UNIPROT:P00750 - FACTA Search

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Query: UNIPROT:P00750 (PLA)
16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to predict a hypercoagulable state in patients with advanced breast cancer receiving medical treatment, the effects of chemoendocrine therapy on the coagulation-fibrinolytic systems were investigated prospectively. The patients were randomly divided into two groups. The ACT group had 38 patients, who received 20 mg/m2 adriamycin (ADM) i.v. on days 1 and 8, 100 mg cyclophosphamide (CPA) p.o. on days 1-14, and 20 mg tamoxifen (TAM) p.o. daily. The ACM group had 44 patients, who received 20 mg/m2 ADM i.v. on days 1 and 8, 100 mg CPA p.o. on days 1-14 and 1200 mg medroxyprogesterone acetate (MPA) p.o. daily. The treatment was repeated every 28 days until there was evidence of progressive disease or until the full ADM dose (550 mg/m2) had been given. The following 9 hematologic parameters were measured every 4 weeks: alpha 2-plasmin inhibitor plasmin complex (PIC), anti-thrombin-III (AT-III), D-dimer (Dd), fibrinogen (Fg), plasminogen (Pg), protein C (PC), thrombin-antithrombin-III complex (TAT-III), tissue plasminogen activator (t-PA), and factor X (FX). Compared to the ACT group, patients in the ACM group showed significantly higher values of AT-III and PC, which exceeded the normal ranges. The levels of Pg, t-PA and FX were significantly higher in the ACM group than in the ACT group, but were still within the normal ranges. The levels of TAT-III, Dd and PIC decreased in the ACT group and were unchanged in the ACM group after the start of treatment. Fg remained unchanged in both groups after the start of treatment. One patient in the ACM group had thrombophlebitis of the lower extremities with high levels of TAT-III, Dd and PIC and a decrease of Fg, but her condition returned to normal after reduction of the MPA dose. Although these data are not directly indicative of a hypercoagulable state in patients receiving chemoendocrine therapy, changes in AT-III, TAT-III, Dd and PIC should be monitored carefully when this type of treatment is given.
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PMID:Effects of chemoendocrine therapy on the coagulation-fibrinolytic systems in patients with advanced breast cancer. Japan Advanced Breast Cancer Study Group and Japan Clinical Oncology Group. 851 13

Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes disease were found to have coagulation abnormalities. Twenty-three children had thrombophilia (a deficiency in antithrombotic factor C or S, with an increased tendency toward thrombosis); nineteen of the twenty-three children had protein-C deficiency and four had protein-S deficiency. Seven children had a high level (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic lipoprotein associated with osteonecrosis in adults. Three children had hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children when the Legg-Perthes disease was first diagnosed was 5.8 +/- 2.7 years, and the mean age at the time of the present study was 10.1 +/- 4.4 years. At least one of the first-degree relatives of eleven of the nineteen probands who had a low protein-C level had a low protein-C level as well; all of these low levels represented previously undiagnosed familial protein-C deficiency. The eleven probands who had familial protein-C deficiency were more likely to have early onset of Legg-Perthes disease (at or before the age of five years) than the eleven children who had normal levels of protein C, protein S, and lipoprotein(a) as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least one first-degree relative of one of the four probands who had a low protein-S level had a low protein-S level and previously undiagnosed familial protein-S deficiency. At least one first-degree relative of six of the seven probands who had a high level of lipoprotein(a) had a familial high level of lipoprotein(a). Six of the seven children who had a high level of lipoprotein(a) also had a low level of stimulated tissue-plasminogen activator activity, the major initiator of fibrinolysis. At least one first-degree relative of one of the three probands who had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated tissue-plasminogen activator activity also had low stimulated tissue-plasminogen activator activity (familial hypofibrinolysis). Legg-Perthes disease, thrombophlebitis, premature myocardial infarction, and stroke, which are ramifications of the familial thrombophilic-hypofibrinolytic disorders, were common in the first and second-degree relatives of the thirty-three children with Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders.
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PMID:Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease. 956 92

