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[Prostatic adenomectomy in patients with a history of myocardial infarct, acute cerebral circulatory disorder and pulmonary thromboembolism].

Immediate and long-term outcomes of adenomectomy have been analyzed for patients with prostatic adenoma with a history of 1-3 myocardial infarctions (185 subjects), 1-2 episodes of cerebral circulation disorder (74 cases) on pulmonary artery thromboembolism (3 cases). The surgery was urgent because of acute urine retention for 88 patients, while it was scheduled in 174 patients. The postoperative developments were uneventful in 84.9%, 87.8%, 100% of postinfarction, postapoplectic and post-thromboembolism patients, respectively. Postoperative lethal outcomes occurred in 6.5% of patients with postinfarction cardiosclerosis, 5.4% of those with postapoplectic complications. As shown by long-term follow-up available for 225 patients, 19 of them died (8.4%), 296 survived 1-11 years after the surgery. One more myocardial infarction developed in 17, apoplexy in 3 patients. Long-term functional results of adenomectomy can be considered good in most of the patients in absence of a significant progression of cardiovascular disease. The authors think adenomectomy not contraindicated and promising in terms of short- and long-term outcomes if made in above kind of patients 4, 6 and 9-12 months after myocardial infarction, pulmonary artery thromboembolism and disturbance of cerebral circulation, respectively.

Acute Disease↗

Heterozygosity for homocysteinuria: a detectable and reversible risk factor for pulmonary thromboembolism.

Heterozygosity for homocysteinuria is a common, inherited autosomal condition that has recently been considered as an independent cardiovascular risk factor. In vitro and in vivo results suggest that this condition, like the homozygous form, is also a risk factor for deep-venous thrombosis and pulmonary thromboembolism. We report a case of recurrent pulmonary thromboembolism in a young woman with familial hyperhomocysteinaemia. The relative frequency of this condition, as well as its simple and harmless cure, make testing for heterozygosity for homocysteinuria useful and profitable in the prevention of pulmonary thromboembolism, above all in younger subjects with a significant case history.

Adult↗

Management of venous thromboembolic disease. The impact of low-molecular-weight heparin.

Prophylaxis for DVT unequivocally is beneficial in patients identified to be at high risk. Heparin prophylaxis with subcutaneous low-dose UFH is adequate in some clinical settings but less effective in others. LMWH preparations are effective and safe as prophylaxis in certain medical patients as well as in general surgery and elective hip replacement. Efficacy and safety are demonstrated in the therapy of established venous thromboembolism. Subcutaneous administration of LMWH once or twice daily may prove more convenient from both the patient and nursing viewpoint, particularly in the treatment of established DVT. Monitoring is not necessary when using LMWH preparations as prophylaxis, and a fixed-dose without weight adjustment has been used in most prophylaxis trials. When treating established DVT, less monitoring is likely to be required than currently is the case with UFH. Although the cost of LMWH preparations is greater than that of UFH, the decrease in the occurrence or recurrence of thromboses that has been demonstrated in some trials might prove an effective balance. Future avenues to explore include discovery of better means to standardize the LMWH preparations and determination of the efficacy and safety of LMWH in specific populations, such as those in intensive care units, cancer patients, nursing home patients, and outpatients in general. Although cost-benefit is favorable thus far, meticulous assessment in other settings may enhance the acceptance of these agents. Long-term follow-up could be helpful in determining the relative effect of different heparin preparations on the frequency of postphlebitic syndrome. Comparison of different LMWH fractions may follow, as well as further investigations of newer ultra-low-molecular-weight agents. One LMWH preparation (enoxaparin) already has been approved in the United States for prophylaxis in the setting of elective hip replacement; and dalteparin has been approved here for use as DVT prophylaxis in patients undergoing abdominal surgery when there appears to be a significant risk of thromboembolism. It is likely that LMWH preparations will become even more widely used in North America and that the approved indications will expand to include prophylaxis in numerous settings and the treatment of established venous thromboembolism.

