Carolyn Drews

von Willebrand disease and other inherited bleeding disorders in women with diagnosed menorrhagia

Objective To estimate the prevalence of von Willebrand disease and other bleeding disorders in women with and without diagnosed menorrhagia. Methods Women with menorrhagia were identified among members of a health maintenance organization in the southeastern United States through a computer search for appropriate International Classification of Diseases, 9th Revision codes. A random sample of members with no such code was selected as controls. The study included 121 women with menorrhagia and 123 controls. Subjects were interviewed in person, and blood was drawn for coagulation testing. Laboratory results for menorrhagia patients were compared with those in controls using race and blood type specific ranges developed from the control group. A test was considered abnormal if it exceeded two standard deviations below the control mean. Results Bleeding disorders (von Willebrand disease, factor deficiency, or a platelet abnormality) were diagnosed in 10.7% of menorrhagia patients and 3.2% of controls (P = .02). von Willebrand disease was present in eight menorrhagia patients (6.6%) and in one control (0.8%) (P = .02); separate analyses by race revealed a von Willebrand disease prevalence of 15.9% among white and 1.4% among black menorrhagia patients (P = .01). Women with bleeding disorders did not differ significantly from controls in other symptoms of bleeding. Conclusion The prevalence of inherited bleeding disorders among white women with menorrhagia was substantial, consistent with European data published recently. For unknown reasons, the prevalence of von Willebrand disease was lower among black women. These findings indicate the importance of considering inherited bleeding disorders as a cause of menorrhagia.

Decrease in the Risk of Bilateral Acute Retinal Necrosis by Acyclovir Therapy

We reviewed the course of 54 patients who had unilateral acute retinal necrosis at initial examination. Thirty-one patients were treated with acyclovir, whereas 23 were not. Of the 31 patients treated with acyclovir, 27 (87.1%) had fellow eyes that remained disease-free throughout a median follow-up of 12 months. Of the 23 patients not treated with acyclovir, seven (30.4%) had fellow eyes that remained disease-free throughout a median follow-up of 11 months. Survival analysis indicated that the fellow eyes of the group of patients treated with acyclovir were more likely to remain disease-free than the fellow eyes of the group not treated with acyclovir (P = .0013). Two years after initial onset, the proportion of fellow eyes that remained disease-free was 75.3% for the group treated with acyclovir and 35.1% for the group not treated with acyclovir. These results suggest that acyclovir treatment reduces the risk of involvement of the fellow eye in patients with acute retinal necrosis.

Medical, reproductive and psychosocial experiences of women diagnosed with von Willebrand's disease receiving care in haemophilia treatment centres: a case–control study

Summary. Objective:  To assess the medical, gynaecological and reproductive experiences of women with von Willebrands disease (VWD) and to evaluate the impact of VWD on mental health and life activities.

Measurement of von Willebrand factor activity: relative effects of ABO blood type and race

Summary.  Tests based on three different principles are reported to measure the activity of von Willebrand factor (VWF): ristocetin cofactor (VWF:RCo), collagen binding (VWF:CB), and the so‐called ‘activity ELISA’ (VWF:MoAb). We measured these and other diagnostic parameters in a population of 123 randomly selected female study controls, age 18–45 years. Type O subjects had significantly lower levels than non‐O subjects in each test. Race differences were seen in all tests except VWF:RCo, with Caucasians having significantly lower levels than African‐Americans. ABO differences accounted for 19% of the total variance in VWF:Ag (P < 0.0001) and race for 7% (P < 0.0001), for a total of 26%. Both effects were mediated through VWF:Ag and were independent. VWF:Ag level was the primary determinant of VWF function, accounting for approximately 60% of the variance in VWF:RCo and VWF:CB and 54% of the variance in factor VIII. The ratio VWF:RCo/VWF:Ag differed significantly by race within blood group. The median ratios were 0.97 for type O Caucasians vs. 0.79 for type O African‐Americans and 0.94 for non‐O Caucasians vs. 0.76 for non‐O African‐Americans. The ratio VWF:CB/VWF:Ag did not vary. This suggests racial differences in the interaction of VWF with GP1b but not with subendothelium. Alternatively, VWF:RCo may be regulated to maintain a relatively constant plasma level in the presence of excessive VWF:Ag. This heterogeneity within the normal population is partially responsible for the difficulty in defining diagnostic limits for von Willebrand disease.

