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PubMed2004

[Coagulation disorders and arterial thromboembolic events in non-small-cell lung cancer. A case report].

Certain coagulation disorders can occur in patients with cancer and thromboembolic complications are frequent. We report the case of a 53-Year-old patient with metastatic adenocarcinoma of the lung treated with chemotherapy who presented several cerebral arterial thromboembolic events leading to death a few weeks after the initial diagnosis of cancer. This case illustrates the important role of certain satellite disorders related to coagulation activation: non-bacterial thrombotic endocarditis, disseminated intravascular coagulation, anti-phospholipid antibody syndrome. The role of anticancer chemotherapy as a favoring factor for thromboembolic events is also emphasized in patients with non-small-cell lung cancer.

Adenocarcinoma↗
PubMed2004

[The risk of thromboembolism in airline passengers].

Long carrier flights favor thromboembolism. The risk is well known to the general public but is probably really very low. The risk is however pertinent due to the volume of air travel in the world. Sitting in the same position for a long time induced venous stasis which is the principal factor favoring thrombosis in travelers, irrespective of the means of transportation. Long carrier flights also expose passengers to specific factors related to air travel: coagulation disorders and alterations of the endothelium related to hypobarism, hypoxia and low hygrometry in the cabin. Presence of pathogenic thrombophilia is not a constant factor. The prevention of venous thrombosis in air travelers calls upon simple measures: abundant hydration, avoiding use of alcohol and tobacco, walking and dorsal flexion of the feet. The only preventive option with proven efficacy is the use of elastic contention which reduces the risk of thromboembolic events. There is no consensus concerning the use of drugs proposed by certain authors; prudence should be the rule. All passengers should become aware of the risk of thromboembolism related to sitting in the same position for a long time.

Aerospace Medicine↗
PubMed2005

Venous thromboembolism prophylaxis guidelines: use by primary care physicians.

Venous thromboembolism (VTE), a prevalent, costly medical condition, is one of the most common causes of death in the United States. Although risk factors for VTE are well known, thromboembolic events cannot be predicted because patients are asymptomatic and screening methods have limitations. Anticoagulant therapy (eg, low-molecular-weight heparin, unfractionated heparin, selective factor Xa inhibitors) has proved effective for preventing thromboembolism, including deep vein thrombosis and pulmonary embolism. While quality care for VTE entails prophylaxis for all relevant patients, many high-risk patients are undertreated or treated incorrectly. Both primary and secondary prevention of VTE remain inadequate for several reasons, including lack of awareness of the American College of Chest Physicians guidelines, of the seriousness of VTE, of the benefits of prophylaxis, and of the relatively low risk of bleeding complications. To provide appropriate treatment, physicians must assess the numbers and types of risk factors for each patient, the underlying illness or surgical procedure, and the benefits and risks of possible therapies. The problem of VTE will grow as the US population ages, as surgery is performed on increasingly sick patients, and as the length of hospital stays continues to decrease.

Anticoagulants↗
PubMed2002

[3rd generation progestagen and thromboembolic disease. How do we decode the information?].

In 1995-1996, four studies published in different medical papers showed an increased risk of veinous thromboembolism among women using third-generation contraceptives compared with those using second-generation pills. These papers had an important mediatic impact. Nevertheless, rereading of the scientific information showed important bias in these studies (methodology, prescription, diagnosis). More recently, two studies published in the British Medical Journal analysing the venous thromboembolism (VTE) relative risk with the third generation contraceptives and using the same database (General Practitioner Research Database) found contradictory results, introducing some confusion. The use of a third-generation progestagen does seem to have led to an unexpected and yet unexplained return of a higher risk of venous thromboembolism but the risk has certainly been overestimated in the first studies.

Bias↗
PubMed2003

Inherited thrombophilia and gestational venous thromboembolism.

