVP induced a similar rise (from 166 to 471 mm2) and after pretreatment with a single dose of aspirin, 600 mg, ingested 5 hr before the DDAVP infusion, the lysis area increased from 159 to 455 mm2. Factor VIII-antigen level increased within 60 min after DDAVP from 104 to 208%; after pretreatment with propranolol from 111 to 230% and after a single dose of aspirin, DDAVP induced a rise from 107 to 206%. From these data we conclude that neither baseline levels nor the release of plasminogen activator or factor VIII after DDAVP infusion are influenced by beta-blockade or by interference with prostaglandin synthesis.
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PMID:The inability of propranolol and aspirin to inhibit the response of fibrinolytic activity and factor VIII-antigen to infusion of DDAVP. 642 80

Peritoneal fluid does not clot spontaneously on collection, due to a lack of prothrombin activation, consequent upon a virtual absence of factors V and VIII. Factor VIII related antigen is present in peritoneal fluid in only very small amounts, suggesting that this factor is excluded from the peritoneal cavity, probably by virtue of its size. Slight thrombin activity is demonstrated by the presence of fibrin monomers in the fluid. That peritoneal fluid also contains fibrinolytic activity is shown by high levels of plasminogen and plasmin-antiplasmin complexes, though no plasminogen activator could be detected. No differences were found in clotting and fibrinolytic activities, between fluid taken from these patients with, and those without, laparoscopic evidence of pelvic endometriosis.
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PMID:Clotting and fibrinolytic activities in peritoneal fluid. 677 52

Impairment of fibrinolysis is supposed to contribute to CVD. In 38 hyperlipoproteinemic patients, known to be at risk for early CVD, fibrinolytic activity was measured before and after stimulation with DDAVP. A negative correlation was found between serum triglyceride levels and fibrinolytic activity, both before and after DDAVP. A subnormal activity was invariably found when serum triglyceride concentration was above 8 mmol/L. The defect can be attributed to low levels of extrinsic plasminogen activator. High cholesterol levels were not associated with impairment of fibrinolysis. Fibrinolytic activity and response to DDAVP were lowest in those patients with hypertriglyceridemia who also had a tendency to develop hyperchylomicronemia. (type V/IV). The low fibrinolytic activity in this type of hyperlipoproteinemia cannot be explained by obesity. Factor VIII was higher than normal in most patients with hyperlipoproteinemia; the level increased after stimulation with DDAVP in every patient. This imbalance between coagulation and fibrinolysis might increase the risk of CVD.
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PMID:Response to fibrinolytic activity and factor VIII-related antigen to stimulation with desmopressin in hyperlipoproteinemia. 680 18

The fibrinolytic system was assessed in 28 hemophiliacs using the chromogenic substrate H-D-Val-Leu-Lys-pNA. To determine whether a state of hyperfibrinolysis might be associated with Factor VIII replacement therapy, 14 patients with severe disease who were intensively treated with Factor VIII concentrates were compared with 14 patients with mild disease who were receiving infrequent transfusions with cryoprecipitate or fresh frozen plasma. Seventeen normal males served as controls. With the exception of an elevated level of plasminogen activator and a decreased level of immediate antiplasmin in the mild group only, no evidence of enhanced fibrinolysis was found. Other components of the fibrinolytic system were either normal (plasmin) or increased (progressive antiplasmin containing both alpha 2PI and alpha 2M, and plasminogen). The elevated plasminogen levels were found only in the severe intensively transfused group. The elevated progressive antiplasmin levels were found in both groups of patients and did not appear to be related to transfusions. These findings do not support the concept of enhanced fibrinolysis associated with intensive Factor VIII replacement therapy.
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PMID:An assessment of the fibrinolytic system in hemophilia A. 681 44