Variation in the influence of selected sociodemographic risk factors for mental retardation.

OBJECTIVES This study explored the utility of subdividing mental retardation into groups based on the presence of other neurological conditions. METHODS Data were abstracted from birth certificates as part of a case-control study of mental retardation among 10-year-old children. The study sample included 458 case children and 563 control children selected from public schools. Case children were subdivided on the basis of intelligence quotient (IQ) score and the presence of other neurological conditions. RESULTS Other neurological conditions were more common with severe mental retardation than with mild mental retardation. Regardless of IQ level or the presence of other neurological conditions, boys were more likely than girls to have mental retardation. Older mothers were more likely than younger mothers to have a child with mental retardation accompanied by another neurological condition. High birth order, Black race, and low maternal education were associated with a higher prevalence of isolated mental retardation. CONCLUSIONS These findings suggest that sociodemographic risk factors for mental retardation vary according to the presence of other neurological conditions and that subdivisions based on medical or physical criteria may be useful in epidemiologic studies of mental retardation.

The administrative prevalence of mental retardation in 10-year-old children in metropolitan Atlanta, 1985 through 1987.

OBJECTIVES In this study, data from the Metropolitan Atlanta Developmental Disabilities Study were used to determine the administrative prevalence (i.e., the number of children previously identified for service provision) of mental retardation among 10-year-old children during the years 1985 through 1987. METHODS Children with mental retardation (intelligence quotient [IQ] of 70 or lower) were identified by review of records from multiple sources, with the public schools as the primary source. RESULTS The overall administrative prevalence of mental retardation was 12.0 per 1000 children. The rate for mild mental retardation (IQ of 50 to 70) was 8.4 per 1000 and the rate for severe mental retardation (IQ lower than 50) was 3.6 per 1000. The prevalence was higher in Black children than in White children (prevalence odds ratio [POR] = 2.7) and in boys than in girls (POR = 1.4). Children with severe mental retardation had more coexisting disabilities than did children with mild mental retardation. CONCLUSIONS The mental retardation prevalence rates reported here, especially the race-specific rates, may reflect social and demographic features unique to the metropolitan Atlanta area and therefore should be used with caution in making comparisons with other populations.

Mild mental retardation in black and white children in metropolitan Atlanta: a case-control study.

OBJECTIVES This study assessed differences in the prevalence of mild mental retardation, defined as an intelligence quotient (IQ) from 50 to 70, between Black and White children. METHODS A case-control study design was used. Ten-year-old children with mental retardation were identified from multiple sources. Information on race, sex, maternal age, birth order, economic status, and maternal education was abstracted from birth certificates of 330 case children and 563 control children (public school students). RESULTS The crude Black-White odds ratio (OR) was 2.6, but it was reduced to 1.8 after the other five covariates were controlled. The disparity was largest among children whose mental retardation was first diagnosed when they were 8 to 10 years old (adjusted OR = 2.5). We found no significant difference in the occurrence of mild mental retardation between Black and White children diagnosed before the age of 6 years (adjusted OR = 1.2). Black children had a higher prevalence of mild mental retardation within all strata of the other five covariates. CONCLUSIONS Five sociodemographic factors accounted for approximately half of the excess prevalence of mild mental retardation among Black children. Possible reasons for the residual difference are discussed.