Thromboembolic disease is a leading cause of maternal morbidity and mortality during pregnancy and the puerperium. To reduce the incidence of venous thromboembolism in pregnancy and improve outcomes, an individual risk stratification based on probability of thrombosis as a rationale for an individual risk-adapted prophylaxis is required. Within the past 10 years, a significant improvement in risk estimation has been achieved due to the identification of new genetic risk factors of thrombosis. In women without prior thrombosis, the presence of a heterozygous factor V Leiden or heterozygous G20210A mutation in the prothrombin gene is associated with a pregnancy-associated thrombotic risk of approximately 1 in 400. Thus, in pregnant carriers of either one of these mutations the risk of venous thromboembolism is low--indicating that pregnancy-associated thrombosis is multicausal, resulting from the interaction of combined defects. A combination of the two genetic risk factors can increase the risk to a modest level (risk 1 in 25). In women with a single episode of prior thrombosis associated with a transient risk factor, for example, surgery or trauma, and no additional genetic risk factor, the probability of a pregnancy-associated thrombosis appears also to be low. In contrast, in women with a prior idiopathic venous thrombosis who carry an additional hereditary risk factor or who have a positive family history of thrombosis, a high risk (>10%) can be expected, supporting the indication for active antepartum and postpartum heparin prophylaxis. Despite the remarkable progress in risk stratification, the absolute magnitude of risk in many cases is unknown and current recommendations remain empirical.

Anticoagulants↗
PubMed2006

[Thromboembolic events in patients after a negative computed tomography pulmonary angiogram: A retrospective study of 165 patients].

OBJECTIVE: To determine the value of computed tomography (CT) angiography of the chest as a diagnostic test to exclude pulmonary embolism and to assess compliance with diagnostic protocols for thromboembolic disease. PATIENTS AND METHODS: We retrospectively studied patients who underwent CT angiography of the chest because of suspected pulmonary embolism in 2004. All the patients were followed for 3 months. The percentage of patients diagnosed with a thromboembolic event based on an objective test during the follow-up period was determined. We analyzed the percentage of patients with a negative CT angiogram on whom additional diagnostic tests (ultrasound of the lower limbs and/or ventilation-perfusion lung scintigraphy) were performed. RESULTS: One hundred sixty-five patients underwent CT angiography of the chest because of suspected pulmonary embolism in 2004. Four of the patients were excluded from the study because they were on chronic anticoagulation therapy and a further 2 were excluded because they had a life expectancy of under 3 months. Of the remaining 159 patients, 60 had CT angiograms that were interpreted as high probability for pulmonary embolism (prevalence of 38%). Thirty-nine of the 99 patients with a negative CT angiogram experienced an objectively confirmed thromboembolic event (63% sensitivity; 95% confidence interval, 53%-73%). Other diagnostic tests were not performed in 46% of the cases. CONCLUSIONS: In our setting, a negative single-detector helical CT angiogram was not sensitive enough to exclude the diagnosis of pulmonary embolism. Furthermore, compliance with internationally accepted diagnostic protocols was far from optimal.

Aged↗
PubMed1997

Prophylaxis for venous thromboembolism in head and neck surgery: the practice of otolaryngologists.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are an important cause of morbidity and mortality in the surgical patient. The first guideline produced by the Scottish Intercollegiate Guidelines Network was for the prophylaxis of venous thromboembolism. Patients undergoing major head and neck cancer surgery commonly exhibit risk factors for venous thromboembolism. Currently, however, there are no data on its incidence in these patients. A questionnaire survey was performed to assess the current practice of consultant otolaryngologists regarding DVT prophylaxis in patients undergoing head and neck cancer surgery. Of those respondents who managed these patients, 57 per cent did not use routine DVT prophylaxis while 43 per cent did. A wide variety of techniques were employed among those practising DVT prophylaxis. A consensus is needed concerning the use of thromboembolism prophylaxis in head and neck surgery patients.

Head and Neck Neoplasms↗
PubMed1997

Cancer-related thromboembolic disease in patients with solid tumours: a retrospective analysis.

