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)

A more concentrated desmopressin (DDAVP) preparation (40 micrograms/ml), which required small injection volumes (less than 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 micrograms/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII:C (factor VIII:Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII:C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p less than 0.05). No serious local or systemic untoward side effects were observed.
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PMID:Subcutaneous injection of desmopressin (DDAVP): evaluation of a new, more concentrated preparation. 249 11

To evaluate the effect of endotoxin on the fibrinolytic response, we administered Escherichia coli endotoxin (4 ng per kilogram of body weight) intravenously to 19 healthy volunteers and measured fibrinolytic proteins, protease inhibitors, neutrophil elastase, and von Willebrand factor in serial blood samples obtained over 24 hours. One hour after endotoxin administration, the level of tissue plasminogen activator (t-PA) antigen rose from 10 to 23 ng per milliliter, peaking at 52 ng per milliliter at three hours. The level of alpha 2-plasmin inhibitor-plasmin complexes increased sevenfold, peaking at three hours. Plasminogen-activator inhibitor-1 activity rose more slowly, from 7 U per milliliter to a maximum of 49 U per milliliter at five hours. The concentrations of neutrophil elastase and von Willebrand antigen were unchanged at one hour, increased approximately threefold by 3 hours, and remained elevated at 24 hours. None of these measures changed in a control group (n = 5) given intravenous saline instead of endotoxin. We studied t-PA functional activity in four subjects. The level of activity rose rapidly, from 1.2 ng per milliliter at base line to 8.3 ng per milliliter at one hour and 13.9 ng per milliliter at two hours; it was undetectable at three hours. This increase in plasminogen activator activity was abolished in vitro by incubation of t-PA with an antiserum specific for human t-PA, suggesting that t-PA may be directly responsible for plasmin generation in the response to endotoxin. We conclude from this study of healthy subjects that endotoxin activates the fibrinolytic system, beginning with release of t-PA in the blood within one hour. The early activation of plasmin by endotoxin may prevent thrombosis, and the increase in fibrinolysis is then offset by the release of plasminogen activator inhibitor.
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PMID:Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. 278 17

The introduction of factor VIII and IX concentrates in the early 1960s brought a significant change in the hemophiliac's life. In consequence hemophilia treatment has been improving rapidly since, and today most life-threatening hemorrhages are controlled by replacement therapy. Hemophilic arthropathy through recurrent joint and muscle bleedings occurs later in life and is often limited to one joint only. Major surgery in hemophiliacs involves little more risk than in non-hemophilic patients, provided of course there is close teamwork between surgeon and hematologist. The most frequent causes of death are no longer hemorrhages but blood-product-associated AIDS and hepatic failure. Fortunately these side effects have been overcome by the use of virus-inactivated concentrates which in Switzerland have been generally administered since 1986. Factor VIII and IX concentrates must contain a precisely declared quantity of factor VIII and IX activity respectively, with a high specific activity. High-purity concentrates should be preferred because of the hazardous effect of foreign proteins administered intravenously in large quantities over a long period. Activation of fibrinolysis with consequent failure of hemostasis or even worsening of hemorrhage may be a clinically relevant side-effect of DDAVP therapy. When DDAVP is used for prophylactic treatment before surgery, an interval of one hour between the intravenous administration of DDAVP and surgery ensures the latter is performed at the time of highest factor VIII and von Willebrand factor level but with already decreased t-PA and fibrinolytic activity. If DDAVP is used in case of hemorrhage or postoperatively, however, the whole fibrinolytic potential must be taken into account. In these cases subcutaneous administration is advantageous due to more protracted t-PA release and the subsequent lower fibrinolytic activity, which can more easily be neutralized by tranexamic acid. To prevent hemophilic arthropathy, correct replacement therapy in hemarthroses is essential: it should be performed as early as possible, preferably in a home therapy program; adequate levels of factor VIII or IX should be achieved and maintained over a sufficient length of time. Hemophiliacs who did not receive replacement therapy during childhood often need major surgery because of severely destructed joints. Joint replacement by total knee and hip prostheses has proved very successful if certain special conditions are fulfilled. Surgical indications should, however, be carefully considered and the possibilities and limits of replacement therapy should be well known. Blood-product-associated hepatitis will be of prognostic relevance in many hemophiliacs treated formerly with non-virus-inactivated concentrates.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Current clinical aspects in hemophilia treatment]. 250 19