Clinical Trials as Topic↗

[Arterial pulmonary thromboembolism as a cause of mortality in thoracic surgery].

Analysis of hospital mortality showed that thromboembolism of the pulmonary artery was a cause of lethal outcomes in thoracic surgery in 0.4% of hospitalized patients, in 0.7% of those who underwent operation, in 14.8% of all patients who died, and in 15.6% of those who died in the postoperative period. The principal causes of death in thromboembolism of the pulmonary artery were various diagnostic errors (79.5%), severity of the patient's initial condition (14.1%), and defective treatment (6.4%). Prevention of thromboembolism of the pulmonary artery is based on timely detection of its sources by wider use of ultrasonic and radionuclide methods, rarer application of invasive diagnostic methods, and the use of anticoagulant therapy after operations in the risk groups.

Adolescent↗

Detection of multiple thromboembolism in congenital antithrombin III deficiency with indium-111-platelet scintigraphy.

Congenital deficiency of antithrombin III (AT III), a physiological inhibitor of blood coagulation, may lead to increased thromboembolism. Here, we report a case of multiple thromboembolism associated with congenital AT III deficiency. The diagnosis of systemic thromboembolism was made by 111In-labeled platelet scintigraphy (In-scan) which allowed for the daily assessment of thromboemboli size. Thromboemboli were found not only in sites predicted clinically, but also in unexpected sites. In these patients, thus, a careful whole-body examination is necessary for full detection of thromboemboli. In-scan may be a useful technique for such screening.

Adolescent↗

[Effect of large doses of nifedipine on pulmonary hypertension in patients with recurrent pulmonary thromboembolism].

Thromboembolic pulmonary hypertension is an uncommon condition with poor prognosis. Vasodilators may be effective in some patients with that disease. The effect of nifedipine on hemodynamics was investigated in two patients with thromboembolic pulmonary hypertension treated with acenocoumarol. Nifedipine was administered in 20 mg doses hourly during right cardiac catheterization and was repeated after 1 hour until a decrease in systemic pressure occurred. Patients received 80 mg and 120 mg of nifedipine. Pulmonary artery pressures decreased in both cases. An increase of cardiac output and decrease of pulmonary vascular resistance were observed after 60-80 mg of nifedipine and continued to the end of the investigation. No effect on heart rate was observed. We suggest that high doses of nifedipine may be--in some patients--effective in reducing thromboembolic pulmonary hypertension.

Adult↗

[Pulmonary hypertension during the course of chronic pulmonary thromboembolism--case report].

Chronic thromboembolic pulmonary hypertension is a rare condition. There are two forms of that disease: major vessel thromboembolic pulmonary hypertension (CTEPH) and a "silent form": recurrent microembolism leading to extensive obstruction of the peripheral pulmonary vasculature and resulting also in severe pulmonary hypertension. On the base of case report the new approaches to the management of patients with two mentioned subgroups of thromboembolic pulmonary hypertension are discussed.

Chronic Disease↗

[Autopsy-proven cases of fatal saddle thromboembolism in the pulmonary artery].

In 544 autopsy cases during the period from 1984 through 1990 at National Okura Hospital, there were 7 cases of fatal saddle pulmonary thromboembolism (1.3%). Pulmonary thromboembolism was included in the differential diagnosis, but not as a primary consideration. Therefore, no case was diagnosed antemortem. Saddle thromboembolus is defined here as a thromboembolus which impacted in the main pulmonary artery or lodged astride the bifurcation. The cases were 5 females and 2 males ranging in age from 53 to 76 years. During the clinical course of the initial disease, sudden symptoms including dyspnea, chest pain or tachypnea developed, and death occurred within one hour or in a relatively short period of time. In case 6, sudden death followed removal of a central venous catheter inserted in the inferior vena cava one week previously. In cases 2, 3, and 5, deep vein thromboemboli were detected at postmortem examination. In cases 3 and 4, the patients were 3- and 5-days postoperative, respectively. Laboratory data obtained before death showed no abnormalities of hematologic and coagulation profiles. At autopsy, the pulmonary artery trunk was completely occluded by embolus, and thromboemboli were detected in the femoral and iliac veins in 3 cases. These thromboemboli were composed of fibrin and red cells enmeshed with platelets. On microscopic examination, endothelial disruption was not observed at the levels of the large and smaller pulmonary vessels, which underlies thrombosis in situ or creates a procoagulant environment. Proximal pulmonary thromboemboli were demonstrated in only one out of seven cases (Case 1). Saddle thromboembolism, in our limited observation, resulted from the impact of large floating embolus, emanating from elsewhere, against the large pulmonary artery, rather than the propagation of a smaller pulmonary embolus originating in a peripheral artery.

