Impaired Procoagulant-anticoagulant Balance during Hormone Replacement Therapy?

2000 ◽  
Vol 83 (01) ◽  
pp. 29-34 ◽  
Author(s):  
W. van Baal ◽  
Jef Emeis ◽  
Marius J. van der Mooren ◽  
Hilda Kessel ◽  
Peter Kenemans ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Levels ◽  
Degradation Products ◽  
Hormone Replacement ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Tissue Type ◽  
Factor Vii ◽  
Negative Results ◽  
Increased Risk

SummaryIn this randomised, placebo-controlled 12-week study, sixty healthy postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E2 group) or combined with a progestagen for 14 days of each cycle (N = 28, E2+P group).As compared to placebo, plasma levels of AT III were reduced only in the E2 group (∼28%), plasma levels of protein C decreased only in the E2+P group (∼4%) and plasma levels of protein S decreased in both the E2 and E2+P group (∼21%). In both the E2 and E2+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (∼10%), whereas no significant change was observed in active factor VII. Plasma levels of tissue-type plasminogen activator (∼22%), urokinase plasminogen activator (∼25%) and plasminogen activator inhibitor type-1 (∼43%) decreased in the E2 and E2+P groups, whereas those of plasminogen increased (∼12%). Treatment was associated with an increase in levels of prothrombin fragment 1+2 (∼31%), but levels of thrombin-antithrombin III complexes, and of plasmin-α2-antiplasmin complexes and total fibrin(ogen) degradation products did not change significantly.Short-term E2 and E2+P treatment is associated with a shift in the procoagulant-anticoagulant balance towards a procoagulant state. A substantial proportion of women do not have a net increase in fibrinolytic activity. These data may be relevant in explaining the increased risk of venous thromboembolism associated with ERT and HRT, and possibly also in explaining the negative results of the Heart and Estrogen/progestin Replacement Study.

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.

FIBRINOLYTIC ACTIVITY IN MALIGNANCY

1987 ◽  
Author(s):  
A Aranda ◽  
J A Páramo ◽  
B Cuesta ◽  
J Fernández ◽  
M J Paloma ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Degradation Products ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Clinical Complications ◽  
Significant Prolongation ◽  
Type Plasminogen Activator ◽  
Lung Malignancies ◽  
Euglobulin Lysis Time

Euglobulin lysis time (ELT), euglobulin fibrinolytic activity on fibrin plate (EFA), plasminogen, tissue-type plasminogen activator (t-PA) activity and antigen, ;2-antiplasmin (α2-AP), plasminogen activator inhibitor (PAI) and fibrinogen degradation products (FDP) were determined in a group of 149 patients (mean age 57 ± 13 years, 93 male), with different malignancies (digestive 61, lung 18, urological 24, ginaecological 16, others 30). Findings were compared with those of 44 age-sex matched healthy subjects. There was a significant prolongation of ELT (p <0.003), a decrease of plasminogen (p < 0.004) and an increase of PAI (p < 0.0001) in patients as compared to controls, being similar EFA, t-PA, α2AP and FDP. No differences in any ot these parameters were found in patients with metastatic disease (n= 65) as compared with those with local disease (n= 84). As regards to tumour localization, plasminogen and t-PA decrease were more pronounced in lung malignancies and PAI increase in lung and digestive malignancies. We conclude that there is an impairment in blood fibrinolytic activity in malignancy. Reduced fibrinolysis seems to be related to localization but not to degree of tumoral activity. That might have clinical complications.

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.

scholarly journals Continuous Active State of Coagulation System in Patients With Nonthrombotic Inflammatory Bowel Disease

2011 ◽  
Vol 17 (6) ◽  
pp. 600-604 ◽  
Author(s):  
Huseyin Alkim ◽  
Selime Ayaz ◽  
Canan Alkim ◽  
Aysel Ulker ◽  
Burhan Sahin
Keyword(s):  
Plasminogen Activator ◽  
Degradation Products ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Plasminogen Activator Inhibitor 1 ◽  
Inflammatory Bowel ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Activator Inhibitor ◽  
D Dimer

This study was planned for searching possible changes of the total coagulation and fibrinolysis system in inflammatory bowel disease (IBD) in order to obtain some clues for explaining the relation between IBD and hypercoagulability. A total of 24 patients with ulcerative colitis, 12 patients with Crohn disease, and 20 healthy controls were studied. Platelets; prothrombin time (PT); partial thromboplastin time (PTT); fibrinogen; d-dimer; fibrinogen degradation products; protein C; protein S; antithrombin; thrombin time; von Willebrand factor; coagulation factors V, VII, VIII, IX, XI, and XIII; plasminogen; antiplasmin; tissue plasminogen activator; plasminogen activator inhibitor 1; and prothrombin fragments 1 + 2 were studied. Most of the procoagulants (platelets, fibrinogen, von Willebrand factor, coagulation factor IX, and plasminogen activator inhibitor 1) were found increased together with decreases in some anticoagulants (protein S and antithrombin) in IBD. Also the activation markers of coagulation (d-dimer, fibrinogen degradation products, and prothrombin fragments 1 + 2) were all increased. The parameters of the total coagulation–fibrinolysis system were increased in IBD, regardless of the form and the activity of the disease.

