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PubMed2004

Inhibition of endogenous leptin protects mice from arterial and venous thrombosis.

OBJECTIVE: Human obesity is associated with an increased risk for arterial and venous thrombosis and with elevated levels of leptin in the blood. Leptin administration promotes arterial thrombosis in mice, and leptin-deficient ob/ob mice have an attenuated thrombotic response to injury. Thus, endogenous leptin may regulate arterial and venous thrombosis in vivo. Experiments were performed to test this hypothesis. METHODS AND RESULTS: A leptin-neutralizing antibody was administered intravenously into wild-type mice 15 minutes before carotid artery injury with ferric chloride. The antibody-treated mice demonstrated prolonged times to thrombotic occlusion and formed unstable, embolizing thrombi. Thus, inhibiting leptin converted the thrombotic phenotype of wild-type mice into one that closely resembled that of ob/ob mice. The effect of leptin inhibition on venous thrombosis and pulmonary embolism was also investigated. Injection of a mixture of collagen and epinephrine into the jugular vein induced fatal pulmonary embolism in >90% of the control wild-type mice but in <40% of their antibody-treated counterparts. Histological analysis revealed that the antibody significantly reduced the number of occlusive thrombi in the pulmonary vessels. CONCLUSIONS: Inhibition of circulating leptin protects against arterial and venous thrombosis in mice and possibly in hyperleptinemic obese individuals.

Animals↗
PubMed2001

[Diagnosis and therapy of progressive thrombophlebitis of epifascial leg veins].

INTRODUCTION: The thrombophlebitis is generally regarded as a harmless disease. However, the progressive varicophlebitis represents a subgroup of thrombophlebitis in which the proximal portion of the thrombus can ascend into the deep vein system with the complication of deep vein thrombosis or pulmonary embolism. PATIENTS AND METHODS: In a period of 15 months ten patients were operated upon in whom a progressive varicophlebitis was diagnosed with color-flow duplex scanning. Eight of them were men, two were women. The average age was 56 years. RESULTS: Nine patients had an ascending thrombosis of the greater saphenous vein. One patient had the origin of the thrombus in the shorter saphenous vein. In one patient the ascending thrombosis of the greater saphenous vein was the reason for a segmental pulmonary embolism. The indication for operation was given when the proximal portion of the thrombus was within 10 cm of the confluence to the deep vein system. The operative procedure comprised the ligature of the epifascial vein. CONCLUSION: The diagnosis of thrombophlebitis should not be restricted only to clinical examination. Color-flow duplex scanning is preferred to compression venous ultrasonography. The ascending contrast venography as invasive diagnostic procedure should only be performed for the clarification of further questions. In ascending varicophlebitis ligature of the confluence from the superficial to the deep vein system is a safe procedure to avoid a progression of the disease or embolism. In case of postoperative recanalisation of the superficial varicose vein a second operation with stripping of the vein can be performed.

Adult↗
PubMed2001

Bedside vena cava filter placement guided with intravascular ultrasound.

OBJECTIVE: The purpose of this study was to report a feasibility trial approved by the Institutional Review Board for insertion of inferior vena cava (IVC) filters with intravascular ultrasound (IVUS) guidance in the intensive care unit. METHODS: Between October 1998 and May 2000, 26 patients (15 men, 11 women; age range, 22-86 years; mean, 55 years) were enrolled. Eight patients (31%) underwent prophylactic filter placement, and 18 patients (69%) had venous thromboembolism (deep venous thrombosis = 16, pulmonary embolism = 2) with contraindications to anticoagulation. A single groin puncture was used for IVUS and filter placement. Location of major branch veins, thrombosis, and caval diameter were readily demonstrated without the use of radiocontrast agents. Mapping of the IVC permitted assessment of ideal filter location. Postprocedure radiographs (23 of 26) were obtained to document filter position. Seventeen of 26 had follow-up lower extremity duplex studies. RESULTS: Twenty-four (92%) of 26 patients underwent successful filter deployment. The two other patients had filters subsequently placed by means of traditional fluoroscopic techniques. One femoral vein insertion site thrombosis resolved after a month. One patient experienced symptomatic caval thrombosis thought to be caused by thrombus trapping 55 days after the procedure. No pulmonary emboli occurred after filter placement. One patient's death was unrelated to vena cava filter placement. The hospital charge for bedside filters was $3623 compared with $4165 (P =.281) for fluoroscopic placement. CONCLUSION: Bedside insertion of an IVC filter with IVUS guidance is feasible and may be an effective alternative in the intensive care unit. No additional costs were incurred in this small series. Protocol refinements should reduce the incidence of complications. The results of this study support the need for further evaluation comparing it with standard techniques.