In healthy nondiabetic women, oral contraceptives (OCs) affect hemostatic function. In diabetic women, there is concern that they may also increase the risk of diabetic vascular complications. This study was designed to examine the balance between coagulation activity and fibrinolytic activity--an indirect measure of endothelial cell function--in women with insulin-dependent diabetes mellitus (IDDM) during long-term use of OCs. The study group included 11 young women with uncomplicated IDDM who were prescribed ethinyl estradiol 30 micrograms and gestodene 75 micrograms. Twelve other diabetic women not taking OCs constituted the control group. Hemostatic function was evaluated at entry and after 1,3,6, and 12 months. In women taking OCs, plasma levels of factor VII(c) increased, while fibrinogen levels did not change. Inhibition of coagulation was affected by increased levels of protein C, although plasma levels of antithrombin III and protein S remained stable. The antigen concentrations of tissue-type plasminogen activator and plasminogen activator levels themselves were unchanged. There was a proportionate increase in the concentrations of thrombin-antithrombin III complexes and D-dimer. None of the hemostatic variables changed significantly in the control group. We conclude that the balance between coagulation activity and fibrnolysis does not change during use of this OC. Our findings suggest that low-dose OCs induce a procoagulatory state that is compensated for by enhanced fibrinolytic activity.
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PMID:Balance of coagulation activity with fibrinolysis during use of oral contraceptives in women with insulin-dependent diabetes mellitus. 857 52

The various components of i.v. regional anaesthesia (IVRA), that is ischaemia, tourniquet compression and the presence of high concentrations of local anaesthetics in the blood vessels of the extremity, may affect haemostatic mechanisms. We performed a cross-over study in 10 healthy male volunteers to examine the role of lignocaine in IVRA on several haemostatic variables, and those indicating fibrinolysis and platelet function in particular. Venous blood samples were obtained from the test arm and the opposite arm before IVRA, at the time of tourniquet cuff deflation and 30 min thereafter. Metal needle punctures were used, and for the sample from the test arm at the time of cuff deflation, cuff pressure was reduced from 300 mm Hg to individual mean arterial pressure. The IVRA technique included exsanguination by arm elevation and axillary artery compression, inflation of the tourniquet cuff for 20 min and deflation of the cuff in one step (after obtaining the venous sample). Each subject received, in random order, either 0.5% lignocaine 3 mg kg-1 or the corresponding volume of saline i.v. All fibrinolysis markers, that is, D-dimer, tissue plasminogen activator antigen (t-PA antigen), tissue plasminogen activator activity (t-PA activity), plasminogen activator inhibitor activity (PAI) and protein C indicated enhanced fibrinolysis by IVRA, but only t-PA antigen and PAI showed greater changes in the lignocaine compared with the saline group in the exposed arm at the time of cuff deflation. Platelet function tests (ADP-induced platelet aggregation, beta-thromboglobulin and thrombelastogram (TEG)) indicated no differences between the lignocaine and saline groups. Although IVRA appeared to induce some platelet dysfunction, there was a small increase in TEG amplitude indicative of improved fibrin-platelet interaction in the lignocaine-exposed arm at the time of cuff deflation. We conclude that the presence of high i.v. lignocaine concentrations (median 144.4 micrograms ml-1 in cubital veins at the end of the tourniquet time) potentiated ischaemia-induced fibrinolysis activation during IVRA. Concomitant platelet dysfunction was not aggravated by lignocaine.
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PMID:Haemostatic changes caused by i.v. regional anaesthesia with lignocaine. 867 57