scholarly journals The role of hypercoagulability in the development of osteonecrosis of the femoral head

2012 ◽  
Vol 4 (2) ◽  
pp. 17 ◽  
Author(s):  
Marios G. Lykissas ◽  
Ioannis P. Kostas-Agnantis ◽  
Ioannis D. Gelalis ◽  
Georgios Vozonelos ◽  
Anastasios V. Korompilias
Keyword(s):  
Plasminogen Activator ◽  
Lupus Erythematosus ◽  
Protein C ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Intravascular Coagulation ◽  
S Deficiency ◽  
Increased Risk ◽  
Von Willebrand

Despite the large number of the outstanding researches, pathogenesis of osteonecrosis remains unknown. During the last decades the hypothesis that increased intravascular coagulation may be the pathogenetic mechanism which leads to osteonecrosis is gaining constantly support. Both primary factors of hypercoagulability, such as resistance to activated protein C, protein C and protein S deficiency, low levels of tissue plasminogen activator, high levels of plasminogen activator inhibitor, von Willebrand factor, lipoprotein (a), and secondary factors of hypercoagulability with factors potentially activating intravascular coagulation, such as pregnancy, antiphospholipid antibodies, systemic lupus erythematosus, hemoglobinopathies and sickle cell disease, and hemato-oncologic diseases are discussed in this article. Although coagulation abnormalities in patients with hip osteonecrosis might represent increased risk factors for the development of bone necrosis by predisposing the patient to thromboembolic phenomena, further investigation is needed to indicate the definite correlation between factors leading to increased intravascular coagulation and pathogenesis of osteonecrosis.

scholarly journals Preoperative Identification of Patients at High Risk of Deep Venous Thrombosis Despite Prophylaxis in Total Hip Replacement

1988 ◽  
Vol 59 (01) ◽  
pp. 093-095 ◽  
Author(s):  
E Rocha ◽  
M J Alfaro ◽  
J A Páramo ◽  
J M Cañadell
Keyword(s):  
Plasminogen Activator ◽  
Total Hip Replacement ◽  
Hip Replacement ◽  
Degradation Products ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Predictive Index ◽  
Total Hip ◽  
Vein Thrombosis ◽  
Predicting Factors

SummaryClinical and laboratory variables were measured on the day before operation in 111 patients who underwent total hip replacement prophylactically treated with acetylsalicilic acid or heparin-dihydroergotamine. Postoperative deep vein thrombosis (DVT) was deteced in 16 patients by ascending venography. Stepwise logistic discriminant analysis was used to identify DVT predicting factors. Three such factors, fibrinogen degradation products (FDP), plasminogen activator inhibitor (PA-inhibitor) and tissue type plasminogen activator (t-PA), were found to be significantly associated with DVT and were used to construct a predictive index. The predictive index, I = —2.09 + 0.46 (FDP) +1.39 (PA-inhibitor)-0.24 (t-PA), was 100% sensitive and 95% specific in the prediction of DVT. This index would allow for identification of those patients in whom routine prophylaxis would be sufficient and for selecting those in whom more effective prophylactic regimens would be necessary.

FIBRINOLYSIS AFTER HEART TRANSPLANTATION

1987 ◽  
Author(s):  
J A Páramo ◽  
R Arcas ◽  
J Fernández ◽  
J Herreros ◽  
R Llorens ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Cardiac Transplantation ◽  
Degradation Products ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Inhibitor Activity ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor

Some aspects of the function of the fibrinolytic system were investigated in 12 patients undergoing cardiac transplantation. Plasminogen, euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor activity (PAI),α2-antiplasmin (α2-Ap) and fibrinogen degradation products (FDP) were determined preo-peratively and on postoperative days 1 and 5. Results showed a significant decrease of plasminogen (p <0.005), EFA (p <0.0001) and t-PA (p ^.0.001) on postoperative day 1 as compared to the baseline value, followed by recovery on day 5. There was a significant increase of PAI (p < 0 . 005) , α2-AP (p <0.0001) and FDP (p < 0.02) on postoperative day 1 as compared to the preoperative value. PAI and FDP reached the baseline value on postoperative day 5, but α2AP also increased on postoperative day 5. Our data show that there is an impairment in blood fibrinolytic activity early after cardiac transplantation, mainly related to a decrease of plasminogen and t-PA and a increase of PAI and α2AP. The clinical relevance of these data needs further evaluation.

