Erroneous clinical diagnosis of leg vein thrombosis in women on oral contraceptives

Most studies demonstrating an increased risk of venous thromboembolism in women on oral contraceptives are based on clinical manifestations of the disease. Because of the fallibility of the clinical diagnosis of suspected leg vein thrombosis, Doppler ultrasonic evaluation (with a 93% accuracy compared to venography) was performed for clinical manifestations in deep vein thrombosis in 54 women taking birth control pills and 75 women of similar age who were not on contraceptives. The clinical diagnosis was confirmed by Doppler in only 16.7% of the women taking contraceptives and 30.7% of women not taking contraceptives (P = 0.052). This study suggests that the clinical diagnosis of leg vein thrombosis is frequently erroneous, particularly in women taking oral contraceptives. Future investigations reporting venous thromboembolism associated with oral contraceptives should be based on diagnoses validated by accurate objective techniques.     

Venous thromboembolism in relation to oral contraceptive use

The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed in a hospital-based study of 61 women suffering from a first episode of idiopathic deep vein thrombosis or pulmonary embolism (cases) and 1278 women admitted for trauma or respiratory infections (controls). Twenty (33%) of the cases and 121 (9%) of the controls had used oral contraceptives within the previous month, yielding an age-adjusted relative risk estimate of 8.1 (95% confidence interval 3.7 to 18) for recent users relative to never-users. For women using oral contraceptives containing less than 50 micrograms estrogen, the relative risk estimate was 11 (3.7 to 22); for preparations with 50 micrograms estrogen, it was 5.5 (2.1 to 15); and for preparations with more than 50 micrograms estrogen, it was 11 (3.9 to 30). Past use of oral contraceptives was not associated with an increased risk. The data suggest that the risk of venous thromboembolism is increased for recent oral contraceptive users relative to nonusers, even if women use oral contraceptives containing low doses of estrogen. Confidence intervals were wide, however, so that a reduction in the risk for users of lower dose formulations relative to users of higher dose formulations cannot be ruled out. Selection bias, if present, would have resulted in overestimation of the relative risk, but should not have distorted the comparisons according to dosage.     

The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives.

OBJECTIVES: To investigate the factors associated with idiopathic venous thromboembolism in combined oral contraceptive users and to estimate the crude and age-specific incidence rates ofidiopathic venous thromboembolism among this population. METHODS: The UK MediPlus Database and the General Practice Research Database were searched to identify women with evidence of venous thromboembolism while exposed to combined oral contraceptives. Cohort and nested case-control studies were carried out using the same methodology on both databases. We conducted a meta-analysis using the individual data for the cases and controls from the two case-control studies to identify factors associated with idiopathic venous thromboembolism in women using combined oral contraceptives. RESULTS: The incidence rate of idiopathic venous thromboembolism among oral contraceptive users was 39.4 per 100,000 exposed woman-years. The age-specific incidence rates were found to rise sharply after the age of 39 years. Factors identified as being significantly associated with idiopathic venous thromboembolism in women using combined oral contraceptives were: body mass index of 25 kg/m2 and over, the association rising dramatically in women with a body mass index of 35 kg/m2 or more; smoking; general ill health; and asthma. CONCLUSION: We believe that, before prescribing combined oral contraceptives, the venous as well as the arterial factors need to be considered and, in addition, age, obesity and smoking are all relevant when assessing an individual patient's risk.     

The effects of age,body mass index,smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives

Objectives To investigate the factors associated with idiopathic venous thromboembolism in combined oral contraceptive users and to estimate the crude and age-specific incidence rates of idiopathic venous thromboembolism among this population.

Methods The UK MediPlus Database and the General Practice Research Database were searched to identify women with evidence of venous thromboembolism while exposed to combined oral contraceptives. Cohort and nested case-control studies were carried out using the same methodology on both databases. We conducted a meta-analysis using the individual data for the cases and controls from the two case-control studies to identify factors associated with idiopathic venous thromboembolism in women using combined oral contraceptives.

Results The incidence rate of idiopathic venous thromboembolism among oral contraceptive users was 39.4 per 100 000 exposed woman-years. The age-specific incidence rates were found to rise sharply after the age of 39 years. Factors identified as being significantly associated with idiopathic venous thromboembolism in women using combined oral contraceptives were: body mass index of 25 kg/m² and over, the association rising dramatically in women with a body mass index of 35 kg/m² or more; smoking; general ill health; and asthma.

Conclusion We believe that, before prescribing combined oral contraceptives, the venous as well as the arterial factors need to be considered and, in addition, age, obesity and smoking are all relevant when assessing an individual patient's risk.     