Aged↗

[Possibilities and limits of local intra-arterial fibrinolysis in thromboembolic vascular occlusions of the central nervous system].

It is now possible with the help of microcatheters to superselectivity catheterize the cerebral vessels right up to the point of thromboembolic vascular occlusion. Short acting fibrinolytic agents such as urokinase and rt-PA are ideally suited for local intraarterial fibrinolysis (LIF) of thromboembolism in cerebral arteries. Despite high dosages (1,000,000-2,000,000 I.U. urokinase/hr), the risk of symptomatic haemorrhage is relatively low if therapy is started within 4-5 hours of the onset of symptoms and is administered only for a short time (1-2 hrs). To reduce the high mortality rate in patients with thromboembolic occlusion in the vertebrobasilar territory, LIF is the treatment of choice. If therapy is promptly started within 4-5 hours of the clinical onset of symptoms, a favourable clinical course may result even in patients with internal carotid artery or middle cerebral artery occlusions. However, further studies are required to optimize the treatment strategy in the latter group of patients. Results of studies to date have shown that the immediate intraarterial fibrinolysis of the acutely occluded central retinal artery is by far superior to conservative therapy.

Cerebral Angiography↗

[Prevention of thromboembolic complications in transurethral resection of the prostate (author's transl)].

1. The effect of 2 X 500 ml Dextran 70 i.v. for prevention of postoperative deep vein thrombosis in patients with transurethral resection of the prostate was investigated in a controlled, prospective and randomized study. The diagnosis of deep vein thrombosis was made by means of the 125I-fibrinogen test. 2. A total of 86 patients were studied. Two out of 47 in the control group developed deep vein thrombosis and 3 out of 39 in the dextran group. The total number of all thromboembolic complications in the control group is 19.2% as compared to 7.7% in the dextran group. This difference is statistically seen not significant. 3. Dextran prophylaxis showed no side effects. 4. A search of the literature on thromboembolic complications in urology shows the following. The incidence of deep vein thrombosis is general urology is about the same as in general surgery, i.e. every third patient develops deep vein thrombosis. There are no studies which would show that the number of fatal pulmonary emboli can be significantly reduced by any sort of preventive method in urologic patients. 5. The incidence of deep vein thrombosis in open prostatectomies is around 50%. In transurethral resection, however, this figure is between 5 and 10%. But nevertheless there are fatal pulmonary emboli. There exist no studies showing a significant reduction in the incidence of deep vein thrombosis after prostatectomy by any form of prevention. In order to avoid the postthrombotic syndrom and fatal complications, a prevention of thromboembolism seems reasonable, if this form of prevention has minimal side effects.

Adult↗

Low molecular weight heparins (LMWH) in the treatment of patients with acute venous thromboembolism.

We have analysed randomized trials comparing unfractionated heparin and low molecular weight heparin in which symptomatic recurrent venous thromboembolism and major bleeding were objectively confirmed. Studies were classified as level 1 if they were double blind or if there was blinded assessment of outcome measures and level 2 if they did not provide assurance of blinded outcome assessment. In studies classified as level 1, the relative risk (RR) of recurrent venous thromboembolism during the first 15 days and over the entire period of anticoagulant therapy was 0.24 (95% confidence intervals [CI] 0.06-0.08, p = 0.02) and 0.39 (95% CI 0.3-0.4, p = 0.006), respectively, in favour of LMWH treatment. The RR for major bleeding was 0.42 (95% CI 0.2-0.9, p = 0.01), in favour of LMWH. In studies classified as level 2, no significant differences in the rates of recurrent venous thromboembolism and major bleeding were observed. Pooling level 1 and level 2 studies, the RR for overall mortality and mortality in cancer patients was 0.51 (95% CI 0.2-0.9, p = 0.01) and 0.33 (95% CI 0.1-1.8, p = 0.01) respectively, in favour of LMWH.

