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[Coincidence of 20210A prothrombin variant and factor V Leiden predisposing to venous thromboembolism].

Coexistence of inherited and environmental risks leads to the high hazard of venous thromboembolism. In such cases, there might be difficulties in the diagnosis and treatment of recurrent episodes. The importance of Factor V Leiden and prothrombin variant 20210A in the pathogenesis of venous thromboembolic disease, is widely accepted, but the carriership of thrombophilic genes' variants is usually not sufficient for the development of the disease. We report two cases of familial thrombophilia with concurrent presence of prothrombin variant 20210A and factor V Leiden. In a 28-year-old woman: pregnancy, immobilization, obstetric intervention appeared to precipitate the thromboembolic complication. In the second patient, the genetic studies revealed both thrombophilic mutations which could predispose to the recurrent venous thromboembolism, previously thought to be idiopathic. We discuss diagnostic and therapeutic difficulties in such patients.

Adult↗

[Therapy of venous thromboembolism].

Deep venous thrombosis and lung embolism are often considered as two different variants of the same disease. This is evident not only in the same pathogenesis but also in a comparable prognosis and therapy. Therefore the term "venous thromboembolism" is used in recent literature. The main therapy of venous thromboembolism is anticoagulation and initially consists of (low molecular weight) heparin followed by a regimen with oral anticoagulants--the duration depending on the indication. Pharmacokinetic advantages of low molecular weight heparin (LMWH) allow weight-adapted dosing with daily subcutaneous injections in most patients. LMWH do not require any laboratory controls. Therefore outpatient treatment should be possible for about 75% of patients with venous thromboembolism. Outpatient treatment of lung embolism, however, is still being studied and therefore not recommended apart from clinical trials. In cases of massive venous thromboembolism additional treatment with thrombolytic agents or surgery is needed. Adequately fit compression stockings can reduce the risk of post-thrombotic syndrome after deep venous thrombosis. Patients on long-term oral anticoagulation may learn to measure their INR with a portable coagulation monitor and adjust the dosage of the anticoagulants themselves--this method is called patient self-management of oral anticoagulation.

Ambulatory Care↗

Current assessment of thromboembolic disease and pregnancy.

This study was undertaken to assess incidence of deep venous thrombosis and pulmonary emboli in an inner-city pregnant population. Thromboembolic disease is believed to occur in 0.05 to 0.1 per cent of all pregnancies. Historically, postpartum thromboembolic disease was more common; decreased hospital stay may shift the thromboembolic disease to the antepartum period. A 5-year retrospective review of 4910 births assessed for incidence of thromboembolic disease, methods of diagnosis and treatment, and risk factors. A total of 4910 deliveries with 3978 transvaginal resulted in 30 episodes of deep venous thrombosis and five pulmonary emboli. All incidences of deep venous thrombosis but one were left-sided; four of five pulmonary emboli were postpartum. Of the epidsodes of deep venous thrombosis 17 per cent were first trimester, 50 per cent second trimester, 27 per cent third trimester, and 6 per cent postpartum. The diagnosis was confirmed by duplex scan in 24 of 30 patients. Heparin was the standard treatment. Deep venous thrombosis in pregnancy is most common in the second trimester; pulmonary emboli remain most common postpartum.

Adolescent↗

[Venous thromboembolic pathology. New acquired risk factors or new data on acquired risk factors].

