Coagulation and Fibrinolytic Profile of Paediatric Patients Undergoing Cardiopulmonary Bypass

1997 ◽  
Vol 77 (02) ◽  
pp. 270-277 ◽  
Author(s):  
Anthony K C Chan ◽  
Michael Leaker ◽  
Frederick A Burrows ◽  
William G Williams ◽  
Colleen E Gruenwald ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Factor Xa ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Poor Correlation ◽  
Heparin Cofactor Ii ◽  
Paediatric Patients ◽  
Sick Children

SummaryThe haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XI, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, α2-macroglobulin, plasminogen, α2-antiplas- min, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, α2AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (<2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.

Laboratory Screening of Inherited Thrombotic Syndromes

1987 ◽  
Vol 57 (03) ◽  
pp. 247-251 ◽  
Author(s):  
Pier Mannuccio Mannucci ◽  
Armando Tripodi
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Laboratory Diagnosis ◽  
Heparin Cofactor Ii ◽  
C Protein ◽  
Inherited Thrombophilia ◽  
Laboratory Screening ◽  
Step Procedure ◽  
Assay Methods

SummaryThe prevalence of inherited thrombotic syndromes in the general population (1 in 2,500/5,000) appears to be higher than that of inherited bleeding disorders. The problems of their laboratory diagnosis are reviewed and a screening procedure is proposed. The most important candidates for screening are patients with unexplained venous thromboembolism at ages of less than 40-45 years, particularly when thrombotic episodes are recurrent. Screening must start from the exclusion of common acquired causes of thrombophilia. A negative family history does not exclude inherited thrombophilia, because the defects have a low penetrance and fresh mutations may have occurred in the propositi. Laboratory screening is based on a two-step procedure. The first step is aimed at detecting, preferably with specific functional assays. the most frequent and well established causes of inherited thrombophilia, i.e. deficiencies or dysfunctions of antithrombin III, protein C, protein S, plasminogen and fibrinogen. The tests included in the second step of the screening are aimed at detecting the less common or less well established causes of inherited thrombophitia (low heparin cofactor II, defective release of tissue plasminogen activator, and high plasminogen activator inhibitor). The simplest, more reliable and specific assay methods to be used in laboratory practice are recommended.

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.

Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S

1988 ◽  
Vol 60 (02) ◽  
pp. 328-333 ◽  
Author(s):  
N J de Fouw ◽  
Y F de Jong ◽  
F Haverkate ◽  
R M Bertina
Keyword(s):  
Plasminogen Activator ◽  
Protein C ◽  
Blood Platelets ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Activator Inhibitor ◽  
Pai 1

summaryThe effect of purified human activated protein G (APC) on fibrinolysis was studied using a clot iysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, 125T-fibrinogen and thrombin. All proteins were of human origin.In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-l) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropylfluorophosphate. Addition of the cofactors of APC:protein S, Ca2+-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca2+-ions.

ARIC Hemostasis Study-IV. Intraindividual Variability and Reliability of Hemostatic Factors

1995 ◽  
Vol 73 (02) ◽  
pp. 256-260 ◽  
Author(s):  
Nghia D Nguyen ◽  
Habib Ghaddar ◽  
Valarie Stinson ◽  
Lloyd E Chambless ◽  
Kenneth K Wu ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Coagulation Factors ◽  
Total Variance ◽  
Intraindividual Variability ◽  
Plasminogen Activator Inhibitor 1 ◽  
Platelet Factor ◽  
Hemostatic Factors ◽  
R Value

SummaryWe have recently reported the short-term intraindividual variability of several coagulation factors and inhibitors included in the ARIC study (Chambless et al. Ann Epidemiol 1992; 2:723). In this paper, we reported the intraindividual variability results of additional hemostatic factors. Blood samples were collected for hemostatic assays three times at 1-2-week intervals from 39 subjects recruited from 4 ARIC field centers. The contributions of within-person, processing and assay (designated “method”) and between-person variances to the total variance were estimated and from them the reliability coefficient, R, was computed as the proportion of total variance in the between-person component. The R value was high for (β-thromboglobulin and tissue- plasminogen activator: 0.83 and 0.81, respectively; and intermediate for D-dimer and plasminogen activator inhibitor-1: 0.73 and 0.72, respectively. Protein S (total and free) and platelet factor 4 had low repeatability (R<0.50) derived mostly from “method” variability while low R value (0.03) for fibrinopeptide A was attributed to high “method” and “within-person” variability. Gender, age and the level of hemostatic factors did not influence the intraindividual variability.

