Expression of the SOX10 gene during human development.

SOX10, a new member of the SOX gene family, is a transcription factor defective in the Dom (Dominant megacolon) mouse and in the human Shah-Waardenburg syndrome. To help unravel its physiological role during human development, we studied SOX10 gene expression in embryonic, fetal, and adult human tissues by Northern blot and in situ hybridization. As in mice, the human SOX10 gene was essentially expressed in the neural crest derivatives that contribute to the formation of the peripheral nervous system, and in the adult central nervous system. Nevertheless, it was more widely expressed in humans than in rodents. The spatial and temporal pattern of SOX10 expression supports an important function in neural crest development.

Residual vascular risk of discontinued oral contraception. Role of antibodies to synthetic sex hormones.

Recent epidemiological data indicate that the risk of thromboembolic disease associated with oral contraception (OC) may persist after discontinuation of the drug. It was demonstrated on the other hand that antibodies to sex steroid hormones which develop in OC users, were significantly correlated with the incidence of thrombosis. It is well known that antibodies may persist years after the antigenic stimulation. So it was of interest to see if the eventual occurrence of thrombosis in ex-users might be correlated with the presence of anti-sex steroid antibodies remaining after stopping OC. Thirty-eight women with thrombosis on OC and positive antibody levels, who were required to stop the pill, were followed for periods ranging from 1 to 10 years. No disappearance of anti-ethinyl-estradiol antibodies (anti-EE ab) was observed except for 2 cases. On the other hand, 109 patients with thrombosis either current- (50), past- (29), or never-users (30) of OC were compared to 102 controls of similar groups. Results indicate that the levels of anti-EE ab, and the percentage of women who had anti-EE ab, were similar in those who experienced thrombosis either in the course of OC or after discontinuation. A significant difference was observed between both cases who were current- or ex-users and their controls.

Lp(a) levels and antiestrogen antibodies in women with and without thrombosis in the course of oral contraception.

Several reports have shown that lipoprotein(a) is associated with ischemic diseases. Two characteristics might explain this association. Firstly, Lp(a) is an LDL-like lipoprotein which may be implicated in the atherosclerotic process and secondly, Lp(a) possesses an additional apolipoprotein(a) whose structure is close to that of plasminogen and might confer to the molecule prothrombotic properties. It seemed of interest to see whether Lp(a) was a risk factor in oral contraceptive users with thrombotic complications, a group of young women with presumably little or no atherosclerosis. Three groups of women were compared: 25 of them served as controls and did not use oral contraceptives (OC) (group 1); 25 women were healthy current users of OC (group 2); 35 women suffered thrombotic complications in the course of OC (group 3). Mean levels of Lp(a), estimated by RID, were not found to be significantly different in the 3 groups: 19 +/- 18, 20 +/- 23 and 16 +/- 22 mg/dl, respectively. Levels above 30 mg/dl were similarly distributed. Among the other risk factors studied, antiestrogen antibodies were absent in group 1, present in 24% of group 2 and 71.4% of group 3 (P < 0.01). Serum cholesterol levels were similar in the 3 groups: 209 +/- 33, 220 +/- 41, 213 +/- 45 mg/dl respectively. Mean serum triglyceride levels were higher in group 2 than in group 1 (61 +/- 18 and 83 +/- 32, P < 0.01), and higher in group 3 than in group 2 (116 +/- 66 and 83 +/- 32, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood changes in sex steroid hormone users. Circulating immune complexes induced by estrogens and progestogens and their relation to vascular thrombosis.

Oral contraceptives (OC) have been shown to induce in some women antiethinylestradiol antibodies which may be detected as circulating immune complexes by precipitation in ammonium sulphate at 25% saturation (CIC.AS). A reevaluation of the presence of CIC.AS in 644 women either receiving sex steroid hormones or not was made, and the respective role of estrogens and progestogens investigated, together with the influence of the dose. The study confirmed that CIC.AS levels were significantly different in controls (442 +/- 246 micrograms/ml serum), healthy gonadal hormone users (754 +/- 700 micrograms) and users with thrombosis (1331 +/- 1099 micrograms/ml). These results indicated that: 1. CIC.AS could be induced by synthetic estrogens as well as progestogens, but not by non-synthetic hormones; 2. the induction of CIC.AS seemed poorly dose-related, and 3. was not correlated with the duration of use; 4. in reactive women, high CIC.AS levels occurred as soon as 3 weeks after the beginning of synthetic gonadal hormones use, persisted throughout treatment and decreased slowly when discontinued; 5. in women with thrombosis CIC.AS were more frequently detected (64.7%) than in healthy users (32.2%) P less than 0.001. The importance of the immunologic changes as a risk factor in thrombosis in OC users was evaluated in comparison with other predisposing factors and tobacco smoking.