Markers of endothelial cell activation were measured in 28 patients presenting with various forms of limited or focal type cutaneous vasculitis. Plasma levels of tissue plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) and PAI-1 activity, fibrin plate, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and soluble thrombomodulin (sTM) were measured. In comparison with the control group (n = 20) there was a significant increase in t-PA:Ag, vWF:Ag and TF (P < 0.05, Mann-Whitney U-test) in the cutaneous vasculitis group. This study confirms that measurable degrees of endothelial activation occur in cutaneous vasculitis. Cutaneous vasculitis includes a diverse group of clinical conditions, which are associated with inflammatory changes in cutaneous blood vessels with local fibrin deposition. The aetiology and pathogenesis of the majority of these entities remain unknown. Causative mediators are thought to include immune complexes, anti-endothelial cell antibodies, cytotoxic lymphocytes and viruses. Histologically, immune complexes and complement are frequently detected on the vessel wall, and serologically anti-endothelial antibodies are often detected in patients with vasculitis and in systemic lupus erythematosus (SLE) which correlate with the severity of cutaneous vasculitis, arthritis and nephritis. Lymphocyte-mediated toxicity to endothelial cells has been reported in a small number of patients with giant cell arteritis and Takayasu's arteritis. The vascular endothelium plays a central part in the control of haemostasis. Under physiological conditions endothelial cells present an anticoagulant surface to blood constituents, partially due to surface expression of heparan sulphate and thrombomodulin (TM). Heparan sulphate binds antithrombin III (ATIII), thereby accelerating inactivation of intrinsic coagulation enzymes. Thrombomodulin is an endothelial cell surface glycoprotein which promotes anticoagulation by forming a complex with thrombin which then activates protein C. Activated protein C together with a cofactor, protein S, inactivates FVa and FVIIIa. von Willebrand factor (vWF) is synthesized by endothelial cells, stored in Weibel-Palade bodies and released into the circulation upon endothelial stimulation. vWF mediates the binding of platelets to the subendothelium and is the carrier molecule for FVIIIC. The endothelium controls fibrinolysis by producing t-PA and its inhibitor PAI-1. Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) activate endothelial cells, causing a shift from an antithrombotic to prothrombotic state, including expression of tissue factor, increased synthesis of PAI-1 and decreased expression of TM. Fibrin deposition and intravascular thrombosis are seen in cutaneous vasculitis syndromes, suggesting local endothelial cell activation. The aim of this pilot study was to assess whether perturbation of the endothelium in cutaneous vasculitis could be detected in the patients' plasma samples. If so, further studies to assess any correlation in levels of these markers with disease activity might prove useful in the future.
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PMID:Endothelial cell activation in cutaneous vasculitis. 868 65

In the experiments on rabbits it was shown, that the administration of prostanoids IOS 3933 caused a reduction of ADP- and collagen induced platelet aggregation, platelet adhesion to collagen and elevation of t-PA level. This prostanoid prevented both a decrease in platelet count and reduction of AT III activity, but did not affect the protein C level during thromboplastin infusion.
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PMID:[The effect of new synthetic prostanoids on the indices of the blood coagulation system]. 870 88

In this study, 176 healthy men and women between the ages of 18 and 25 yrs were tested for fibrinolytic activity before and after a 5 min period of venous occlusion (VO) at 100 mm Hg. Using this protocol, 140 demonstrated an increase in fibrin plate lysis following this brief period of venous occlusion and were classified as "Responders." There were 36 individuals in the study who showed either a decrease or no change in fibrin plate lysis after 5 min of venous occlusion and they were classified as "Non-Responders." Responders showed a decrease in PAI-1 following VO. However, neither Responders nor Non-Responders demonstrated any significant differences in the levels of plasminogen, antiplasmin, protein C, free t-PA, or total t-PA following this brief exposure to venous occlusion. When comparing women and men in this study, women had significantly greater fibrin plate lysis both before and after 5 min of VO. They also demonstrated higher pre- and post-VO levels of circulating plasminogen. Also, women had less PAI-1 pre- and post-VO than men. When examining Responders and Non-Responders according to gender, women who were Responders had significantly greater fibrin plate lysis before and after VO than male Responders. Also, women Responders demonstrated a significant decrease in PAI-1 following 5 min of VO when compared to men who were Responders in this study.
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PMID:A study of the fibrinolytic response in healthy men and women following a brief exposure to venous occlusion. 874 28