Adult↗
PubMed1999

Deep-vein thrombosis.

Deep-vein thrombosis is an important complication of several inherited and acquired disorders, but may also occur spontaneously. Prevention of recurrent venous thrombosis and pulmonary embolism is the main reason for accurate diagnosis and adequate treatment. This seminar discusses only symptomatic deep-vein thrombosis. The diagnosis can be confirmed by objective tests in only about 30% of patients with symptoms. Venous thromboembolic complications happen in less than 1% of untreated patients in whom the presence of venous thrombosis is rejected on the basis of serial ultrasonography or ultrasonography plus either D-dimer or clinical score. Initial anticoagulant treatment (intravenous or subcutaneous heparin) should continue until oral anticoagulant treatment, started concurrently, increases the international normalised ratio above 2.0 for more than 24 h. The optimum duration of oral anticoagulant treatment is unresolved, but may be guided by the presence of temporary or persistent risk factors or presentation with recurrent venous thromboembolism.

Humans↗
PubMed1977

Thrombosis of the cranial vena cava in a cow.

Thrombosis of the cranial vena cava in a cow was followed by the formation of aneurysms in the pulmonary arteries. Embolism, pulmonary hypertension and the development of a collateral venous and lymphatic circulation are the suggested causes of these uncommon arterial lesions.

Aneurysm↗
PubMed1999

[Economy class syndrome: fiction or fact?].

Several reports about the occurrence of deep vein thrombosis and pulmonary embolism following long-distance flights have led to the term "economy class syndrome". The underlying hypothesis was that a long term immobilisation in narrow economy class chairs of modern jet aircraft plays an important role for the development of deep vein thrombosis. Studies in healthy volunteers during several simulated long distance flights and during an actual long-distance flight confirmed the swelling of the lower legs complained by many long distance passengers, however, failed to reveal relevant changes of hemorheological or hemostaseological parameters. From these investigations no increased risk for thromboembolic diseases during long distance flights for healthy volunteers could be derived. Since this may be completely different for patients with risk factors for thromboembolic diseases prophylactic measures (compression stockings, anticoagulation) might be necessary.

Aircraft↗
PubMed1997

Pulmonary embolism is associated with the combination of isolated calf vein thrombosis and respiratory symptoms.

PURPOSE: Overall prevalence of pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) isolated to calf veins is low. However, the prevalence of PE in the subgroup of patients with respiratory symptoms and isolated calf vein thrombosis (CVT) is unknown. Such information is important in determining whether patients with CVT only and respiratory symptoms should undergo evaluation for PE. The purpose of this study was to determine the prevalence of PE in patients with respiratory symptoms and isolated CVT. METHODS: From 1992 through 1994, all patients assessed by duplex scanning for lower extremity DVT were reviewed, and those found to have isolated CVT and lower extremity or respiratory symptoms were identified. Patients who had respiratory symptoms or later developed respiratory symptoms in addition to lower extremity symptoms underwent pulmonary angiography or ventilation/perfusion (V/Q) scanning. Positive results on pulmonary arteriograms or "high probability" V/Q scans were considered diagnostic of PE. RESULTS: There were 105 patients with isolated CVT and symptoms. Twenty-six patients had respiratory symptoms; nine (35%) had PE and two died. Seventy-nine patients had only lower extremity complaints; five later developed respiratory symptoms. All five had PE and none had progression of CVT on repeat duplex scanning. Neither age, gender, prior DVT/PE, obesity, pregnancy, medication, known malignancy, smoking, recent surgery, or trauma predicted PE. CONCLUSIONS: Patients with respiratory symptoms and duplex diagnosed isolated CVT have a high prevalence of PE and require pulmonary angiographic or V/Q scanning to rule out PE.

Adult↗
PubMed1981

Venous thromboembolic disease in Klinefelter's syndrome.

