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PubMed1998

[Intracardiac thrombosis and consecutive thromboembolisms in patients with heart valve diseases: predisposition and concepts for prevention].

For patients with acquired heart valve lesions with increased risk for intracardiac thrombosis and consequent cardiogenic embolism there is consensus that oral anticoagulation therapy improves the overall prognosis. In mitral valve lesions anticoagulation is necessary after manifestation of atrial fibrillation or in cases of unstable sinus rhythm. The risk for thromboembolic events is increasing parallel to the enlargement of the left ventricular enddiastolic diameter, the left atrial size and dropping cardiac index. Spontaneous echo contrast (so called smoke like echos) indicate a prethrombotic state. In these cases an intensive anticoagulation is indicated. Aortic valve lesions require anticoagulation after manifestation of atrial fibrillation, the first manifestation of a thromboembolism or of spontaneous echo contrast. The risk for thromboembolism is increasing parallel to the reduction of left ventricular pump function. Life long oral anticoagulation therapy should be managed by use of the International Normalized Ratio (INR), and should be individualized taking into account patient related cardiac morphology and physiology, which may predispose to cardiogenic embolism. The target INR can range between 2.0 and 4.0.

Fibrinolytic Agents↗
PubMed1998

Prevention of thromboembolism with ticlopidine shortly after valve repair or replacement with a bioprosthesis.

BACKGROUND AND AIMS OF THE STUDY: This study investigated the efficacy of postoperative ticlopidine as antiplatelet therapy in patients shortly after heart valve repair or replacement. METHODS: Between 1990 and 1995, 235 consecutive patients underwent either valve repair (n = 67) or replacement with a bioprosthesis (n = 168). The bioprostheses used were Carpentier-Edwards porcine or pericardial (n = 158) valves, Prima stentless valves (n = 3) and cryopreserved homografts (n = 7). Types of repair were aortic (one), mitral annuloplasty with Carpentier ring (65) and tricuspid repair (one). Mean patient age was 67 (range: 16 to 83) years for valve replacement and 57 (range: 32 to 74) years for repair (p < 0.01). Atrial fibrillation occurred in 34% of patients. The hospital mortality rate was 11% (26 patients). Of the 209 survivors, 137 were assigned to antiplatelet treatment with ticlopidine for the first three months of follow up. The other 72 received either oral anticoagulation (coumadin; n = 40), aspirin (n = 14) or no medication (n = 18). In 15 patients, ticlopidine treatment was interrupted due to diarrhea (13 cases), mild allergic reaction (one) or anemia (one). The mean follow up was 3.2 years (range: 1 month to 6 years); cumulative follow up was 684 patient-years (pt-yr) and was complete in 96% of cases. RESULTS: There were two episodes of thromboembolism in the ticlopidine group at 1 month and 6 months respectively, with a linearized incidence of 0.5% pt-yr. In the coumadin group there were four episodes of thromboembolism, three within the first three months of follow up. The linearized incidence was 3% pt-yr (p < 0.01). There were three episodes of hemorrhage in the ticlopidine group in the first three months of follow up and one in the coumadin group. The linearized incidence was 0.75% pt-yr. CONCLUSIONS: Following heart valve repair or replacement with a bioprosthesis, the first three months is a high-risk period for thromboembolism. Ticlopidine seems to prevent this complication better than conventional therapy with oral anticoagulants. Nevertheless, hemorrhage continues to be a problem with ticlopidine therapy.

Aortic Valve↗
PubMed1998

[New methods for effective prevention of thromboembolism in surgical medicine exemplified by trauma surgery].

Under conventional prevention (pharmacological and physical) of thromboembolism 30-40% of surgical patients develop deep vein thrombosis (DVT). Mechanical methods significantly increase the efficacy of prophylaxis for thromboembolism: these include intermittent pneumatic compression, A-V impulse systems and ankle motion devices. For all trauma patients it is advisable that conventional prophylaxis of thromboembolism be supplemented with elements of mechanical prophylaxis in order to reduce the continuing high thrombosis rate significantly.

Anticoagulants↗
PubMed1998

Prothrombotic disorders in infants and children with cerebral thromboembolism.

