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)

Eleven patients with systemic sclerosis (SSc) were studied for plasma and cutaneous fibrinolytic activity, residual (potential fibrinolysis) fibrinolytic activity (FA) fo the dermal vessels that is related to the endothelial storage of plasminogen activators that become available due to particular stimuli such as intradermic injection of histamine, and the serum levels of circulating von Willebrand antigen, antithrombin III, plasminogen, beta-thromboglobulin, and platelet aggregate ratio (PAR). Cutaneous FA (autohistographic fibrin film method) appeared normal or increased in non-affected skin, normal in lesional skin, and increased after intradermal (i.d.) injection of 0.1 ml of 0.01% histamine. Monoclonal antibodies directed against the catalytic site of tissue type plasminogen activator completely blocked the fibrinolytic activity, while anti-urokinase antibodies did not abolish the lysis areas. Plasmatic FA, euglobulin lysis time test, (ELT) and the levels of beta-thromboglobulin resulted similar to the controls. A significant increase in von Willebrand Factor VIII antigen (but not of Factor VIII coagulant) was observed in the patients (p less than 0.01). Platelet aggregate ratio, levels of plasma plasminogen and Antithrombin III showed a significant difference (p less than 0.01) when compared with the control subjects. Data suggest that primary injured microvessels in SSc are likely to be arteriolae while venulae could be affected by secondary hypoxia due to the arteriolar damage with consequent release of tissue type plasminogen activator. Therefore, the authors suggest that the fibrinolytic potential is maintained in SSc and that the fibrinolytic therapy should not be used in all patients with SSc but only in those cases with documented exhaustion of plasmatic and/or cutaneous FA.
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PMID:Cutaneous and plasma fibrinolytic activity in systemic sclerosis. Evidence of normal plasminogen activation. 212 82

Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PAP), von Willebrand factor antigen (vWF:Ag) plasminogen activator antigen (PA) and plasminogen activator inhibitor-1 antigen (PAI-1), were determined in 110 patients with arterial thromboembolic diseases within 4 weeks after attack (Th; 41 cases with myocardial infarction and 69 with cerebral infarction), 67 patients with various types of carcinoma (Ca; 31 cases without metastasis and 36 with metastasis) and 50 age-matched healthy individuals (Co). The following results were obtained: 1) Mean plasma levels of TAT, PAP, vWF:Ag, PA and PAI-1 were significantly higher in Th than Co. 2) Mean plasma levels of TAT, PA and PAI-1 were significantly higher in Ca than Co regardless of metastasis but those of PAP and vWF:Ag were significantly higher only in Ca with metastasis than Co. 3) Significant relationship was observed between plasma levels of TAT and PAP both in Th and Ca. 4) Significant relationship was also observed between plasma levels of TAT and vWF:Ag, PA or PAI-1 in Th, but not in Ca. It is suggested from these results that the coagulopathies observed in these patients result from the activation of intravascular blood coagulation and fibrinolysis, and that vascular endothelial cell damage may play an important role in the activation in Th.
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PMID:Studies on the pathogenesis of coagulopathy in patients with arterial thromboembolism and malignancy. 214 28

The influence of invasive investigations on parameters of hemostasis and fibrinolysis is generally unknown, although this has consequences for the design of prospective studies on the association between those parameters and regression or progression of atherosclerosis. We therefore determined hemostatic and fibrinolytic factors in 12 patients who were admitted to the hospital for coronary angiography (CAG; n = 5) or percutaneous transluminal coronary angioplasty (PTCA; n = 7). Blood samples were drawn under basal circumstances on the day before, the day of and the day after CAG or PTCA. Significant changes occur in the concentrations of platelets and white blood cells, hematocrit (Ht), von Willebrand factor antigen (vWF:ag), antithrombin III-activity (AT III-ag), antithrombin III-antigen (AT III-ant), fibrinogen, plasminogen, alpha2-antiplasmin (alpha2-AP), histidine-rich glycoprotein (HRG), and plasminogen activator inhibitor (PAI)-activity. Mean values of beta-thromboglobulin, platelet factor 4, factor VIII:C, tissue-type plasminogen activator activity (t-PA act) and euglobulin clot lysis time (ECLT) do not differ significantly. After correction for Ht, no significant differences exist between the day before and the day of the procedure; but on the day after CAG and PTCA significant differences occur in white blood cells, factor VIII:C, AT III-ag, alpha2-AP and PAI-act. It is concluded that principally blood samples for investigations on fibrinolysis may be taken on the day before or the day of CAG or PTCA without a loss of quality, if the values are corrected for Ht. Samples taken on the day after the procedure are not useful for such purposes.
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PMID:The influence of coronary angiography and angioplasty on parameters of hemostasis and fibrinolysis. 214 44

