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

The mechanism of tissue plasminogen activator (t-PA) release during arm and leg venous occlusions and DDAVP (1-desamino-8-D-arginine vasopressin) infusion was studied in 10 healthy males. The following determinations were carried out on venous blood: t-PA antigen (ELISA), t-PA activity, and t-PA inhibitor (PAI) activity (amidolytic assays). Before DDAVP, there was a 270% t-PA antigen increase in the arm at the end of occlusion as opposed to only a 40% increase in the leg. After DDAVP, t-PA antigen at the end of arm and leg occlusion reached an equal level which was significantly higher than in the arm before DDAVP. The study produced no evidence of PAI release during venous occlusion of a limb. It is concluded that DDAVP is able to elicit t-PA release from arm as well as from leg vessels. The poor fibrinolytic response of leg vessels to venous occlusion is not due to a high PAI release or t-PA stores depletion in leg vessels, but rather to low basal t-PA release in leg vessels.
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PMID:Different tissue plasminogen activator release in the arm and leg during venous occlusion is equalized after DDAVP infusion. 211 Oct 49

In perfused rat hindlegs, platelet-activating factor and bradykinin induced the acute release of both tissue-type plasminogen activator (t-PA) and von Willebrand Factor (vWF). The time course of release was similar for both proteins, and the amounts of t-PA and vWF released under various conditions were closely correlated. Release of both t-PA and vWF required extracellular calcium, and could be induced by the calcium ionophore A-23187. Protein synthesis was not required for release to occur. Phorbol myristate acetate also induced release of t-PA and vWF, though with a different time course; DDAVP was inactive. The results suggest that the release of t-PA, and that of vWF, are closely linked at the cellular level.
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PMID:The simultaneous acute release of tissue-type plasminogen activator and von Willebrand factor in the perfused rat hindleg region. 211 27

Three patients with congenital, nephrogenic diabetes insipidus (NDI) from two unrelated families were tested for haemostatic and fibrinolytic responses to DDAVP infusion and venous occlusion. None of the three patients showed a response of factor VIII:C, vWF:Ag or t-PA to DDAVP, a V2-agonist. However, the baseline levels of these factors in the patients' plasma were normal and during venous occlusion a rise in t-PA antigen and t-PA activity was observed in all patients. One patient showed a definite response of the t-PA antigen level to exercise. It is concluded that (extrarenal) V2-receptor-mediated responses are absent in these patients, but that baseline homeostasis and the response to venous occlusion and physical exertion are intact. Presumably, these depend on other mechanisms. This observation denies a central role for vasopressin receptors in the on-demand regulation of clotting and clot dissolving properties of the blood.
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PMID:Normal homeostasis of fibrinolysis in nephrogenic diabetes insipidus in spite of defective V2- receptor-mediated responses of tissue plasminogen activator release. 213 55

A change in the response of the blood coagulation system to the intravenous injection of vasopressin (AVP), DDAVP and DGAVP has been studied in the experiments on white rats. Intensification of the procoagulant activity on AVP is of the dose-dependent character. Maximal effect is observed 5-15 min after i.v. injection of AVP in a dose of 4 mg/kg. The administration of this peptide increases the fibrinolytic activity, that is connected with an increase in the level of plasminogen activator. DDAVP and DGAVP have a weaker effect on fibrinolysis. AVP and DDAVP increase the level of FVIII by 5-6% during the first minutes, but DGAVP increases the level of FVIII only after 15-30 minutes. While using AVP, DDAVP and DGAVP in clinical practice it is necessary to allow for their hormonal action, the initial state of haemostasis and the age of patients.
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PMID:[Effect of vasopressin and its analogs on blood coagulation in rats]. 239 44

Impairment of the release of plasminogen activator has been looked for in patients with a predisposition to vascular disease or venous thrombosis. In normal people the fibrinolytic activity of the blood rises sharply after strenuous physical exercise or after the administration of certain drugs, among which DDAVP. These measures fail to elicit a normal response in many of these patients. In most cases this turned out to be due to a high level of a circulating plasminogen activator inhibitor which suppresses the rise in fibrinolytic activity. Release of activator can only be demonstrated reliably by the assay of t-PA-antigen. An impaired release appears to be very rare and in the experience of the author it occurs with some regularity only in patients with terminal renal insufficiency.
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PMID:[Disorders in the release of plasminogen activators]. 242 2

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

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

A set of fibrinolytic parameters was measured in 40 healthy subjects before and after a venous occlusion (VO) test lasting 10 min. After VO, plasma levels of tissue-type plasminogen activator (t-PA) antigen increased in all subjects, t-PA activity increased only in 25 subjects who were considered responders and remained unchanged in 15 (non-responders). High levels of plasminogen activator inhibitor (PAI) in the non-responder group explain this discrepancy. The non-responders had basal levels of PAI activity and t-PA antigen higher than responders (p less than 0.0001) and their basal levels of t-PA activity were lower (p less than 0.001). DDAVP infusion elicited good responses in 7 of 9 non-responders to VO with a fall of PAI activity to 0. Our data indicate that a high proportion of healthy subjects do not have a fibrinolytic response after VO, that a lack of fibrinolytic response to VO is due to high plasma levels of PAI and that DDAVP infusion appear to be more selective than VO for detecting non-responders.
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PMID:Fibrinolytic response in normal subjects to venous occlusion and DDAVP infusion. 251 62

The response of components of the coagulation and fibrinolysis systems to infusion of DDAVP has been examined in patients undergoing elective surgery. In the DDAVP treated group there was a significant increase, compared to control, in plasminogen activator (by fibrin plates p less than 0.005, ECLT p less than 0.0125, by Student's t test) before operation. No difference between groups was seen by either methods in the activator levels in samples 24 h postoperation, whereas a significant drop (p less than 0.002) in protein C concentration was observed at this stage in the treated group. Levels of factor VIII components were significantly higher (p less than 0.005) than control at all stages of operation and a significant shortening (5 sec p less than 0.05) of the APTT was seen at all stages (apart from 24 h samples). DDAVP infusion therefore may exacerbate the hypercoagulable state observed in surgical patients without preventing the (post-operatively) fibrinolytic shutdown. Instead, infusion tends to produce fibrinolytic depletion at the key mid-operative stage.
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PMID:The influence of DDAVP infusion on the coagulation and fibrinolytic response to surgery. 308 64

Quantitative abnormalities of fibrinolytic system factors (tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PA-inhibitor) are often found in the patients exhibiting an idiopathic thromboembolic pathology. Exploration of fibrinolytic system is performed by taking blood samples prior and after stimulation (after venous occlusion or DDAVP injection). Patients can be "good responders" (that is presenting with an increase of fibrinolytic activity after stimulation) or "bad responders". Among these latter (that is 30 p. 100 of cases), there are two groups: patients exhibiting an increase of PA inhibitor level, this concealing fibrinolytic role of t-PA released by stimulation (20 p. 100 of cases), patients failing to present any t-PA release through endothelial cells stimulation (10 p. 100 of cases). Furthermore, an hypofibrinolysis was demonstrated a long time ago, in certain thrombogenic conditions (post-operative period, obesity, elderly patients). Hypofibrinolysis was recently demonstrated, according to such conditions, as liable to an increase in the PA inhibitor levels. As pathogenic role of hypofibrinolysis is then demonstrated, therapeutic studies reducing the PA inhibitor level or increasing the t-PA rate produced and released by endothelial cells are to be developed.
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PMID:[Thromboembolic disease and anomalies of fibrinolysis]. 310 64


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