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ABSTRACT: Background: We aimed to document enoxaparin use in real world and identify the risk factors for bleeding complications. Methods: Postauthorization study in 448 surgical patients receiving enoxaparin prophylaxis. Complete compression ultrasound (CCUS) was performed at day 10 ± 3. Results: During treatment, 11 of 448 patients had suspected deep venous thrombosis (DVT) but none confirmed. One patient had symptoms of pulmonary embolism ([PE] 0.22%; 95% confidence interval [CI] -0.21-0.66). There were no asymptomatic cases detected upon CCUS. At the 90-day follow-up, 4 (0.9%) of the 440 patients had DVT symptoms (95% CI 0.02-1.80) and none had PE; 5.4% had major and 11.6% any type of bleeding complications. Major bleeding was more frequent in those with kidney disease (odds ratio [OR] 5.53), those who are bedridden (OR 5.49), those with peridural indwelling catheters (OR 4.01), and those on nonsteroidal anti-inflammatory drugs (OR 3.33). Conclusions: Enoxaparin is effective and safe in surgical patients to prevent venous thromboembolism.
Clinical and Applied Thrombosis/Hemostasis 10/2012; · 1.33 Impact Factor
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ABSTRACT: Novel oral anticoagulants (NOACs) have become available for prevention of venous thromboembolism after major orthopaedic surgery, treatment of venous thromboembolism, and stroke prevention in patients with atrial fibrillation. The thrombin inhibitor Dabigatran has a plasma half life of 11-14 hours which prolongs significantly in renal insufficiency. The two Xa-inhibitors Rivaroxaban and Apixaban have slightly shorter half lifes, and renal elimination is confined to about 30% of active drug. Prior to elective surgery, drug intake needs to be halted. The time period depends on the actual drug half life in that particular situation. Bridging anticoagulation is not necessary. The management of bleeding complications does not differ from that in other anticoagulants. The most uncertainties in clinical practice will arise from the fact that NOACs derange the global clotting tests without any conclusive information about the actual intensity of anticoagulation.
ains · Anästhesiologie · Intensivmedizin 04/2012; 47(4):266-72; quiz 273. · 0.41 Impact Factor
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ABSTRACT: Despite the elevated risk for developing venous thromboembolic events in patients with heart failure, there are no randomized, double-blind, controlled trial data on the comparison of low-molecular-weight heparin with unfractionated heparin (UFH) in this patient population.
This was a subgroup analysis of the CERTIFY trial, which included 3,239 nonsurgical, acutely ill medical patients 70 years or older. Patients were randomized to receive 3,000-U anti-Xa certoparin once daily or 5,000-IU UFH 3 times a day. The analysis was performed on a subgroup of 542 patients diagnosed with heart failure at hospital admission.
Patients with heart failure differed from patients without heart failure in that they were more likely using antiplatelets (67.2% vs 48.9%; P < .0001) and had a lower glomerular filtration rate (8.0% vs 5.5%; ≤ 30 mL/min per 1.73 m²; P = .0232). Thromboembolic risk was comparable except for a higher incidence of distal deep venous thrombosis (DVT) in patients with heart failure (10.80% vs 7.26%; P = .0144). Within the heart failure population, patient characteristics were comparable between randomized treatment groups. The incidence of the primary end point (proximal DVT, symptomatic nonfatal pulmonary embolism, and venous thromboembolism-related death combined) was numerically, slightly smaller with certoparin (3.78% vs 4.74% with UFH; odds ratio 0.79, 95% CI 0.32-1.94), and the incidence of major bleeding was 0.72% with certoparin versus 0.38% with UFH.
Patients hospitalized for heart failure are at high risk for developing distal DVT and bleeding complications compared with acutely ill medical patients without heart failure. Within the heart failure population, the observed differences in prophylactic efficacy between 3,000-U anti-Xa certoparin once daily and 5,000-IU UFH 3 times a day were similar to those observed in the overall study population; this suggests that certoparin might be at least as effective as UFH also in this subgroup. There were no relevant differences in bleeding risk or frequency of adverse events.
