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The most important side effects of oral contraceptives (OCs) and their incidence, together with advice and monitoring of the patient at risk, are pointed out. There is a mild increase in blood pressure in longterm contraceptive use caused by increased angiotensinogen production by the liver. It is significant only for women with a history of familial hypertension, diabetes mellitus, or pre-eclampsia. Smoking increases this risk. Urinary tract infections are 25-50% more frequent in pill users. Glucose tolerance is slightly decreased. Contraceptives' diabetogenic effect is higher in women with hereditary tendency for diabetes, latent diabetes, and/or obesity. They are contraindicated in latent diabetes. Findings are contradictory in their effects on cholesterol and triglyceride serum level, but the pill is contraindicated in lipid metabolism disorders. There is an increased incidence in cholecystitis and cholelithiasis in pill-users (70-80 additional cases/100,000 user years). Liver diseases, intrahepatic cholestasis, occur rarely and benign liver tumors have not conclusively been proved to be caused by the pill. A variety of laboratory findings have been related to contraceptive use and drug interactions occur with barbiturates, rifampicin, hydantoin, and phenylbutazone. Blood coagulation is increased, partially by increased production of various blood coagulation factors; but more importantly, by a decreased synthesis of antithrombin III, a natural protective mechanism against intravascular coagulation. This increases thrombosis risk. Risk doubles with simultaneous cigarette smoking. Various epidemiological studies indicate a 5-10 fold increase in thromboembolism and thrombophlebitis, deep vein thrombosis, and pulmonary embolism. There is a correlation between contraceptive use and cerebrovascular disorders and myocardial infarction. This risk increases with age and years of pill use. The pill is contraindicated with symptoms of thrombophlebitis and thromboembolism, sickle cell anemia, proposed surgery, and longterm immobilization. Overall risk factors are not too high. Recommendations for rational pill use related to age are given and further contraindications are mentioned.
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PMID:[Adverse effects of oral contraceptives]. 55 52

In elderly patients thromboses are especially important because of their frequency and consequences (invalidity) often demanding measures of rehabilitation. In thrombophilia there are prophylactic measures necessary founding upon new perceptions on pathogenesis (vascular wall factors; rheologic and microcirculatory factors and factors of hemostasis: increasing of factor VIII; decreasing of antithrombin III; hypofibrinolysis; increased aggregation of thrombocytes). In prophylaxis you should influence the predisposing factors (hypertension, diabetes, arteriosclerosis, adipositas), use dietetic and hygienic measures and also from the pharmalogical point medicines with complex effect, which not only act on one factor (blood coagulation) like the anticoagulants, but also on other pre-disposing factors; and at the same time activate the fibrinolysis and stop the aggregation of thrombocytes. Thrombolytica should be used in elderly patients with precaution. In hemorrhages in the age especially capillary protecting medicaments should be used to correct the increased fragility of capillaries. Of there is at the some time a arteriosclerosis, hypertension, diabetes mellitus, obesity.
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PMID:[Thromboses and haemorrhages in geriatrics (author's transl)]. 101 38

The rise in cardiovascular disease (CVD) risk after menopause may be reduced by hormone replacement therapy (HRT) although the mechanism is unclear. Because little is known about the potential role of hemostatic factors, fibrinogen level and other coagulation parameters were measured in a study on the change in CVD risk factors through the climacteric (the Healthy Women Study). Of 239 subjects measured to date, 32 taking aspirin or other medications thought to alter coagulation were excluded from analyses. Results (adjusted for age and obesity) showed that women taking HRT had lower plasma concentrations of fibrinogen and higher levels of plasminogen and factor VIIc than did postmenopausal subjects not taking HRT. Pre- as compared with postmenopausal women had lower plasma levels of fibrinogen, factor VIIc, and antithrombin III. Adjusting for cigarette smoking did not change the findings. Thus, among women aged 49 to 55, selected hemostatic measures varied (within normal ranges) by menopausal status and were altered by HRT. These findings generally support a hypothesis of hemostatic change contributing to the increase of CVD after menopause. The fact that subjects taking HRT showed no increase in fibrinogen relative to premenopausal women is consistent with an observed decreased risk of CVD among women taking HRT, while the implication of an elevation in factor VIIc among these women is uncertain.
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PMID:Hemostatic factors according to menopausal status and use of hormone replacement therapy. 134 95

PAI-1 antigen, tPA antigen and thrombin - antithrombin III complexes (TAT) levels were measured in 10 males with stable angina and type-II diabetes mellitus and in 16 males with stable angina without diabetes or other risk factors (hyperfibrinogenaemia, hyperlipidaemia, diabetes, hypertension, smoking and obesity) known to increase PAI levels. Ten healthy men of equivalent age served as controls. Because only diabetics with coronary artery disease (CAD) showed a decreased fibrinolytic capacity, a second study was performed on the 16 non-diabetic CAD patients to determine whether submaximal workload induces significant changes of tPA and PAI levels. TAT levels were increased in CAD, and significantly so in the diabetic group. tPA levels were increased only in the CAD patients without diabetes. PAI levels were significantly increased in diabetic CAD patients (5.26 +/- 1.96 ng/ml) but not in the stable angina patients without diabetes (2.97 +/- 1.44 ng/ml). Immunologically-reactive tPA released after exercise was higher in the 16 CAD patients without diabetes than in controls. Our data could indicate that in stable angina without diabetes there is no chronic latent activation of the clotting system, with no impairment of fibrinolytic activity. On the other hand, the presence of diabetes mellitus seems to influence the fibrinolytic capacity in CAD, particularly increasing PAI levels.
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PMID:Increased plasminogen activator inhibitor antigen levels in diabetic patients with stable angina. 177 97