Many acquired risk factors may be identified to avoid the scholarly nature of these interminable lists, they may be reclassified with respect to their originality or their mechanism of action and those of current interest, whose data is still often hypothetical but recent, can be underlined. The following order may be proposed: risk factors which cannot be changed: age (which remains the principal factor) and gender (women being at higher risk than men); true acquired risk factors such as cancer, dysimmune conditions (more specifically, the antiphospholipid syndrome) and hormone replacement therapy (oestroprogestative contraception which has been updated by the debate about "third generation pills" and the risk related to progesterone-like substances themselves; hormone replacement therapy of the menopause which still has no clinical trials to assess "our" forms with natural hormones administered transdermally or transmucosally). Smoking has also been accused of being a risk factor for venous thrombosis in the latest clinical trials. Metabolic factors increase the risk of thrombosis: this is established for obesity, still suspected for hyperhomocystonaemia, the abnormalities being the result of complex gene-environment interactions. Other dysmetabolic conditions (diabetes, hypercholesterolaemia, hypertriglyceridaemia), responsible for arterial complications, are not clearly related to increased venous thromboembolic risk although a preventive effect of statins (yet another I) has just been reported. Similarly to these metabolic factors, the origin of which, genetic or environmental, is difficult to establish, interest has recently been shown in quantitative and functional changes in blood clotting factors. This has been established for arterial disease for fibrinogen but, in addition to this factor which slightly increases the risk of venous thrombosis, increases of factor VIII independent of inflammatory conditions, of blood group and Von Willebrand factor, which all influence the level of factor VIII, an increase by 150% of the normal increases the risk of venous thromboembolic disease by 3 or 4 times. As for factor VIII, increases in factor IX, factor XI, and resistance to activated C protein (independently of the Leiden mutation on the gene for factor V), are also associated in increased venous thromboembolic risk. Without knowing into which category to classify them, previous personal and family history of thromboembolic disease, in the absence of the already mentioned hereditary risk factors, must be noted. Finally, amongst the acquired risk factors, the authors also list conditions of blood stasis and vascular lesions with or without hypercoagulability (surgery, prolonged hospital stays, cardiac failure, paralysis, pregnancy...). Of these acquired conditions which increase the risk of thrombotic complications, particular attention has been given over the last few years to forced immobilisation in uncomfortable positions as in certain forms of transport. Although clinical reports have discordant results, it would seem that the risk is increased and the benefits of supportive elastic stockings have been confirmed. If the acquired risk is identified and quantified for a patient, it allows evaluation of global risk and the installation of appropriate therapeutic measures.

Animals↗

[Etiopathogenesis of venous thrombosis and pulmonary thromboembolism: pathophysiologic changes in the cardiovascular system].

It is known that pulmonary embolism is accompanied by quite complex pathophysiological changes in cardiovascular system. From cardiovascular point of view, the diagnosis of pulmonary thromboembolism may be easily based on echocardiographic signs of right ventricular hypokinesia. Physiologic abnormalities caused by venous emboli are related to the cross-sectional area of occluded pulmonary arterial bed. Recent studies has demonstrated, that in patients with massive pulmonary thromboembolism and signs of pulmonary hypertension, increase of right ventricular afterload can lead to both right ventricular failure and reduction of left ventricular preload. Despite development of pulmonary hypertension in acute massive pulmonary thromboembolism, there are no signs of right ventricular hypertrophy. The main ECG changes include right ventricular overload. Previous normal ECG is of special importance. Documentation of serious increase of pulmonary arterial pressure by Doppler echocardiography will assist to link right ventricular pressure overload and dysfunction with embolisms. Transesophageal echocardiography had the similar diagnostic value as transthoracic one, but especially is helpful in bedside diagnosis in patients with signs of shock secondary to pulmonary thromboembolism.

Cardiovascular System↗

[Clinical experience with retrievable vena cava filters for prevention of pulmonary thromboembolism].