In 103 patients with peripheral arterial disease (PAD) of the lower limbs, coagulation and fibrinolytic parameters were evaluated to identify hemostatic abnormalities characteristic of this patient population. PAD was defined as clinically stable Leriche stage 2 (based on clinical history, peripheral pulses, ankle-arm index, and treadmill test) for at least 3 months, walking distance > 100 m, and no other major illnesses, rest pain, or trophic lesions. Defibrotide, a polydeoxyribonucleotide derivative with vascular effects, was administered to the patients as part of a multicenter trial. The PAD patients exhibited a prothrombotic state as evidenced by high D-dimer in all but 24% of the patients (average 797 +/- 802 vs. 163 +/- 54 ng/mL normal population; p < 0.001) and high thrombin-antithrombin III complex (TAT) levels (10.2 +/- 8.9 vs. 2.5 + 1.5 ng/mL; p < 0.001) with low to normal levels of protein C (86 +/- 25 vs. 102 +/- 18%; p < 0.01) and plasminogen activator inhibitor-1 (PAI-1) antigen (5.9 +/- 4.5 vs. 1.3 + 0.7 ng/mL; p < 0.001) were elevated in 79% of the patients. These results suggest that there is ongoing thrombosis in the majority of PAD patients. Differences from normal controls were observed for t-PA, PAI-1, protein C, and protein S; however, it is not certain that the thrombosis in patients with PAD is due to these factors.
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PMID:Plasma levels of the molecular markers of coagulation and fibrinolysis in patients with peripheral arterial disease. 880 27

Barley serpin BSZx is a potent inhibitor of trypsin and chymotrypsin at overlapping reactive sites (Dahl, S.W., Rasmussen, S.K. and Hejgaard, J. (1996) J. Biol. Chem., in press). We have now investigated the interactions of BSZx with a range of serine proteinases from human plasma, pancreas and leukocytes, a fungal trypsin and three subtilisins. Thrombin, plasma kallikrein, factor VIIa/tissue factor and factor Xa were inhibited by BSZx at heparin independent association rates (k(ass)) of 4.5 X 10(3)-1.3 x 10(5) M(-1) s(-1) at 22 degrees C. Only factor Xa turned a significant fraction of BSZx over as substrate. Complexes of these proteinase with BSZx resisted boiling in SDS, and amino acid sequencing showed that cleavage in the reactive center loop only occurred after P1 Arg. Activated protein C and leukocyte elastase were slowly inhibited by BSZx (k(ass)=1-2 x 10(2) M(-1) s(-1)) whereas factor XIIa, urokinase and tissue type plasminogen activator, plasmin and pancreas kallikrein and elastase were not or only weakly affected. The inhibition pattern with mammalian proteinases reveal a specificity of BSZx similar to that of antithrombin III. Trypsin from Fusarium was not inhibited while interaction with subtilisin Carlsberg and Novo was rapid but most BSZx was cleaved as a substrate. Identification of a monoclonal antibody specific for native BSZx indicate that complex formation and loop cleavage result in similar conformational changes.
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PMID:Inhibition of coagulation factors by recombinant barley serpin BSZx. 884 56

Cancer is often associated with abnormal activation of coagulation leading to a prothrombotic state. Some chemotherapeutic agents used for cancer may induce thrombosis but their biological alterations in the hemostatic system are not yet well understood. This study evaluated alterations of coagulative and fibrinolytic parameters following chemotherapy. In plasma samples of 38 patients (median age: 49 years) receiving CMF (schedule 1-21 or 1-8) for Stage II breast cancer, we evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (TAT), prothrombin fragment F 1 + 2 (F 1 + 2), fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and D-dimer (D-D). PT, aPTT, and Fbg were determined with routine methods; AT-III, PC, and PS were measured with coagulative tests; PC and PS were also evaluated with immunoenzymatic methods, t-PA, PAI-1, D-D, TAT, and F 1 + 2 were measured with immunoenzymatic methods. All tests were performed immediately before starting therapy and after each cycle. A PC antigen decrease appeared soon after beginning therapy and lasted throughout chemotherapy. The lowest values were present after the first treatment both in the CMF 1-21 group (mean +/- SD = 72.5 +/- 10.8%) and in the CMF 1-8 group (mean +/- SD = 77.2 +/- 6.9%): PC activity was also decreased. PS antigen decreased after the first administration (mean +/- SD = 73.3 +/- 10% in CMF 1-21 group, and 72.5 +/- 4.9% in CMF 1-8 group): PS activity also decreased. PAI-1 antigen levels increased (mean +/- SD = 43.1 +/- 20.4 ng/ml in the CMF 1-21 group, and 37.5 +/- 12.2 ng/ml in CMF 1-8 group) lasting up to the last cycle. CMF provokes a trend toward hypercoagulability; this effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.
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PMID:A prothrombotic state in breast cancer patients treated with adjuvant chemotherapy. 887 81

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