Cuticle bleeding time (CBT) measurements in anesthetized rabbits were performed to assess the potential bleeding risks which may accompany the administration of tissue-type plasminogen activator (tPA) or vampire bat salivary plasminogen activator (BatPA). The dose of BatPA or tPA used in this study, 42 nmol/kg, was previously shown to be efficacious using a rabbit femoral artery thrombosis model (Gardell et al, Circulation 84:244, 1991). CBT was determined by severing the apex of the nail cuticle and monitoring the time to cessation of blood flow. CBT was minimally elevated (1.6-fold, p = NS) following bolus intravenous administration of BatPA; in contrast, bolus intravenous administration of tPA dramatically elevated CBT (6.2-fold, p < 0.05). Rabbits treated with tPA, but not BatPA, displayed profound activation of systemic plasminogen and consequent degradation of Factor VIII and fibrinogen. Elevations in CBT after the administration of tPA were reversed by the replenishment of plasma Factor VIII activity to 40% of control, but were unaffected by complete replenishment of plasma fibrinogen. The results of this study suggest that the administration of BatPA, at a dose that promotes thrombolysis, may evoke a minimal bleeding risk, relative to an equi-efficacious dose of tPA. In addition, the tPA-provoked proteolytic consumption of Factor VIII may be a key contributor to the heightened bleeding risk.
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PMID:Vampire bat salivary plasminogen activator evokes minimal bleeding relative to tissue-type plasminogen activator as assessed by a rabbit cuticle bleeding time model. 754 21

The objectives of this study were (1) To assess human umbilical cord vein endothelial cell (HUVEC) fibronectin (Fn) content and integrity in patients with preeclampsia and (2) to investigate the ability of Fn and Fn fragments (FnDP) to disrupt endothelial cell attachment to an Fn matrix through modulation of plasminogen activator activity. Intact Fn was released from normal cord veins, while Fn and FnDP (70 and 21 kd) were released from cord veins in culture from patients with severe preeclampsia. Factor VIII and Fn immunostaining of normal cord sections revealed endothelial integrity and low Fn content, while immunostaining of cord sections from patients with preeclampsia revealed a disrupted endothelium and high concentrations of Fn. Both intact Fn and FnDP isolated from patient plasma or prepared by plasmin digestion of pure Fn had no effect on chromium 51 release from HUVECs. These FnDP, but not intact Fn, stimulated HUVEC urokinase plasminogen activator production within 2 hours (p < 0.05) and caused a time- and concentration-dependent detachment and disruption of the HUVEC monolayers and HUVEC-mediated degradation of immobilized iodine 125-labeled Fn underneath the HUVEC monolayer (p < 0.02) after 2 hours. This 125I-labeled Fn release was enhanced by plasminogen and inhibited by aprotinin. Thus FnDP appear to cause endothelial cell disruption that may be due to plasmin generation in vitro.
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PMID:Degradation of fibronectin in association with vascular endothelial disruption in preeclampsia. 770 9

These experiments were designed to study the effect of resistance exercise on parameters pertinent to the hemostatic and fibrinolytic systems. Seven normal healthy subjects (6 male, 1 female, 25 +/- 3 yr mean SD) were studied under three conditions: control (C) [no exercise], high volume resistance exercise (HVRE), and low volume resistance exercise (LVRE), which were randomized for each subject, with 7 d separating tests. Both HVRE and LVRE trials encompassed the performance of five sets of nine exercises. After establishing one repetition maximum (1 RM), the HVRE involved the performance of moderate resistance, higher repetition, and shorter resting periods, whereas LVRE involved the use of high resistance, lower repetition, and longer resting intervals. Heart rate (HR) was monitored at rest and continuously during trials and venous blood was removed with minimum stasis, before and immediately after HVRE, LVRE, and before and after 38 min of supine rest (C). The blood was enzymatically analyzed for lactic acid (LA) and assayed using chromogenic substrates for the determination of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), and Factor VIII (FVIII) activities. Global fibrinolysis (GF) was also screened in the fibrin plate and hematocrit ratios were employed to calculate percent plasma volume changes. Values were corrected for changes in plasma volume then data were analyzed using repeated measures ANOVA. There were no significant (P > 0.05) changes in the parameters measured in the resting condition over the three testing occasions and no significant differences (P > 0.05) were observed during the control experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrinolytic and hemostatic parameter response after resistance exercise. 849 88