OBJECTIVES: To evaluate the feasibility, effectiveness and complications of the retrievable vena cava filter [Güther tulip vena cava filter(GTF)] for the prevention of pulmonary thromboembolism in patients with deep vein thrombosis. METHODS: Seventeen patients, 3 males and 14 females, aged 21 to 82 years (mean age 59 +/- 19 years), underwent implantation of GTFs between December 2000 and February 2002 at Mie University Hospital. All patients were treated under diagnoses of deep vein thrombosis with or without pulmonary thromboembolism based on venous ultrasonography, venography or computed tomography. Eleven patients were treated with thrombolysis. RESULTS: Significant thromboembolus was trapped within the filter in 3 of 12 patients. No acute pulmonary thromboembolism occurred during implantation or at retrieval of the GTF. Retrieval of the GTF was attempted in 9 patients, and 8 GTFs were retrieved successfully. Mean interval of the filter implantation was 13.4 +/- 6.3 days and the mean retrieval time was 4.8 +/- 3.2 min. No complications occurred except for one case of minor hemorrhage at the puncture site. CONCLUSIONS: The placement and retrieval of the retrievable vena cava filter was feasible and safe. This filter was also effective for the prevention of pulmonary thromboembolism. This retrievable vena cava filter may be a good first-choice filter for both permanent and temporary use.

Adult↗

Thromboembolic events associated with Guglielmi detachable coil embolization of asymptomatic cerebral aneurysms: evaluation of 66 consecutive cases with use of diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Although Guglielmi detachable coil (GDC) endovascular treatment of intracranial aneurysms has become an accepted alternative to surgery, the main complication continues to be thromboembolic events. We sought to determine the frequency and radiologic appearance of thromboembolic events during GDC embolization for asymptomatic cerebral aneurysms by using diffusion-weighted (DW) MR imaging and to determine whether aneurysmal anatomic factors or use of the balloon-assisted technique affected the frequency. METHODS: In 74 patients, 79 asymptomatic cerebral aneurysms were treated with GDC embolizations at the National Cardiovascular Center from 1999 to 2001. Thirty-nine of these aneurysms (49%) were treated with the balloon-assisted technique. DW imaging was performed in 66 patients at 2-5 days after GDC embolization. All DW images were reviewed by two radiologists for depiction of abnormalities. RESULTS: DW images showed hyperintense lesions in 40 patients (61%), with 16 of these patients (40%) incurring neurologic deteriorations. Fifteen of the symptomatic patients (94%) fully recovered by discharge, and the remaining one experienced permanent deficits. Hyperintense lesions were detected more frequently in wide-neck (73%) or large (100%) aneurysms and in procedures that used the balloon-assisted technique (73%) than in small aneurysms (50%) or in procedures with the simple GDC method (49%). The occurrence of new lesions was significantly associated with use of the balloon-assisted technique and with aneurysm diameter in multivariate analysis (P <.05). CONCLUSION: In our experience, thromboembolic events related to the use of GDC embolization are relatively common, especially in wide-neck or large aneurysms or in association with the balloon-assisted technique. Although permanent deficits are rare, the high rate of thromboembolic events suggests that improvements in the technique such as the addition of antiplatelet agents and the development of new embolic materials are mandatory.

Adult↗

Prospective assessment of the natural history of positive D-dimer results in persons with acute venous thromboembolism (DVT or PE).

The natural history of initially positive D-dimers for venous thromboembolism is not known. If it returns to negative in the majority of patients, it would be potentially helpful to diagnose a recurrence. In this study, we prospectively measured D-dimer levels in outpatients with a diagnosis of venous thromboembolism. There were a total of 152 patients with an average age of 57. D-dimer results were performed at baseline and repeated at one week, one month and three months. At baseline 120 of 152 (79%) had a positive D-dimer result. Of those with an initially positive result, 80% were still positive at one week and 39% were still positive at one month. Finally at three months, 13% remained positive. Seven patients had recurrent events and all had persistently elevated D-dimers at one month. This study suggests that a persistently positive D-dimer result after one month of treatment may indicate a higher risk of recurrent venous thromboembolism. D-dimer testing for the diagnosis of recurrence of venous thromboembolism deserves further study.

Adult↗

[Acute pulmonary thromboembolism and deep-venous thrombosis at post-operative period in urologic surgery].