PIP: Oral contraceptives (OCs) have been shown to induce antiethinyl estradiol antibodies in some women which may be detected as circulating immune complexes by precipitation in ammonium sulphate at 25% saturation (CIC.AS). A reevaluation of the presence of CIC.AS in 644 women either receiving sex steroid hormones or not was made, and the respective role of estrogens and progestogens investigated, together with the influence of the dose. The study confirmed that CIC.AS levels were significantly different in controls (442 +or- 246 mcg/ml serum), healthy gonadal hormone users (754 +or- 700 mcg) and users with thrombosis (1331 +or- 1099 mcg/ml). These results indicated that: 1) CIC.AS could be induced by synthetic estrogens as well as progestogens but not by nonsynthetic hormones; 2) the induction of CIC.AS seemed poorly dose-related; and 3) the induction was not correlated with the duration of use; 4) high CIC.AS levels occurred as soon as 3 weeks after the beginning of synthetic gonadal hormone use in reactive women and persisted throughout treatment and decreased slowly when discontinued; and 5) CIC.AS was detected more frequently (64.7%) in women with thrombosis than in healthy users (32.2%), P0.001. The importance of the immunologic changes as a risk factor in thrombosis in OC users was evaluated in comparison with other predisposing factors and tobacco smoking.

Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors for thrombosis in women on oral contraceptives.

Hyperhomocyst(e)inemia was shown to be associated with vascular occlusion in atherosclerotic patients. We have conducted a study to determine if hyperhomocyst(e)inemia was also related to the vascular events observed in women on oral contraceptives, presumably having little or no atherosclerosis. Two hundred women receiving oral contraceptives were included in the study: 100 were healthy controls and 100 had documented vascular occlusion. Determination of serum homocyst(e)ine and anti-estrogen antibody levels wore performed under blind conditions. They were evaluated in logistic regression models in which age and smoking were also included. Women with vascular occlusion had higher levels of homocyst(e)ine (P less than 0.001) and of anti-estrogen antibodies (P less than 0.001) when compared to controls. They were also older (P less than 0.001) and more frequently smokers (P less than 0.05). The above mentioned variables were, in isolation, independent predictors of vascular occlusion. Moreover, a model assessing those variables and their interactions indicated that the levels of anti-estrogen antibodies and smoking increased the predictability in older women, as well as the levels of age-adjusted homocyst(e)ine. The study suggests that the above factors can identify women at risk and that determination of anti-estrogen antibodies and homocyst(e)ine levels may help to detect women predisposed to vascular occlusions when taking oral contraceptives.

PIP: This study was conducted to test the hypothesis that hyperhomocyst(e)inemia may be an additional risk factor for vascular occlusions in women taking oral contraceptives (OCs). A total of 200 women who were regular users of OC tablets containing 30 or 50 mcg ethinyl estradiol were studied: 100 were controls and 100 had documented vascular occlusion. Serum levels of homocyst(e)ine and anti-estrogen antibody were determined under blind conditions. These were evaluated in logistic regression models in which age and smoking were also included. Women with vascular occlusion had higher levels of homocyst(e)ine and anti-estrogen antibodies when compared to controls. They were also older and frequent smokers. The variables investigated--namely, anti-estrogen antibody, age-adjusted log, transformed homocyst(e)ine, age, and smoking--were independent predictors of vascular occlusions when considered in isolation. Moreover, a model assessing these variables and their interactions, indicated that the levels of anti-estrogen antibodies and smoking increased the predictability in older women, as well as the levels of age-adjusted log and homocyst(e)ine. The study suggests that these variables can identify women at risk, and the determination of anti-estrogen antibody and homocyst(e)ine levels may help to detect women predisposed to vascular occlusions when taking OCs.

Plasma lipoprotein distribution and lipid transfer activities in patients with type IIb hyperlipidemia treated with simvastatin.