BACKGROUND: To our knowledge, the contribution of prothrombotic conditions to cerebral thromboembolism has never been prospectively studied in a large series of pediatric patients. METHODS: The Hospital for Sick Children, Toronto, Ontario, established a program in January 1992 to diagnose and treat children (term newborn to 18 years old) with arterial ischemic stroke or sinovenous thrombosis. The routine evaluation for prothrombotic conditions included plasminogen, antithrombin, protein C, free protein S, activated protein C resistance, IgG and IgM anticardiolipin antibody, and lupus anticoagulant. We analyzed samples taken within 2 years of the event. We report results on patients seen from January 1, 1992, to January 1, 1997. RESULTS: Ninety-two patients (47 males and 45 females) entered the program during the study interval. Patients ranged from newborn to 18 years in age. Arterial ischemic stroke occurred in 78% of patients while sinovenous thrombosis occurred in 22%. All were tested for prothrombotic disorders. One or more abnormal results were present in 35 (38%) of the 92 patients. The majority (21/35) had multiple abnormal test results. The abnormal test results were anticardiolipin antibody (33%), plasminogen (9.5%), activated protein C resistance (9%), protein C (7%), antithrombin (12.5%), lupus anticoagulant (8%), and free protein S (11.5%). Male sex predicted the presence of prothrombotic abnormalities (relative risk, 1.7; 95% confidence interval, 1.2-2.5), but stroke type (relative risk, 0.8; 95% confidence interval, 0.7-1.1), age group, and presence of other risk factors did not predict abnormal testing. CONCLUSIONS: A significant proportion (38%) of children with cerebral thromboembolism had evidence of prothrombotic conditions. In particular, there was a predominance of children with anticardiolipin antibody (33%). These data support a recommendation that children with cerebral thromboembolism be evaluated for prothrombotic disorders.

Adolescent↗
PubMedDate not supplied

Catheter-directed thrombolysis for thromboembolic disease during pregnancy: a viable option.

Anticoagulation with intravenous heparin has been the standard treatment for the management of gestational thromboembolic complications. Catheter-directed thrombolysis is an encouraging approach for the treatment of thromboembolic disease and has not been previously reported during pregnancy. One gravid woman with pulmonary embolism, critically ill, and hemodynamically compromised, and two gravid women with iliofemoral venous thrombosis, who failed to respond to standard treatment with intravenous heparin, were treated with catheter-directed urokinase. All three patients experienced rapid resolution of symptoms and successful pregnancy outcomes. In our three patients, catheter-directed thrombolysis for thromboembolic disease during pregnancy allowed rapid resolution of hemodynamic abnormalities and/or resolution of thrombus. Catheter-directed thrombolysis offered a reasonably safe alternative to prolonged medical management in these young, otherwise healthy, patients. Long-term, it may prevent the postphlebitic syndrome.

Adult↗
PubMed2003

Factor V Leiden and prothrombin gene G20210A mutation in children with cerebral thromboembolism.

We investigated whether there is an association between factor V Leiden (FVL) and/or prothrombin gene G20210A mutation (PT20210A) and cerebral thromboembolism in a pediatric Argentinean population. From May 1992 to January 2002, 44 consecutive children with arterial ischemic stroke (AIS) and 23 children with cerebral sinovenous thrombosis (SVT) were prospectively studied at a single center. The prevalence of both mutations was compared with a 102 age-matched controls. In children with AIS, the frequencies (patients vs. controls), odds ratio (OR), and 95% confidence interval (95% CI) for the presence of FVL were as follows: 2.3% vs. 2%, OR/95% CI, 1.16/0.2 to 13.2; P value = 0.99. No cases of PT20210A were found in this group. In children with SVT, the frequencies (patients vs. controls), OR, and 95% CI were as follows: FVL (4.3% vs. 2%, OR/95% CI, 2.27/0.22 to 6.2; P value = 0.99) and PT20210A (4.3% vs. 1%; OR/95% CI, 4.6/0.3 to 76.3; P value = 0.3354). One child with PT20210A also had an inherited protein C deficiency. In 12 (18%) out of the 67 children with cerebral thromboembolism, without the aforementioned mutations, other prothrombotic disorders were detected. Although a multi-center prospective study with a large number of Argentinean pediatric patients is needed to obtain considerable evidence, no association between factor V Leiden and/or prothrombin gene G20210A mutation and cerebral thromboembolism was found in this pediatric series.