Anticoagulants↗

Clinical diagnosis and management of the patient with deep venous thromboembolism and acute pulmonary embolism.

Pulmonary embolism is the third most common acute cause of death in the United States. There are approximately 500,000 cases annually in this country, leading to death in 50,000. Subjective symptoms and objective findings can oftentimes be confusing and nonspecific. A pulmonary embolism is defined as an occlusion of one or more pulmonary vessels by material that has traveled there from outside of the lung and is usually caused by a dislodged thrombus that originated in the deep veins of the legs or pelvis. Risk factors include older age, prior thromboembolism, immobility, cancer, chronic disease, congestive heart failure, pelvic and lower extremity surgery, varicosities, obesity, and oral contraception. This article will discuss current modalities that are used in the evaluation of deep venous thromboembolism and pulmonary embolism and include ventilation/perfusion scan, ultrasonography, impedance plethysmography, pulmonary angiography, and newer tests including D-dimer assays and spiral computed tomography. Medical management including simple and complex decision making, anticoagulation, and thrombolytic therapy will also be discussed. An ounce of prevention is worth a pound of gold--identification of risk factors and the use of appropriate therapeutic measures can reduce an individual's risk for deep venous thromboembolism and pulmonary embolism.

Anticoagulants↗

[Pulmonary thromboembolism and diagnostic imaging: integration of techniques and methods].

Thromboembolism is presently the third most frequent cardiovascular disease, with an incidence of deep venous thrombosis of 800,000 cases a year in the USA. The clinical diagnosis of the condition is difficult and noninvasive procedures are poorly reliable, which makes the diagnosis and treatment of deep venous thrombosis appropriate in the patient with clinically suspected pulmonary embolism. Color-Doppler US is now replacing phlebography in the diagnosis of deep venous thrombosis. Proximal deep venous thrombosis is always at high risk for embolism (50%). Isolated calf thrombi may spread into proximal veins and thus cause severe embolism. Therefore, the early detection of thrombus site and extent and a timely treatment before embolism are of the utmost importance. Color-Doppler US is a noninvasive technique which can show deep venous thrombosis with 95% sensitivity in the proximal and 55% sensitivity in the distal districts in asymptomatic patients. This examination must be used not only to confirm a diagnostic suspicion of deep venous thrombosis, but also to screen high-risk patient and to monitor distal thrombosis. In the secondary prophylaxis of pulmonary embolism, the radiologist must perform a mechanical interruption of inferior vena cava by positioning a caval filter. Caval filters can be temporary or definitive; standard indications for caval filter positioning are a contraindication to anticoagulant therapy and the onset of pulmonary embolism in spite of anticoagulant drugs. A further indication is the presence of floating thrombi in the femoroiliac-caval trunk. Multidisciplinary groups including the hematologist, the radiologist and the clinician should plan the diagnostic and therapeutic approach and participate in the decision-making process. In our department, from January, 1992, to June, 1995, sixty-five caval filters were positioned in 62 patients selected out of 260 candidates. Three complications only were observed; one patient had recurrent pulmonary embolism and three patient had caval thrombosis spreading beyond the filter. In 198 patients in whom no caval filter was implanted, pulmonary embolism did not recur. At present, the role of the radiologist is markedly changing, especially in the management of this condition. On the one hand, radiologists must diagnose thromboembolism as a whole and not only its pulmonary evidence; on the other hand, they play a major operational and interventional role in the treatment of thromboembolism patients.

