Thromboembolism and oral contraceptives

Prophylaxis for Thromboembolic Disease: Recommendations From the American College of Chest Physicians—Are They Appropriate for Orthopaedic Surgery?

Deciphering the Risk of Thromboembolism in COVID-19.

Embolic burden of incidental pulmonary embolism diagnosed on routinely performed contrast‐enhanced computed tomography imaging in cancer patients

A large number of individuals develop venous thromboembolism (VTE) every year.1 Each patient’s episode of DVT or PE is, naturally, unique. To highlight a variety of aspects about VTE a compilation case is presented that is composed of clinical data and images from several real patients. ### History of Present Illness A 36-year-old woman presents to the Emergency Department with severe shortness of breath and moderately intense anterior chest pain, worse on deep inspiration, which had started suddenly that morning. She also reports a 6-wk history of mild shortness of breath, for which she had been seen 4 wk earlier by her primary care physician who diagnosed her with “asthma.” Bronchodilators and steroids were prescribed but led to no significant improvement in her symptoms. She also gives a history of mild left calf pain that had started about 2 months earlier without preceding trauma, immobilization, or surgery. Her primary care physician had seen her and prescribed Ibuprofen for a “pulled muscle.” However, in the 1 week before her present presentation her leg symptoms worsened, and she had increased diffuse leg pain and swelling and slightly bluish discoloration of the whole leg. Her past medical history is only significant for an appendectomy at age 16. She has never been pregnant. She is on no medications, except for an estrogen and progestin-containing oral contraceptive, started 10 months earlier. She does not smoke. There is no family history of venous thromboembolism, although the patient reports that her paternal grandmother had a “swollen leg for many years” until she died in her 70’s, but no further details are known of the patient. ### Physical Examination The patient’s weight is 86 kg and her height 165 cm, calculating to a body mass index (weight divided by [height in meters]2) of 31.6 kg/m2, ie, she has grade 1 obesity. Her …

Third-generation oral contraceptives and venous thrombosis

To evaluate the corresponding influence on pulmonary embolism incidence between immobilization and exercise in different stage of thrombus after acute deep vein thrombosis in rabbits. Forty-eight New Zealand rabbits were randomly divided into three groups depending on the different organized stage of thrombus: the early, medium and later stage group.Each group was subdivided into two sub groups: the immobile and mobile subgroup. Rabbit modeling of deep vein thrombosis was made by ligating the right femoral vein. Among the early-stage group, rabbits of the immobile subgroup were fixed for 3 days, while that of the mobile subgroup were free to move for 3 days, then each was euthanized to extract the lungs for pathological examination. Among the medium-stage group, each of the immobile subgroup were fixed for 7 days, while the mobile subgroup ones were fixed for 3 days, then released free-moving for 4 days following the pathological extraction. Among the later-stage group, animals in the immobile subgroup were fixed for 14 days comparing the mobile subgroup fixed for 7 days and next free-moving for 7 days, then each was euthanized. Among the early-stage group, pulmonary embolism incidence (PEI) of the immobile and mobile subgroup was 4/8 vs.3/8, the pulmonary lobe embolism incidence (PLEI) was 17.5% (7/40) vs. 15.0% (6/40). Among the medium-stage group, PEI of the immobile and mobile subgroup was 3/8 vs. 2/8, PLEI was 37.5% (7/40) vs. 25.0% (10/40). Among the later-stage group, PEI of the immobile and mobile subgroup was 3/8 vs. 3/8, PLEI was 12.5% (5/40) vs. 15.0% (6/40). There was no statistical difference between immobilization subgroup and mobilization subgroup among different stage group. On the premise of given anticoagulation treatment, early ambulation do not significantly increase pulmonary embolism incidence after acute deep vein thrombosis of lower extremity in rabbits.