American heart journal 02/2011; 161(2):322-8. · 4.65 Impact Factor
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ABSTRACT: Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.
Acutely-ill, non-surgical patients ≥ 70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.
1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).
Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.
clinicaltrials.gov, NCT00451412.
BMC Cancer 01/2011; 11:316. · 3.01 Impact Factor
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ABSTRACT: Guidelines recommend low-dose unfractionated heparin (UFH) and low-molecular-weight heparin for the prophylaxis of venous thromboembolism (VTE) in acutely ill medical patients. We report the findings of an open-label, active-controlled, multicenter study in acutely ill medical patients comparing certoparin and UFH.
Open-label, active-controlled, multicenter study. Patients received certoparin 3000 IU daily or UFH 7500 IU twice daily.
The primary endpoint was a composite of symptomatic or asymptomatic proximal or distal deep vein thrombosis, symptomatic pulmonary embolism, or VTE-related death.
172 patients were randomized to UFH and 163 to certoparin for 8.5 ± 2.1 days. The incidence of the primary endpoint was 18.0% in patients receiving UFH and 10.7% with certoparin [absolute difference -7.3; 95% confidence interval (CI) -16.9 to 2.3; p = 0.1353]. The incidence during follow-up was 2.6% in the UFH and 2.0% in the certoparin group (absolute difference -0.6; 95%CI -4.0 to 2.8; p = 0.7150). Major bleeding events occurred in three patients with UFH and one patient with certoparin.
In acutely ill medical patients of at least 40 years of age, thromboprophylaxis with certoparin 3000 IU daily is effective and safe in comparison with 7500 IU twice daily UFH.
Expert Opinion on Pharmacotherapy 10/2010; 11(18):2953-61. · 3.20 Impact Factor
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ABSTRACT: Current guidelines recommend optimised algorithms for diagnosis of suspected deep-vein thrombosis (DVT). There is little data to determine to what extent real-world health care adheres to guidelines, and which outcome in terms of diagnostic efficiency and safety is achieved. This registry involved patients with clinically suspected DVT of the leg recruited in German ambulatory care between October and December 2005. Registry items were: diagnostic methods applied, diagnostic categories at day 1, and venous thromboembolic events up to 90 days in patients without firmly established DVT. A total of 4,976 patients were recruited in 326 centres. Venous ultrasonography was performed in 4,770 patients (96%), D-dimer assay in 1,773 patients (36%) and venography in 288 patients (6%). At day 1, DVT was confirmed in 1,388 patients (28%), and ruled out in 3,389 patients (68%), and work-up was inconclusive in 199 patients (4%). The rate of venous thromboembolism at 90 days was 0.34% (95% confidence interval [CI]: 0.09 to 0.88) in patients in whom the diagnosis of DVT had been ruled out, and 2.50% (95% CI: 0.69 to 6.28) in patients with inconclusive diagnostic workup. This nationwide evaluation in German ambulatory care revealed that the diagnostic work-up for suspected DVT did not adhere to current guidelines. However, the overall diagnostic safety was excellent, although there is potential for improvement in a well defined minority of patients.
Thrombosis and Haemostasis 12/2009; 102(6):1234-40. · 5.04 Impact Factor
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Sebastian M Schellong
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ABSTRACT: Venous ultrasound is a major tool in both routine clinical care and clinical research. Since the last review, major attempts have been made to improve its methodological strength, and therefore, its value in assessing diagnostic criteria, risks, and outcomes in venous thromboembolism.
In symptomatic patients, further evidence has been provided that the approach of a single examination of the entire venous system is feasible and safe. This holds true for patients with suspicion of deep vein thrombosis as well as of pulmonary embolism. In asymptomatic patients, several attempts have been made to validate venous ultrasound against venography. Even if no direct comparison has been made, the results seem to be more promising in medically ill patients than in those early after major orthopaedic surgery.
