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Factors affecting performance and thromboembolism after porcine xenograft cardiac valve replacement.

Long-term durability and the need for anticoagulation in conjunction with the use of porcine valves remain questionable. We analyzed valve dysfunction and thromboembolism in 325 adult (older than 20 years) and 31 pediatric survivors who received 407 porcine xenograft valves from June, 1974, to September, 1980 (46% of all valve replacements). Valves at risk in the adults were 216 aortic, 138 mitral, and 22 tricuspid; in children, 14 aortic, eight mitral, seven pulmonary, and two tricuspid. Mean follow-up was 38 (9 to 85) months. Twenty-seven valved conduits also were followed up for 9 to 85 (mean 52) months. Two late deaths in children resulted from dysfunction and another from endocarditis. One late death in an adult was caused by embolism. The other 36 deaths in the entire group were not valve related. Dysfunction requiring reoperation at 12 to 37 months occurred in eight of 325 adults (six mitral, one aortic, and one tricuspid). Dysfunction was due to recurrent endocarditis in six and to primary tissue failure in two (both older than 35 years of age); all survived reoperation. However, in children, severe dysfunction due to primary tissue failure occurred in seven (23%) cardiac valves, necessitating replacement at 21 to 48 months, and three of 27 conduits had to be replaced at 39 to 70 months. Thromboembolism occurred in six adults with mitral xenografts but none with aortic or tricuspid valve. Four of the patients with thromboemboli (one of whom died) were among 16 who had atrial fibrillation and no warfarin, but aspirin and persantine (11.7%/patient-year) and two were among 14 with sinus rhythm on no medication. No thromboembolism occurred in patients with mitral xenografts who were in sinus rhythm and receiving antiplatelet agents or in those with atrial fibrillation receiving warfarin. This experience indicates a high incidence of relatively early failure of porcine xenograft cardiac valves in children and young adults but excellent medium and long-term performance in older adults, in whom severe dysfunction occurred mainly with recurrent endocarditis. Thromboembolism occurred primarily in patients with mitral replacement especially with atrial fibrillation and no anticoagulants.

Adult↗

[Recent morphofunctional findings on the left atrium: their relations to thromboembolic risk].

In the past, the left atrial appendage has been considered a "useless" structure but associated to thromboembolic complications; its physiologic role is still undefined. Owing to its great distensibility, left atrial appendage positively influences atrial compliance and left ventricular performances. In addition this structure seems to play an important role in circulatory homeostasis by the release of atrial natriuretic factor in response to volume loading and atrial stretch. Transesophageal echocardiography provides a detailed anatomical characterization of this structure and, by means of Doppler flow velocities recordings, supplies relevant functional data. Despite their anatomical contiguity, the left atrium and atrial appendage result from a separate embryonic development; likewise, their function may differentiate. In the left atrial appendage a quadriphasic flow pattern has been described in subjects with sinus rhythm; however, as we reported, in some patients a more complex Doppler pattern can be observed, with an additional systolic forward flow wave which is presumably due to reflection phenomena. In patients with atrial fibrillation, an irregular flow pattern has been detected, which is mostly dependent on the duration of the arrhythmia, the underlying heart disease and the left atrial pressure. By transesophageal echocardiography a clear correlation has been established between the left atrial appendage slow flow and the occurrence of thromboembolic events; however, while waiting data from large studies, stratification of patients according to thromboembolic risk and decisions about anticoagulant prophylaxis should be performed by clinical information and transthoracic echocardiographic findings. No clinical or echocardiographic parameter has been found to be predictive of the thromboembolic events after cardioversion; in this setting the exclusion of atrial or atrial appendage thrombi by transesophageal echocardiography does not rule out the need for anticoagulation in patients with atrial fibrillation undergoing electrical or pharmacological cardioversion.

Atrial Function, Left↗

[Heart failure and arrhythmia: modalities and indications of prevention of thromboembolism].