Adolescent↗
PubMed2001

Recurrent thromboembolic disease following splenectomy for pyruvate kinase deficiency.

We report a case of recurrent thromboembolic disease and chronic pulmonary hypertension in an adult patient with pyruvate kinase deficiency who underwent splenectomy as a child. Thromboembolism has been reported as a complication following splenectomy for various hereditary chronic hemolytic anemias. To our knowledge, this association has not been described in patients specifically with pyruvate kinase deficiency. Our patient presented at age 37 with recurrent pulmonary emboli, 36 years after splenectomy for severe hemolytic anemia. Work-up for other hypercoagulable states was negative. The mechanism for hypercoagulability in this condition is unclear but may involve a quantitative or qualitative change in disrupted thrombogenic red blood cell membranes that would normally be removed by the spleen. Clinicians should have a high index of suspicion for thrombotic events in these patients, as early diagnosis and treatment can reduce morbidity and mortality, and chronic anticoagulation may help prevent the sequelae of repeated thromboembolic events.

Adult↗
PubMedDate not supplied

Pulmonary artery sarcoma mimicking chronic thromboembolic disease: computed tomography and magnetic resonance imaging findings.

PURPOSE: The diagnosis of the rare primary malignant tumors of the pulmonary arteries is often delayed as symptoms are nonspecific. METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) of three patients with occlusion of the right pulmonary artery, two with sarcoma and one with chronic thromboembolic disease were analyzed for discriminating diagnostic criteria. RESULTS: Criteria suggesting pulmonary artery sarcoma are inhomogeneous high or low attenuation (hemorrhage, necrosis), soft-tissue density in pulmonary arteries, vascular distension, enhancement after administration of gadopentetate dimeglumine. Criteria for chronic thromboembolic disease are homogeneous soft-tissue lesions, abrupt vascular narrowings and cut-offs, as well as regional parenchymal hyperdensities. CONCLUSION: CT and MRI provide complementary findings suggesting advanced pulmonary artery sarcoma instead of chronic thromboembolism.

Adult↗
PubMedDate not supplied

Thromboembolic complications in thermally injured patients.

The frequency of thromboembolic complications in burn patients has been estimated to range from 0.4% to 7%. The clinical significance of these events is often debated and has prompted some centers to adopt the routine prophylactic use of low dose heparin prophylaxis. A 10 year review of 2,103 burn patients treated at this institution was undertaken. Twenty-five (1.2%) patients, with a mean age of 40.0 years and an average burn size of 49.3% total body surface area (TBSA), were identified as having significant pulmonary thromboembolism (PTE). In only 3 (0.14%) patients was the thromboembolism considered to be a cause of death. Nineteen (0.9%) patients, with an average age of 36.7 years and a mean burn size of 48.3% TBSA, developed clinically evident deep venous thrombosis (DVT); however, in only 1 (0.05%) patient did the disease progress to fatal PTE. A review of the literature reveals a 0.6% to 5% incidence of complications related to low dose heparin therapy which includes bleeding, thrombocytopenia, and arterial thrombosis. We feel that the infrequency of clinically significant PTE and DVT in burn patients and the comparable or greater rate of complications associated with heparin prophylaxis mitigate against the routine use of low dose heparin therapy except in patients at high risk for these events.

Adolescent↗
PubMed2001

Acute pulmonary thromboembolism with a floating right-heart thrombus. 4 surgical cases.

OBJECTIVE: We determined the efficacy of surgery for acute pulmonary thromboembolism with a floating right-heart thrombus. METHODS AND RESULTS: Thrombi were diagnosed by transthoracic echocardiography and electron beam computed tomography in 4 patients with acute pulmonary thromboembolism with a floating right-heart thrombus, and thromboembolectomy was done in all patients. Surgical procedure included intermittent deep hypothermic circulatory arrest. One patient died of endobronchial hemorrhage and 3 survived. CONCLUSION: Because acute pulmonary thromboembolism with a right-heart thrombus is life-threatening, immediate thromboembolectomy is required to decrease mortality.