The aim of the present study was to search in type IIb hyperlipidemic patients for putative concomitant effects of simvastatin on the physicochemical characteristics of low density lipoproteins (LDL) and high density lipoproteins (HDL), as well as on the activities of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) that were determined in both endogenous lipoprotein-dependent and endogenous lipoprotein-independent assays. In a double-blind, randomized trial, patients received either placebo (one tablet/day; n = 12) or simvastatin (20 mg/day; n = 12) for a period of 8 weeks after a 5-week run-in period. Simvastatin, unlike placebo, reduced the lipid and apolipoprotein B contents of the most abundant LDL-1, LDL-2, and LDL-3 subfractions without inducing significant changes in the overall size distribution of LDL and HDL. Whereas simvastatin significantly increased PLTP activity in an endogenous lipoprotein-dependent assay (P < 0.01), no variation was observed in a lipoprotein-independent assay. Simvastatin significantly decreased plasma CETP activity in an endogenous lipoprotein-dependent assay (P < 0.01), and the reduction in plasma cholesteryl ester transfer rates was explained by a 16% drop in CETP mass concentration (P < 0.01). In contrast, the specific activity of CETP was unaffected by the simvastatin treatment reflecting at least in part the lack of significant alteration in plasma triglyceride-rich lipoprotein acceptors. The simvastatin-induced changes in plasma CETP mass levels correlated positively with changes in plasma CETP activity (r = 0.483, P = 0.0561), in total cholesterol levels (r = 0.769; P < 0.01), and in LDL-cholesterol levels (r = 0.736; P < 0.01). Whereas the observations suggest that simvastatin might exert concomitant beneficial effects on plasma CETP and LDL levels, neither plasma cholesteryl ester transfer activity nor plasma phospholipid transfer activity appeared as the main determinants of the LDL and HDL distribution profiles in type IIb hyperlipidemic patients.

The SOX10 transcription factor: evaluation as a candidate gene for central and peripheral hereditary myelin disorders.

The SOX10 transcription factor is involved in development of neural crest derivatives and fate determination in glial cells. SOX10 mutations have been found in patients with intestinal aganglionosis and depigmentation with deafness (Waardenburg-Hirschsprung). Associated neurological signs have been reported in some cases, including a patient exhibiting a central and peripheral myelin deficiency. Therefore, we screened for SOX10 mutations in a large cohort of patients with peripheral and central myelin disorders. 56 were affected by classical demyelinating Charcot-Marie-Tooth disease without identified mutations in the genes encoding PNS myelin proteins (PMP22, P0), connexin 32 and the zinc-finger transcription factor, EGR2. 88 patients with undetermined leukodystrophy were selected from a large European prospective study. Associated clinical, magnetic resonance imaging and electrophysiological signs were consistent with a defect in CNS myelination in 83 and with an active degeneration of the CNS myelin in 5. No abnormalities in the proteolipid protein gene (PLP) were found. The absence of SOX100 mutation in this large cohort of patients suggests that this gene is not frequently involved in peripheral or central inherited myelin disorders.

[Detection of pill-induced antiethinylestradiol antibodies (author's transl)]. / Détection des anticorps anti-éthinyl-oestradiol induits par les contracetifs oraux.

The synthetic hormones contained in contraceptive pills were shown to induce antiethinylestradiol (EE) antibodies in some women. These antibodies can be detected by the presence of circulating immune complexes (CIC) which are precipitated from serum in 25 p. cent saturated ammonium sulphate. A method of analysis of the anti-EE antibodies is described, in which binding of tritiated EE is measured with and without addition of unlabeled EE in excess. This method allows to identify specific reversible binding on saturable sites. Because of the large excess of non specific sites, the whole serum was enriched in antibodies before the binding measurement, either by previous separation of CIC, or by an affinity chromatography on a EE column. Results of this method confirmed the presence in a number of women on oral contraceptives, of immunoglobulins which were able to bind EE reversibly. The antibodies were found in CIC. in the absence of CIC, they were occasionally found in serum after an affinity chromatography on a EE column. This method is felt to allow a more accurate detection of women immunoreactive to the pill.