A case-control study of endometrial cancer in relation to cigarette smoking, serum estrogen levels, and alcohol use

OBJECTIVES The purpose of this study was to evaluate the effect of cigarette smoking and alcohol use on the risk of endometrial cancer. The impact of smoking on serum estrone, estradiol, and androstenedione levels also was examined. STUDY DESIGN This hospital-based case-control study included 168 women with endometrial carcinoma and 334 control women. RESULTS Women who were current smokers had a lower risk of endometrial cancer than did women who did not smoke (relative rate 0.69; 95% confidence interval 0.40-1.19), whereas women who were exsmokers and women who had never smoked had similar rates (relative rate 0.83; 95% confidence interval 0.46-1.48). There was little overall association between serum estrogen levels and cigarette smoking, although estradiol levels in overweight control subjects were lower among women who were current smokers than among women who had never smoked. Androstenedione levels were slightly higher among women in the control group who smoked than among women in the control group who did not smoke, but the difference was not statistically significant (p = 0.28, two-tailed). Alcohol use was unrelated to endometrial cancer in this study. CONCLUSIONS The study provides additional support for the hypothesis that smoking is inversely related to endometrial cancer. The inverse smoking association with endometrial cancer may be more directly related to higher serum androstenedione levels than to lower serum estrogen levels except, perhaps, among overweight women.

Mid-pregnancy maternal plasma levels of interleukin 2, 6, and 12, tumor necrosis factor-alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor and spontaneous preterm delivery

Background. Few studies have investigated the relationship between inflammation and spontaneous preterm delivery (sPTD) in women before preterm labour. The authors examine whether mid‐pregnancy plasma cytokine levels are associated with sPTD, and whether associations vary by maternal age, body mass index, prior preterm delivery, or gravidity. Methods. This case‐control study was nested within the Danish National Birth Cohort, a cohort of women with 101,042 pregnancies from 1997 to 2002. Included in this study are 61 women delivering at 24–29 weeks, 278 delivering at 30–33 weeks, 334 delivering at 34–36 weeks, and 1,125 delivering at ≥37 weeks. Maternal plasma interleukin (IL)‐2, IL‐6, tumor necrosis factor (TNF)‐α, interferon (IFN)‐γ, and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) at 25 weeks’ gestation were measured using multiplex flow cytometry. Results. For IL‐2, TNF‐α, and GM‐CSF, the proportion of women with levels >75th or >90th percentile did not differ by gestational age at delivery. IFN‐γ >90th percentile was associated with an increased risk of delivering at 30–33 weeks (crude odds ratio (cOR): 1.56; 95% confidence interval (CI): 1.07–2.30), while IFN‐γ >75th percentile and IL‐6 >75th percentile were associated with an increased risk of delivering at 34–36 weeks (cOR: 1.32; 95% CI: 1.01–1.73); estimates changed little after adjusting for confounders. There was no effect‐measure modification by maternal factors. Conclusion. Elevated mid‐pregnancy plasma IL‐2, TNF‐α, and GM‐CSF did not appear to be associated with an increased risk of sPTD, while elevated IFN‐γ and IL‐6 levels were weakly associated with moderate and late sPTD. The value of using mid‐pregnancy cytokines in predicting spontaneous preterm delivery appears limited.

A Survey of Gynecologists Concerning Menorrhagia: Perceptions of Bleeding Disorders as a Possible Cause

We sought to determine perceptions and practices of American gynecologists when treating with a woman complaining of menorrhagia, specifically with regard to an underlying bleeding disorder as a potential cause. A mail survey of Georgia members of the American College of Obstetricians and Gynecologists was conducted. The survey response was 52%, and the analysis includes 376 physicians who reported seeing at least one gynecological patient per week. On average, respondents were in practice 20 years and reported that 8% of their patient population complain of menorrhagia. Virtually all physicians reported employing a menstrual history as a starting point for the workup for menorrhagia, and 95% order a hemoglobin/hematocrit determination. About 50% of physicians considered saturating three tampons/pads per 4 hours as excessive, although the criterion varied widely (range 0-24 per 4 hours, SD = 3). The diagnoses considered most likely among reproductive age women were anovulatory bleeding or benign lesions or that the heavy bleeding was within normal limits. Only 4% of physicians would consider von Willebrand disease (VWD) for this age group (women of reproductive age). Among girls near menarche, physicians overwhelmingly consider anovulatory bleeding or bleeding within normal limits the likely diagnoses, and 16% would consider VWD in this age group. Only rarely (3%) do surveyed physicians refer menorrhagia patients to other specialists. Most respondents believe that most menorrhagia is caused by anovulation or is within normal limits. Bleeding disorders are believed to be a rare cause of menorrhagia.