Total and free levels of tissue factor pathway inhibitor: a risk factor in patients with factor V Leiden?
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Biomedical subjects
Publications and source records attributed to P Van Dreden.
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Activated protein C (APC) resistance is related to a single point mutation in the factor V gene (FV:Q506) and appears to be the most common inherited risk factor for venous thromboembolism. A reliable screening test is therefore useful. We aimed to evaluate a new APC resistance test, on the basis of the procoagulant activity present in one snake venom of a crotalidae family: STA Staclot APC-R. We studied 36 consecutive patients with an acute deep venous thrombosis (DVT) confirmed by compression ultrasonography and carrying the FV:Q506 allele, assessed by DNA analysis, 103 of their family members and 35 consecutive patients with a proven DVT but who did not carry the FV:Q506 allele. Blood samples were collected within 24 h of admission for the DVT cases and on the day of medical registration for the family members. Tests were performed blind. The STA Staclot APC-R test, using a cut-off value of 0.80, had an overall sensitivity of 100% (95% CI, 95-100) and a specificity of 98.8% (95% CI, 92.0-99.6). An acute thrombosis process did not influence the performance of the test. We conclude that this test is easy and rapid to perform in every day practice and fulfills the criteria for a screening test.
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We describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.
The present study was carried out from in vitro fertilization (IVF) attempts to analyze further the total and specific protein contents of 47 follicular fluids yielding one oocyte. The aim was to find correlations between the follicular concentrations of such proteins and the occurrence of coupled oocyte cleavage. These findings would be used as markers of IVF outcome. Two groups of follicular samples were distinguished: one group with cleavage occurrence (25 cases) and another group without cleavage or even fertilization (22 cases). In the group with cleavage a significantly higher level was observed for six proteins: C3 complement fraction and ceruleoplasmin (P less than 0.02), alpha-antitrypsin and transferrin (P less than 0.01), and alpha 2-macroglobulin and beta 2-microglobulin (P less than 0.001). The data are discussed with respect to changes in follicle permeability with advancing maturity.
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1. To investigate the age-related changes in factor VII activation in healthy women, a regular factor VII clotting assay (factor VIIc) was carried out simultaneously with a new enzyme immunoassay for the quantification of antigen factor VII (factor VIIag). 2. Both factor VIIc and factor VIIag levels were positively correlated with age (r = 0.79 and r = 0.62, respectively, n = 25, P less than 0.001). The rise with age in factor VIIc was steeper than in factor VIIag and the ratio of factor VIIc to factor VIIag (an indicator of the activity state of factor VII) increased with age (r = 0.42, P less than 0.05). 3. The results show that an increased conversion of native single-chain factor VII to the fully active double-chain form is associated with advancing age in women. 4. This finding is consistent with a possible role of activated factor VII in the pathogenesis of thrombo-occlusive vascular disease in women.
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A group of 37 patients with myocardial infarction less than 6 hours old was given 5,000 IU of heparin and 0.75 mg/kg of tissue plasminogen activator (rt-PA) (Group A, N = 18) or placebo (Group B, N = 19) intravenously over 90 minutes in a double blind study. Blood sampling was performed before, during and after treatment. The plasma rt-PA concentrations (micrograms/ml) of Group A were as follows: (Table: see text) The concentrations of plasminogen and antiplasmin have decreased significantly as did the fibrinogen level: a concentration of 1 g/l was observed in 7 cases during rt-PA therapy, lasting for 4 to 8 hours after the end of the infusion of rt-PA in 3 cases. The increase of FDP during rt-PA (m = 551 and 222 micrograms/ml at the 60th and 90th minutes) was relatively moderate considering the average level of defibrination (61%). No significant biological changes were observed in Group B. These results support those of our in vitro trials: at comparable thrombolytic activities, the reduction of plasma fibrinogen is less with rt-PA than with streptokinase (SK) or urokinase (UK). However, at concentrations 1 microgram/ml, rt-PA causes almost complete defibrination.
A congenital deficiency in protein C (physiological inhibitor of coagulation) was identified in 57 patients: the deficiency was quantitative (type I) in 20 families, qualitative (type II) in two families. The transmission was autosomal dominant in 21 families but was suspected to be recessive in one family: the 18 years old homozygous propositus has a severe deficiency (protein C = 16 p. 100): both parents are heterozygous (consanguinity was present) and 5 other family members with heterozygous deficiency are asymptomatic. In the 49 patients (25 women, 24 men) belonging to the 21 other families, 9 men and 4 women (27 p.100) are asymptomatic although precipitating factors had existed in 5 patients. In the remaining 36 symptomatic patients, a deep venous thrombosis was observed in 34, a pulmonary embolism in 18. Recurrent arterial thromboses were diagnosed in 3 patients. The first thrombotic episode was observed at the mean age of 27 +/- 11 years and a triggering factor was found in 26 patients (72 p. 100). Thrombosis was recurrent in 21 (60 p. 100). In the patients without oral anticoagulant treatment, mean protein C antigen concentrations were 47 +/- 9 p. 100 and mean protein C activity was 46 +/- 10 p. 100. In 4 patients with type II deficiency, protein C antigen levels were normal (113 +/- 15 p. 100), contrasting with decreased protein C activity (43 +/- 6 p. 100). Thirty-eight patients have been treated with oral anticoagulants and a skin necrosis developed in the homozygous patients only.(ABSTRACT TRUNCATED AT 250 WORDS)
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The determination of tissue plasminogen activator (t-PA) antigen in semen by a new immunoenzymatic method was done in 152 men without genito urinary pathology. The seminal value is one hundred higher than the blood value with a log normal distribution. These levels are not influenced by freezing temperature, by the sequences freezing-thawing, by centrifugation. From split ejaculates a correlation has been established between t-PA antigen and zinc and not with fructose. These results indicate the major prostatic origin of the t-PA antigen.
The determination of total fibrinolytic activity of ejaculates was realized by fibrin plate method. For the same seminal samples, tissue plasminogen activator (t-PA), urinary plasminogen activator (uPA) antigens and uPA activity were specifically quantified. The seminal values were fifty times higher than in the blood for t-PA and fifteen times for uPA. There was no correlation between the both levels but from split ejaculates measurements a higher concentration was observed in all first fractions. By zymography assays, it was shown that seminal plasminogen activators are under active forms. The lack of proUrokinase in semen was also demonstrated.
The aim of this study was to correlate human seminal fructose determinations by enzymatic UV method with protein content, using three different methods (Biuret, Lowry, Meulemans). On one hand, the incidence on fructose levels of partial deproteinization after treatment by perchloric acid was tested: the fructose levels values increased after deproteinization 14.1 +/- 3.7 versus 4.2 +/- 1.7 mMol/l. On the other hand, physiologically, semen proteolysis occurs for many hours after collection and concerns mainly low molecular weight proteins. No modifications were found in protid levels and fructose concentrations during the first four hours, at 20 degrees C. All these data seem to indicate a better linkage of fructose to the highest molecular weight proteins and might explain the absence of fructose rise during the first four hours.