It is well known that in thrombotic disease the alteration of biological factors such as antithrombin III, protein C, and protein S deficiency, and congenital disfibrinogenimias and displasminogenemias are determining factors being the acquired alterations not so well known. With this in mind was studied 85 patients with arterial thrombosis and 196 with venous thrombosis, who were again divided into three groups: unique or of repetition, less or more than 35 years and with or without immediate apparent cause. The general clinical-biological profile in patients with thrombosis in whom a congenital deficit is not detected, can help establish prognosis and treatment in these patients. In our patients, together with the importance of factors such as obesity, hyperlipemia, and tabaquism, an increase in fibrinogen (Fg), antigenic Factor VII (vWF:Ag), total protein S is observed as well as a decrease in total fibrinolytic activity related to an increase in the inhibitor of the plasminogen tissue activator (PTA).
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PMID:[Hemostasis profiles in thrombotic disease]. 178 55

Postoperative deep-vein thrombosis can lead to fatal pulmonary embolism on one side, and the development of a disabling postthrombotic syndrome, which can occur after some time. General thrombo-embolic prophylaxis can reduce the risk of postoperative thrombo-embolic complications. Predisposing factors include age, obesity, immobilization and recumbency. Cardiovascular diseases, malignant neoplasms, venous disorders, diseases associated with increased viscosity of blood, past deep-vein thrombosis and pulmonary embolisms, some infectious diseases with raised fibrinogen levels, and inherited or acquired clotting factor deficiency syndromes (antithrombin III, protein C, protein S) have an elevated risk of thrombosis. The surgery itself, when taking more than 20 minutes and performed under general anesthesia, is a major risk factor, as proven initiation of thrombosis is often on the operation table. Patients receiving regional or local anesthesia have a clearly reduced risk of thrombosis. After general surgery without thrombosis prophylaxis, a deep-vein thrombosis can be demonstrated by the fibrinogen uptake test in about 30% of all patients over the age of 40. After abdominal surgery an incidence of thrombosis of 14-33%, and after hip surgery an incidence of nearly 50%, have been established by means of the fibrinogen uptake test. However only 10% of these thromboses are expressed clinically. We therefore recommend Liquid Crystal Contact Thermography, which has a sensitivity of 94% and a specificity of over 80%, as a non-invasive, easily performed screening method in the diagnosis of deep-vein thrombosis. Apart from the physical methods, the use of heparin is also indicated in thrombo-embolic prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The thrombo-embolic risk in surgery. 193 69

The chronometric method was applied to 141 diabetics and 151 reference subjects from both sexes aged between 19 and 60 years, all of Black race and Senegalese nationality, to study the effects of Antithrombin III (AT III). A significant reduction in the physiological activity of antithrombin III (AT III) was observed for ages 36-45 and 56-60 and correlated with obesity and other complications. With our patients, insulin dependence does not seem provoke any reduction in antithrombin III's effectiveness.
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PMID:[Antithrombin III in the Senegalese diabetic]. 213 94

Deep venous thrombosis and its complication pulmonary embolism are responsible for more than 50,000 deaths annually in the US, 2/3 of which occur postoperatively. Nearly 75% of such deaths could be avoided by adequate prophylaxis. All forms of surgery entail some risk of deep venous thrombosis, ranging from 10% after endoscopic prostate resection to over 50% for total hip replacement. 1.6 of thromboses will embolize and 1/4 of pulmonary emboli are fatal. The goal of prevention is to decrease the incidence of fatal pulmonary emboli while limiting the risks related to prevention. A secondary goal is to reduce the frequency of postthrombotic syndrome, a late complication of deep venous thrombosis which frequently causes invalidism. A preoperative evaluation of risks of deep venous thrombosis and of the likelihood of bleeding problems should be followed by selection of appropriate preventive measures. The evaluation should be repeated postoperatively, taking into account such factors as the duration of the intervention, the diagnosis, and the predicted duration of bed rest. Evaluation of the risk of deep venous thrombosis requires knowledge of its etiopathogenesis. Deep venous thrombosis results from a multifactorial process involving venous stasis, lesion of the vascular wall, and anomalies of blood composition. All the clinical risk factors for deep venous thrombosis are related to 1 or more of these elements. Risk factors related to stasis include immobilization, postoperative or postpartum status, pregnancy, and Cockett's syndrome. Risk factors related to lesions of the vascular wall include hip surgery, trauma, age, sepsis, varices and obesity, and postthrombotic syndrome. Risk factors related to blood anomaly include postoperative status, pregnancy, oral contraceptive use, cancer, nephrotic syndrome, hypercoagulability, trauma, and heredity. The most common clinical risk factors for deep venous thrombosis are age, surgical intervention, trauma, burns, cancer, pregnancy and delivery, oral contraceptive use, varices, obesity, and postthrombotic syndrome. The relative risk of deep venous thrombosis among OC users is 4.0 overall and higher for those with type A blood. The pathogenic mechanisms are similar to those of pregnancy except that the fibrinolytic capacity is not change. The principal mechanism is perhaps the declining level of antithrombin III, observed with estrogens and some progestins. Among methods of prevention are different forms of compression, use of heparin alone or in combination with other drugs, and oral anticoagulants.
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PMID:[Epidemiology and etiopathogenesis of deep venous thrombosis of the lower limbs]. 224 Apr 6