Patients with atrial fibrillation are at risk for peripheral embolism. Congestive heart failure, a history of hypertension, previous arterial embolism or myocardial infarction are related to an increased risk for thromboembolism. Left ventricular enlargement and dysfunction, focal akinesia, protruding and mobile thrombi, spontaneous echo contrast are echocardiographic predictors of thromboembolism in patients with atrial fibrillation. Clinical trials have shown that antithrombotic therapy can reduce the rate of embolic events. In patients with heart failure the efficacy of antithrombotic therapy has not been tested in randomized, prospective trials. However in these patients oral anticoagulants are recommendable in the following conditions: atrial fibrillation; rheumatic mitral valve disease; previous thromboembolism; left ventricular enlargement and dysfunction; mobile and/or protruding thrombi; spontaneous echo contrast. The target INR in treated patients should be maintained within a range of 2 to 3 times the control. A more intense range of intensity of anticoagulation is indicated for patients with mechanical prosthetic valves or with relapsing thromboembolism. Current estimates of the effects of aspirin vary too much to allow any conclusions.

Anticoagulants↗

[Resistance to activated protein C in venous thromboembolic complications. Incidence and clinical manifestations].

OBJECTIVES: The frequency of activated protein C resistance is not well established for patients with venous thromboembolic disease. We studied resistance to activated protein C in patients with a past history of deep vein or superficial vein thrombosis. METHODS: Activated protein C resistance was measured in 175 patients (37 males, 138 females; mean age 40.9 +/- 13.8 years; range 15-77) who had suffered a venous thromboembolic event more than one month earlier. Exclusion criteria were malignancy, known autoimmune disease or known coagulopathy. A control population of 50 healthy subjects were also tested to establish a normal lower limit (mean ratio minus 2 SD). RESULTS: The lower limit was established at 2.14. According to this definition, there were 29 thromboembolic patients who were resistant to activated C protein (17%). Two of the subjects considered healthy in the control group were also resistant (4%). There was no difference for age or sex between resistant and non-resistant subjects. Comparing our findings with those reported in the literature confirmed that 3 to 5% of healthy subjects and 15 to 25% of patients with history of venous thromboembolism are resistant to activated C protein. CONCLUSION: Resistance to activated C protein thus appears as a risk factor for thrombotic events which is comparatively more frequent than other causes of thrombotic disease.

Adolescent↗

[Oral contraceptives and cerebral thromboembolism. A Danish case-control study].

A retrospective case control study was carried out in order to assess the risk of developing cerebral thromboembolism by use of low dose oral contraceptives (OC). The subjects were all the 794 women in Denmark aged 15-44 who had suffered a cerebral thromboembolic attack (CTA) during the period 1985-1989, and an age-matched randomly selected control population of 1588 women. CTA included occlusion of precerebral arteria (ICD 432), cerebral thrombosis (ICD 433), cerebral embolism (ICD 434), transitory cerebral ischaemia (TCI; ICD 435) and the unspecified group apoplexia cerebri (ICD 436). Of 692/1584 case/control questionnaires sent out, 590/1396 (85.1/88.1%) were returned. Among the cases, 15 refused to participate, 69 had a revised or unreliable diagnosis, 40 had previously had thromboembolic disease, 13 were pregnant, and 152 had a disease predisposing them for CTA, leaving 323 without known predisposition, of whom 320 reported use/non-use of OC. Among 1396 controls, eight either refused to participate, were mentally retarded or resident in foreign countries; 18 returned an uncompleted questionnaire, 17 had previously had thromboembolic disease, 31 were pregnant, and 130 had a disease predisposing them to CTA. Thus, 1198 non-predisposed controls were provided, among whom 1197 reported use/non-use of OC. Among 320 cases, 116 (36.3%) were OC users at the time of the CTA, vs. 191 users (16.0%) among 1197 controls, corresponding to a crude odds ratio (OR) of 3.00.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Etiology and pathogenesis of spontaneous venous thromboembolism].