Acute pulmonary thromboembolism (APTE) and deep venous thrombosis (DVT) are categorized into venous thromboembolism. APTE is one of the most critical post-operative complications because of its high mortality. Meanwhile, DVT is responsible for more than 80-95% of APTE cases. APTE occurred in 6 patients and DVT in 3 patients in the post-operative period during the past eleven years at our hospital. The median age of these patients, 5 men and 4 women, was 62 years (45-77). In many cases, the course of APTE showed a rapid progression. Four of the six patients with APTE died, and two of these four patients died within a few hours following the onset. Once it occurs, it is often lethal. Therefore, the prevention of thromboembolism is most important. In this study, we examined these 6 APTE cases and 3 DVT cases and discussed low dose heparin and intermittent sequential pneumatic compression (ISPC), prophylaxis against APTE in the post-operative period. We have been using ISPC for the high-risk group of thromboembolism in the post-operative period since 1999. In addition to using ISPC, we have been administering low dose heparin since November 2001. These 3 cases of DVT occurred regardless of adoption of ISPC. However, there were no cases of APTE after adoption of ISPC, and no cases of DVT or APTE after adoption of ISPC and administration of low dose heparin.

Acute Disease↗

[Personal experience in the diagnosis and therapy of pulmonary thromboembolism].

The analysis of both clinical findings and diagnostic procedures results were performed in 26 patients with thromboembolic pulmonary disease in order to determine the incidence of signs indicating pulmonary thromboembolism. Sudden dyspnea, hemoptysis and chest pains are the most common symptoms of the disease. These symptoms associated with radiographically confirmed pulmonary infiltrations with the elevation of hemidiaphragm and pleural effusion, particularly if they are bilateral, are the main clues for the diagnosis of pulmonary embolism. Perfusion defect on the pulmonary scintigraphy makes this diagnosis almost certain. Hypoxemia and hypocapnia and respiratory alkalosis are frequent findings in thromboembolic pulmonary disease, as well. Fever, increases RBC sedimentation rate and leukocytosis are present in a great deal of patients. In addition, the presence of risk factors related to the development of thrombosis of the lower limbs deep veins, and particularly those related to the long term immobilization as well as diagnostically confirmed venous thrombus are basic guidelines for the diagnostic of pulmonary thromboembolism.

Adult↗

Successful pulmonary thromboendarterectomy in a patient with subacute pulmonary thromboembolism.

Pulmonary thromboembolism can lead to serious hemodynamic instability or even death. Treatment for subacute pulmonary thromboembolism is not standardized. We report a case of subacute pulmonary thromboembolism successfully treated by pulmonary thromboendarterectomy. A 63-year-old woman without underlying disease was admitted due to progressive shortness of breath with episodic exacerbation for more than 5 months. Hypoxemia was noted on admission. Contrast-enhanced spiral computed tomography of the chest revealed multiple thrombi in the central pulmonary arteries. Pulmonary thromboendarterectomy was performed 5 days after admission. The surgical specimens showed acute, subacute, and chronic stages of thrombi. Her clinical condition improved markedly after operation. She was discharged and had recovered fully at follow-up 6 months after discharge. This case suggests that pulmonary thromboendarterectomy may be beneficial for patients with subacute pulmonary thromboembolism.

Endarterectomy↗

[Prevention of pulmonary thromboembolism in medical patients].

In contrast to surgical patients, prevention of acute pulmonary thromboembolism has been less well studied in hospitalized medical patients even in Western countries. But some data apparently showed the high prevalence of venous thromboembolism in medical patients. The combination of mechanical prophylactic measures should be indicated for medical patients with risk factors including stroke, cancer, prolonged bedrest, heart failure and severe lung disease. Prospective studies to evaluate the frequency of venous thromboembolism in medical patients with risk factors and the efficacy and safety of each prophylactic measure, especially of pharmacological prophylaxis are necessary to establish the guidelines for prevention of pulmonary thromboembolism for Japanese people.

Bed Rest↗

Venous thromboembolism and travel: is there an association?