BACKGROUND: Cancer patients frequently suffer thromboembolic events. This study assessed the incidence and resource implications of cancer-related thromboembolic disease (CTD) in a single, large cancer centre. PATIENTS AND METHODS: A retrospective analysis of patients admitted with CTD and/or the complications of treatment of CTD over a two-year period has been conducted. Forty-eight patients (23 male, 25 female, median age 60 years) with a variety of solid tumours were identified. RESULTS: The initial presentations were venous thromboses (28 patients) and pulmonary embolism (20 patients). The median interval from cancer diagnosis to the initial episode of CTD was eight (range 0-112) months. Twenty-two patients suffered additional thromboses, despite maintenance warfarin anticoagulation in 18 patients. Six patients experienced anticoagulation-induced haemorrhage. Forty-one (85.4%) patients have died. The median survival from the first thromboembolic event was 8.5 months. The median inpatient stay for management of the first event was 10 (range 4-75) days, accounting for 729 inpatient days during the study period. Recurrent episodes of CTD or complications of anticoagulation resulted in 28 readmissions, accounting for 295 inpatient days. During the two-year period 1024 inpatient days were directly caused by CTD and its complications, representing 6.1% bed occupancy on our unit. CONCLUSION: This study demonstrates that CTD represents a significant cause of morbidity in cancer patients with considerable resource implications for cancer centres. Improvements in prevention and management of CTD would reduce morbidity and lead to considerable cost savings.

Adult↗
PubMed1999

Outpatient management of venous thromboembolism.

Low molecular weight heparins (LMWHs) have provided the necessary pharmacologic tool to facilitate the outpatient management of selected patients presenting with acute venous thromboembolism. A growing collection of clinical trial results supports the safety and efficacy of this cost-efficient management strategy. However, this approach requires careful patient selection and meticulous care planning. Several randomized multicenter trials have compared a primarily outpatient approach to treating uncomplicated proximal venous thrombosis with a LMWH administered subcutaneously once or twice daily to the inpatient use of unfractionated heparin (UFH). The results have been very encouraging and suggest that the use of subcutaneous LMWH in highly selected, uncomplicated venous thrombosis patients is as safe and effective as intravenous UFH, and that most patients can be treated as outpatient or be discharged early. Irrespective of parenteral anticoagulant approach, warfarin therapy was commenced on day 1 and continued for 3 months. A recent publication by Dedden and colleagues describes a 1-year experience with a pharmacy-managed program for the home treatment of patients presenting with proximal deep vein thrombosis. A plan for coordinated patient care was implemented which included a process for patient referrals, standardized protocol orders, a plan for holding area processing and home healthcare agency follow-up, and subsequent oral anticoagulation management. Results of the program demonstrate a significant healthcare savings (as compared with standard inpatient management) with no significant compromise in patient outcomes. Recently published trials by the Columbus Investigators and Simonneau and colleagues have looked beyond uncomplicated proximal venous thromboembolism to include patients presenting with recurrent venous thrombosis and pulmonary embolism. Results suggest the subcutaneous use of LMWH is as safe and effective as intravenous UFH. Such data begin to lay the scientific foundation for the expanded clinical base of patients who may be candidates for an outpatient management approach. In today's cost-conscience environment, managing the treatment of select venous thromboembolism patients with LMWH(s) and warfarin therapy in an outpatient environment represents an evolving approach that is economically logical, does not compromise patient outcomes, but requires considerable planning to address a myriad of logistical issues.

Fibrinolytic Agents↗
PubMed2006

Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke.