For routine clinical use, the single examination strategy still awaits full recognition and implementation into practice. For clinical trials, there is insufficient data about the accuracy of centrally read ultrasound. This fact directly points to the unmet need of a consensus of standardization of venous ultrasound as an endpoint measure in clinical trials regarding the examination procedure itself, its documentation, and the adjudication process.
Current opinion in pulmonary medicine 10/2008; 14(5):374-80. · 3.08 Impact Factor
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ABSTRACT: The peripheral venous system is subdivided into a superficial (epifascial) and a deep (subfascial) system by the superficial fascia. The two systems are interconnected by the transfascial system, called perforanting veins. The blood from the superficial system (great saphenous vein and small saphenous vein) is drained to the deep system. The deep veins accompany the arteries. The direction of venous blood flow is controlled by valves. The number of valves is variable. The veins are surrounded by a venous sheath in which they are movable. The deep veins of the lower leg are arranged in three groups consisting of paired veins. The peroneal vein and the posterior tibial vein unite to form the tibioperoneal trunk. The tibioperoneal trunk is joined by the anterior tibial vein to form the popliteal vein. The superficial femoral vein which arises from the popliteal vein is joined by the deep femoral vein to form the common femoral vein. The latter vessel becomes the external iliac vein above the inguinal ligament. It unites with the internal iliac vein to form the common iliac vein. Both common iliac veins unite to form the inferior vena cava. The veins of the systemic circulation perform two basic tasks, returning venous blood to the heart and storing the blood volume that is not immediately needed. Several factors like venous valves, thoracoabdominal venous pump and peripheral venous pump are necessary to maintain venous return. The second task results from the elastic compliance of the venous system, especially the mesenteric channels.
Herz 03/2007; 32(1):3-9. · 0.92 Impact Factor
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ABSTRACT: Deep vein thrombosis (DVT) and pulmonary embolism (PE) represent two clinical manifestations of the same disease. Therefore,
the search for DVT is an integral part of the diagnostic workup of PE. However, out of the wide range of possible tests for
diagnosing DVT, only few show acceptable sensitivity and specificity, which also may vary depending on the diagnostic setting
in which these tests are performed. This chapter describes the diagnostic procedures for DVT testing, namely clinical examination,
pretest probability scores, D-dimers, compression ultrasound, and venography, including computed tomographic and magnetic
resonance venography. Advantages and limitations, and the interpretation of test results, are discussed. Because compression
ultrasound (CUS) has become the method of choice in suspected DVT, different protocols (2-CUS, E-CUS, and C-CUS) and the validity
of their results are described in more detail. Notably, even though the available data suggest that venous ultrasound applied
as a single test has low diagnostic sensitivity in suspected PE, it should be an integral part of the diagnostic workup of
PE. For example, because lung scans often show indeterminate results, the confirmation of DVT by ultrasound may establish
the diagnosis of PE in these patients without further tests. The second domain of venous ultrasound is to reduce the number
of direct PE-imaging procedures in patients with high pretest probability and/or positive D-dimer, in whom CUS should be applied
first, whenever possible. Venous ultrasound can also be particularly useful if PE is suspected in hemodynamically unstable
patients, in whom a fast and reliable diagnosis at the bedside is necessary. The confirmation of DVT by ultrasound establishes
the diagnosis of PE in these patients and treatment can be initiated without delay.
12/2006: pages 43-55;
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ABSTRACT: Die Venen der unteren Extremitäten werden durch die Fascia superficialis in ein oberflächliches und ein tiefes System geteilt.