Thromboembolic disease is a major clinical problem. This article reviews the etiology and pathogenesis of spontaneous venous thromboembolism. There is an association between thromboembolism and hereditary deficiency of antithrombin III, protein C or protein S. In young patients, impaired fibrinolytic activity may represent the most common haemostatic abnormality associated with thrombosis. Dysfibrinogenaemia has been related to thrombotic disease in some patients. Moreover, the presence of phospholipid directed antibodies is associated with thrombosis in patients with connective tissue disorders. Therefore, for young patients with spontaneous thromboembolic disease, a thorough laboratory investigation is recommended.

Adult↗

[Postoperative venous thromboembolism in bariatric surgery].

The authors discuss the problem of venous thromboembolism as a complication of bariatric surgery. They consider obese patients at risk for these complications, even if different opinions exist about this topic in the literature. They report their experience in bariatric surgery consisting of 53 patients submitted to biliopancreatic diversion. Antithrombotic prophylaxis consisted for every patient in elastic bandaging of the lower limbs, preoperative hemodilution, early post-operative mobilization, and subcutaneous heparin. Complications consisted in one popliteo-femoral deep venous thrombosis (DVT) (1.6%), and two pulmonary embolisms (PE) (3.2%) of which one caused patient's death; total morbidity for venous thromboembolism. These results compared with literature are similar with other series of bariatriac surgery and slightly higher than general surgery series. This difference is not however significant. Even in the absence of this significance, thromboembolism, as desumed from more than 2900 cases considered in the literature, remains the main cause of morbidity and mortality in the post-operative course of bariatric surgery patients, deserving particular attention in terms of prevention, also because of difficulty existing in early clinical diagnosis of DVT in obese people. Further studies intended to identify pathogenesis and risk factors of venous thromboembolism in obese people will allow a more correct prophylactic and therapeutic approach.

Adolescent↗

Incidence of thromboembolic events in congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial. METHODS AND RESULTS: The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials (V-HeFT I and II) was examined retrospectively to address these issues. In V-HeFT I, 642 men with heart failure were followed an average of 2.28 years, providing 1,464 patient-years of follow-up. In V-HeFT II, 804 men were followed an average of 2.56 years, with 2,061 patient-years of follow-up. Mean left ventricular ejection fraction was 30% in V-HeFT I and 29% in V-HeFT II: Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL.kg-1 x min-1 in V-HeFT I and 13.7 mL.kg-1 x min-1 in V-HeFT II: Warfarin and antiplatelet agents were administered at the discretion of individual investigators. The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin. Patients experiencing events had a lower peak exercise oxygen consumption (p < 0.03 in V-HeFT I and p < 0.001 in V-HeFT II) and a lower mean ejection fraction (p = 0.10 in V-HeFT I and p = 0.07 in V-HeFT II). Atrial fibrillation was not associated with an increased risk of thromboembolic events. CONCLUSIONS: The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment. Routine use of anticoagulants in patients with heart failure may not be justified.

Cerebrovascular Disorders↗

[Should postoperative thromboembolism prevention be extended to the post-hospitalization phase?].

A large number of patients medically treated for deep vein thrombosis and pulmonary embolism have a history of surgery in the immediate past. We therefore inquired whether it is possible to identify specific risk factors which would allow general recommendations for anticoagulation therapy in the postdischarge period. During the 30-month study period 325 patients were treated at the Cantonal Hospital, Aarau, for DVT and/or pulmonary embolism. 35 (10.8%) had undergone surgery 8 weeks previous to admission. Perioperative management (anticoagulation, chronology, mobility etc.) was analyzed retrospectively. 20% of the 35 patients with postdischarge deep vein thrombosis and/or pulmonary embolism had previously undergone an ambulatory surgical procedure. A large number of thromboembolic complications occurred between the 4th and 12th day after discharge. In 40% of the patients, however, they occurred after the 14th posthospital day. High- and low-risk patients were impossible to define on the basis of the type of surgery, length of hospital stay and time course of thromboembolic complications. We conclude that prophylaxis of thromboembolism in ambulatory surgery should be re-thought: patients undergoing arthroscopy should receive prophylaxis for thromboembolism for at least 4-6 weeks post discharge.