Combined estrogen/progestagen oral contraceptives (OC) have been reported to be associated with a deterioration of glucose tolerance and a decrease in insulin sensitivity; thus, since it has been suggested that steroids affect insulin receptor properties, the influence of OC on insulin receptors was investigated. The study groups were composed of nine normal menstruating women (controls), nine pill users, and two healthy women on OC for the first time. Insulin receptors on monocytes were evaluated at 7-day intervals during the 28 days between menses. Insulin receptor concentration and/or affinity did not show any variation in pill users during the test period and did not differ from values observed in controls in the luteal phase; consequently, the insulin receptor concentration in pill users is lower than that during the follicular phase or in men. The physiological variation of insulin receptor concentration and the increase of receptor affinity in the midfollicular phase, which characterize the normal menstrual cycle, are therefore abolished by OC. This effect occurs rapidly because it was also evident in the two women on OC for the first time. No difference was observed in fasting blood glucose and serum immunoreactive insulin concentrations between control subjects and pill users. The present data appear to confirm that sex steroids affect the insulin receptor and lend further support to the concept that caution must be used in clinical studies of insulin receptors when women are included. In addition, the results suggest that insulin receptors may play a role in the glucose intolerance and insulin insensitivity which have been described in pill users.

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.

Oral contraceptives and dysmenorrhea

Enrico Fermi’s piano tuner problem is the classic example of making estimates. The Italian physicist used to ask students to estimate the number of piano tuners in Chicago given only the population of the city. By making a few common sense assumptions (average family size, percentage of families with a piano etc.) he would come up with an estimate within a factor 2 to 3 of the correct result [1]. Applying Fermi’s approach to the recent discussion of air-travel-triggered death by pulmonary embolism could give some indication as to the magnitude of the problem. In 1996 the total number of air-passengers was 1.3 billion [2]. Last year the total number of deaths due to accidents of multiengined airliners was 1131. The average death toll over the last 30 years is 1464 casualties per year [3]. Based on clinical data, the overall yearly incidence of pulmonary embolism in the United States is estimated to be 139 per 100 000 [4]. Based on autopsy data, the yearly incidence of fatal pulmonary embolism lies at 94 per 100 000 [4]. A study in France found a yearly incidence of diagnosed pulmonary embolism of 60 per 100 000 [5]. An extrapolation from the USA data gives an estimate of 40 per 100 000 cases of fatal pulmonary embolism in France. In an epidemiological case-control study of deep vein thrombosis 12.6% had undergone a long-distance journey during the 3 weeks before diagnosis [6]. Assuming that 10% of cases of fatal pulmonary embolism occur following long-distance journeys, of which a quarter are by air [7], and that only 1 in 10 air-passengers is a long distance traveller, the estimated total number of cases of fatal pulmonary embolism is as follows: Using the USA data, air-travel would lead to 3000 cases of fatal pulmonary embolism, whereas with the French data, the yearly number would be 1300. It could well be that more air-travellers worldwide die from pulmonary embolism than through air-traffic disasters. In the event of these estimates being confirmed by prospective studies, air-travel-induced pulmonary embolism would represent an example of biased risk perception, caused by an “out of sight, out of mind” mechanism as described by Fischhoff et al in their classical experiment on fault trees [8].

Cardiovascular disease is the leading cause of death in women. Pulmonary embolism (PE) is the third most-common cause of cardiovascular death, after myocardial infarction (MI) and stroke. We aimed to evaluate the attributes and outcomes of PE specifically in women and explore sex-based differences. We conducted a systematic review of the literature using electronic databases PubMed and Embase up to 1 April 2022 to identify studies investigating PE in women. Of the studies found, 93 studies met the eligibility criteria and were included. The risk of PE in older women (especially >40 years of age) superseded that of age-matched men, although the overall age- and sex-adjusted incidence of PE was found to be lower in women. Risk factors for PE in women included age, rheumatologic disorders, hormone replacement therapy or oral contraceptive pills, pregnancy and postpartum period, recent surgery, immobilization, trauma, increased body mass index, obesity, and heart failure. Regarding pregnancy, a relatively higher incidence of PE has been observed in the immediate postpartum period compared to the antenatal period. Women with PE tended to be older, presented more often with dyspnea, and were found to have higher NT-proBNP levels compared to men. No sex-based differences in in-hospital mortality and 30-day all-cause mortality were found. However, PE-related mortality was higher in women, particularly in hemodynamically stable patients. These differences form the basis of future research and outlets for reducing the incidence, morbidity, and mortality of PE in women.