Venous thromboembolism in pregnant Chinese women

OBJECTIVE: To evaluate the incidence, disease pattern, and risk factors for thromboembolism in pregnant Chinese women. METHODS: We conducted a study from January 1998 to December 2000. Women with thromboembolic diseases were identified and their case records retrieved and reviewed. Demographic characteristics were compared between women with and without thromboembolism. RESULTS: Thirty-two women were diagnosed as having thromboembolic disease during the study period. The total number of deliveries over the study period was 16,993, giving an incidence of 1.88 per 1000 deliveries. There were two cases of pulmonary embolism and one resulted in a maternal death. The others had deep vein thrombosis of which over 80% were limited to calf veins only. The ultrasound examinations requested for suspected deep venous thrombosis before and after the event of maternal death were 1.62 and 10.7 per 1000 deliveries (P <.001); and the corresponding cases of deep venous thrombosis diagnosed were 0.29 and 2.94 per 1000 deliveries, respectively (P <.001). The majority (75%) of cases were diagnosed in the postpartum period, mainly after cesarean delivery. Women with venous thromboembolism were older, had higher body mass index, and a higher incidence of preeclampsia. CONCLUSION: Thromboembolic disease is not uncommon among pregnant Chinese women. The incidence was similar to that of the white population, although the sites of vascular occlusion were different. The long-standing belief that thromboembolism is rare among Chinese is at least partly because of underdiagnosis.     

Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study

OBJECTIVE: We sought to determine risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum. STUDY DESIGN: We performed a population-based case-control study. All Olmsted County, Minnesota, residents with a first lifetime deep vein thrombosis or pulmonary embolism during pregnancy or post partum from 1966 to 1990 were identified (N = 90). Where possible, a resident without deep vein thrombosis or pulmonary embolism was matched to each patient by date of the first live birth after the patient's child. The medical records of all remaining patients and all control subjects were reviewed for >25 baseline characteristics, which were tested as risk factors for deep vein thrombosis or pulmonary embolism. RESULTS: In multivariate analysis smoking (odds ratio, 2.4) and prior superficial vein thrombosis (odds ratio, 9.4) were independent risk factors for deep vein thrombosis or pulmonary thrombosis during pregnancy or post partum. CONCLUSION: Venous thromboembolism prophylaxis may be warranted for pregnant women with prior superficial vein thrombosis. Smoking cessation should be recommended, especially during pregnancy and the postpartum period.     

Thromboembolism in pregnancy

Venous thromboembolism in pregnancy is a clinical emergency that has been associated with significant risk for maternal and fetal morbidity and mortality. The adaptation of the maternal hemostatic system to pregnancy predisposes women to an increased risk of thromboembolism. A timely diagnosis of deep venous thrombosis is crucial because up to 24% of patients with untreated deep venous thrombosis develop a pulmonary embolism. Recent clinical guidelines identify compression venous ultrasound as the best way to diagnose deep venous thrombosis in pregnancy and CT pulmonary angiography as the best way to diagnose pulmonary embolism in pregnancy. Therapy involves supportive care and anticoagulation with unfractionated or low molecular weight heparin, depending on the clinical scenario.     

Factor V leiden and venous thromboembolism in a woman taking second generation oral contraceptives: a case report]

The most common cause of thrombophilia is a point mutation in factor V gene (G1691A), leading to factor V Leiden synthesis, which is resistant to the inhibition by activated protein C. Administration of oral contraceptives is associated with an increased risk of venous thromboembolism in carriers of factor V Leiden mutation. We describe here a case of 44-year-old woman who developed right popliteal and superficial deep vein thrombosis after a 2-month use of a contraceptive which consists of 0.15 mg levonorgestrel and 0.03 mg ethynylestradiol. The mutation G1691A of factor V gene was detected with the polymerase chain reaction. No other inherited or acquired risk factors for thrombosis was found in this patient. Treatment with low molecular weight heparin and subsequently, oral anticoagulation was effective. Women with factor V Leiden should be discouraged from taking oral contraceptives. Screening for factor V Leiden in these women appears to be useful and contribute to the prevention of thrombosis in risk situations.     

Saga of the newer generation pills and the concept of risk

The World Health Organization is conducting a case-control study in centres in Africa, Asia, Europe and Latin America on the cardiovascular side effects of different types of oral contraceptives. Previous studies have mostly taken place in North America and Europe, and may not apply to women elsewhere. The first results, focusing only on possible vein problems, were published in December 1995.1 As with previous studies, it was found that oral contraceptives increase the risk of deep vein thrombosis and pulmonary embolism2 and that women using pills containing two newer progestogens - desogestrel and gestodene - seemed to have a higher risk of deep vein thrombosis than those containing older progestogens. This paper explains the significance of these results and describes how a number of European drug regulatory authorities and doctors reacted, what they advised women to do and what women actually did.     