In a series of 412 patients with Klinefelter's syndrome observed over periods ranging from 1 to 20 years, the frequency of hypostatic ulceration, deep vein thrombosis and pulmonary embolism was found to be raised. The prevalence of past or present hypostatic ulceration was 6%, which is 20-50 times higher than in the general population. The incidence of deep vein thrombosis in subjects aged between 30 and 70 years was 22.8 cases per 10,000 patient-years at risk. In community studies the incidence of this condition is around 4 new cases per 10,000 men per year. The frequency of pulmonary embolism was 16 cases per 10,000 patient-years at risk, compared with an expected figure of 0.9 to 3 cases per 10,000 men per year.

Adolescent↗
PubMed2001

Pulmonary embolism after minor elective orthopedic procedure.

The occurrence of pulmonary embolism, in spite of thromboprophylaxis after a minor elective orthopedic surgery (release of m. rectus femoris tendon) is reported. In case of this severe complication, an early diagnosis is of outmost importance to enable optimal therapy introduction. Deep vein thrombosis and pulmonary embolism are frequent complications after total joint replacement, however, they may also develop after minor surgical orthopedic procedures. The possible causes of pulmonary embolism after release of m. rectus femoris tendon included the history of varicose veins and sclerozation of calf veins, and operative procedure with intraoperative pressure upon large veins of the iliofemoral region, which may and is expected to occur during this procedure. The importance of thrombopropylaxis in orthopedic surgical procedures is emphasized by this case presentation.

Adult↗
PubMed1992

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↗
PubMed2005

Delay of transverse rectus abdominis myocutaneous flap reconstruction improves flap reliability in the obese patient.

BACKGROUND: Since its introduction in 1982, the transverse rectus abdominis musculocutaneous (TRAM) flap has been a mainstay of breast reconstruction. However, in certain high-risk individuals, such as the obese, smokers, and irradiated patients, flap reliability is decreased, which leads to a higher rate of flap complications. The authors hypothesized that although the nonflap complication rate is increased in the obese patient, flap complications are not increased in those who undergo a delayed TRAM procedure. METHODS: From 1995 to 2003, 107 consecutive patients who underwent a delayed TRAM procedure were examined in a retrospective study. The delayed TRAM procedures were all performed by the senior author (Georgiade) at a single institution. Patients were classified by their body mass index (weight in kilograms and height in square meters). RESULTS: No patient had complete loss of her flap regardless of body mass index. Patients with an index of 30 kg/m2 and under had a partial fat necrosis rate of 11.4 percent (10 of 88 patients), whereas two of 19 patients (10.5 percent) with an index of greater than 30 kg/m2 had partial fat necrosis of their flap (not significant). The average body mass index of the group with flap complications was 27.8 +/- 4.3 kg/m2, whereas that of the group with no flap complications was 26.5 +/- 4.3 kg/m2 (not significant). The rate of non-flap-related complications, such as deep venous thrombosis and pulmonary embolism, was 8 percent (seven of 88 patients) for those with a body mass index of less than 30 kg/m2 and 31.6 percent (six of 19 patients) for those with an index greater than 30 kg/m2 (p = 0.0112). The average body mass index of the group with nonflap complications was 29.9 +/- 4.9 kg/m2, compared with 26.3 +/- 4.0 kg/m2 for the group with no non-flap-related complications (p = 0.031). Of note, patients with a history of smoking and those who had received radiation therapy did not show a statistically significant increase in flap complications. CONCLUSIONS: Despite a progressively increasing overall complication rate for patients with a higher body mass index, there was not a similar trend for flap-related complications. The authors' data support the idea that the delayed TRAM procedure is a safe and reliable technique for obese and morbidly obese patients.

Adult↗
PubMed2006

Prospective evaluation of patients hospitalized with venous thromboembolism: comparison between cancer and non-cancer patients.