Effects on Haemostasis of Hormone Replacement Therapy with Transdermal Estradiol and Oral Sequential Medroxyprogesterone Acetate: A 1 -year, Double-blind, Placebo-controlled Study

1996 ◽  
Vol 75 (03) ◽  
pp. 476-480 ◽  
Author(s):  
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Physiological State ◽  
Hormone Replacement ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Continuous Treatment ◽  
Factor Vii ◽  
Controlled Study ◽  
Double Blind ◽  
Transdermal Estradiol

SummaryAfter menopause the haemostatic balance shifts towards a latent hypercoagulable state. To evaluate the effects of two regimens of transdermal estradiol (E2) combined with progestin on the balance between procoagulant factors and inhibitors, 255 women in physiological menopause for 1-5 years were randomly allocated to 1 year of treatment with cyclic transdermal E2 (50 Μg/day for 21 days) plus medroxyprogesterone acetate (MPA) (10 mg/day from days 10 to 21), continuous transdermal E2 (50 Μg/day for 28 days) plus MPA (10 mg/day from days 14 to 25), or placebo. Fibrinogen, factor VII (FVII), factor VIII:C (FVIII:C), antithrombin III (ATIII), protein C, protein S, heparin cofactor II (HCII) and plasminogen activator inhibitor (PAI-1) levels were measured at baseline and after 6 and 12 cycles. 167 women who took the treatment for at least 6 cycles were evaluable. The continuous treatment group had significantly lower final values of fibrinogen, FVII, ATIII, protein S and HCII than the placebo group; the cyclic treatment reduced fibrinogen in comparison with placebo but the difference was not significant.In conclusion, both regimens produce a clinically relevant decrease of fibrinogen levels; the continuous regimen affects also the levels of FVII and inhibitors suggesting that the haemostatic balance is shifted to a more physiological state.

The Effects of Sex Steroids on Plasma Levels of Marker Proteins of Endothelial Cell Functioning

1998 ◽  
Vol 79 (05) ◽  
pp. 1029-1033 ◽  
Author(s):  
P. J. M. van Kesteren ◽  
T. Kooistra ◽  
M. Lansink ◽  
G. J. van Kamp ◽  
H. Asscheman ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Cyproterone Acetate ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Marker Proteins ◽  
Activator Inhibitor Type ◽  
Pai 1 ◽  
Endothelial Marker

SummaryWe studied thirteen male-to-female (M→F) and ten female-to-male (F→M) transsexuals who, for four months, received cross-sex treatment with, respectively, ethinylestradiol and cyproterone acetate, and with testosterone esters. We assessed the effects of treatment on plasma levels of tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), vWF-propeptide (vWF:AgII) and bigendothelin-1 (big-ET-1), four proteins that are markers of endothelial cell functioning. We also measured urokinase-type PA (uPA) and plasminogen activator inhibitor-type 1 (PAI-1), which may not be endothelium-derived but share major clearance pathways with tPA.In M→F transsexuals, mean plasma levels of tPA (minus 4.4 ng/ml), big-ET-1 (minus 0.8 pg/ml), uPA (minus 0.5 ng/ml) and PAI-1 (minus 26 ng/ml) decreased (all Ps ≤0.02). The level of vWF increased (plus 24%; P = 0.005), while vWF:AgII did not change (P = 0.49).In F→M transsexuals, levels of big-ET-1 increased (plus 0.4 pg/ml; P = 0.02), while tPA, uPA and PAI-1 did not change (all Ps >0.25). In this group vWF decreased (minus 14%; P = 0.06), but vWF:AgII did not change (P = 0.38).Estrogens and androgens have clear effects on plasma levels of endothelial marker proteins. The mechanisms behind these effects are complex and appear to involve both altered secretion (big-ET-1) and processing and/or clearance (vWF and possibly tPA). Therefore, effects of hormones on the levels of endothelial marker proteins do not necessarily reflect changes in endothelial cell functioning, at least with regard to changes in vWF level associated with the oral administration of high doses of ethinylestradiol and cyproterone acetate to healthy men and the parenteral administration of testosterone to healthy women.

Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers

2003 ◽  
Vol 89 (06) ◽  
pp. 990-995 ◽  
Author(s):  
Charalambos Antoniades ◽  
Costas Tentolouris ◽  
Marina Toutouza ◽  
Kyriakoula Marinou ◽  
George Goumas ◽  
...  
Keyword(s):  
Vitamin E ◽  
Vitamin C ◽  
Endothelial Function ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Reactive Hyperemia ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Factor Vii ◽  
Pai 1

SummarySmoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400IU/day (group B), vitamin C 2g/day plus vitamin E 800IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.

Sign in / Sign up

Export Citation Format

Share Document