Adult↗

[Prevention of thromboembolic disease in gynecologic surgery].

We presented two groups of patients gynecologically operated and examined in a five year period; the first group of 11536 patients was under thromboembolic protection, whereas the second group of 8532 patients was without thromboembolic protection. Protective measures concerning thromboembolic disease were carried out by applying elastic stockings 24 hours before operation and by early post-operative getting up from bed. Low-molecular dextran was applied before operation as well as during the operation in the amount of 500-1000 ml. In risky patients with varicosities, recidive thrombophlebitis and cardiovascular diseases, we applied small doses of heparin subcutaneously two hours before the operation and after the operation every eight hours five days long. With such prevention of thromboembolic disease in gynecologic surgery, we achieved very favorable effects in reducing mortality to 0.05% concerning the operated, while it amounts to 0.3% in those who were without this kind of protection.

Female↗

[Thromboembolic complications in ambulatory surgery. A retrospective study of 1691 patients].

The risk of thromboembolic complications in outpatient surgery is regarded as being low. Thromboembolic prophylaxis is seldom administered as a routine. A retrospective study in our outpatient department, based upon patients readmitted for clinical thromboembolism, showed an incidence of deep vein thrombosis of 0.05% (8/1 691) and of pulmonary embolism 0.0006% (1/1 691). None of the patients received prophylaxis for thrombosis, and all operations were performed under regional anaesthesia of the lower extremity. 50% of the operations were performed using a tourniquet. 2/3 of the patients were women and 2/3 were over the age of 50. Operation time was usually 30-45 minutes. Our study indicates that patients undergoing knee arthroscopy, and operations for varicose veins and hallux valgus are at risk of thromboembolism. Prospective studies of these risk groups are necessary to figure out the need for thrombosis prophylaxis.

Adult↗

Risk of venous thromboembolism and stroke associated with oral contraceptives. Role of congenital thrombophilias.

To assess the risk of thromboembolism in women using oral contraceptives (OCs), we identified through computer search in the hospitals of the province of Parma, Italy, all women aged 15-44 who were resident in the province and had a documented thromboembolic event in the years 1989-93. The number of users and nonusers of OCs was estimated by the drug sale data for the province and by the demographic statistics. In cases with venous thromboembolism (VT) the prevalence of concomitant deficiency of antithrombin III, protein C, protein S, and of factor V gene mutation Arg506GIn was evaluated. The incidence rate of VT was 37/59,603 woman-years in users (0.62 per 1000) and 13/303,954 woman-years in nonusers (0.042 per 1000), for a relative risk (RR) of 14.5 (95% confidence interval: 7.8-27.1; P < 0.001); the rate of stroke per 1000 woman-years was 0.17 in users and 0.036 in nonusers (RR = 4.6; 2.9-10.7; P < 0.01). A congenital thrombophilia involving the protein C anticoagulant system was documented in about 25% of young women developing venous thromboembolism while on OCs.

Adolescent↗

The John Charnley Award. Natural history of thromboembolic disease after total hip arthroplasty.