The following problems are considered: Thrombosis: Safe diagnosis with phlebographic verification is recommended. Heparin has been an established treatment with the great advantage that it does not enter the fetal blood stream. In selected cases surgery or thrombolytic therapy has to be considered. Owing to the high risk of recurrence, prophylactic treatment with Heparin is required throughout pregnancy. Coumarol derivatives traverse the placental membrane to the foetus and have to be avoided because of a risk for teratogenetic injury and intracranial hemorrhage in the foetus. During the puerperium, warfarin might be given because its concentration in breastmilk is low. However, administration of vitamin K1 is recommended to prematures. Attention should be given to the side-effects of Heparin i.e. thrombocytopenia and osteoporosis. The possibility of antithrombin III deficiency should not be overlooked. In such cases it is also risk of thrombosis in the newborn. Premature separation of placenta: In most cases of abruptio placenta immediate delivery by caesarean section is necessary. In cases with partial separation of placenta and immature foetus, treatment with the fibrinolytic inhibitor tranexamic acid (Cyklokapron) has proved useful to prolong pregnancy with maturation of the foetus. Thrombocytopenia: Severe hemorrhage seldom occurs above a level of 50 x 10(9)/l. Treatment with Prednisolon has proved to be of great value. The risk of the child having thrombocytopenia is about 50%. Intraventricular bleedings: Such bleedings mainly occur in prematures. Preliminary results have shown decreased concentrations of specific plasminogen activator inhibitors.
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PMID:[Thrombotic and hemostatic problems in pregnancy and labor and their significance for the fetus and newborn infant]. 218 68

Hemostatic abnormalities are present in a majority of patients with metastatic cancer. These abnormalities can be categorized as 1) increased platelet aggregation and activation, 2) abnormal activation of coagulation cascade, 3) release of plasminogen activator, and 4) decreased hepatic synthesis of anticoagulant proteins like Protein C and antithrombin III. The abnormal activation of coagulation cascade is mediated through release of Tissue Factor, Factor X activators, and other miscellaneous procoagulants from the plasma membrane vesicles of tumor cells. Macrophages of a tumor-bearing host also produce increased amounts of Tissue Factor. Production of Factor X activators and macrophage Tissue Factor is decreased by warfarin. The ability of the tumor cells to produce platelet-aggregating activity and plasminogen activator parallels their metastatic potential in animal and experimental systems. These studies also show that antiplatelet agents and antibodies against plasminogen activator can suppress the metastatic process. One or more laboratory abnormalities of hemostasis can be shown in up to 95% of patients with metastatic cancer. These abnormalities, however, are unable to predict subsequent development of thromboembolic or hemorrhagic complications. Clinical complications occur in 9-15% of the patients in the form of thrombotic or hemorrhagic disorders. The therapy of tumor-related coagulopathy should be guided by its clinical expression. Subclinical DIC should not be treated. Coumadin is generally ineffective for therapy of thrombosis in cancer patients. There is no consensus regarding the use of heparin in acute promyelocytic leukemia (APL). The defibrination in APL may be from disseminated intravascular coagulation as well as systemic fibrinolysis, as shown by decreased alpha 2 antiplasmin levels. In such cases, epsilon aminocaproic acid plus heparin therapy may be of benefit.
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PMID:Hemostasis in malignancy. 174 46

Patients received 2,000 ml of dialysate intraperitoneally with five exchanges per day during continuous peritoneal dialysis (CAPD) for the treatment of terminal renal insufficiency. During a dwell time of 4 h the dialysate reached a total protein concentration up to 100 mg/dl by mass transfer of intravascular proteins. The composition is dependent on the molecular weight of the proteins. This results in an intraperitoneal hemostatic system of low concentration and different composition. We found an intraperitoneal fibrinogen cleavage and thrombin-antithrombin III-complex formation leading to increased levels of fibrinopeptide A (FPA: 33.3 +/- 7.0 ng/ml) and thrombin-antithrombin III-complex (TAT: 4.7 +/- 0.4 ng/ml) in plasma by mass transfer from dialysate to plasma. t-PA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) concentrations in plasma were within the normal range. The dialysate concentrations indicated a low local secretion. The fibrinolytic fibrin fragment D-dimer and the fibrinogen degradation product concentrations in plasma were greater than in dialysate. But the relations of the proteins between plasma and dialysate refer to a local intraperitoneal production as well. The results show that intraperitoneal coagulation predominates over fibrinolysis which is accompanied by an intravascular fibrinolysis in patients undergoing CAPD. Neoantigens produced in dialysate and diffused to plasma are comparable to changes seen in disseminated intravascular coagulation.
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PMID:Relation of intraperitoneal and intravascular coagulation and fibrinolysis related antigens in peritoneal dialysis. 220 48