Abnormalities of coagulation and fibrinolysis were studied in a group of 28 children and young adults with homozygous sickle cell disease (SCD), either in the steady state (n = 12) or during painful crisis (n = 16). Coagulation was explored by standard clotting tests and by measurement of prothrombin complex factors, factor VIII (VIII:C) and antithrombin III (ATIII), protein C (PC) and protein S (PS) activities, while fibrinolytic potential was evaluated using D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) assays. In SCD patients, thrombin time (TT) was constantly shortened, both in the steady state (ratio to control 0.83 +/- 0.08, p < 0.0001) and in crisis (0.76 +/- 0.06, p < 0.0001). Mean levels of prothrombin complex were similar in asymptomatic patients to those in controls, but were significantly decreased during sickle cell crisis (p < 0.05 for factor V and p < 0.0001 for factors II, VII and X). Factor VIII:C was significantly increased, both in the steady state (207 +/- 35%, p < 0.0001) and during crisis (208 +/- 34%, p < 0.0001). PS activity was reduced int he steady state (81 +/- 12%, p < 0.01) and further diminished in crisis (68.5 +/- 27.5%, p < 0.001), while D-dimers were significantly elevated during sickle cell crisis (1028 +/- 675 ng/ml, p < 0.001). In all SCD patients, baseline levels of t-PA antigen were comparable to those in controls, whereas concentrations of PAI-1 antigen were significantly increased, either in the steady state (89.7 +/- 26.3 ng/ml, p < 0.0001) or in crisis (75.0 +/- 24.8 ng/ml, p < 0.0001). These results provide evidence for the presence of circulating activated clotting factors in SCD and for an imbalance of the profibrinolytic and antifibrinolytic systems most likely due to increased PAI-1 levels.
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PMID:Abnormalities of coagulation and fibrinolysis in homozygous sickle cell disease. 897 93

Formation of the blood clot is a slow but normal physiological process occurring as a result of the activation of blood coagulation pathways. Nature's guard against unwanted blood clots is the fibrinolytic enzyme system. In healthy people, there is a delicate dynamic balance between blood clot formation and blood clot dissolution. Available evidence suggests that exercise and physical training evoke multiple effects on blood hemostasis in normal healthy subjects and in patients. A single bout of exercise is usually associated with a transient increase in blood coagulation as evidenced by a shortening of activated partial thromboplastin time (APTT) and increased Factor VIII (FVIII). The rise in FVIII is intensity dependent and continues into recovery. The effects of acute exercise on plasma fibrinogen have yielded conflicting results. Thus, the issue of whether exercise-induced blood hypercoagulability in vitro mirrors an in vivo thrombin generation and fibrin formation remains disputable. Exercise-induced enhancement of fibrinolysis has been repeatedly demonstrated using a wide range of exercise protocols incorporating various exercise intensities and durations. Moderate exercise appears to enhance blood fibrinolytic activity without a concomitant activation of blood coagulation mechanisms, whereas, very heavy exercise induces simultaneous activation of blood fibrinolysis and coagulation. The increase in fibrinolysis is due to a rise in tissue-type plasminogen activator (tPA) and decrease in plasminogen activator inhibitor (PAI). The mechanism of exercise-induced hyperfibrinolysis is poorly understood, and the physiological utility of such activation remains unresolved. Strenuous exercise elicits a transient increase in platelet count, but there are conflicting results concerning the effect of exercise on platelet aggregation and activation. Few comprehensive studies exist concerning the influence of exercise training on blood hemostasis, making future investigation necessary to identify whether there are favorable effects of exercise training on blood coagulation, fibrinolysis, and platelet functions.
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PMID:Blood hemostasis in exercise and training. 1079 81

Intra-arterial desmopressin caused dose and time dependent increases (p <0.001 for all) in forearm blood flow (all doses) and plasma tissue plasminogen activator (t-PA) concentrations (desmopressin > or = 70 ng/min). Although plasma t-PA concentrations rose in both forearms, there was a modest local release of t-PA in the infused forearm (14 ng/100 mL of tissue/min, p <0.05). At desmopressin doses > or = 300 ng/min, plasma von Willebrand factor (vWf) and Factor VIII:C concentrations rose in both forearms (p <0.001) and correlated with the rise in interleukin-6 concentrations (r = 0.92, p <0.001: r = 0.85, p = 0.002 respectively). Neither desmopressin nor substance P caused t-PA, vWf or Factor VIII:C release in the patients, although desmopressin increased plasma interleukin-6 concentrations as in healthy volunteers. We conclude that desmopressin releases t-PA, vWf and Factor VIII:C predominantly via systemic mechanisms, possibly mediated by cytokine release. Patients with type 3 vWD appear to have a generalised failure to release t-PA acutely despite a normal interleukin-6 response to desmopressin infusion.
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PMID:Local and systemic effects of intra-arterial desmopressin in healthy volunteers and patients with type 3 von Willebrand disease. Role of interleukin-6. 1095 89


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