Sie sind in ihrem gesamten Verlauf durch Venae perforantes miteinander verbunden. Das Blut aus den oberflächlichen Venen wird
durch zwei Sammelstämme, die Vena saphena magna und die Vena saphena parva, in die tiefen Venen abgeleitet. Die tiefen Venen
sind Begleitvenen der Arterien. Die Zirkulationsrichtung des Blutes in den Venen wird durch Klappen bestimmt, deren Anzahl
variabel ist. Die Venen sind von einer Venenscheide umgeben, innerhalb deren sie verschiebbar sind. Die tiefen Venen des Unterschenkels
werden in drei paarig angelegte Gruppen eingeteilt. Durch die Vereinigung dieser Venen entsteht die Vena poplitea. Diese geht
in die Vena femoralis über. Durch Vereinigung mit der Vena profunda femoris wird die Vena femoralis communis gebildet, die
oberhalb des Leistenbandes in die Vena iliaca externa übergeht. Diese wiederum vereinigt sich mit der Vena iliaca interna
zur Vena iliaca communis, die mit der Vene der Gegenseite die Vena cava inferior bildet. Die Venen des Herz-Kreislauf-Systems
haben zwei wesentliche Aufgaben, den Rücktransport des venösen Blutes zum Herzen und die Speicherung des Blutvolumens, das
nicht sofort benötigt wird. Der Rücktransport des Blutes wird durch verschiedene Faktoren gewährleistet. Dazu zählen die Venenklappen,
die thorakoabdominale Venenpumpe sowie die periphere Muskelpumpe. Die Speicherung des Blutes wird durch die Elastizität der
Venenwand erreicht.
The peripheral venous system is subdivided into a superficial (epifascial) and a deep (subfascial) system by the superficial
fascia. The two systems are interconnected by the transfascial system, called perforanting veins. The blood from the superficial
system (great saphenous vein and small saphenous vein) is drained to the deep system. The deep veins accompany the arteries.
The direction of venous blood flow is controlled by valves. The number of valves is variable. The veins are surrounded by
a venous sheath in which they are movable. The deep veins of the lower leg are arranged in three groups consisting of paired
veins. The peroneal vein and the posterior tibial vein unite to form the tibioperoneal trunk. The tibioperoneal trunk is joined
by the anterior tibial vein to form the popliteal vein. The superficial femoral vein which arises from the popliteal vein
is joined by the deep femoral vein to form the common femoral vein. The latter vessel becomes the external iliac vein above
the inguinal ligament. It unites with the internal iliac vein to form the common iliac vein. Both common iliac veins unite
to form the inferior vena cava. The veins of the systemic circulation perform two basic tasks, returning venous blood to the
heart and storing the blood volume that is not immediately needed. Several factors like venous valves, thoracoabdominal venous
pump and peripheral venous pump are necessary to maintain venous return. The second task results from the elastic compliance
of the venous system, especially the mesenteric channels.
Herz 12/2006; 32(1):3-9. · 0.92 Impact Factor
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Sebastian M Schellong
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ABSTRACT: Since its first appearance in the 1980s, venous ultrasound has increasingly gained interest of both clinicians and researchers. However, a majority of authors currently are convinced that venous ultrasound has inherent limitations that preclude it from safely ruling out distal deep vein thrombosis (DVT) in symptomatic patients and from detecting proximal and distal DVT accurately in asymptomatic patients. The aim of this review is to present recent lines of evidence indicating that venous ultrasound has developed beyond these limitations.
The major development does not arise from technical progress of imaging but from standardizing the examination procedure. The most efficient protocols now focus on B-mode sonography only but extend the examination to the paired deep calf veins and the calf muscle veins. For such an examination protocol, the term complete compression ultrasound (CCUS) has been coined. Interobserver variability of CCUS resembles that of venography, as do the technical failure rates. By means of a CCUS protocol, the diagnostic work-up of patients with suspected DVT can be simplified significantly. Studies in asymptomatic patients indicate that CCUS has the potential to generate valid data in prevalence and incidence studies and in intervention trials.
Complete compression ultrasound protocols are ready for implementation into clinical practice for diagnosing patients with symptomatic DVT. Research has already benefited from CCUS and benefits further with an increasing number of CCUS-driven trial designs. However, the value of a CCUS protocol critically depends on sound training and on strict compliance with all its details.