BACKGROUND: Little is known about the epidemiology of venous thromboembolism in hospitalized patients in Israel. Also, a direct comparison of the clinical and laboratory features between cancer and non-cancer patients has not yet been reported. OBJECTIVES: To investigate and compare the epidemiologic, clinical and laboratory characteristics of cancer and non-cancer patients hospitalized with venous thromboembolism in a large referral medical center in Israel. METHODS: Between February 2002 and February 2003, patients diagnosed at the Rambam Medical Center as suffering from VTE (deep vein thrombosis and/or pulmonary embolism), based on diagnostic findings on Doppler ultrasonography, spiral computed tomography scan or lung scan showing high probability for pulmonary embolism, were prospectively identified and evaluated. In addition, at the conclusion of the study period, the reports of spiral chest CT scans, performed during the aforementioned period in this hospital, were retrospectively reviewed to minimize the number of unidentified cases. Blood samples were drawn for evaluation of the coagulation profile. RESULTS: Altogether, 147 patients were identified and 153 VTE events diagnosed, accounting for 0.25% of all hospitalizations during the study period. The cancer group included 63 patients (43%), most of whom had advanced disease (63%). The most common malignancies were cancer of the lung (16%), breast (14%), colon (11%) and pancreas (10%). Of 122 DVT events (with or without pulmonary embolism) there were 14 upper extremity thromboses (12%). The most common risk factors for VTE, except malignancy, were immobilization (33%), surgery/trauma (20%) and congestive heart failure (17%). There was no difference in prevalence of various risk factors between cancer and non-cancer patients. During an acute VTE event, D-dimer levels were higher in cancer patients than non-cancer patients (4.27 +/- 4.04 vs. 2.58 +/- 1.83 mg/L respectively, P = 0.055). Relatively low values of activated protein C sensitivity ratio and normalized protein C activation time were observed in both cancer and non-cancer groups (2.05 +/- 0.23 vs. 2.01 +/- 0.33 and 0.75 +/- 0.17 vs. 0.71 +/- 0.22, respectively). These values did not differ significantly between the groups. CONCLUSION: The proportion of cancer patients among patients suffering from VTE was high. Their demographic, clinical and laboratory characteristics (during an acute event) were not different from those of non-cancer patients, except for higher D-dimer levels.

Adolescent↗
PubMed1984

[Digestive hemorrhage under anticoagulant treatment. Retrospective analysis of a series of 178 consecutive cases].

The aim of this study was to describe the clinical characteristics, prognosis and epidemiological pattern of gastrointestinal bleeding occurring in patients receiving anticoagulant therapy. From 1971 to 1981, among 3,194 consecutive patients admitted to a gastrointestinal unit because of acute gastrointestinal bleeding, 178 were under anticoagulant therapy (i.e. antivitamin K and heparin or heparin derivative in respectively 85 and 13 p. 100 of the cases). Fourteen percent of these 178 patients had also taken gastrotoxic drugs before the bleeding occurred. Indications for anticoagulant therapy were as follows: ischemic heart disease (21 p. 100), arrhythmias (20.3 p. 100), venous thrombosis and pulmonary embolism (15.8 p. 100), arteritis (10.8 p. 100), aortic, coronary or peripheral arterial grafts (8.4 p. 100), prophylaxis of venous thrombosis (8.4 p. 100), valve prosthesis (7.3 p. 100). The lesion responsible for bleeding was found in 80 p. 100 of the cases. Surgical hemostasis was required in only 4 patients. Ten patients died (2 postoperatively). During the study period, the incidence of bleeding associated with anticoagulant therapy in the group of patients admitted to the unit with gastrointestinal hemorrhage increased from 1.5 p. 100 to 8.0 p. 100. This fact appeared to be closely related to new indications (valve prosthesis, arterial grafts, prophylaxis of venous thrombosis) and to an increased incidence of gastrointestinal bleeding especially in association with acenocoumarol treatment. These results show that, although occurring in a high risk population, gastrointestinal bleeding related to anticoagulant therapy generally has a favorable outcome. They also suggest that a prospective epidemiological study may be of interest to determine the reasons for the increasing incidence and to propose preventive measures.

Adult↗
PubMed1989

[Prevention of recurrence of thromboembolic disease: maintenance of anticoagulant therapy].

Deep venous thrombosis and pulmonary embolism are frequently diagnosed in patients encountered in a primary-care practice. Poor prognosis is related to acute sudden death and to recurrent thromboembolic disease. Anticoagulant therapy with heparin followed by coumarin derivatives is highly effective in preventing such recurrences, but the intensity of anticoagulation must be strictly monitored. Treatment with heparin, sufficient to prolong the activated partial prothrombin time to 1.5 to 2.0 times the control, should be continued for five to ten days, and oral anticoagulation should be overlapped with heparin for four to five days. The recommended therapeutic range for the prothrombin time during coumarin therapy is an INR of 2.0 to 3.0. The duration of anticoagulant treatment must be tailored to the individual patient. Patients with slowly resolving risk factors must be treated for at least three months after an acute deep vein thrombosis and for six months after a pulmonary embolism. Patients with tumors, antithrombin III, protein C or S deficiency should be treated indefinitely.