This paper reviews the literature on the association between venous thromboembolism and travel. There are plausible physiological reasons why sitting still for long periods (particularly in the cramped conditions of most aircraft) might predispose to venous thromboembolism. This may have been the explanation for the apparent excess of deaths from pulmonary embolism seen during the first months of the London blitz. No published controlled studies of thromboembolism and travel were identified, but eight case reports were analysed. They covered 25 people aged from 19 to 84 years with deep vein thrombosis or pulmonary embolism following travel. The reports suggest that long journeys are a particular risk and that there are often no symptoms until many hours after leaving the plane (so conventional methods of assessing the hazards of air travel may underestimate the problem). It is concluded that the literature tends to support the hypothesis that venous thromboembolism is associated with travel, but that carefully controlled studies are needed to test this properly.

Adult↗

[Surgical treatment of chronic pulmonary thromboembolism].

OBJECTIVE: To evaluate the perioperative management and safety of pulmonary thromboendarterectomy for chronic pulmonary thromboembolism. METHODS: From March 1999 to March 2004, 12 patients with chronic pulmonary thromboembolism received thromboendarterectomy. The operation was performed under cardio-pulmonary bypass with low flow or circulative arrest and deep hypothermia. The clinical data of the 12 cases were reviewed retrospectively. RESULTS: Pulmonary pressure immediately decreased 20 to 40 mm Hg (1 mm Hg = 0.133 kPa) after operation in 6 cases. Various degrees of postoperative pulmonary edema happened in 8 cases. One patient died at the 19th day after operation due to severe lung infection and pulmonary re-embolism. Eleven patients were followed-up for 2 months to 5 years, the clinical symptom and routine daily activity were improved after surgery. CONCLUSION: Pulmonary thromboendarterectomy is an effective treatment for chronic pulmonary thromboembolism. It is very important to management of postoperative reperfusion injury and pulmonary edema. A key point to enhance the safety of surgical treatment for chronic pulmonary thromboembolism is preoperative correct evaluation and indication selection.

Adult↗

[Effects of thrombolysis and anticoagulation on the functions of vascular endothelial cells and coagulation and fibrinolysis in patients with pulmonary thromboembolism].

OBJECTIVE: To investigate the effects of thrombolysis and anticoagulation on the functions of vascular endothelial cells and coagulation and fibrinolysis in patients with pulmonary thromboembolism. METHODS: Twenty-four patients with documented pulmonary thromboembolism and 20 normal subjects were included. Of the 24 patients with pulmonary thromboembolism, 7 were treated with recombinant tissue-type plasminogen activator intravenously, and 17 with low molecular weight heparin. The plasma levels of endothelin 1 (ET-1), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), antithrombin III (AT-III) and D-dimer and the blood serum levels of nitrogen monoxide (NO) were measured in the control group and in the patients at different time points before and after therapies. RESULTS: In patients receiving thrombolytic therapy, ET-1 [(103.7 +/- 26.6) ng/L] and D-dimer [(5.0 +/- 1.7) mg/L] increased significantly at 4 h after the treatment, and were higher than those at other time points (P < 0.05 and P < 0.01, respectively). The level of ET-1 was correlated positively with PaO(2) and D-dimer (r = 0.751, and 0.782 respectively, P < 0.05). In patients receiving anticoagulation therapy, compared with pretreatment data, NO and AT-III increased and ET-1 decreased significantly at 14 d after the start of low molecular weight heparin therapy, (48 +/- 14) micromol/L vs (66 +/- 24) micromol/L for NO, (90 +/- 7)% vs (99 +/- 4)% for AT-III, (72.0 +/- 18.3) ng/L vs (52.8 +/- 13.9) ng/L for ET-1, all P < 0.05. CONCLUSIONS: ET-1 and D-dimer changed significantly after thrombolytic therapy, while ET-1, NO and AT-III showed dramatic change after anticoagulation therapy. The change of ET-1 and D-dimer reflects the therapeutic effects. Thrombolytic and anticoagulation therapies are beneficial in keeping the balance between coagulation and fibrinolysis and protecting the functions of vascular endothelial cells in patients with pulmonary thromboembolism.