Clinical Protocols↗

Epidemiology, pathophysiology and natural history of venous thromboembolism.

Venous thromboembolism is a relevant social and health care problem for its high incidence, pulmonary embolism-related mortality, and long-term sequels which may be disabling. In the United States, there are at least 100,000 deaths per year from pulmonary embolism, found in over 10% non selected autopsy findings. The use of noninvasive diagnostic procedures has improved our knowledge on venous thromboembolism, with reference to surgery in particular. Deep vein thrombosis represents one of most common postoperative complications. Fatal pulmonary embolism is observed at least in one over thousand operated patients. From data of literature and in the authors' experience, the incidence of pulmonary embolism is decreasing in last years. Deep vein thrombosis is caused by several factors associated with Virchow's triad. Its evolution is site-related. While deep vein thrombosis of the calf can be considered a "benign" pathological condition for the incidence and severity of the embolic complication, as well as for the long-term outcomes, when the proximal venous trunks are involved, it is related to a high incidence of severe pulmonary embolism and relevant postphlebitic sequels. Pulmonary embolism is often the first manifestation of thromboembolism. Mobilization of thrombi is easier in the first phases, when they do not adhere as yet to the venous wall. Of 52 consecutive cases of pulmonary embolism, 21% occurred in the absence of signs or symptoms of deep vein thrombosis. In rare cases, thrombosis may be massive with total block of venous return flow and onset of ischemia. These forms have a severe prognosis apart from the embolic complication.

Humans↗

[An autopsy case of pulmonary thromboembolism: a delayed complication of a victim by traffic accident].

A 35-year-old male had fallen down from his motor bike caused a fracture of the medial condyle of the right tibia and the acromion of the left scapula. He had received screw fixed operation for his right tibia and had been in the hospital for one month. He died suddenly in the hospital and was autopsied to find out the cause of death. On external examination, it was found that affected leg was bruised and swollened. Partially organized thrombosis in the posterior tibial vein was revealed and bilateral pulmonary arteries were packed with reddish massive thromboemboli. The causes of the posterior tibial vein thrombosis were intimal damage and decreased venous flow, attributable to bed rest for long days and external fixation of the lower extremity. We presumed that direct cause of death was a large thromboemboi which were migrated from posterior tibial vein and lodged at the bifurcation of the pulmonary artery causing obstruction of pulmonary blood flow. Finally we opened the direct cause of death was pulmonary thromboembolism due to leg injury. Clinical instability may hinder the diagnostic elevation and delay therapeutic intervention, it is the most often happened in sudden death cases within the hospital. The importance of early diagnosis and early prevention is underscoped, because the symptoms of pulmonary thromboembolism are not always produced. To prevent fatal pulmonary thromboembolism in trauma, prophylactic use of low-dose heparin therapy and/or the use of oral anticoaglant (warfarin) have been effective and recommended in USA and Western Europe. The routine use of these therapy has not yet been spread in Japan, because the incidence is still apparently lower than in USA and Western Europe as well as the risk of hemorrhage. If the victims of road traffic accident receive the prophylactic use of low-dose heparin and/or oral anticoaglant (warfarin), it might be an effective way to reduce mortality.

Accidents, Traffic↗

Efficacy of prevention of thromboembolic complications with LMW-heparin in experiment.

The authors used an antithrombotic agent (Nadroparin Calcium) with anti-Xa effect in their experiments to prevent thromboembolic complications in the model of endoprosthetic replacement of the hip joint in mongrel dogs. 10 experimental animals (Group I.) were given doses of 100 A Xa ICU/kg/bwt of Nadroparin Calcium subcutaneously 4 hours prior to the operation and also once a day until the 3rd postoperative day; between the 4th and 10th postoperative days doses of 150 A Xa ICU/kg/bwt Nadroparin Calcium were given. The 10 control animals (Group II.) did not receive anticoagulant treatment. In both groups platelet count, activated partial thromboplastin times (APTT), prothrombin and fibrinogen levels as well as activated factor X inhibition (F Xa) were measured prior to surgery and also until the 14th postoperative day. No changes in APTT and prothrombin levels were detected during the experiment, however platelet count and fibrinogen levels as well as the extent of F Xa inhibition showed significant and different changes in groups I. and II. The Group I. which had received thromboembolic prophylaxis did not develop deep venous thrombosis or pulmonary embolism, but the control group did. Based on their investigations, the authors concluded that they had been able to achieve F Xa inhibition by giving the above mentioned doses of Nadroparin Calcium which was enough to prevent thromboembolic complications in their model experiment of implanting hip endoprosthesis.