The plasminogen activator inhibitor-1 (PAI-1) promoter haplotype is related to PAI-1 plasma concentrations in lean individuals

2005 ◽  
Vol 181 (2) ◽  
pp. 275-284 ◽  
Author(s):  
Maartje Verschuur ◽  
Annemarie Jellema ◽  
Else M. Bladbjerg ◽  
Edith J. M. Feskens ◽  
Ronald P. Mensink ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1 ◽  
Promoter Haplotype

scholarly journals Epinephrine Exerts Anticoagulant Effects during Human Endotoxemia

1997 ◽  
Vol 185 (6) ◽  
pp. 1143-1148 ◽  
Author(s):  
Tom van der Poll ◽  
Marcel Levi ◽  
Mieke Dentener ◽  
Patty M. Jansen ◽  
Susette M. Coyle ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Systemic Infection ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Coagulation System ◽  
Type I ◽  
Maximal Activation ◽  
Antithrombotic Effects ◽  
Activator Inhibitor Type

To determine the effect of a physiologically relevant elevation in the plasma concentrations of epinephrine on the activation of the hemostatic mechanism during endotoxemia, 17 healthy men were studied after intravenous injection of lipopolysaccharide (LPS, 2 ng/kg), while receiving a continuous infusion of epinephrine (30 ng/kg/min) started either 3 h (n = 5) or 24 h (n = 6) before LPS injection, or an infusion of normal saline (n = 6). Activation of the coagulation system (plasma concentrations of thrombin–antithrombin III complexes and prothrombin fragment F1+2) was significantly attenuated in the groups treated with epinephrine when compared with subjects injected with LPS only (P &lt;0.05). Epinephrine enhanced LPS-induced activation of fibrinolysis (plasma levels of tissue-type plasminogen activator and plasmin-α2–antiplasmin complexes; P &lt;0.05), but did not influence inhibition of fibrinolysis (plasminogen activator inhibitor type I). In subjects infused with epinephrine, the ratio of maximal activation of coagulation and maximal activation of fibrinolysis was reduced by &gt;50%. Hence, epinephrine exerts antithrombotic effects during endotoxemia by concurrent inhibition of coagulation, and stimulation of fibrinolysis. Epinephrine, whether endogenously produced or administered as a component of treatment, may limit the development of disseminated intravascular coagulation during systemic infection.

Fibrate-modulated Expression of Fibrinogen, Plasminogen Activator Inhibitor-1 and Apolipoprotein A-I in Cultured Cynomolgus Monkey Hepatocytes

1998 ◽  
Vol 80 (12) ◽  
pp. 942-948 ◽  
Author(s):  
M. Kockx ◽  
H. M. G. Princen ◽  
T. Kooistra
Keyword(s):  
Plasminogen Activator ◽  
Cynomolgus Monkey ◽  
Plasma Concentrations ◽  
Plasminogen Activator Inhibitor ◽  
Peroxisome Proliferator ◽  
Plasminogen Activator Inhibitor 1 ◽  
Apolipoprotein A ◽  
Activator Inhibitor ◽  
Pai 1

SummaryFibrates are used to lower plasma triglycerides and cholesterol levels in hyperlipidemic patients. In addition, fibrates have been found to alter the plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein A-I (apo A-I). We have investigated the in vitro effects of fibrates on fibrinogen, PAI-1 and apo A-I synthesis and the underlying regulatory mechanisms in primary monkey hepatocytes.We show that fibrates time- and dose-dependently increase fibrinogen and apo A-I expression and decrease PAI-1 expression in cultured cynomolgus monkey hepatocytes, the effects demonstrating different potency for different fibrates. After three consecutive periods of 24 h the most effective fibrate, ciprofibrate (at 1 mmol/l), increased fibrinogen and apo A-I synthesis to 356% and 322% of control levels, respectively. Maximum inhibition of PAI-1 synthesis was about 50% of control levels and was reached by 1 mmol/l gemfibrozil or ciprofibrate after 48 h. A ligand for the retinoid-X-receptor (RXR), 9-cis retinoic acid, and specific activators of the peroxisome proliferator-activated receptor-α (PPARα), Wy14,643 and ETYA, influenced fibrinogen, PAI-1 and apo A-I expression in a similar fashion, suggesting a role for the PPARα/RXRα heterodimer in the regulation of these genes. When comparing the effects of the various compounds on PPARα trans-activation activity as determined in a PPARα-sensitive reporter gene system and the ability of the compounds to affect fibrinogen, PAI-1 and apo A-I antigen production, a good correlation (r = 0.80; p <0.01) between PPARα transactivation and fibrinogen expression was found. Apo A-I expression correlated only weakly with PPARα transactivation activity (r = 0.47; p = 0.24), whereas such a correlation was absent for PAI-1 (r = 0.03; p = 0.95). These results strongly suggest an involvement of PPARα in the regulation of fibrinogen gene expression.