Estimated Incidence of Acute Pulmonary Embolism in a Community/Teaching General Hospital

Physicians’ management approach to an incidental pulmonary embolism: an international survey

Focus in this discussion of pulmonary embolism is on the following: risk factors (age heredity and blood type obesity estrogen and oral contraceptive use/pregnancy cardiovascular disease cancer and other risk factors); pathophysiology and presenting symptoms; laboratory procedures and findings (radiography electrocardiography lung scanning and evaluation of lower extremity veins); treatment modalities (heparin therapy thrombolysis and surgery); and prevention. Pulmonary embolism may be the primary cause or a major contributory cause in as many as 200000 deaths per year in the US. Most of these deaths occur in patients in whom the diagnosis is not suspected and thus not treated. The mortality rate for untreated pulmonary embolism is approximately 30%. 90% of patients survive the initial embolic event but the correct diagnosis is made in no more than 2/3 of cases. Risk factors for the development of deep venous thrombosis are based upon the Virchow-Aschoff postulates which include: trauma or disruption of the vein wall; stasis of blood flow in the veins; and increased coagulability of the blood. More than 85-90% of all pulmonary emboli originate from deep venous thromboses in the popliteal and femoral deep veins. Other important although less frequent sites of origin of venous thromboembolism include the pelvic veins the renal and hepatic veins the axillary veins in the upper extremities and the right atrium. Accurate diagnosis and effective prevention and treatment depend on the clinicians awareness of risk factors for development of deep vein thrombosis. Estrogen may accelerate intimal proliferation in arteries and veins and it may also increase permeability of venous vascular endothelium. The risk of thromboembolism increases as the dose of estrogen increases. Both pregnancy and oral contraceptive use significantly decrease venous tone and the velocity of blood flow in the calf of the leg. Appropriate treatment includes thrombolytic therapy for patients with massive pulmonary embolism which results in hypotension or shock. Anticoagulant therapy with herapin followed by an oral anticoagulant is the primary treatment for most patients with submassive emboli in which there is less cardiovascular compromise. When thrombolytic therapy is used it should always be followed by anticoagulant therapy. Prevention of primary or recurrent deep vein thrombosis is directed toward improving venous blood flow and reducing hypercoagulability.

The aim of this study was to assess preferential prescribing of OC according to different thrombotic risk factors. The control group in an ongoing Danish case-control study on stroke and OCs collected in 1994 and 1995 underwent a control-only analysis concerning the occurrence of thrombotic risk factors among users of different types of OC. Specific attention was given to differences between OCs with second and third generation progestagens. The association between specific risk factors and the pill types was assessed crude and after multivariate analysis with confounder control for age and other risk factors, in order to identify risk factors, which after these corrections still had a significant confounding influence on the prescribing of OC. Users of OCs with third generation progestagens had a significantly higher proportion of familial thrombotic disposition (23.1%) than users of OCs with second generation progestagens (7.1%) (p = 0.01). After correction for age and other risk factors this difference was still highly significant (p = 0.002). Among users of third generation pills the proportion of short time users (< 1 year) (22.4%) was significantly higher than the per cent among users of OCs with second generation progestagens (5.5%) (p < 0.001). This difference was still significant after correction for age and other risk factors (p < 0.001). Smoking, years of schooling, migraine, and body mass index did not differ significantly between the two pill groups. In Denmark, women with familial thrombotic disposition are four times more likely being prescribed OCs with third versus second generation progestagens compared with women without such a disposition. At the same time users of OCs with third generation progestagens include significantly more short time users than users of OCs with second generation progestagens. For thrombotic diseases where familial disposition or duration of use of OCs play a role for the pill-associated risk, these differences may significantly influence the thrombotic risk measures in case-control studies and non-randomized cohort studies unless confounder control is conducted for this selection.