Acute Disease↗
PubMed2001

Pulmonary thromboembolism after one and a half ventricle repair. Successful catheter-directed thrombolysis.

Acute pulmonary thromboembolism in a patient who had undergone bidirectional Glenn anastomosis was treated by percutaneous selective intravascular thrombolysis. A 20-year-old woman was diagnosed with pulmonary stenosis and right ventricular hypoplasia, complete occlusion of the left pulmonary artery secondary to a Blalock-Taussig shunt, and atrial septal defect. The patient developed thromboembolism of the subsegmental branches of the right pulmonary artery resulting in critical hemodynamic deterioration 2 weeks after undergoing one and a half ventricle repair (bidirectional Glenn shunt). The patient was treated with tissue plasminogen activator administered directly into the right pulmonary artery via an intravascular catheter. Progressive recanalization of the obstruction began immediately. Pulmonary angiography 3 months after thrombolytic therapy demonstrated patent subsegmental vessels. Early detection of the pulmonary thromboembolism and prompt intervention are crutial to relieving this fatal complication after a Fontan operation.

Adult↗
PubMed2003

[Therapy and secondary prevention of venous thromboembolism with vitamin K antagonists].

Oral anticoagulation with vitamin-K-antagonists is very effective in secondary prevention of venous thromboembolism. In Germany, most commonly Phenprocoumon is used, while most of the evidence-based data are available for Warfarin. The initial treatment of acute venous thromboembolism requires immediate anticoagulation with heparin and a subsequent overlapping treatment with oral anticoagulants. During this phase, anticoagulation may be unstable with increased risk for bleeding. An INR target range between 2 and 3 provides effective protection with minimal risk for major bleeding. The individual risk for bleeding may be estimated by a clinical score. Six months of oral anticoagulation is the standard duration for a first episode of venous thromboembolism, while recurrencies are treated for at least one to two years. The duration may be tailored to the individual patient according to underlying risk factors for recurrencies and for bleeding. Because of a plethora of practical problems and the narrow therapeutic window, there is a need for new antithrombotic agents. These may allow a longer duration of secondary prevention with improved protection against recurrencies without sacrificing safety.

Administration, Oral↗
PubMed2006

Incidence of recurrent venous thromboembolism of patients after termination of treatment with ximelagatran.

OBJECTIVE: Recurrent thromboembolic events may occur after termination of anticoagulant therapy for acute venous thromboembolism (VTE) using oral direct thrombin inhibitor ximelagatran. METHODS: Patients with VTE recruited at the German study centres were followed-up for an additional 18 months, treated initially with 2x36 mg ximelagatran daily or with enoxaparin/warfarin over 6 months (THRIVE Treatment study) and 2x24 mg ximelagatran daily or placebo over 18 months (THRIVE III study). Recurrent VTE and the combined outcome events consisting of recurrent VTE, other thrombotic complication, major bleeding and mortality were analysed. RESULTS: In the THRIVE Treatment study, no patient suffered from a recurrent VTE, but 1 patient randomised to enoxaparin/warfarin experienced major bleeding. During follow-up, 4/32 and 3/32 patients initially randomised to ximelagatran and enoxaparin/warfarin developed recurrent VTE (p=0.7024). No major bleed occurred. One patient in each group died. The incidences of the combined outcome events were not different (p=0.9326). In the THRIVE III study, 0/9 versus 5/14 patients randomised to ximelagatran and placebo developed recurrent VTE including 1 fatal pulmonary embolism (p=0.0501). During follow-up, 3/9 and no patients initially randomised to ximelagatran and placebo developed recurrent VTE. One and 3 other outcome events occurred in patients initially randomised to ximelagatran or placebo. During follow-up, recurrent VTE (p=0.6893) and combined outcome events (p=0.3642) were not different between the groups. CONCLUSION: The results of the follow-up studies suggest that thromboembolic events may re-occur in patients with acute VTE after termination of treatment with both vitamin K-antagonists and ximelagatran.

Administration, Oral↗
PubMed2004

Impaired fibrinolytic potential related to elevated alpha1-proteinase inhibitor levels in patients with pulmonary thromboembolism.