Forty six patients admitted for precordial chest pain were included in this study. The clinical, electrocardiographic, enzymatic and angiographic features allowed retrospective identification of 6 subgroups (nos 1 to 6): all transmural myocardial infarction (Q-MI) (Group 1), Q-MI without intracoronary thrombus (Group 2), Q-MI with intracoronary thrombus (Group 3), acute non-Q wave infarction (non Q-MI) (Group 4), unstable angina (Group 5) and atypical chest pain (Group 6). Several blood clotting factors were studied; von Willebrand factor (VWF), fibrinogen, tissue plasminogen activator (t-PA) and its inhibitor (PAI-1) and factor VII. There was no significant difference in the fibrinogen, t-PA, PAI-1 or factor VII levels between the 6 groups. On the other hand, the VWF was increased in the all transmural myocardial infarction (Q-MI) groups (n. 1). In Group 3 with visible intracoronary thrombus the VWF was high or very high in all patients, attaining three times the normal values. The values were lower in Group 5 (unstable angina) patients in whom no thrombus was observed on coronary angiography. The differences between Group 1 and Groups 4, 5 and 6 were statistically significant (p less than 0.05). The VWF was higher in the Q-MI group with intracoronary thrombus than in the group without thrombus, but the difference was not statistically different. In conclusion, the VWF may be considered to be a marker for thrombus and/or endothelial activation but a larger study population would be required to identify more accurately the subgroups with thrombosis or risk of thrombosis.
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PMID:[Relation of an increase of von Willebrand factor in the blood, acute myocardial infarction, unstable angina and coronary thrombosis]. 251 33

The profile of blood coagulation and fibrinolysis was studied in detail in eight patients with acute thrombotic thrombocytopenic purpura (TTP). In the majority of the patients, fibrinogen, factor XIII, antithrombin III, alpha 2-plasmin inhibitor, plasminogen, and alpha 2-macroglobulin were normal, whereas FDP, plasmin-alpha 2-plasmin inhibitor complex, and tissue-type plasminogen activator antigen were marginally or moderately elevated. Low fibronectin values were observed in four patients. Protein C and C4b-binding protein were nearly normal, whereas total protein S and free protein S were reduced in five and six patients, respectively. A positive correlation was found between total protein S and C4 and between free protein S and C3. von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCof) were either normal or elevated, but RCof/vWf:Ag ratio was decreased in seven patients. Crossed immunoelectrophoresis and sodium dodecyl sulfate (SDS)-agarose gel electrophoresis revealed that the large vWf multimers were either absent from or relatively decreased in all patients except one. In addition, one patient had unusually large vWf multimers, and a low-molecular-weight vWf fragment was apparently observed in three patients. These findings indicate that the intravascular generation of thrombin and plasmin was minimal in TTP and suggest that the alterations of the vWf molecule were caused not only by consumption through its participation in platelet thrombus formation but also by accelerated proteolysis. Low protein S values would be related to the immunological abnormalities underlying TTP.
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PMID:Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von Willebrand factor and protein S. 252 Dec 76

Cytosols of malignant breast tissue contained significantly higher levels of thrombospondin (TSP) and von Willebrand factor (vWF) than non-malignant breast. TSP and vWF content of human breast were significantly correlated whereas there was no correlation between TSP and the platelet-specific protein beta-thromboglobulin (beta TG). Whilst TSP in pre-menopausal breast cancer was slightly lower than in post-menopausal breast cancer, it did not correlate with oestrogen receptors (ER) or progesterone receptors (PR), but was negatively correlated with tissue-type plasminogen activator (tPA), an oestradiol-inducible enzyme. Secretion of TSP by MCF-7 cells was low and refractory to hormones. High levels of TSP appeared to be associated with the centre of the tumour mass. It is suggested that activation of the endothelium may be responsible, at least in part, for the high levels of TSP found in malignant breast tissue and could be a factor in the growth and spread of breast cancer.
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PMID:Thrombospondin in malignant and non-malignant breast tissue. 252 76

Excess production of growth hormone (GH) in poorly controlled diabetes is believed to be a causal factor in the development of diabetic angiopathy, the mechanism(s) of which is unknown. The present study was undertaken to determine whether exogenous growth hormone would specifically change some quantities and functional parameters known to often be abnormal in long-standing diabetes and thought to result from the development of vascular lesions in general. The authors studied capillary resistance, factor VIII coagulant antigen (F VIII:Ag), von Willebrand factor (vWf:Ag), fibronectin, fibrinogen, and tissue-type plasminogen activator (t-PA) before, during, and after 1 week's subcutaneous GH administration (6 IU per day divided into two doses). Capillary resistance decreased insignificantly, but returned to higher levels (p less than 0.05) 1 week after withdrawal. F VIII:Ag, vWf:Ag, fibronectin, and fibrinogen all increased significantly during GH treatment. Except for F VIII:Ag, these quantities returned to pre-medication levels 7 days after termination of GH administration. The present results may contribute to the clarification of the role of GH hypersecretion in diabetic microangiopathy and macroangiopathy.
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PMID:Diabetes-like alterations in hemostatic parameters after growth hormone administration for one week in normal man. 252 35