In 1079 consecutive patients undergoing total hip arthroplasty between 1984 and 1992, complications of thromboembolic disease and related anticoagulation were reviewed for 6 months after hospital discharge, including cost data. Of 347 patients having venograms, 78 (22.5%) had positive results and 269 (77.5%) had negative results for deep venous thrombosis. In patients with negative venograms, 3 (1.1%) were readmitted with 2 symptomatic deep venous thromboses and nonfatal pulmonary embolism. There were no readmissions among the 55 patients who had venographically evident deep venous thrombosis diagnosed and treated with outpatient warfarin. Overall, 3 of 324 (0.9%) patients with true positive or negative venograms were readmitted for complications of thromboembolic disease. In contrast, 12 of 732 (1.6%) patients not receiving contrast venography were readmitted, including 9 (1.2%) deep venous thromboses and 3 (0.4%) nonfatal pulmonary embolisms. Four of 23 patients (17.4%) with untreated calf deep venous thrombosis suffered 2 nonfatal pulmonary embolisms resulting in readmission and 2 fatal pulmonary embolisms outside the hospital. Untreated calf deep venous thrombosis after total hip arthroplasty represents a significant threat of extension to more proximal veins and distant embolization. Routine thromboembolic disease prophylaxis combined with screening contrast venography and selective therapeutic anticoagulation is effective in preventing late thromboembolic disease complications and, compared with a strategy of extended prophylaxis for all, is cost effective management by reducing exposure of the elderly population to outpatient anticoagulant therapy.

Aged↗

[Thromboembolic events in women treated with hormones. Acute cerebrovascular thrombosis in 2 young women receiving ovulation inhibitors, and experiences of SANZ (Swiss Drug Monitoring Center) 1991-1995].

We describe 2 young patients with severe cerebrovascular thrombotic events whose only risk factor was intake of oral contraceptives. A 41-year-old woman suffered thrombosis of the basilar artery and remained disabled with a locked-in syndrome; a 23-year-old woman had thrombosis of the sinus sagittalis. These 2 cases and the current discussion regarding the use of hormones either as oral contraceptives or hormonal replacement therapy with estrogens and/or progestins prompted a review of the literature and a review of all spontaneous reports from 1991 to 1995 to SANZ (Schweizerische Arzneimittel-Nebenwirkungs-Zentrale), the Swiss Drug Side Effects Monitoring Center. The spontaneous reporting under this system does not allow conclusions on prevalence and incidence of adverse events. In these 5 years 33 vascular events associated with different hormones were reported. There were 28 reports of venous thrombosis of the lower and upper limb or pulmonary embolisms, and 5 reports of cerebrovascular complications. In 9 of 33 cases the hormones were used as hormonal replacement therapy and in 24 of 33 cases as oral contraceptives. In half of these women other risk factors for thromboembolic events such as overweight, family history of thrombosis and immobilization were known. Complications occurred with different preparations containing different estrogens and progestins. According to the literature, third generation progestins seem to involve a slightly increased risk of venous thromboembolism but a reduced risk of arterial thromboembolic events, which was confirmed by the SANZ data (17 of all 24 cases). Increasing age and rising estrogen dosage of oral contraceptives are associated with increased risk of vascular events. Although thromboembolic events also occur during hormonal replacement therapy with naturally occurring estrogens, the prophylactic potential of these drugs with regard to osteoporosis and cardiovascular events certainly outweighs this risk.

Adult↗

[Predictive factors of thromboembolic complications in mitral stenosis in sinus rythm].

The authors analyse the predisposing factors to the development of thromboembolic complications in mitral stenosis in sinus rhythm and propose preventive therapeutic measures. Eighty five consecutive patients with pure or very predominant mitral stenosis in sinus rhythm were included in this study and divided into two groups according to the presence (Group I: n = 27, age: 34.2 +/- 8.31 years) or absence (Group II: n = 58, age: 32.6 +/- 9.7 years) of thromboembolic complications. No significant difference was observed between the two groups for age, sex and functional class. Patients of group I had a more dilated left auricle (57.3 +/- 4.5 vs 48.4 +/- 4.7 mm; p < 0.001) and a smaller mitral surface area (0.8 +/- 0.15 vs 1.1 +/- 0.21 cm2, p < 0.05). The spontaneous left intra-atrial contrast phenomenon was more frequently observed in patients with thromboembolic complications (23 out of 27) than in those not presenting this complication (17 out of 58), (p < 0.001). This phenomenon was the only independent predictive factor on multivariate analysis. In conclusion, left atrial dilatation, the severity of mitral stenosis and especially the presence of spontaneous contrast are the main predictive factors of the development of thromboembolic complications in mitral stenosis in sinus rhythm. Patients presenting one or several of these factors may benefit from prophylactic anticoagulant treatment.

