Prospective Evaluation of the Prevalence of Haemostasis Abnormalities in Unexplained Primary Early Recurrent Miscarriages

SummaryThe prevalence of haemostasis abnormalities was evaluated in 500 consecutive women with unexplained primary recurrent miscarriages. Two matched reference groups with no antecedent of miscarriage were studied: 100 healthy mothers and 50 childless women.In the prospective part of the study, we found 9.4% of the patients (95% C.I.: 6.8-12%) with an isolated factor XII deficiency, 7.4% of the patients (5.0-9.8%) with primary antiphopholipid antibodies, 47% of the patients (42.6-51.4%) with an insufficient response to the venous occlusion test and an isolated hypofibri- nolysis was found in 42.6% (38.2-47%) of the patients (reference groups: respectively 0/150, 3/150, 2/150, 2/150, pclO’3). Willebrand disease, fibrinogen deficiency, antithrombin, protein C or protein S deficiencies were not more frequent in recurrent aborters than in members of the reference groups. In the retrospective part of the study, cases of plasma resistance to activated protein C were not abnormally frequent.Patients had higher Willebrand factor antigen (vWF), tissue-type plasminogen activator antigen (t-PA), plasminogen activator inhibitor activity (PAI) and D-dimers (D-Di) than the reference women. Values of vWF, t-PA, PAI and D-Di were altogether correlated but were not related to C-reactive protein concentrations. Among patients, those with an antiphospholipid syndrome and those with an insufficient response to the venous occlusion test had higher vWF, t-PA, PAI and D-Di values than the patients with none of the haemostasis-related abnormalities.Thus, factor XII deficiency and hypofibrinolysis (mainly high PAI) are the most frequent haemostasis-related abnormalities found in unexplained primary recurrent aborters. In patients with antiphospholipid antibodies or hypofibrinolysis, there is a non-inflammatory ongoing chronic elevation of markers of endothelial stimulation associated with coagulation activation. This should allow to define subgroups of patients for future therapeutic trials.

Download Full-text

A Study of Fibrinogen and Fibrinolysis in 10 Adults with Nephrotic Syndrome

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647513 ◽

1988 ◽

Vol 59 (03) ◽

pp. 445-450 ◽

Cited By ~ 6

Author(s):

S Gandrille ◽

M H Jouvin ◽

P Toulon ◽

P Remy ◽

J N Fiessinger ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Serum Albumin ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Venous Occlusion ◽

Thrombin Time ◽

Coagulation Inhibitors ◽

Increased Activity ◽

Activator Inhibitor ◽

Venous Occlusion Test

SummaryIn 10 patients with nephrotic syndrome (NS), the coagulation inhibitors, the fibrinolytic system and several functions of the fibrinogen-fibrin molecule were studied.Among the coagulation inhibitors, only antithrombin III (AT III) was found decreased and correlated with serum-albumin levels. Venous occlusion test provoked a normal tissue plasminogen activator (tPA) release in all patients. The plasminogen activator inhibitor (PAI) had an increased activity in 5 out of the 10 patients.Thrombin and reptilase times were found abnormal in most patients. The thrombin time (TT) prolongation correlated with serum albumin levels and was corrected by adding purified albumin.The fibrinogen was purified from each of the 10 patients’ plasma. Only 2 of them showed abnormal polymerization in purified system, suggesting dysfibrinogenaemia. Other functions (thrombin binding, tPA stimulating activity, lysis by purified plasmin) were found normal except in one of the 2 patients with dysfibrinogenaemia whose fibrinogen lysis by plasmin was delayed.It is concluded that an abnormal fibrinogen molecule is not the most frequent explanation for thrombin time prolongation in NS.