In order to carry out a multicenter study aimed at understanding the association of hemostatic factors with atherosclerotic vascular disorders for the Atherosclerosis Risk In Communities (ARIC) Study, we compared a blood collection and processing system developed in our laboratory with the state-of-the-art-procedures. The salient features of our system included the use of a new phlebotomy set for venipuncture, the use of Millipore filters for removing platelet residues in the plasma and the use of a mixture of anticoagulants and antiplatelet agents for inhibiting the in vitro activation of platelets, coagulation and fibrinolytic system. The results derived from systematic evaluations indicate that this newly developed system yields the lowest values of plasma beta TG, PF 4 and FPA when compared with the reported values. The technique also gave reliable values of representative hemostatic measurements such as fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin-III, protein C, tissue-type plasminogen activator, and serum thromboxane B2. Further experiments revealed that the samples withstood temporary storage at -70 degrees C and overnight "shipping" manipulations without significant changes in the hemostatic values. We conclude that the described blood collection and processing system may be a valuable asset for conducting multicenter cooperative clinical trials and epidemiologic studies involving blood collection by multiple field centers or clinics.
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PMID:ARIC hemostasis study--I. Development of a blood collection and processing system suitable for multicenter hemostatic studies. 252 84

Plasma levels of von Willebrand factor(vWF) and plasminogen activator(PA) in the plasma of venous blood before and after 5 minutes' venous occlusion were studied in 104 patients with various types of arterial thromboembolic disease and 30 age-matched healthy subjects. Levels of beta-thromboglobulin(beta-TG) were determined in plasma prior to the venous occlusion. In 29 patients and 7 control subjects, turnover of intravenously injected 125I-labeled fibrinogen was studied. Mean plasma levels of von Willebrand factor antigen(vWF: Ag) and ristocetin cofactor activity(vWF: RCo) were significantly higher in patients than in controls both before and after the venous occlusion. Mean plasma PA activity was significantly lower in patients than in controls both before and after the venous occlusion, but mean plasma PA antigen before the venous occlusion was significantly higher in patients than in controls. Plasma clearance of i.v. injected 125I-labeled fibrinogen was significantly accelerated, and the catabolic flux(j3x) of fibrinogen calculated according to a two-compartment model was significantly higher in patients than in controls. Significant relationships were observed between T1/2 of 125I-labeled fibrinogen and the following: plasma levels of vWF: Ag both before and after the venous occlusion, PA activities after the occlusion, PA antigen before the occlusion, and the net decrease in PA activities and the net increase in PA antigen as a result of the occlusion. Significant relationships were also observed between j3x of fibrinogen and the following: plasma levels of vWF: Ag both before and after the venous occlusion, vWF: RCo after the occlusion, PA activities after the occlusion, PA antigen before the occlusion, and the net decrease in PA activities resulting from the occlusion. Plasma levels of beta-TG, which were significantly higher in patients than in controls, were not correlated to plasma levels of vWF and PA or to parameters of fibrinogen turnover. These results suggest that the change in endothelial cell function is responsible for the abnormal plasma levels of both vWF and PA and for the acceleration of fibrinogen metabolism in patients with thromboembolic disease.
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PMID:Plasma levels of von Willebrand factor and plasminogen activator in patients with arterial thromboembolism--with special reference to their correlation to the increased catabolism of both fibrinogen and platelets. 258 60

We performed a hemostatic evaluation in detail in a patient with suspected amyloidosis who was suffering from several bleeding episodes. He had a shortened euglobulin clot lysis time, decreased alpha 2-plasmin inhibitor (alpha 2-PI), decreased plasminogen, elevated tissue-type plasminogen activator (t-PA), elevated plasmin-alpha 2-PI complex, and decreased ratio of ristocetin cofactor to von Willebrand factor (vWF) antigen. Fibrinogen and fibrin/fibrinogen degradation products levels fluctuated, with abnormal values on several occasions. On crossed immunoelectrophoresis, plasmin-alpha 2-PI complex and vWF fragment were demonstrated in the patient plasma. These abnormal findings and bleeding symptoms improved following the administration of tranexamic acid. Discontinuation of tranexamic acid resulted in deterioration of these parameters. These observations indicate that pathologic fibrinolysis (continuous intravascular plasmin generation) characterized by the consumption of alpha 2-PI and plasminogen, formation of plasmin-alpha 2-PI complex, and fragmentation of vWF contributed to the bleeding in this patient. It is important to recognize excessive fibrinolysis as the underlying cause of bleeding in these patients, since specific treatment with antifibrinolytic agents is effective in controlling the bleeding.
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PMID:Excessive fibrinolysis in suspected amyloidosis: demonstration of plasmin-alpha 2-plasmin inhibitor complex and von Willebrand factor fragment in plasma. 294 78


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