甾体避孕药不增加血栓栓塞性疾病危险(病例对照研究)

本文采用1:3病例对照研究方法,对甾体避孕药的使用与血栓栓塞性疾病(急性心肌梗塞、脑栓塞、脑血栓形成和深静脉血栓形成)间的关联进行多因素分析。结果提示在我国广泛应用的甾体避孕药(主要为国产Ⅰ号避孕药)并不增加血栓栓塞性疾病的危险性。用药和停药时间的长短与血栓栓塞性疾病的发生无关,并与高血压病之间亦不存在协同作用。     

Cerebral Venous Sinus Thrombosis in a Woman Using the Etonogestrel-Ethinyl Estradiol Vaginal Contraceptive Ring: A Case Report

BackgroundThe vaginal contraceptive ring is a hormonal contraceptive that releases etonogestrel and ethinyl estradiol. Cerebral venous sinus thrombosis (CVST) is a rare but serious complication of hormonal contraceptive use.CaseWe present a case of CVST in a 33-year-old nulligravid woman who was using a vaginal contraceptive ring. At the time of presentation, she had been using the ring for 18 months, having previously used oral contraceptives for 13 years. She had no additional risk factors for thrombosis apart from cigarette smoking. Despite vigorous management, the patient died from the effects of the CVST.ConclusionThe serious adverse effects of the vaginal contraceptive ring are not well known, although deep vein thrombosis, pulmonary embolism, and aortic thrombosis in association with use of the ring have been reported to Health Canada. Continuing post-market surveillance of thrombotic risk in users of the vaginal contraceptive ring is critical.     

Contraceptive choices in women with coagulation disorders

When compared with older reports on the thromboembolic effects of high-dose oral contraceptives, new studies with low-dose oral contraceptives have a significantly reduced risk of thromboembolism. In the absence of risk factors such as smoking or inherited disorders predisposing to thrombosis, the modern low-dose oral contraceptive (< 50 μg of estrogen) is a safe and effective choice for contraception in women without symptoms who have family histories of sporadic thromboembolism. An intrauterine device or some form of barrier method is recommended for women who have a personal history of venous thrombus disease. The low-dose oral contraceptive may be a good choice in women taking oral anticoagulants because of the risk of teratogenic effects of anticoagulants and the risks of intraperitoneal bleeding associated with ovulation. In addition, oral contraceptives help diminish the excessive menstrual bleeding often seen in these women. (Am J Obstet Gynecol 1993;168:1990-3.)     

Venous thromboembolism in pregnancy

Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). In pregnancy, deep vein thrombosis accounts for 75–80% of venous thromboembolism, the remainder are pulmonary embolisms. One half of these VTEs occur during pregnancy and the other half in the postpartum period. Venous thromboembolism is one of the leading causes of maternal mortality worldwide and is also the cause of significant maternal morbidity. This article discusses the risk factors for VTE in pregnancy, the management of the pregnant woman at risk both antenatally and postpartum and the acute management of VTE when it occurs during pregnancy.     

Venous thromboembolism in pregnancy

Venous thromboembolism remains a common cause of direct maternal deaths in high-income settings such as the United Kingdom. Pregnancy alone increases the risk of deep vein thrombosis and pulmonary embolus at least five-fold, and many women develop or have additional risk factors for venous thrombosis during pregnancy and the puerperium, the latter representing the period of highest risk. Early and repeated risk stratification and adequate thromboprophylaxis, usually with low molecular weight heparin, is the key to preventing venous thromboembolism (VTE). Women with a past history of VTE, and those affected by thrombophilia, require multidisciplinary care involving an obstetric haematologist. Women suspected of having acute thromboembolism should be commenced on empirical treatment promptly prior to diagnostic confirmation. Pulmonary embolism should be considered as a differential diagnosis in maternal collapse.     