Anticoagulants↗
PubMed1991

Venous thromboembolic disease.

During the past year, the findings of several clinical trials have been published that have important implications for the care of patients with venous thromboembolism. These clinical trials have produced advances in the diagnosis and treatment of venous thrombosis and pulmonary embolism and in the prevention of venous thromboembolism in high-risk patients. In patients with clinically suspected pulmonary embolism, the value and limitations of ventilation-perfusion lung scanning have been established, and it is now accepted that objective tests for deep vein thrombosis have an important role. There have been important advances also in the diagnosis of deep vein thrombosis; these advances include the finding that impedance plethysmography is effective in pregnant symptomatic patients and the development of an objective technique for Doppler ultrasound. The optimal duration of initial intravenous heparin treatment of established thrombosis has been determined. In the prevention of venous thromboembolism, the effectiveness of sequential intermittent compression in patients having hip replacement has been established, and further data on the effectiveness of low-molecular-weight heparin in high-risk patients have become available.

Heparin↗
PubMed1998

Long-term, low-dose warfarin among venous thrombosis patients with and without factor V Leiden mutation: rationale and design for the Prevention of Recurrent Venous Thromboembolism (PREVENT) trial.

Standard therapy for patients with deep venous thrombosis and pulmonary embolism typically includes anticoagulation for a 3-6 month period with full dose warfarin. However, patients following this regimen experience high rates of recurrent thrombosis, re-hospitalization and mortality in the years immediately following cessation of anticoagulation. This is true for patients at average risk of disease recurrence, and for patients at elevated risk due to the presence of inherited defects of anticoagulation such as factor V Leiden mutation. Unfortunately, no clinical regimen currently available has proven to have sufficient benefit to support long-term prophylaxis. In particular, full dose warfarin is associated with substantially increased risks of hemorrhage when used on a long term basis. In contrast, while targeted low-dose warfarin (INR 1.5-2.0) is safe for long-term therapy, the efficacy of this approach in the prevention of recurrent venous thromboembolic disease has remained untested. The Prevention of Recurrent Venous Thromboembolism (PREVENT) trial will evaluate the efficacy of prolonged treatment with low-dose warfarin in the secondary prevention of venous thromboembolism (VTE). Patients with a history of documented idiopathic venous thrombosis who have completed a standard course of anticoagulation therapy will be enrolled in a randomized, double-blind, placebo-controlled trial comparing usual care plus targeted low-dose warfarin to usual care plus placebo for a period of up to 4 years. Trial endpoints will include recurrent VTE, major bleeding episodes and all-cause mortality in the total patient population and separately in those patients with factor V Leiden. The potential clinical impact of the PREVENT trial is broad since a positive finding would strongly support chronic low-intensity anticoagulation among patients with venous thrombosis who are at risk for recurrence following cessation of standard outpatient anticoagulation.

Adult↗
PubMed1979

Preoperative normovolaemic haemodilution with dextran 70 as a thromboembolic prophylaxis in total in hip replacement.

The effect of preoperative normovolaemic haemodilution with dextran 70 in 57 patients undergoing total hip replacement for osteoarthritis, was evaluated with respect to the production of thrombosis and pulmonary embolism. The patients were randomly allocated to one group undergoing preoperative haemodilution and one control group receiving 500 ml dextran 70 during operation and again on the second postoperative day. Before operation blood was replaced by dextran 70 to lower the hematocrit to between 25 and 30. The blood drained from the patients was used to replace blood lost at operation. Between 10 and 14 days after operation the patients were examined by perfusion lung scan, chest radiography and bilateral phlebography. Twelve patients also had 133Xe ventilation scans. The incidence of deep vein thrombosis in the two groups did not differ significantly. Pulmonary embolism was significantly decreased in the preoperative haemodilution group. One patient in the control group had clinical symptoms of, and died from, pulmonary embolism.

Aged↗