Download Full-text

Studies on Platelet Aggregation before and after Carotid Endarterectomy (Part2) : Relationship between Coagulo-fibrinolytic Activities and Platelet Aggregation following Venous Occlusion Test

Japanese Journal of Neurosurgery ◽

10.7887/jcns.4.351 ◽

1995 ◽

Vol 4 (4) ◽

pp. 351-358

Author(s):

Noboru Asano ◽

Shin Ueda

Keyword(s):

Platelet Aggregation ◽

Carotid Endarterectomy ◽

Venous Occlusion ◽

Occlusion Test ◽

Before And After ◽

Venous Occlusion Test

Download Full-text

Decreased fibrinolytic stimulation by a short-term venous occlusion test in patients with cerebrovascular disease

Thrombosis Research ◽

10.1016/0049-3848(95)00124-a ◽

1995 ◽

Vol 79 (4) ◽

pp. 363-368 ◽

Cited By ~ 5

Author(s):

Bernhard Kempter ◽

Alexander Peinemann ◽

Oliver Biniasch ◽

Roman L. Haberl

Keyword(s):

Cerebrovascular Disease ◽

Venous Occlusion ◽

Short Term ◽

Occlusion Test ◽

Venous Occlusion Test

Download Full-text

Study of the venous occlusion test in smokers

Fibrinolysis and Proteolysis ◽

10.1016/0268-9499(90)90192-m ◽

1990 ◽

Vol 4 ◽

pp. 65

Author(s):

J.C. Gris ◽

J.F. Schved ◽

P. Martinez ◽

A. Arnaud ◽

N. Sanchez ◽

...

Keyword(s):

Venous Occlusion ◽

Occlusion Test ◽

Venous Occlusion Test

Download Full-text

Curve analysis of tissue oxygen desaturation after a venous occlusion test does not identify the central venous hemoglobin oxygen saturation

Critical Care ◽

10.1186/cc10864 ◽

2012 ◽

Vol 16 (S1) ◽

Author(s):

G Friedman ◽

C Alan ◽

A Meregalli ◽

A Lima ◽

J Bakker

Keyword(s):

Oxygen Saturation ◽

Venous Occlusion ◽

Curve Analysis ◽

Oxygen Desaturation ◽

Tissue Oxygen ◽

Central Venous ◽

Hemoglobin Oxygen Saturation ◽

Occlusion Test ◽

Venous Occlusion Test

Download Full-text

Activation of platelets in the venous occlusion test

Thrombosis Research ◽

10.1016/0049-3848(84)90314-1 ◽

1984 ◽

Vol 35 (1) ◽

pp. 77-80

Author(s):

Torbjörn Nilsson

Keyword(s):

Venous Occlusion ◽

Occlusion Test ◽

Venous Occlusion Test

Download Full-text

Use of a Low-Molecular Weight Heparin (Enoxaparin) or of a Phenformin-like Substance (Moroxydine Chloride) in Primary Early Recurrent Aborters with an Impaired Fibrinolytic Capacity

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653781 ◽

1995 ◽

Vol 73 (03) ◽

pp. 362-367 ◽

Cited By ~ 38

Author(s):

Jean-Christophe Gris ◽

Sylvie Neveu ◽

Marie-Laure Tailland ◽

Christophe Courtieu ◽

Pierre Marès ◽

...