Oral contraceptives and thromboembolism: A reassessment

The relationship between oral contraceptive usage and thromboembolism is controversial. Since thromboembolism is often undiagnosed, both clinically and at routine autopsy, most epidemiologic analyses rest on a very uncertain factual base. There are increases in blood coagulation factors in oral contraceptive users similar to, but less than, those seen in pregnancy, which isnot associated with increased thromboembolism. Hematologists emphasize that these changes do not define a “hypercoagulable” state, and they do not define or predict the occurrence of thrombosis. Intrinsic vascular wall changes, unrelated to drug use, may play a role in sporadic cases of thromboembolism. When the incidence of thromboembolism in very large Phase III trials of conventional oral contraceptives is compared to that in other populations (patients admitted to the hospital, women who visit a physician, pregnant women, or users of nonestrogenic oral contraceptives), no difference is seen. Epidemiologic studies by the “case-control” (“trohoc”) method consistently show an increased “relative risk” associated with oral contraceptive use in subjects with “idiopathic” thromboembolism but no increased risk in thromboembolism patients as a whole or in those with predisposing factors. This retrospective epidemiologic technique, its particular applications, and the inferences drawn are open to serious criticism, as are studies claiming a relationship between estrogen dose and thromboembolism incidence. An Australian prospective survey found no increased risk among users, and a large British study which initially reported an increased risk is currently undergoing recalculation. The only controlled clinical experiment (with random assignment of subjects to vaginal versus high-estrogen contraceptives) showed no increased incidence in the drug-treated group. Statistical associations derived from “trohoc” studies do not establish causal relationships; moreover, their risk estimates are in conflict with the findings of large Phase III clinical surveys including subjects using estrogen-free contraceptives, with at least one prospective clinical survey, and with a randomized, controlled clinical trial. The data relating estrogen dosage to thromboembolism incidence are ambiguous, at best. Thus, the claim of a causal relationship between oral contraceptive steroids and thromboembolism does not appear to be firmly founded, and the belief that predisposing factors increase the risk to contraceptive users is equally insubstantial.     

影像学检查在妊娠期静脉血栓栓塞症诊断中的应用

静脉血栓栓塞症在妊娠期发生率较正常人明显增高,是妊娠期的一种严重并发症。下肢深静脉血栓形成与肺栓塞有重要相关性,及早发现,及时治疗可改善孕产妇预后。影像学检查在静脉血栓栓塞症的诊断方面具有重要作用。     

Symptomatic venous thromboembolism in Chinese patients after gynecologic surgery: incidence and disease pattern

BACKGROUND: Venous thromboembolism is a common cause of postoperative morbidity and mortality in Caucasian populations, but it is widely believed that this complication is rare in Chinese. METHODS: We conducted a retrospective study from January 1998 to December 2000. Women with thromboembolic diseases after gynecologic surgery were identified and their medical records were reviewed. RESULTS: During the study period, thirty-one women were diagnosed as having thromboembolic disease after gynecologic surgery. Over the study period, the total number of operations was 6077, giving an incidence of 5.10/1000 operations. There were two cases of pulmonary embolism and the others had deep vein thrombosis of which 90% were limited to calf veins only. The incidences were significantly higher in 1999 and 2000 (7.59 and 6.85/1000 operations, respectively) than that in 1998 (1.7/1000 operations) (P = 0.015), after a case of maternal death due to pulmonary embolism in early 1999. Most cases of thromboembolism were diagnosed after major surgery for malignancy (n = 14) or benign conditions (n = 12). In the remaining cases, three had evacuation of the uterus for retained products of conception and two had laparoscopy for suspected ectopic pregnancies. CONCLUSIONS: Thromboembolic disease is not uncommon among Chinese women after gynecologic surgery. The incidence is similar to that of the Caucasian population, although the sites of vascular occlusion were different. The long belief that thromboembolism is rare among Chinese is at least partly due to under-diagnosis.     

Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial.

OBJECTIVE: To compare the efficacy and treatment-related complications of low molecular weight heparin and external pneumatic compression in the prevention of venous thromboembolism of postoperative gynecologic oncology patients. METHODS: A total of 211 patients over age 40 years, undergoing a major operative procedure for gynecologic malignancy, were randomized to receive perioperative thromboembolism prophylaxis with either low molecular weight heparin (n = 105) or external pneumatic compression (n = 106). Demographic data and clinical outcome were recorded for each patient. All patients underwent bilateral Doppler ultrasound of the lower extremities on postoperative days 3-5 to evaluate for the presence of occult deep vein thrombosis. A follow-up interview 30 days after surgery sought to detect patients who developed deep vein thrombosis or pulmonary embolism after hospital discharge. RESULTS: Venous thrombosis was diagnosed in two patients receiving low molecular weight heparin and in one patient receiving external pneumatic compression. The frequency of bleeding complications, measured by the number of required perioperative transfusions, and estimated intraoperative blood loss was similar between the two groups. CONCLUSION: Low molecular weight heparin and external pneumatic compression are similarly effective in the postoperative prophylaxis of thromboembolism. The use of low molecular weight heparin is not associated with an increased risk of bleeding complications when compared with external pneumatic compression. We believe that both modalities are reasonable choices for prophylaxis in this high-risk group of patients.     

剖宫产术后的抗凝治疗

产科手术尤其是急诊剖宫产术导致静脉血栓栓塞疾病发病率及病死率呈显著上升趋势，多表现为术后的深静脉血栓形成和肺栓塞，这不仅与手术因素相关，也与大多数合并的病理产科因素相关。术后是否常规抗凝治疗目前尚存在争议，国内亦无大规模临床研究数据支持。本文从临床角度出发，探讨如何评估产科手术后发生血栓的风险，确定抗血栓预防干预的有效时机以及合理的治疗方案。