Uric acid is a natural antioxidant that protects the brain in a model of transient focal ischemia in rats. Here we sought to investigate whether uric acid was protective in a model of thromboembolic brain ischemia in rats, and whether the global benefit of recombinant tissue plasminogen activator (rt-PA) was improved by the combined treatment. Adult male Sprague-Dawley rats underwent either ischemia by thromboembolic middle cerebral artery occlusion (MCAO) or sham operation. Uric acid (16 mg/kg) was injected intravenously (i.v.). 20 mins after MCAO, whereas rt-PA (10 mg/kg) was administered i.v. at 3 h. A group of rats received the combined treatment. Rats underwent two neurologic examinations (30 mins and 24 h after MCAO). At 24 h, infarct volume was measured and brain neutrophil infiltration and protein tyrosine nitration were assessed. Treatment with either uric acid or rt-PA reduced infarct volume versus controls (P<0.05). The protective effect against brain ischemia was greater after cotreatment of uric acid with rt-PA (P<0.001), which added further benefit to rt-PA alone (P<0.05). The neurologic score worsened during the first 24 h in treatment controls, whereas it improved in rats receiving uric acid and/or rt-PA. Uric acid strongly reduced ischemia-induced tyrosine nitration, but it was more effective alone than combined with rt-PA, suggesting that reperfusion enhances nitrotyrosine formation. All treatments reduced postischemic brain neutrophil infiltration. These results show that uric acid administered early after thromboembolic stroke is neuroprotective in the rat brain, as it reduces infarct volume, ameliorates the neurologic function, attenuates the inflammatory response, and extends the benefits of rt-PA.

Animals↗
PubMed2002

The incidence of recurrent venous thromboembolism in carriers of factor V Leiden is related to concomitant thrombophilic disorders.

The duration of anticoagulant treatment after a first episode of venous thromboembolism primarily depends on the risk of recurrence. Variability of recurrence rates in factor (F) V Leiden carriers may be due to concomitant thrombophilic disorders. A retrospective study was performed in 329 FV Leiden carriers with a history of venous thromboembolism (262 probands, 67 relatives). The annual rate of first recurrence was estimated in relatives. The contribution of concomitant thrombophilic disorders to the recurrence rate was evaluated in probands and relatives by a nested case--control analysis in 105 matched pairs of carriers either with or without recurrence. The overall annual recurrence rate was 2.3 per 100 patient-years. The adjusted risk of recurrence for concomitant thrombophilic disorders was: 9.1 (1.3-62.8) for the FII mutation; 1.0 (0.2-4.9) for homozygosity for FV Leiden; 1.5 (0.2-9.5) for inherited deficiencies of protein C or S; 1.8 (0.7-4.9) for FVIII coagulant activity (FVIII:C) levels >122%; 5.4 (1.6-18.6) for fasting homocysteine levels >15.2 micromol/l; and 4.4 (1.0-18.7) for loading homocysteine levels >45.8 micromol/l. Of these disorders, only the FII mutation and hyperhomocysteinaemia significantly increased the risk of recurrence in FV Leiden carriers. The estimated recurrence rate ranged from 0.45 per 100 patient--years after a secondary first event in the absence of concomitant disorders to 4.8 per 100 patient-years when a spontaneous first event was combined with concomitant disorders. Our study provides supportive evidence that the incidence of recurrent venous thromboembolism in heterozygous FV Leiden carriers depends on the concomitance of other thrombophilic disorders, in addition to whether the first thrombotic event occurred spontaneously.

Adolescent↗
PubMed2000

Effect of the angiotensin-converting enzyme gene deletion polymorphism on the risk of venous thromboembolism.

Allele frequencies for the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene were determined in a large case-control study of 517 unselected patients with venous thromboembolism and 478 blood donors. The D allele frequency was 0. 53 [95% confidence interval (CI) 0.50-0.56] in patients and 0.54 (95% CI 0.50-0.57) in controls, giving an odds ratio for the D allele of 0.97 (95% CI 0.81-1.16). In the same population, the odds ratio for the factor V Leiden mutation (F5G1691A) was 6.9 (95% CI 4. 0-11.9). Therefore, the ACE I/D polymorphism is not a risk factor in a representative group of unselected patients with venous thromboembolism. The possibility that the I/D polymorphism is a risk factor for venous thromboembolism specifically after hip replacement cannot be excluded.

Arthroplasty, Replacement, Hip↗
PubMed1999

Prevalence of APC resistance and its relationship to arterial and venous thromboembolism in a general population sample of elderly Swedish men: The Study of Men Born in 1913.

