Plasminogen Activator and Factor VIII in Cirrhosis Following Infusion of Lysine Vasopressin and Triglycyl Lysine Vasopressin

1979 ◽  
Author(s):  
C.V. Prowse ◽  
J.G. Douglas ◽  
J.D. Cash
Keyword(s):  
Clinical Trials ◽  
Gastrointestinal Bleeding ◽  
Factor Viii ◽  
Plasminogen Activator ◽  
Half Life ◽  
Normal Subjects ◽  
Oesophageal Varices ◽  
Lysine Vasopressin ◽  
Cirrhotic Patients ◽  
Fibrinolytic Potential

While lysine vasopressin (LVP) has been used for many years for the treatment of cirrhotic patients with bleeding oesophageal varices, on the basis of its ability to cause splanchnic vasoconstriction, its use remains contraversial. Previous studies have shown that infusion of this drug to normal subjects results in a rapid increase in plasminogen activator and factor VIII. When infused into cirrhotic patients with varices we found that LVP caused a large increase in the, already raised, level of plasminogen activator (and factor VIII). This increase in fibrinolytic potential might contribute to poor deposition of fibrin in bleeding patients. .In contrast infusion of the analogue triglycyl lysine vasopressin (GVP) in the same patients produced no change in plasminogen activator or factor VIII. GVP retains the vasoconstrictive properties of LVP and has a considerably longer half-life. In view of these advantages clinical trials of the use of GVP in gastrointestinal bleeding are warranted.

Association between High Values of D-dimer and Tissue-plasminogen Activator Activity and First Gastrointestinal Bleeding in Cirrhotic Patients

1996 ◽  
Vol 76 (02) ◽  
pp. 177-183 ◽  
Author(s):  
Francesco Violi ◽  
Stefania Basili ◽  
Domenico Ferro ◽  
Claudio Quintarelli ◽  
Cesare Alessandri ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Degradation Products ◽  
High Serum ◽  
Oesophageal Varices ◽  
Risk Of Bleeding ◽  
Tissue Plasminogen ◽  
Cirrhotic Patients ◽  
D Dimer

SummaryCirrhotic patients with decompensated state and high serum levels of fibrin(ogen) degradation products are at high risk of bleeding. The aim of this study was to further analyse the relationship between hyperfibrinolysis and bleeding in cirrhosis by measuring plasma values of D-dimer and tissue plasminogen activator (t-PA) activity. One-hundred-twelve cirrhotic patients with oesophageal varices and without previous upper-gastrointestinal bleeding entered the study and were followed-up for 3 years. Patients were considered to have hyperfibrinolysis if they concomitantly had high values of D-dimer and t-PA activity. During the follow-up 34 (30%) patients bled. They had more severe liver failure (p = 0.0001) and variceal size (p = 0.0031) and higher prevalence of ascites (p = 0.0003), varices with red signs and hyperfibrinolysis (p = 0.0001) than patients who did not bleed. Multivariate analysis disclosed hyperfibrinolysis as the only marker predictive of bleeding (Hazard Ratio = 42.5, p <0.001). Our findings suggest that screening for hyperfibrinolysis may be useful to identify cirrhotic patients at risk of bleeding.

Factor VIII and Fibrinolytic Response to DDAVP and Adrenaline in Normal Subjects and Dissociate Response in Von Willebrand’s Disease

1979 ◽  
Author(s):  
C. A. Ludlam ◽  
I.R. Peake ◽  
N. Allen ◽  
B.L. Davies ◽  
R.A. Furlong ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Factor Viii ◽  
Plasminogen Activator ◽  
Electrophoretic Mobility ◽  
Arginine Vasopressin ◽  
Plasma Levels ◽  
Bleeding Time ◽  
Normal Subjects ◽  
Venous Occlusion ◽  
Factor Activity

The effect of intravenous administration of deamina-D-arginine vasopressin (DDAVP) and adrenaline an levels of factor VIII and plasminogen activator (PA) was studied. In normal subjects and mild haemophiliacs DDAVP caused a rise of plasma levels of PA, procoagulant factor VIII (V IIIC) and its antigen (VIIICAg), factor VIII related antigen (VIIIRAg) and ristacetin co-factor activity (VIIIRiCoF). Similarly in most patients with vWd (including those with VIIIRAg of increased electrophoretic mobility) an increase of PA and all FVIII activities was observed. In one patient with vWd (VIIIC 9u/dl, VIIICAg 13u/dl, VIIIRAg 3u/dl; VIIIRiCoF <3u/dl, bleeding time > 15 min.) in whom an inhibitor of VIIIRiCoF was excluded neither DDAVP nor adrenaline caused the expected rise of PA, VIIIRAg or VIIIRiCoF although VIIIC and VIIICAg were markedly increased. The bleeding times did not shorten. No rise of PA or VIII-related activities was observed after venous occlusion. The results suggest that in some patients with vWd there is defective synthesis/release of both VIIIRAg/VIIIRiCoF and PA. They are consistent with the presence of a primary endothelial cell defectin this disorder.