PIP: OC (oral contraception) use provokes in some women the production of EE (ethinyl estradiol) antibodies which circulate in the blood as immune complexes. These CIC (circulating immune complexes) precipitate when the serum is brought to 25% saturation in ammonium sulphate. The localization of CICs in OC users has allowed the detection of reactive women, and has shown that vascular thrombosis happens almost exclusively in reactive users. The method of detection described above is the one commonly used, being simple and practical; however, it can be at times erroneous. The authors of this article describe a new method of analysis of EE antibodies which allows to detect the presence of proteins able to fix EE in a reversible way in OC users. In this method binding of tritiated EE is measured with and without addition of unlabeled excess EE. Because of the large excess of nonspecific sites, the whole serum was enriched in antibodies before the binding measurements, either by previous separation of CIC, or by an affinity chromatography on an EE column. The method confirms the presence of immunoglobulins which were able to bind EE reversibly in a number of OC users. The antibodies were found in CICs; in the absence of CICs they are sometimes found in the serum after affinity chromatography on an EE column. This method allows a more accurate detection of women immunoreactive to the pill.

[Vascular complications of oral contraception. In whom and how to prevent them?]. / Complications vasculaires de la contraception orale. Chez qui et comment les prévenir?

Oral contraception entails an increased risk of arterial and venous thrombosis which can only be prevented by detecting women at risk. The relative importance of various predisposing or precipitating factors was evaluated by comparing 3 groups of women: 50 oral contraceptive (OC) users with thrombosis; 50 healthy OC users and 30 controls who had never used OC's. The factors investigated were: duration of use and dose of oestrogens, age, blood pressure, serum lipid levels and tobacco smoking. In addition, all women were tested for the presence of anti-ethinylestradiol antibodies (anti-EE ab) which we had previously shown to be induced by OC's in a number of women. Our results indicated that the most frequently encountered risk factor associated with vascular thrombosis was the presence of anti-EE ab and that the risk was further increased by smoking in women with these antibodies.

Oral contraceptive, pulmonary artery thrombosis and anti-ethinyl-oestradiol monoclonal IgG.

Pulmonary artery thrombosis and an anti-ethinyl-oestradiol monoclonal IgGlambda were found to be associated in a 36-year-old woman (Mrs MAI.) who took an oral contraceptive containing 50 mug ethinyl-oestradiol and 500 mug nor-ethisterone daily. After appropriate purification including methods by which the IgG was separated of bound circulating hormones, its binding activity was demonstrated by several methods: passive haemagglutination of oestradiol-benzoate sensitized red blood cells; gel filtration on Sephadex G-25; ultracentrifugation and equilibrium dialysis. IgGlambda MAI bound ethinyl oestradiol (Ka=2-7 X 10(1) M-1) and also 17-beta-oestradiol, with a lower affinity (Ka=0-4 X 10(7) M-1). The valency for these two hormones was near 2. Ethinyl-oestradiol bound to the IgG was displaced by ethinyl-oestradiol itself and in decreasing order of potency by 17-beta-oestradiol, progesterone, oestriol, and testosterone. Oestrone and hydrocortisone had no effect. Although the localization of the binding sites of this IgGlambda was not studied, it is likely that they were the antibody sites of the molecule and, according to immunochemical criteria, it may be classified as a monoclonal anti-ethinyl-oestradiol antibody. It is felt that its association with the pulmonary thrombosis and the oral contraceptive may be significant. This supports the hypothesis of an immunological mechanism for the unexplained thrombotic risk of oral contraceptives.

PIP: A 35-year-old woman who had taken an oral contraceptive (50 mcg ethinyl estradiol (EE) plus 500 mcg norethisterone) for 2 1/2 years was hospitalized for a massive left pulmonary thrombosis. A monoclonal IgGgamma gammopathy of about 700 mg/100 ml was found from electrophoretic patterns. After purifying the IgG, including separation from bound circulating hormones, its binding activity for several steroids was determined by equilibrium dialysis, which revealed several steroids as inhibitors of EE binding by IgG with potencies in the following order (decreasing): EE itself, 17beta-estradiol, progesterone, estriol, and testosterone. It appears likely that the binding sites of this KgGgamma were the antibody sites and that it may be classified as a monoclonal anti-ethinyl-estradiol antibody. The occurrence of thrombosis and a rare gammopathy in a young woman is unlikely and lends support to the hypothesis that an immunological mechanism is responsible for the thrombotic risk associated with oral contraceptives.