Indicating activation of coagulation fibrinopeptide A (FPA) was elevated in 80.1% (mean = 10.5 ng/ml; P less than 0.01) and thrombin-antithrombin III complexes in 58.3% (TAT; mean = 5.3 ng/ml; p less than 0.05) in patients with adenocarcinomas (n = 57). In patients with non-Hodgkin's lymphomas (n = 30), however, elevation was observed only in 66.6% (FPA) and in 42.8% (TAT). Incidence of thrombosis is high only in the first group Local fibrinolysis explains elevated D-dimer in adenocarcinomas (1,818 ng/ml; p less than 0.01) and in non-Hodgkin's lymphomas (576 ng/ml; p less than 0.05). Significantly increased t-PA antigen was not committed by adequately increased t-PA activity in adenocarcinomas, because of high levels of the acute-phase protein, plasminogen activator inhibitor (mean = 25.3; p less than 0.01), indicating systemic hypofibrinolysis. Hemostatic disorder in patients with malignancy can be attributed to a combination of acute-phase reaction and an activation of coagulation.
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PMID:Investigations of coagulation system and fibrinolysis in patients with disseminated adenocarcinomas and non-Hodgkin's lymphomas. 221 92

Although Virchow postulated 100 years ago that hypercoagulability states exist, it has only been in recent years that methods of documenting hypercoagulability have been developed. These clotting tendencies can be acquired or congenital. The common causes of acquired clotting tendencies include conditions which result in tissue and cellular damage, shock, transfusion reactions, and tissue necrosis. Certain drugs and drug reactions, and certain disease states which include blood dyscrasias and cancer are also associated with clotting problems. In certain diseases such as homocystinuria, hyperlipidemia, and lupus erythematosus, abnormal clotting tendencies may also develop. Important advances in the recognition of hypercoagulability have come with the documentation that congenital clotting abnormalities exist. Moreover, these abnormalities are proving to be more common than are congenital bleeding syndromes. Patients who appear to have spontaneous clotting manifestations and are under 40 years of age should be screened for one of these abnormalities. These congenital clotting tendencies can be classified as defects in thrombosis inhibitors, dysfibrinogenemias, or defects in fibrinolysis. The first thrombotic inhibitor defect recognized was antithrombin III deficiency which was reported in 1965. Subsequently, Protein C, Protein S, and Heparin cofactor II deficiencies have been recognized as contributing to thrombotic tendencies. Dysfibrinogenemias are relatively rare and most are associated with bleeding problems; however, 11% of the abnormal fibrinogens are associated with a clotting tendency. The reason appears to be that these fibrins are resistant to fibrinolysis. The most common defects which are associated with thrombotic tendencies appear, at the present time, to be due to defects in fibrinolysis. These include hypoplasminogenemia, decreases in plasminogen activator, increases in plasminogen activator inhibitor, and Factor XII deficiency.
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PMID:Acquired and congenital clotting syndromes. 223 69

Epidemiologic studies have suggested a relationship between the use of oral contraceptives and mortality from cardiovascular diseases in older women. Therefore we studied generation and resolution of fibrin in 28 healthy women above age 30 years, using oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol. Thirty healthy nonusers served as control subjects. The oral contraceptive group had increased plasma concentration of thrombin-antithrombin III complexes (p less than 0.01), which indicated an enhanced generation of thrombin, increased plasma activity of tissue-type plasminogen activator (p less than 0.01), decreased plasma activity of plasminogen activator inhibition (p less than 0.01), and increased plasma concentration of fibrin degradation products (p less than 0.04). Interestingly, the ratio of thrombin-antithrombin III complexes/fibrin degradation products did not deviate significantly between groups. Twelve of the 28 women using oral contraceptives were light smokers, that is, less than 15 cigarettes per day. There were no differences in the determined variables between smokers and nonsmokers. Our study suggests that healthy women older than 30 years who use oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol have an enhanced generation and resolution of fibrin, while the hemostatic balance is unaltered. These findings are unaffected by moderate cigarette smoking.
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PMID:Enhanced generation and resolution of fibrin in women above the age of 30 years using oral contraceptives low in estrogen. 237 37

A human endothelial cDNA expression library, based on the Escherichia coli plasmid pUC9, was screened with a heterologous antibody raised against purified bovine aortic endothelial plasminogen activator inhibitor (PAI). A synthetic oligonucleotide, derived from a partial PAI cDNA expression clone, was used to select a full-length PAI cDNA, the size of which coincides with the length of PAI mRNA (approximately 2350 nucleotides) as determined by Northern blot analysis. The authenticity of full-length PAI cDNA is demonstrated by the expression of biologically active PAI both in lysates of transformed E. coli cells and in conditioned media of mouse Ltk- cells, transfected with PAI cDNA inserted into vector pSV2. Analysis of the de novo synthesized anti-plasminogen activator activity, employing reverse fibrin autography, shows that transfected mouse Ltk- cells synthesize a polypeptide with a mol. wt identical to that of the native PAI glycoprotein (Mr 52,000), whereas in E. coli an unglycosylated, active product with a mol. wt of 43,000 is made. The amino acid sequence, derived from the determined nucleotide sequence, shows that pre-PAI consists of 402 amino acids. It is proposed that the mature PAI is preceded by a signal peptide of 23 amino acid residues. The amino acid sequence of mature PAI includes three potential asparagine-linked glycosylation sites and lacks cysteine residues. The predicted amino acid sequence reveals significant homology with members of the serine protease inhibitor (Serpin) family, e.g. alpha 1-proteinase inhibitor and antithrombin III.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family. 243 Jul 93


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