The contribution of neutrophil leukocyte elastase (NE) to in vivo thrombolysis is still an open question. The present study examines the impact of variable levels of alpha1-proteinase inhibitor (alpha1-PI) (the major plasma inhibitor of NE) on fibrinolysis within the setting of thromboembolic diseases. Blood samples were taken from 56 patients with pulmonary thromboembolism prior to treatment. alpha1-PI and alpha1-PI-NE complex were measured in the serum and plasma with immunoturbidimetric and enzyme-linked immunosorbent assay (ELISA) methods, respectively. The fibrinolytic potential [spontaneous, tissue-type plasminogen activator (tPA) induced, and plasmin induced] of the plasma was evaluated in vitro with turbidimetric clot lysis assay. Correlation analysis (Pearson product-moment correlation coefficient, r) of the turbidimetric lysis parameters and the blood levels of alpha1-PI and alpha1-PI-NE complex was carried out. Fibrinolysis is slower in clots prepared from plasma containing elevated levels of alpha1-PI and alpha1-PI-NE complex. The maximal turbidity of the plasma clots shows significant correlation with the alpha1-PI level (r=0.39, p=0.003) and the correlation of the maximal turbidity and the tPA-induced lysis time is also significant (r=0.77, p<0.001). The lysis time correlates with the plasma level of alpha1-PI-NE complex, if fibrinolysis is induced with tPA (r=0.37, p=0.02), but not with plasmin (r=0.19, p=0.4). Our study shows that in pulmonary thromboembolism elevated levels of alpha1-PI are associated with suppressed plasma fibrinolytic potential. This effect can be at least partially explained by the coarse fibrin network structure and retarded plasminogen activator-dependent fibrinolysis.

Adult↗
PubMed2006

Chronic thromboembolic pulmonary hypertension - assessment by magnetic resonance imaging.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe disease that has been ignored for a long time. However, with the development of improved therapeutic modalities, cardiologists and thoracic surgeons have shown increasing interest in the diagnostic work-up of this entity. The diagnosis and management of chronic thromboembolic pulmonary hypertension require a multidisciplinary approach involving the specialties of pulmonary medicine, cardiology, radiology, anesthesiology and thoracic surgery. With this approach, pulmonary endarterectomy (PEA) can be performed with an acceptable mortality rate. This review article describes the developments in magnetic resonance (MR) imaging techniques for the diagnosis of chronic thromboembolic pulmonary hypertension. Techniques include contrast-enhanced MR angiography (ce-MRA), MR perfusion imaging, phase-contrast imaging of the great vessels, cine imaging of the heart and combined perfusion-ventilation MR imaging with hyperpolarized noble gases. It is anticipated that MR imaging will play a central role in the initial diagnosis and follow-up of patients with CTEPH.

Chronic Disease↗
PubMed2006

Temporary inferior vena cava filter for deep vein thrombosis and acute pulmonary thromboembolism: effectiveness and indication.

Although the temporary inferior vena cava filter (IVC-F) is being used increasingly for protection against pulmonary thromboembolism (PTE), indications for its use are not established. Our strategy for the prevention of PTE is: (1) contraindication or failure of anticoagulation: permanent IVC-F; (2) for patients with residual proximal deep vein thrombosis (a) who have permanent risk factor: permanent IVC-F; (b) who have transient risk factor: temporary IVC-F; (3) others: no IVC-F. Temporary IVC-F was also implanted in deep vein thrombosis (DVT) patients without PTE who were preoperation or had floating thrombus. We investigated the outcome of patients given a temporary IVC-F versus those given a permanent IVC-F to clarify the efficacy and our strategy for implantation of a temporary IVC-F. Subjects were 12 men and 38 women with acute PTE and/or floating DVT admitted to our hospital between April 1999 and April 2002. Patient age was 25-91 years (mean 63 years). Eighteen patients were given a permanent IVC-F (group A) and 32 patients were given a temporary IVC-F (group B) as primary treatment, according to our criteria. There were no major complications in either group. Mortality after implantation of the IVC-F was 35% (6/17) in group A and 16% (4/25) in group B, with no significant difference (P = 0.14). Pulmonary thromboembolism recurred in 18% (3/17) of group A patients but in no group B patients (P = 0.10). All recurrences resulted in death. The 14 patients in group B who were not given a permanent IVC-F after removal of the temporary IVC-F survived. The temporary IVC-F can be used safely in patients with venous thromboembolism and is efficacious in preventing recurrence of PTE. Prognosis after removal of the temporary IVC-F is excellent.