Current opinion in pulmonary medicine 10/2004; 10(5):350-5. · 3.08 Impact Factor
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ABSTRACT: Noninvasive diagnosis of deep vein thrombosis (DVT) is based on ultrasound examination of the leg veins, usually restricted to only compression of the proximal veins (CUS). Patients with negative CUS findings require a second examination or a combination with other tests, which impairs clinical efficiency. In this prospective outcome study, 1646 consecutive patients with clinically suspected DVT were examined once by a standardized protocol of complete compression ultrasound comprising all proximal and distal veins (CCUS) as the only diagnostic test. The examination was equivocal in 15 patients (1% technical failure rate). Another 366 patients (22%) were tested positive for proximal DVT, distal DVT, muscle vein thrombosis, or phlebitis. Of 1265 patients in whom CCUS findings were negative, 242 met exclusion criteria for follow-up (age <18, life expectancy <3 months, other reasons for anticoagulation, postthrombotic lesions of the leg veins, or lack of informed consent). During the 3 months of follow-up, three of 1023 patients with negative CCUS findings experienced a symptomatic venous thromboembolic event (0.3% [95% CI 0.1%-0.8%]). We conclude that the CCUS protocol has a low technical failure rate and is safe with respect to excluding DVT, thereby reducing the diagnostic workup of patients with suspected DVT to a single ultrasound examination.
Thrombosis and Haemostasis 02/2003; 89(2):228-34. · 5.04 Impact Factor
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ABSTRACT: Circannual rhythmicity in plasma catecholamines is well known, but no chronobiologic data are available on endothelin-1 and angiotensin II. This study was designed to investigate in healthy human subjects whether endothelin-1 and angiotensin II exhibit seasonal variations. Furthermore, we assessed the relation of both variables to plasma catecholamines, to environmental temperature, and to relative humidity in northern Germany, a region of a temperate climate. Plasma concentrations of endothelin-1, angiotensin II, epinephrine, and norepinephrine were prospectively determined in venous blood from 10 healthy subjects at monthly intervals during 13 consecutive months. The single-cosinor method was applied to evaluate the seasonal rhythmicity of these parameters and to assess their temporal relation to both relative humidity and ambient temperature. Whereas relative humidity did not significantly change throughout the year, outdoor temperature was lowest in January and highest in August. Endothelin-1 levels displayed a significant variation, with a sinusoid pattern throughout the year: nadir values occurred in January, peak values in July. Angiotensin II demonstrated a significant correlation with endothelin-1 and paralleled its rhythmicity. In contrast, the two plasma catecholamines exhibited an opposite pattern. We noted a significant inverse correlation between endothelin-1 and norepinephrine. Outside temperature correlated positively with endothelin-1 and angiotensin II levels and correlated negatively with levels of both catecholamines. This is the first study to report a seasonal variation of endothelin-1 and angiotensin II in normal subjects. According to our data, environmental temperature is the climate variable most closely related to the rhythmicity of endothelin-1, angiotensin II, epinephrine, and norepinephrine.
Journal of Laboratory and Clinical Medicine 11/2002; 140(4):236-41. · 2.62 Impact Factor
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ABSTRACT: The interobserver variability of compression ultrasound of proximal and distal veins in clinically suspected deep vein thrombosis was assessed. One hundred one symptomatic legs of all patients referred for clinically suspected deep vein thrombosis on 21 consecutive workdays were examined by two investigators independently according to a standardized protocol of complete compression ultrasound (CCUS) with 28 predefined venous segments between groin and ankle. Incompressible vein segments were defined as thrombotic. Cohen's kappa coefficient was used to calculate interobserver variability regarding diagnosis of deep vein thrombosis. Kappa for entire lower extremity was 0.94 (95% CI, 0.87-1). Kappa for proximal veins was 1; for calf veins 0.9 (95% CI, 0.79-1). For the posterior tibial veins and peroneal veins, kappa was 0.84 (95% CI, 0.66-1) and 0.77 (95% CI, 0.59-0.94), respectively. The results show that almost complete interobserver agreement can be achieved in compression ultrasound of both proximal and distal deep veins conducted according to a standardized examination protocol in clinically suspected deep vein thrombosis.