Adult↗

Oral contraceptives and venous thromboembolism: a case-control study designed to minimize detection bias.

BACKGROUND: Previous epidemiologic studies of venous thromboembolism and oral contraceptive use are susceptible to bias in the detection of venous thromboembolic events. This case-control study uses a unique design to minimize the influence of detection bias. METHODS: Nonpredisposed women younger than the age of 40 years who underwent pulmonary angiography, lower extremity venography, or lower extremity duplex Doppler sonography at a large urban hospital were classified into a case group or control group based on results of their diagnostic studies. Medical records were reviewed for a history of current oral contraceptive use. RESULTS: Fifty-seven women met the study criteria during the 11-year study period. Seven of 9 women in the case group and 17 of 48 women in the control group were currently using oral contraceptives (odds ratio 6.38; 95 percent confidence limits 1.19, 34.2). CONCLUSIONS: The association previously noted between venous thromboembolism and oral contraceptive use is not due to bias in the detection of venous thromboembolic events.

Adult↗

[Prevention of thromboembolic side effects of oral contraceptives: methodologic recommendations].

The authors analyse the incidence of thromboembolic complications during combined oral contraception. Among genetic factors predisposing to venous thrombosis and thromboembolic disease, they present, with the help of three case histories, the molecular biology of activated protein-C resistance, the newly discovered and most frequently implicated pathogenetic factor of inherited thrombophilia. Among 350 asymptomatic women requesting prescription for an oral contraceptive they found a 9.1% frequency of heterozygote Leiden-mutation carriers. For the prevention of a rare, however, almost always life-threatening complication the authors recommend activated protein C-resistance analysis to be carried out whenever an oral contraceptive is prescribed for the first time. Positive results will provide life-time aid in avoiding factors which increase the risk of thromboembolic disease. Negative results may help reducing the number of those who, risking an unwanted pregnancy, are hesitant to start on oral contraceptives for their implication in thromboembolic disease.

Adolescent↗

[Atrial fibrillation and thromboembolism: a multicenter cooperative study. Research Group for Antiarrhythmic Drug Therapy].

A multicenter, retrospective study was undertaken to determine the prevalence of and risk factors for thromboembolism and efficacy of therapy in patients with atrial fibrillation. The primary prevention group consisted of 1,819 Japanese patients (mean age 64 years). During the mean follow-up period of 4.6 years. 158 patients developed cerebral thromboembolism or peripheral embolism (1.9%/year). The annual rate of thromboembolic complications was 0.9% for patients without underlying heart disease which was significantly lower compared with that for patients with underlying heart disease (p < 0.001). The annual rate was 1.4% among patients treated with aspirin (alone and in combination with other drugs except for warfarin), 1.4% with warfarin (alone and in combination with other drugs) and 1.1% with ticlopidine. The risk was lower for patients receiving these drugs (2.2%/year, p < 0.001). Among 801 patients not receiving treatment for thromboembolism, the annual rate was 0.9% for patients without underlying heart disease, which was significantly lower compared with patients with underlying heart diseases (e.g., 2.5% for ischemic heart disease and 2.1% for mitral valve disease, p < 0.001). Multivariate analysis using quantification method II revealed hypertension, sick sinus syndrome and left ventricular dysfunction (> or = NYHA class II) as risk factors for embolism. Although limited due to its retrospective nature, the present study suggests that the risk for embolism seems low in patients with atrial fibrillation but is not associated with underlying heart diseases or other risk factors, and antiplatelet treatment seems beneficial for these patients.

Anticoagulants↗