Aged↗
PubMed2004

The beneficial effect of mild hypothermia in a rat model of repeated thromboembolic insults.

The post-thrombotic brain has recently been reported to have an enhanced vulnerability to a second embolic insult. Although postischemic hypothermia is neuroprotective in global and focal ischemia models, the effect of mild hypothermia on outcome after thromboembolic insults has not been evaluated. This study therefore determined whether brain hypothermia (33 degrees C) was neuroprotective against repeated thromboembolic insults. Photochemically induced non-occlusive common carotid artery thrombosis (CCAT) leading to platelet embolization to the brain was induced in anesthetized rats ( n=35). Thirty minutes after CCAT, brain temperature was maintained at normothermic (37 degrees C) or hypothermic (33 degrees C) levels for 4 h followed by a slow rewarming period (1.5 h). Three days later, rats underwent a secondary CCAT insult under normothermic conditions and were allowed to survive for an additional 3 days prior to perfusion fixation and quantitative histopathological assessment. Compared to normothermic animals, mild hypothermia after the first embolic insult produced a significant reduction ( P>0.05) in overall infarct volume. Hypothermia reduced total infarct volume from 7.55+/-2.32 mm(3) (mean +/- SEM) in normothermic rats to 2.56+/-0.88 mm(3) in hypothermic animals undergoing repeated insults. Histopathological analysis also demonstrated less evidence for focal hemorrhage in the cooled groups. These data demonstrate that mild hypothermia is protective in a thromboembolic stroke model. In addition, post-thrombotic hypothermia decreases the histopathological vulnerability of the post-thrombotic brain to secondary embolic insults. These findings may be important in the prevention of stroke in patients at risk.

Animals↗
PubMed2004

Evaluation of venous thromboembolism and coagulation-fibrinolysis markers in Japanese patients with inflammatory bowel disease.

BACKGROUND: Arterial or venous thromboembolism is rarely encountered clinically as an extradigestive tract complication in inflammatory bowel disease (IBD). However, it is one of the important prognostic factors for IBD patients. The present study was designed to evaluate the relationship between pulmonary embolism (PE) and deep vein thrombosis (DVT) with coagulation-fibrinolysis markers in patients with active IBD. METHODS: In 47 consecutive cases hospitalized due to active IBD [26 with Crohn's disease (CD) and 21 with ulcerative colitis (UC)], we evaluated the disease severity, blood tests, pulmonary ventilation-perfusion scan (V/Q scan), and magnetic resonance venography (MRV) or conventional venography. RESULTS: PE was diagnosed by V/Q scan in 5 (2 with CD and 3 with UC; 10.6%). DVT was diagnosed in 5 (2 with CD and 3 with UC; 10.6%). Of the 47 patients, 8 (17.0%) had venous thromboembolism (either PE or DVT), and 2 of them (4.3%) had both conditions. In UC patients, the thrombosis group was in more severe stages based on endoscopic grading than the nonthrombosis group. In all patients, the thrombosis group were older (50.3 +/- 14.3 years) than the nonthrombosis group (29.2 +/- 11.7 years). Furthermore, the thrombosis group had higher thrombin-antithrombin III complex (13.1 +/- 17.7 ng/ml) and d-dimer (964 +/- 1402 ng/ml) values than the nonthrombosis group (5.3 +/- 5.5 ng/ml, P=0.0245, and 207 +/- 192 ng/ml, P=0.0016, respectively). There were no significant differences in leukocyte and platelet counts, C-reactive protein, and fibrinogen between the two groups. CONCLUSIONS: A high incidence of venous thromboembolism was suggested in Japanese patients with active IBD. We should be careful with thrombosis in treatment of IBD patients, especially those who are of older age and in more severe stages.

Adult↗