[Monoclonal human immunoglobulin (IgG lambda) with antiethinylestradiol activity, oral contraceptives, and arterial pulmonary thrombosis]. / Immunoglobuline humaine monoclonale (IgG lambda) anti-éthinylaestradiol, contraceptif oral et thrombose artérielle pulmonaire

In a 36-year-old woman taking an oral contraceptive containing 50 mug of ethinyloestradiol each day, a pulmonary arterial thrombosis and a monoclonal gammapathia were associated. The monoclonal IgI lambda Mai... was prepared. When purified, this IgG lambda binds ethinyloestradiol with strong affinity (Ka= 2.7 times 10(7)M-1) and also 17-beta-oestradiol with a little less affinity (Ka = 0.4 times 10(7)M-1. For those ligands each IgG lambda Mai... molecule has two sites of same affinity and specificity so that a Scatchard plot of the experimental values gives a straight line. It is likely that the antibody sites of the IgG lambda Mai... are the binding sites. These facts support the hypothesis of an immunological mechanism of the thromboembolic disease which may be induced by oral contraceptives.

PIP: An IGG lambda was purified and its binding properties analyzed from the serum of a woman who had suffered a pulmonary embolism after taking an oral contraceptive (50 mcg ethinyl estradiol and 500 mcg norethisterone) for over 2 years. The purification steps were 1) precipitation with 25% ammonium sulfate; 2) gel filtration on DEAE Sepha dex A25-Sephadex G-25 at pH 10.5 with 6 M urea; 3) repeat gel filtration, but at pH 8.6 without urea; 4) chromatography on Sepharose 4B CNBr coupled with ethinyl estradiol. The activities of the fractions were analyzed by double diffusion immunoelectrophoresis. Scatchard plots by both dialysis and by ultracentrifugation generated an association constant of 2.7 X 10 7 M -1 for ethinyl estradiol, .4 X 10 7 M -1 for 17beta-estradiol, and a valence of 2. Normal human sera had such low affinities for ethinyl estradiol that the Ka could not be calculated. Immunoelectrophoresis showed only a single protein, of about 150,000 molecular weight in polyacrylamide gel. Equilibrium dialysis against other steroids demonstrated that the IgC was specific for ethinyl estradiol, but binding was inhibited to a lesser extent by the following, in order of potency: 17beta-estradiol, progesterone, estr adiol, testosterone, and estrone. The Ka was midway between that of albuinn and the highly specific steroid binding protein. The relationships between oral contraception, this apparent monoclonal gammapathy, and the pulmonary embolism are discussed.

[Automatic assay of circulating immune complexes induced by oral contraceptives (author's transl)]. / Dépistage automatique des complexes immuns circulants induits par les hormones contraceptives.

PIP: The authors describe an automatic method to assay circulating immune complexes induced by OC (oral contraception). The method is simple, quick, and cheap; it consists of detecting the immune complexes precipitating by ammonium sulphate at 25% saturation, as in the manual method. In the automatic method the procedure is done on an Auto Analyzer apparatus, which allows direct reading of the floculation, and does not require washing of the precipitate. Results obtained for 164 sera tested automatically were compared with results obtained by the manual method; the correlation was very significant. The same method can be used for screening other immune complexes.^ieng

Oral contraceptives, sex steroid-induced antibodies and vascular thrombosis: results from 1318 cases.

The role of antiethinyl estradiol antibodies (anti EE Ab) and associated risk factors was evaluated in 1318 cases of venous or arterial thrombosis in oral contraceptives (OC) users, and compared to 61 non-users and 124 healthy current users. Anti EE Ab were absent in non-users and present in 33% of healthy users and 72% of those with thrombosis, either arterial or venous. Age, duration of use, hyperlipidaemia and smoking were factors associated with thrombosis only in women with an arterial disease. While the two predominant factors, anti EE Ab and smoking may be risk factors in their own right, the combination of both was found in 47.7% of women with thrombosis. It is proposed that thrombosis associated with OC use may be explained by an immunological disease in which anti EE Ab and their complexes with the circulating synthetic hormones may be harmful to the vessels, as also suggested by the type of lesions already described in OC users. The determination of anti EE Ab in healthy users may identify a group at risk of thrombosis.