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Venous Occlusion ◽

Clot Lysis ◽

Primary Study ◽

Low Molecular Weight ◽

Occlusion Test ◽

Number Of Patients ◽

Fibrinolytic Capacity ◽

Venous Occlusion Test

SummaryAn impaired fibrinolytic capacity, defined as an insufficient venous occlusion-induced shortening of the plasma euglobulin clot lysis time, is a common feature in women suffering from primary early recurrent unexplained miscarriages (1,2). We investigated the therapeutic effect of a low-molecular-weight heparin and of a phenformin-like substance.In a prospective, randomized trial, 30 consecutive patients initially received either enoxaparin, 20 mg per day during one month, or moroxydine chloride, 1200 mg per day during one month. In case of fibrinolytic status normalization, they were treated during 6 months by the beneficial treatment which was planned to be continued during eventual pregnancies. Patients with hypofibrinolysis persistence received the alternative treatment during another month and a new evaluation was performed. No treatment was given when a persistent abnormal response to the venous occlusion test was evidenced. In case of positive response, the treatment was continued during 6 months. The primary study end-points consisted of any of the following: effect of the treatments on the fibrinolytic response; number of patients becoming pregnant during the 6 months following the last venous occlusion test; number of full-term pregnancies.Concerning the effects on the fibrinolytic system, 20 out of 29 women responded to the first or second-line enoxaparin treatment whereas only 1 woman out of 19 responded to moroxydine chloride (p=0.00002). Concerning the effects on fertility, responders to LMWH were more likely to initiate a new pregnancy than non-responders (16/20 vs 2/10, p=0.002). In patients conceiving, LMWH responders were more likely to obtain live births than nonresponders (13/16 vs. 0/2, p=0.02). The 9 women who had not responded to both treatments and the one who had responded to moroxydine chloride are still childless. Thirteen of the 20 previously childless women who had responded to enoxaparin had a successful pregnancy whilst taking the low-molecular weight heparin (p=0.0009).The low-molecular weight heparin enoxaparin was associated with successful pregnancies in patients with recurrent unexplained miscarriages associated with an impaired fibrinolytic capacity.

Download Full-text

Thromboembolic Disease – Critical Evaluation of Laboratory Investigation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656308 ◽

1992 ◽

Vol 68 (01) ◽

pp. 007-013 ◽

Cited By ~ 71

Author(s):

Johan Malm ◽

Martin Laurell ◽

Inga Marie Nilsson ◽

Björn Dahlbäck

Keyword(s):

Plasminogen Activator ◽

Laboratory Investigation ◽

Patient Group ◽

Vitamin K ◽

Protein C ◽

Protein S ◽

Venous Occlusion ◽

Thromboembolic Disease ◽

Fibrinolytic System ◽

Laboratory Evaluation

SummaryPrevious studies of patients with thromboembolic disease have revealed an association either with hereditary anticoagulant protein deficiencies or with defects in the fibrinolytic system. To obtain a more comprehensive picture and to investigate which analyses are useful in the evaluation of such patients, we have performed an extensive laboratory investigation in 439 individuals with thromboembolic disease. Anticoagulant protein deficiencies were found in 24 patients. Deficiencies of protein C (n = 10) and protein S (n = 9) were most common followed by deficiencies of antithrombin III (n = 3) and plasminogen (n = 2). Six of the nine protein S deficient patients demonstrated a selective deficiency of free protein S with normal total protein S concentrations. To diagnose protein C and S deficiencies among the 201 patients receiving oral vitamin K antagonists, the concentrations of protein C and S were compared with the mean concentration of several other vitamin K-dependent proteins. One protein C and three protein S deficiencies were identified among the treated patients. The number of protein C deficiencies found in this group was significantly lower than the number found among untreated patients. Although fewer protein S deficiencies were also identified among the treated patients, than in the untreated group, the difference was not statistically significant. The results suggest that protein C deficiencies went undetected in the treated group and that oral anticoagulant therapy should be discontinued before efforts to diagnose protein C deficiency are made. We found no cases with heparin cofactor II deficiency. Lupus anticoagulant was present in 10 patients. Evaluation of the fibrinolytic system revealed that the patient group had slightly lower mean euglobulin fibrinolytic activity (EFA) after venous occlusion than controls and a subgroup (approximately 15%) of patients with EFA below the level of the 5th percentile of controls, could be distinguished. Repeated analysis demonstrated a substantial individual day-to-day variation in both patients and controls and the combined EFA results did not clearly distinguish patients from controls. There was a significant negative correlation between EFA and plasminogen activator inhibitor (PAI) levels in both patients and controls and the patient group had significantly higher levels of PAI than the control group. In contrast, there was no difference between controls and patients in tissue plasminogen activator (tPA) release after venous occlusion and no correlation between EFA and tPA was observed. These results suggest that although a statistically significant difference between patients and controls in values of fibrinolytic parameters was found, an extensive laboratory evaluation of the fibrinolytic system in individual patients may not be warranted. The association between patients with thrombosis and deficiencies of anticoagulant proteins suggests that the investigation of individual patients should focus on these components.

Download Full-text