Effect of Propranolol, Barbiturate Anesthesia and Splenectomy on Factor VIII: C and Plasminogen Activator Release Induced by DDAVP

1989 ◽  
Vol 62 (02) ◽  
pp. 784-787 ◽  
Author(s):  
J M Pina-Cabral ◽  
A Cunha-Monteiro ◽  
M C Sousa-Dias ◽  
J A Andrade
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Biological Activities ◽  
Beta Blockade ◽  
Synthetic Analogue ◽  
Pentobarbital Anesthesia ◽  
Activity Factor ◽  
Baseline Values ◽  
Fibrinolytic Potential

SummaryAfter the injection of DDAVP in 39 non-anaesthezised dogs (0.4 μg/kg) factor VIII: C activity rose to 145% of baseline values (p <0.0001) and the fibrinolytic potential of euglobulin precipitate rose to 196% (p <0.0001). The injection of DDAVP was repeated three times in each dog of a group of good responder animals at weekly intervals, but after: A) Pentobarbital anesthesia (30 mg/kg) - the increase of factor VIII: C was reduced from 164% to 116% (n = 11; p <0.0005) and the increase in fibrinolytic activity was reduced from 270% to 192% (n = 11; p <0.05). B) Injection of propranolol (1 mg/kg) - the increase of factor VIII :C was reduced from 167% to 110% (n = 13; p <0.0005) and there was no significant decrease of fibrinolytic activity (n = 13; n.s.). C) Splenectomy - the increase of factor VIII: C was reduced from 166% to 122% (n = 10; p <0.0005) and fibrinolytic activity was not significantly changed from 196% to 256% (n = 9; n.s.). There were no statistically significant differences in the increases of factor VIII :C and fibrinolytic potential of euglobulin precipitate after repeating only the injection of DDAVP three times in the same animal at weekly intervals (n = 5; n.s.). We conclude that the increases in factor VIII: C and fibrinolytic activities observed after DDAVP infusion in the dog are due to different mechanisms of action. Pentobarbital anesthesia reduced the increase of factor VIII: C and fibrinolytic activity, but on the other hand, beta-blockade and splenectomy influenced differently the behaviour of both biological activities.Injection of the synthetic analogue of vasopressin 1-deamino-8-d-arginine vasopressin (DDAVP) increases the plasma levels of factor VIII procoagulant activity (factor VIII: C) and plasminogen activator both in man and dog (1, 2, 3, 4).The mechanism of action of DDAVP in determining these responses is not well known. In this work, after having confirmed that DDAVP increases factor VIII: C and fibrinolytic activity in the blood of the unanaesthezised dog, and in order to clarify the mechanisms involved in these pharmacological effects, we repeated the DDAVP injection in animals previously submitted to propranolol, pentobarbital anesthesia and splenectomy.

Acute gastrointestinal bleeding due to oesophageal varices: An unusual case of a thoracic spleen

2011 ◽  
Vol 59 (S 01) ◽  
Author(s):  
B Danner ◽  
A Emmert ◽  
G Hagenah ◽  
T Tirilomis ◽  
T Stojanovic ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Unusual Case ◽  
Oesophageal Varices ◽  
Acute Gastrointestinal Bleeding

APC Resistance and other Haemostatic Variables during Pregnancy and Puerperium

1999 ◽  
Vol 81 (04) ◽  
pp. 527-531 ◽  
Author(s):  
U. Kjellberg ◽  
N.-E. Andersson ◽  
S. Rosén ◽  
L. Tengborn ◽  
M. Hellgren
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Protein C ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Reference Level ◽  
Soluble Fibrin ◽  
Prothrombin Fragment ◽  
D Dimer

SummaryForty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type 1 and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

Binding of 131I-Labeled Tissue-Type Plasminogen Activator on De-Endothelialized Lesions in Rabbits

1987 ◽  
Vol 26 (05) ◽  
pp. 224-228 ◽  
Author(s):  
Y. Isaka ◽  
H. Etani ◽  
K. Kimura ◽  
S. Yoneda ◽  
T. Kamada ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Abdominal Aorta ◽  
Half Life ◽  
Balloon Catheter ◽  
Biochemical Properties ◽  
Tissue Type ◽  
Fibrin Deposition ◽  
Tissue Type Plasminogen Activator ◽  
High Affinity ◽  
Type Plasminogen Activator