Clinical and Applied Thrombosis/Hemostasis 02/2002; 8(1):45-9. · 1.33 Impact Factor
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ABSTRACT: Pulmonary embolism as a part of venous thromboembolic disease has a broad spectrum of clinical presentations from minimal disease to life-threatening right heart failure. Therapy has to be guided by the risk associated with the individual clinical state of the patient. As long as hemodynamics are entirely stable, anticoagulation is given in order to prevent early or late recurrence, thereby allowing for endogeneous thrombolysis and recovery. In hemodynamically instable patients, i.e. patients under cardiopulmonary resuscitation or in shock, there is the need for a rapid reduction of thrombus mass in order to restore right ventricular function. Systemic thrombolysis is the most feasible modality to reduce the thrombus burden of the pulmonary circulation in the short term. For hemodynamically stable patients with right ventricular dysfunction as assessed by echocardiography, there is still some controversy as to whether thrombolysis improves the long-term outcome. At the least, thrombolysis may positively modify the short-term course of acute disease in patients with an extremely low risk of bleeding. When the acute phase has been overcome, secondary prophylaxis with vitamin K antagonists has to be given. The duration of secondary prophylaxis requires an individual assessment of both the risk of recurrence and the risk of bleeding. In the near future, new anticoagulant drugs such as direct thrombin and factor Xa inhibitors will offer new treatment modalities for the acute phase as well as for secondary prophylaxis.
Respiration 70(6):559-68. · 2.26 Impact Factor
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Thomas Schwarz,
Gabriele Siegert,
Wolfram Oettler,
Kai Halbritter,
Jan Beyer,
Roswitha Frommhold,
Siegmund Gehrisch,
Florian Lenz,
Eberhard Kuhlisch,
Hans-Egbert Schroeder, Sebastian M Schellong
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ABSTRACT: The risk for venous thromboembolism after long-haul flights represents a controversial issue. The aim of our study was to assess the incidence of venous thrombosis associated with long-haul flights in a prospective, controlled cohort study.
We included 964 passengers returning from long-haul flights (flight duration, > or =8 hours) and 1213 nontraveling control subjects. We excluded participants who were being treated with anticoagulant drugs or who used compression stockings. Main outcome measures were the incidence of ultrasonographically diagnosed thrombosis in the calf muscle and deep veins, symptomatic pulmonary embolism, and death.
We diagnosed venous thrombotic events in 27 passengers (2.8%) and 12 controls (1.0%) (risk ratio [RR], 2.83; 95% confidence interval [CI], 1.46-5.49). Of these, 20 passengers (2.1%) and 10 controls (0.8%) presented with isolated calf muscle venous thrombosis (RR, 2.52; 95% CI, 1.20-5.26), whereas 7 passengers (0.7%) and 2 controls (0.2%) presented with deep venous thrombosis (RR, 4.40; 95% CI, 1.04-18.62). Symptomatic pulmonary embolism was diagnosed in 1 passenger with deep venous thrombosis (P =.44). All of these individuals had normal findings at baseline ultrasonography. Passengers with isolated calf muscle venous thrombosis or deep venous thrombosis had at least 1 risk factor for venous thrombosis (>45 years of age or elevated body mass index in 21 of 27 passengers). The follow-up after 4 weeks revealed no further venous thromboembolic event.
Long-haul flights of 8 hours and longer double the risk for isolated calf muscle venous thrombosis. This translates into an increased risk for deep venous thrombosis as well. In our study, flight-associated thrombosis occurred exclusively in passengers with well-established risk factors for venous thrombosis.
Archives of Internal Medicine 163(22):2759-64. · 11.46 Impact Factor
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Sebastian M Schellong
ACP journal club 148(2):46.