THROMBOPHILIA:ITS CAUSES AND A ROUGH ESTIMATE OF ITS PREVALENCE

1987 ◽  
Author(s):  
E Briët ◽  
L Engesser ◽  
E J P Brommer ◽  
A W Broekmans ◽  
R M Bertina
Keyword(s):  
Plasminogen Activator ◽  
Protein C ◽  
Antithrombin Iii ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Factor Vii ◽  
Type I ◽  
Factor V ◽  
Protein C Deficiency ◽  
Familial Cases

Idiopathic venous thrombosis and embolism have gained widespread interest since the discovery that, deficiencies of antithrombin III, protein C, and protein S are associated with familial venous thrombophilia. The purpose of our study was to obtain an estimate of the prevalence of this syndrome and to establish the etiology in as many cases as possible.We collaborated with specialists from 37 Dutch hospitals, covering about 10% of the Dutch population. A history as well as blood samples were obtained from 113 unrelated cases with familial thrombophilia and from 90 isolated cases. Assuming that each proband in a family with thrombophilia has an average of four affected relatives, a rough estimate of the prevalence of familial thrombophilia in The Netherlands is 40 cases per 100.000. The prevalence of non-familial thrombophilia is probably lower.In 35 out of the 113 familial cases we established a diagnosis of hereditary antithrombin III deficiency (n=5), protein C deficiency (type I: n=9; type II: n=4), protein S deficiency (n=15) and dysfibrinogenemia (n=2). In 36 cases we found no abnormality at all and in the remaining 42 cases abnormalities were found in one or more of the following: heparin cofactor II, factor V, factor VII, factor VIII, von Willebrand factor, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor, alpha 2 antiplasmin and histidine rich glycoprotein. In most of these cases, however, the hereditary nature of the abnormalities could not be demonstrated and the causal relationships remain to be established.In the 90 isolated cases, we diagnosed hereditary deficiencies of anti thrombin III, protein C and protein S each in one case and a lupus anticoagulant in two cases. In 54 cases no abnormality was found and in the remaining 31 cases various abnormalities were found in one or more of the proteins mentioned above.We conclude that the syndrome of thrombophilia is not rare but its true prevalence needs to be established by more rigorous means. An etiological diagnosis can be made with confidence in only one third of the familial cases and in less than 10 percent of the isolated cases.

REDUCED TISSUE PLASMINOGEN ACTIVATOR RELEASE AND NORMAL PLASMINOGEN ACTIVATOR INHIBITOR LEVEL IN A FAMILY WITH RECURRENT VENOUS THROMBOSES

1987 ◽  
Author(s):  
J Petäjä ◽  
G Myllylä ◽  
V Rasi ◽  
E Vahtera
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Venous Occlusion ◽  
C Protein ◽  
Tissue Plasminogen ◽  
Inhibitor Level ◽  
Fast Acting ◽  
Activator Inhibitor

We have studied the fibrinolytic system in one asymptomatic and six symptomatic members of a family with recurrent DVTs in three generations. Tissue plasminogen activator activity (TPA) and fast acting inhibitor of TPA (PAI) were determined using chromogenic substrate and TPA antigen with ELISA. Measurements were made at rest and after 10 and 20 minutes of venous occlusion (VO). 17 healthy subjects served as controls. The mean TPA in the seven family members was significantly lower than in controls at 10 and 20 min VO (p< 0.01).TPA was below the lowest value of controls (<1.7 U/ml) in five of the six patients with DVT at 10 min VO and remained below the range of controls in three at 20 min VO (<3.3 U/ml). The lowered TPA activity was associated with impaired release of TPA antigen (mean level at 10 min VO 12.A ng/ml, controls 19.5 ng/ml, p<0.05; at 20 min VO 18.2 ng/ml, controls 43.2 ng/ml, p<0.01). Four .patients with and one without DVT had TPA antigen below the lowest level of controls at 10 and/or 20 min VO. The level of'PAI at rest was normal in all cases (from 0.6 to 1.7 U/ml, controls from 0 to 3.7 U/ml). In accordance with low release of TPA antigen PAI was consumed less during VO in patients than in controls (mean level at 20 min VO 0.9 U/ml, controls 0.4 U/ml, p<0.05). The levels of antithrombin III, protein C, protein S, plasminogen, fibrinogen, F V, F VIII:C, vWf:Ag, fibrinopeptide A and beta-thromboglobulin were normal . Circulating anticoagulant was not found. It is concluded that impaired release of TPA, independent of PAI, is associated with DVT in this family. The pattern of inheritance suggested autosomal dominant trait.

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