PIP: The significance of antibodies against ethinyl estradiol (anti-EE-Ab) and other risk factors was discussed for a series of 1318 cases of venous and arterial thrombosis in oral contraceptive users, in comparison to 61 non-users and 124 health current pill users. The cases included 264 deep vein thromboses, 159 pulmonary embolism, 37 coronary artery, 33 systemic artery, 763 cerebrovascular artery thromboses, and 10 hepatic vein thromboses collected from 88 French hospitals from 1976-1988. There were 98 cases with successive or multiple sites involved. The mean age of contraceptive users with thrombosis was 32.1, compared to 28.8 in healthy users. Duration of use was slightly longer in affected users than healthy users, but some cases were affected as early as their 1st cycle. 87.2% had no related history. The anti-EE-Ab were absent in never users, averaged 318 c./min in pill users with thrombosis, but 60 in healthy pill users. There was no correlation between anti-EE-Ab level and dose or duration of pill use. Similar anti-EE-Ab levels were found in those with venous or arterial thrombosis, but women with arterial thrombosis were older, had used pills longer, had fewer predisposing factors of surgery or labor and delivery, but more frequent incidence of hyperlipidemia, smoking, and hypertension. The most frequent associated factors with thrombosis were presence of anti-ee-Ab and smoking: 15.6% smoked, 31.1% had anti-EE-Ab, and 47.6% had both, but only 9.5% had neither factor. It is interesting that lowering the estrogen dose of oral contraceptives has decreased the frequency of venous thrombosis, but not that of arterial thrombosis or mortality, nor anti-EE-Ab levels. The vascular lesions in arterial thrombosis seen in pill users are thought to resemble those in many autoimmune diseases.

Evaluation of risk factors associated with vascular thrombosis in women on oral contraceptives. Possible role of anti-sex steroid hormone antibodies.

Women on oral contraceptives have an increased risk of thrombosis. The prevention of the vascular complications relies on the detection of women who are at risk. In order to find out which characteristics correlate with the occurrence of the vascular disease, 3 groups of women were compared; 50 oral contraceptive users with thrombosis, 50 healthy users, and 30 controls. Apart from the modality of oral contraception (duration of use, dose of estrogens), the following parameters were tested as possible risk factors: age, serum lipid levels, tobacco smoking, and especially presence of antiethinylestradiol antibodies (anti-EE ab) which we had previously shown to be induced by oral contraceptives in a number of women. Results indicated that the major risk factor associated with vascular thrombosis was the presence of anti-EE ab. Furthermore, the risk was highly increased by the association of tobacco smoking to anti-EE ab.

Oral contraception, circulating immune complexes, antiethinylestradiol antibodies, and thrombosis.

Circulating immune complexes were detected in women on oral contraceptives (OC) by a simple antigen nonspecific method using precipitation of serum in 25% saturated ammonium sulfate (CIC-AS). A significant correlation was found between the presence of CIC-AS and the OC vascular risk. A radioimmunoassay with tritiated ethinylestradiol indicated that CIC-AS contained antiethinylestradiol antibodies (anti-EE Ab) in a number of OC users, but indicated also that 1) anti-EE Ab may be found in cases with no detectable CIC-AS, 2) CIC-AS containing no anti-EE Ab are found in nonusers, and 3) even in OC users the CIC-AS may contain antibodies to other ligands than EE. The study demonstrated also that, in OC users with a vascular complication, anti-EE Ab were more frequently detected (78% of cases) than CIC-AS (60%). Moreover, among OC users with CIC-AS, anti-EE Ab were found in 95% of women with a vascular complication and only 37% of current healthy users. The detection of anti-EE Ab appears to be more predictive, with regard to the vascular risk of OC, than the detection of CIC-AS.

Vascular thrombosis and oral contraceptives - a risk correlated study.

An immunological mechanism of the vascular complications related to oral contraceptives (O.C.) was suggested by the demonstration of circulating anti-ethinylestradiol antibodies in several cases. According to the characteristics of the specific immunoglobulins (Ig), a test based upon Ig precipitability in 25% saturated ammonium sulfate was developed. This test was applied to several groups of women on O.C. with and without thrombosis, and to a control group. Results indicated: (1) that the test was positive in nearly 100% of women with a vascular thrombosis on O.C.; and (2) that the test could detect among healthy contraceptive users a group of women who may be considered as at risk. The role of adjuvant factors is considered.