Tissue-type plasminogen activator (t-PA) which has a high affinity for fibrin in the clot, was labeled with 131I by the iodogen method, and its binding to de-endothelialized lesions in the rabbit was measured to assess the detectability of thrombi. The de-endothelialized lesion was induced in the abdominal aorta with a Fogarty 4F balloon catheter. Two hours after the de-endothelialization, 131I-labeled t-PA (125 ± 46 μCi) was injected intravenously. The initial half-life of the agent in blood (n = 12) was 2.9 ± 0.4 min. The degree of binding of 131I-labeled t-PA to the de-endothelialized lesion was evaluated at 15 min (n = 6) or at 30 min (n = 6) after injection of the agent. In spite of the retention of the biochemical properties of 131I-labeled t-PA and the presence of fibrin deposition at the de-endothelialized lesion, the binding of t-PA to the lesion was not sufficiently strong. Lesion-to-control ratios (cpm/g/cpm/g) were 1.65 ± 0.40 (at 15 min) and 1.39 ± 1.31 (at 30 min), and lesion-to-blood ratios were 1.39 ± 0.32 (at 15 min) and 1.36 ± 0.23 (at 30 min). These results suggest that radiolabeled t-PA may be inappropriate as a radiopharmaceutical for the scintigraphic detection of a pre-existing thrombotic lesion.

CHARACTERISTICS OF UPPER GASTROINTESTINAL BLEEDING IN CIRRHOTIC PATIENTS

2018 ◽  
Author(s):  
F Errabie ◽  
A Elmekkaoui ◽  
W Khannoussi ◽  
G Kharrasse ◽  
Z Ismaili
Keyword(s):  
Gastrointestinal Bleeding ◽  
Upper Gastrointestinal Bleeding ◽  
Cirrhotic Patients ◽  
Upper Gastrointestinal

Desmopressin Stimulates Parallel Norepinephrine and Tissue Plasminogen Activator Release in Normal Subjects and Patients with Diabetes Mellitus

1988 ◽  
Vol 59 (02) ◽  
pp. 269-272 ◽  
Author(s):  
M B Grant ◽  
C Guay ◽  
R Lottenberg
Keyword(s):  
Diabetes Mellitus ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Time Course ◽  
Vascular Endothelial Cells ◽  
Normal Subjects ◽  
Plasma Norepinephrine ◽  
Endogenous Catecholamine ◽  
Tissue Plasminogen ◽  
Patients With Diabetes

SummaryDesmopressin acetate administration markedly stimulates release of tissue plasminogen activator (t-PA) from vascular endothelial cells. The mechanism for this effect is unknown. Because infusion of epinephrine has been shown to increase t-PA levels, we examined the role of endogenous catecholamine mediation of t-PA release by desmopressin. Intravenous desmopressin acetate (0.3 μg/kg) was infused over 30 min in 9 controls and 11 subjects with diabetes mellitus, a condition associated with abnormalities of the fibrinolytic system. Plasma was collected in the supine, overnight fasted state at 15 min intervals (0-60 min) for measurement of t-PA activity, t-PA antigen and fractionated catecholamines. t-PA activity peaked at 30-45 min and subsequently decreased. The norepinephrine levels paralleled the t-PA activity. t-PA activity increased 10-fold from 0.14 ± .12 to 1.49 ± 0.79 IU/ml (Mean ± SD) and plasma norepinephrine increased 2- fold from 426 ± 90 to 780 ± 292 pg/ml. However, epinephrine and dopamine levels did not change significantly. The response to desmopressin of control and diabetic subjects was not shown to differ and their data were combined. We conclude that desmopressin increases plasma norepinephrine in addition to t-PA and that the parallel time course of change suggests a possible role for norepinephrine in mediating endothelial cell t-PA release.

Recombinant Variants of Tissue-Type Plasminogen Activator Containing Amino Acid Substitutions in the Finger Domain

1992 ◽  
Vol 68 (06) ◽  
pp. 672-677 ◽  
Author(s):  
Hitoshi Yahara ◽  
Keiji Matsumoto ◽  
Hiroyuki Maruyama ◽  
Tetsuya Nagaoka ◽  
Yasuhiro Ikenaka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Plasminogen Activator ◽  
Half Life ◽  
Tissue Type ◽  
Clot Lysis ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Plasma Clot ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

SummaryTissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7–9, 10–14, 15–19, 28–33, and 37–42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37–42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37–42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37–42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37–42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.

A Specific Immunologic Assay for Functional Plasminogen Activator Inhibitor 1 in Plasma – Standardized Measurements of the Inhibitor and Related Parameters in Patients with Venous Thromboembolic Disease

1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Normal Subjects ◽  
Tissue Type ◽  
Blood Collection ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Significant Difference ◽  
Activator Inhibitor ◽  
Pai 1

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.

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