BACKGROUND: Most studies of hereditary resistance to activated protein C (APC resistance) as a risk factor for venous thromboembolism are derived from case-control studies of hospitalized patients, whilst the importance of this condition in the general population has been only sparsely investigated. OBJECTIVE: To study the prevalence of APC resistance and its relationship to morbidity and mortality in a general population sample of elderly men. DESIGN: Cross-sectional and prospective follow-up study. SETTING: General community: The Study of Men Born in 1913. SUBJECTS: A random population sample of 404 men, all 75 years of age. MAIN OUTCOME MEASURES: Four hundred and four men participated in a screening examination in 1988. The APC ratio was analysed in 382 of them. All the men were followed up for 5 years. Medical records were reviewed for all the men with a history of deep vein thrombosis, pulmonary embolism, myocardial infarction or stroke. RESULTS: Twenty-five men (6.5%) were found to have APC resistance. The incidence of venous thromboembolism, myocardial infarction or stroke did not differ between men with or without APC resistance, either retrospectively or during follow-up. Only two men experienced a deep vein thrombosis before the age of 80 and there was no case of pulmonary embolism. Mortality during 5 years of follow-up did not differ between men with and without APC resistance. CONCLUSION: The prevalence of APC resistance was 6.5% in this study of Swedish men. Although the size of the population sample is somewhat small, the study shows that, amongst elderly men, the association between APC resistance and venous thromboembolic disease was weak and men with this hereditary condition did not have any increase in morbidity or mortality compared with men without APC resistance.

Aged↗
PubMed2003

Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE Study.

Plasma thrombomodulin (soluble TM; sTM) is considered to be a marker of endothelial injury, but a recent report indicated that the relationship of sTM with thrombosis is complex. Venous thromboembolic events were identified in adults in two longitudinal cohort studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, totaling 21 690 participants. After 8 years of follow-up, sTM was measured in baseline plasma of 305 participants who developed venous thrombosis and 607 who did not. Thrombomodulin A455V genotype was determined in 302 cases and 626 controls. There was no difference in the prevalence of the three TM genotypes between cases and controls and no difference in age-adjusted mean values of sTM by genotype. There were no associations of age-adjusted sTM or TMA455V genotype with overall venous thromboembolism or with thrombosis in any subtype of venous thromboembolism.

Age Factors↗
PubMed2003

Contribution of indirect computed tomography venography to computed tomography angiography of the chest for the diagnosis of thromboembolic disease in two United States emergency departments.

Recent reports suggest that physicians in non-ambulatory settings can use indirect CT venography (CTV) of the lower extremities immediately following spiral CT angiography (CTA) of the chest to identify patients with a negative CTA who have thromboembolic disease identified on CTV. We sought to determine the frequency of isolated deep venous thrombosis (DVT) discovered on CTV in emergency department (ED) patients with complaints suggestive of pulmonary embolism (PE) yet having a negative CTA. This study was conducted in a suburban and urban ED where patients with symptoms suspicious for PE were primarily evaluated with CTA and CTV. A total of 800 patients were studied, including 360 from the suburban ED and 440 from the urban ED. 88 (11%) patients were diagnosed with thromboembolic disease by CTA, or CTV, or both. Seventy-three patients had a CTA of the chest that was positive for PE, 42 (5.2%) of whom had evidence of both PE on CTA and DVT on CTV. Fifteen patients (2%, 95% CI = 1-3%) had a negative CTA and were subsequently found to have isolated DVT on CTV, all of whom received anticoagulation therapy. These data suggest that indirect CT venography of immediately following CT angiography of the chest significantly increased the frequency of diagnosed thromboembolic disease requiring anticoagulation in ED patients with suspected PE.

Adult↗
PubMed1999

Feline distal aortic thromboembolism: a review of 44 cases (1990-1998).