Adult↗

[Morphological changes in the lungs and characteristics of thromboemboli in patients with thromboembolism of the pulmonary artery].

Basing on results of pathologoanatomical investigations, performed in 26 cases, the lungs changes in pulmonary thromboembolism were analyzed. It was shown, that an acute thromboembolism of a. pulmonalis main branches did not cause an acute necrosis of pulmonary alveolar tissue, but induces progressive diffuse changes of their microcircular bed, concomitant with pulmonary hypertension. In cases of chronical pulmonary thromboembolism the diffuse vascular sclerosis of the nonaffected lung and the alveolar tissue emphysema are formed, and in such cases the signs of pulmonary hypertension showing hypertrophy of the muscular vessels middle layer as well as their intima hyperplasia are revealed. This determines the expediency of earlier start of thrombolytic therapy conduction as well as surgical intervention in an acute pulmonary thromboembolism.

Autopsy↗

[Antiphospholipid syndrome and venous thromboembolism: the role of congenital thrombophilia].

The antiphospholipid syndrome is associated with complications of pregnancy or venous or arterial thrombosis in the presence of antiphospholipid antibodies. Venous thromboembolism is the most common clinical feature. Pathogenetic mechanisms underlying the syndrome are not completely understood and several hypotheses have been raised. Secondary prophylaxis after venous thromboembolism episodes requires oral anticoagulants (prothrombin time-international normalized ratio 2-3) for 6 to 12 months. More intensive anticoagulant regimens are indicated in case of recurrence. A longer or life-long course of treatment is indicated in patients with recurrent or life-threatening events or in the presence of high titers of antiphospholipid antibodies. Among risk factors for venous thromboembolism, inherited thrombophilia is recently described, such as defects of the physiological coagulation inhibitors, genetic mutations of factor V and factor II of the coagulation cascade and hyperhomocysteinemia. High levels of factor VIII, factor IX and lipoprotein(a) have recently been proposed as new risk factors for venous thromboembolism. The coexistence of inherited thrombophilia seems to enhance the thrombogenic risk, in particular in the venous vascular bed. The new insights into the diagnosis of inherited thrombophilia could allow a better evaluation of the thrombotic risk, leading to tailor the prophylactic strategy.

Antiphospholipid Syndrome↗

[The prophylaxis against venous thromboembolic complications in internal medicine--the gap between theory and practice].

Venous thromboembolism is an important cause of morbidity and mortality in internal medicine but antithrombotic prophylaxis is not being sufficiently used in comparison with surgical settings. In medical patients there are usually multiple risk factors, often with cumulative effect and the comprehensive risk assessment is complicated. The most important agents for pharmacological thromboprophylaxis are heparins - unfractionated and low-molecular-weight. The metaanalysis of randomised trials comparing unfractionated or low-molecular-weight heparin against control (placebo or aspirin) in medical patients has confirmed a significant risk reduction for deep vein thrombosis (56 %) as well as pulmonary embolism (58 %). Low-molecular-weight heparin is as effective as unfractionated heparin in reducing mortality as well as venous thromboembolism but has the advantage of significantly fewer bleeding complications. A novel synthetic pentasaccharide antithrombotic agent fondaparinux has been successfully proved in thromboprophylaxis in medical patients too. In most trials the duration of pharmacological prophylaxis was up to 2 weeks, the possible benefit of extended prophylaxis has not been clarified yet. Specific groups are intensive care patients; the elderly for their high thromboembolic as well as bleeding risk and significant comorbidity; the patients with acute ischaemic stroke who have very high thromboembolic risk but there are concerns about the risk of haemorrhagic transformation of stroke. The economic studies have shown that low-molecular-weight heparin in prophylactic doses in acutely ill medical patients is cost-effective strategy.

Anticoagulants↗