Animals↗

Aging and venous thromboembolism influence the pharmacodynamics of the anti-factor Xa and anti-thrombin activities of a low molecular weight heparin (nadroparin).

Venous thromboembolism may be efficiently treated by one single daily administration of a high dose of low molecular weight heparin (LMWH). The present study investigates if the physiological deterioration of renal function associated with normal aging or the presence of an acute venous thromboembolism influences the pharmacodynamic pattern of the anti-factor Xa and anti-thrombin activities. Three groups of 12 subjects were investigated. The first 2 groups were composed of healthy volunteers differing by age (25 +/- 4 and 65 +/- 3 yrs) and creatinine clearance (114 +/- 15 and 62 +/- 6 ml x min(-1)). The third group was composed of patients hospitalized for deep vein thrombosis, having a mean age of 65 +/- 11 yrs and creatinine clearance of 76 +/- 8 ml x min(-1). Nadroparin was administered subcutaneously once daily at the dose of 180 anti-factor Xa IU.kg(-1) for 6 to 10 days. Serial sampling on day 1 and on the last day of administration (day n) allowed the pharmacodynamic parameters of the anti-factor Xa and anti-thrombin activities to be compared at the beginning and at the end of the treatment. The main findings were the following: (1) After repeated administration, a significant accumulation of the anti-factor Xa activity was observed in the healthy elderly and in the patients but not in the healthy young subjects (accumulation factor: 1.3). There was no evidence of accumulation of anti-thrombin activity; (2) There were significant correlations between the clearance of creatinine and the clearance of the anti-factor Xa activity but not with that of the anti-thrombin activity; (3) In the patients, the clearance of the anti-factor Xa and of the anti-thrombin activities were 1.4 and 2 times higher respectively than those calculated in the healthy elderly; (4) The mean ratio of the of anti-factor Xa and anti-thrombin clearances was close to 2 in the healthy subjects but equal to 5.4 in the patients. These results suggest that the mechanisms involved in the clearance of polysaccharide chains which support the anti-thrombin activity are different from those of the anti-factor Xa activity and that the enhanced binding properties of plasma proteins to unfractionated heparin reported in patients presenting an acute venous thromboembolism also exists for LMWH, predominantly for the anti-thrombin activity.

Adult↗

[Pulmonary embolism. Risk factors of venous thromboembolic disease].

RISK FACTORS: Management of deep venous thromboembolism both in terms of diagnosis and therapeutic and prophylactic strategies has been greatly improved by advances in knowledge of the main acquired and intrinsic risk factors. RESISTANCE TO ACTIVATED PROTEIN C: This is by far the most frequent coagulation disorder predisposing to venous thromboembolism. Other intrinsic factors favoring thrombus formation (anti-thrombin II, protein C or protein S deficiencies) are much more uncommon. Laboratory tests in search for these anomalies are indicated essentially for patients who develop repeated episodes of venous thrombus formation. PROPHYLAXIS: Excepting specific cases, anticoagulant prophylaxis is not indicated in any of these anomalies beyond the usual treatment of a first episode. Among the risk factors for acquired deep vein thromboembolism, only surgery and certain obstetrical indications have been investigated sufficiently to define validated prophylaxis strategies. For medical risks, the benefit of anticoagulant prophylaxis has been demonstrated in certain disease states such as cancer, antiphospholipid syndrome and the acute phase of myocardial infarction although no widely accepted strategy has yet been established.

Anticoagulants↗