The pre-surgery identification of patients at risk for the development of post-operative venous thromboembolism has not yet been achieved. It is a well recognized fact that major surgery without prophylaxis encompasses a high risk for thrombosis, in particular orthopaedic operations (hip/knee surgery approximately 50%) and abdominal surgery (approximately 20%). Other well-defined risk factors, though rarely occurring, are deficiencies of the major inhibitors of blood coagulation (i.e. protein C, protein S and antithrombin III). Less well-defined risk factors are a history of previous thrombosis, obesity, varicosis, cancer etc. In an attempt to identify patients at risk for thrombosis prior to surgery, several investigators have developed complicated risk predictors, i.e. formulae comprising combinations of coagulation test results and physical characteristics such as body weight. However, the clinical usefulness has only been demonstrated in two small studies evaluating gynaecological surgery patients. These prognostic indices have not, however, found general acceptance and are not used routinely. The importance of all these risk factors for patient management with regard to thrombosis prevention is relatively small. Irrespective of the absence or presence of identified risk factors, currently the majority of patients will receive some formal thrombosis prophylaxis. The major problem at present is the development of proximal vein thrombosis despite the best possible thrombosis prophylaxis (approximately 10% after hip surgery). Identification of these patients pre-operatively or in an early stage in the post-operative phase by single screening tests should be a major research issue. Furthermore, the development of a prophylactic regimen which eliminates proximal deep vein thrombosis is still desperately needed.
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PMID:Pre-surgical identification of the patient at risk for developing venous thromboembolism post-operatively. 228 76

In acute thrombosis of deep veins of the lower extremities, post-thrombotic syndrome develops in 75% of cases and leads to premature debilitation in 1/3 of the patients. Besides known thrombogenic causes, hormonal preparations more and more often are factors in occurrence of acute thrombosis. There is no doubt that hormonal contraceptive agents are the most reliable method of preventing pregnancy. Their widespread use has resulted in a significant decrease in septic abortions with serious consequences. The purpose of this article is not to discredit this method of preventing pregnancy, but merely to ascertain the presence or lack of a link between thromboembolic diseases and the use of hormonal contraceptive agents. Disturbance of the balance between clotting and anti-clotting systems contributes to development of thrombosis. Etiological factors include changes in vascular walls and functional impairment of hemodynamics. A decrease in the level of antithrombin III in the blood and also in the amount of heparinocytes after using hormonal contraceptive agents has also been proven. Postoperative and postnatal hypodynamics, thrombophlebitis with chronic venous insufficiency, neoplastic syndrome and trauma are causes of acute thrombosis. Age, obesity, hypertonic disease and smoking serve as other risk factors. From 1975 to 1981, 72 women were in the surgical clinic of the Mardeburg Medical Academy for treatment of acute thromboembolic diseases: 34 were using hormonal contraceptive agents before onset of the disease; 19 smoked up to 10 cigarettes a day; and 5 smoked occasionally. After operative intervention, 20 women developed acute thrombosis; only 2 of them were using hormonal contraceptives. No clear causes of thrombosis were found in 35 women, but 32 of them were using hormonal contraceptives. Trauma was the cause in 1 woman with thrombosis of the cartoid artery. On the average, the women used hormonal contraceptives for 4.1 years before onset of the disease (3.1 years in thrombosis of veins of the lower extremities and pelvis; 5.1 in arterial thrombosis). In 28 of 34 women with acute thromboses, they were localized in the veins of the lower extremities and pelvis after taking hormonal contraceptives. Women with thromboembolic diseases after taking hormonal contraceptives had general examinations at periods from 6 months to 5 years. Development of post-thrombotic syndrome was observed in 12 women with thrombosis of veins in the lower extremities and pelvis. Thromboses without any thrombogenic causes were observed in women under 30 after taking hormonal contraceptives. Although a direct link between the use of hormonal contraceptive agents and thromboembolic diseases cannot be proven presently, taking these preparations is believed to be 1 of the risk factors in the development of these diseases.
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PMID:[Hormonal contraceptive agents as a risk factor in the development of acute thromboembolic diseases]. 382 Oct 1


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