The clinical case records of 44 cats with distal aortic thromboembolism were reviewed. These detailed 49 separate episodes of thromboembolism. Of the 44 cats, 33 (75%) were neutered males, and 43 (98%) were domestic shorthairs. The mean age was 8.7 years (age range 2-16 years). Evidence of pre-existing heart disease had been noted in 23% of cases. Heart failure was a concurrent diagnosis in 51% of episodes and 36% of these cases survived their thromboembolic episodes. Overall, cats survived 39% of the episodes. Cats died during 28% of the episodes, while 33% of the episodes resulted in the cats being euthanased. The median survival time was 6 months. Seventeen per cent of cats on prophylactic aspirin therapy experienced an episode of re-embolisation. Forty-three per cent of episodes occurred in the spring.

Age Distribution↗
PubMed1998

Oral contraceptives and venous thromboembolic disease: the findings from database studies in the United Kingdom and Germany.

OBJECTIVE: Three research articles published in late 1995 and early 1996 suggested that oral contraceptives containing either of the newer progestogens (gestodene or desogestrel) could be associated with an increased risk of venous thromboembolism. During the months after the initial publications, the results have been scrutinized with great care and further studies have been published. The findings of 2 recent database studies, 1 in the United Kingdom and 1 in Germany, are presented in this article. PATTERNS OF USE: The average age of users of combined oral contraceptives in Germany was 27 years, compared with 26 years in the United Kingdom. In Germany the use of gestodene-based products was lower than that in the United Kingdom. In the United Kingdom the users of desogestrel with 20 microg ethinyl estradiol (Mercilon) were older than the users of desogestrel with 30 microg ethinyl estradiol (Marvelon). CRUDE INCIDENCE: The crude incidence of venous thromboembolism in the UK study was 4.1 cases/10,000 woman-y exposure to combined oral contraceptives. In Germany it was 4.2 cases/10,000 woman-y. In Germany the rates among users of second-generation combined oral contraceptives were higher than those among users of third-generation products. The reverse was the case in the United Kingdom. In the United Kingdom the crude incidence rates were higher for the 20 microg estrogen desogestrel product than for the 30 microg product. CASE-CONTROL ANALYSIS: The adjusted odds ratios in the UK study did not show significant increases for desogestrel or gestodene compared with levonorgestrel products. There were inconsistencies in the results among centers in the 2 international studies (the World Health Organization and Transnational studies). In both there was a consistent inverse dose-response relationship with estrogen in all centers. CONCLUSION: The limitations of the observational studies are such that the hypothesis that the newer progestogens are more likely to cause venous thromboembolism cannot be proved.

Adult↗
PubMed1999

[Therapy of thromboembolic blockages in the crural arteries: Clinical experience with the Angiojet thrombectomy catheter].

UNLABELLED: To investigate the clinical impact of a new hydrodynamic thrombectomy catheter in thromboembolic occlusion of tibial arteries. METHOD: 10 patients with thromboembolic occlusion of all tibial arteries were treated with the Angiojet thrombectomy device in order to reestablish blood flow. Depending on angiographic and clinical results of thrombectomy, additional thrombolysis, PTA, recanalization, or surgical bypass grafting was performed. RESULTS: Antegrade blood flow in at least one tibial artery was reestablished in 6 cases with the thrombectomy device. However, additional treatment modalities were used in order to improve the outcome and to resolve adherent thrombi or to treat vessel stenoses and occlusions: thrombolysis (n = 9), PTA (n = 3), recanalization (n = 1), bypass grafting (n = 3), suction thromboembolectomy (n = 1), replacement of popliteal aneurysm (n = 1). The limb salvage rate was 7/10. The ratio of injected volume to aspiration volume was 1.04 +/- 0.07 indicating that the system works isovolumetrically. The device induced moderate hemolysis with plasma free hemoglobin rising by the factor 12.91 +/- 11.59, (P < 0.01). CONCLUSION: In cases with thromboembolic occlusions of tibial arteries the Angiojet thrombectomy catheter is a valuable addition to the interventional instrumentarium. It works isovolumetrically but induces moderate hemolysis and thereby may compromise renal function. However, in most cases additional treatment modalities are required.

Aged↗