Traveler's thrombosis

It is pathophysiologically conceivable that prolonged sitting in a tight space (e.g., in airplane or other transport vehicle) may lead to leg vein thrombosis. The association between the incidence of venous thromboembolism and long travel has not been sufficiently documented but seems probable. However, this association is only weak and the incidence of symptomatic thromboembolism much lower than the impression given by the recent publicity. In a healthy person, the risk of suffering a clinically relevant leg vein thrombosis solely because of a flight is extreme low. In persons with risk factors for venous thromboembolism, the flight represents an additional, as yet not quantifiable risk. This risk increases with the duration of the travel. The most important cause of thrombosis during long journeys seems to be venostasis due to relative immobilization. It is not clear whether flight travel represents a higher risk of thrombosis compared to other transport vehicles with comparable duration and immobilization. Until more exact information becomes available, it seems reasonable to recommend simple isometric and isotonic leg exercises during long travel. More aggressive measures must be considered for persons with risk factors for thromboembolism, but these measures should be individualized.     

The effects of race/ethnicity and sex on the risk of venous thromboembolism

PURPOSE OF THE REVIEW: Recently, studies on large diverse populations have described important ethnic/racial differences in venous thromboembolism incidence, and sex has been reported as an important predictor of recurrence. We review the influence of race/ethnicity and sex on venous thromboembolism, concentrating on articles from 2005 to 2007. RECENT FINDINGS: Most studies found that women have a 40-400% lower risk of recurrent venous thromboembolism than men. Studies of ethnicity/race on risk provide strong evidence that African-American patients are the highest risk group for first-time venous thromboembolism, while Hispanic patients' risk is about half that of Caucasians. African-Americans and Hispanics have a higher risk of recurrence than Caucasians, but sex and the type of index venous thromboembolism event seem to play a role in this risk. Asian/Pacific Islanders have a markedly lower risk of first-time and cancer-associated venous thromboembolism. There is little difference in incidence in African-Americans, Hispanics, and Caucasians diagnosed with cancer. Sex does not seem to be associated with risk in cancer patients. SUMMARY: Sex and race/ethnicity are important factors in the risk of first-time and recurrent venous thromboembolism and need to be included as risk assessment and diagnostic prediction tools are developed or updated.     

Age as a risk factor for venous thromboembolism after major surgery

PURPOSE OF REVIEW: Postoperative deep venous thrombosis and pulmonary embolism are serious and potentially life-threatening complications that frequently occur after major surgery. Most guidelines for thromboprophylaxis use advancing age as a key component to estimate thromboembolic risk. The reported effect of age on postoperative venous thromboembolism varies widely, making it unclear whether age alone is a significant risk factor. This article reviews the recent literature on the effect of age on the incidence of postoperative venous thromboembolism. RECENT FINDINGS: Between 2003 and 2005, several cohort studies assessed the risk factors for postoperative venous thromboembolism, showing a variable effect of age on its incidence in the 2- to 3-month period after major surgery. Studies also revealed a significant difference in the effect of age on the incidence of venous thromboembolism depending on the type of surgery. Obesity, postoperative immobilization, the use of thromboprophylaxis, the nature of the surgery, and underlying comorbid conditions such as heart failure seem to have a greater influence on the risk of venous thromboembolism than does age. SUMMARY: The variation in the effect of age on postoperative venous thromboembolism likely depends on whether or not other comorbid conditions or age-related changes in functional status are considered as risk factors. When these other risk factors are taken into account, the effect of advanced age decreases. More research is needed to develop validated venous thromboembolism risk-prediction tools for specific types of surgery. By use of this information, the intensity and duration of postoperative thromboprophylaxis can be tailored to the level of risk, not just age alone.     

Changes in plasma coagulation markers with prophylactic treatment of low molecular weight heparin after cesarean section

Cesarean section has been identified as a major risk factor for thromboembolism, and additional risk factors place some women at a much higher risk during puerperium. Recently, low molecular weight heparins (LMWHs) have been used for thromboembolism prophylaxis after cesarean section. We investigated the effect of risk factors of thromboembolism on plasma coagulation markers when the LMWH dalteparin was used following cesarean section. Twenty-four women with risk factors other than cesarean section (high-risk group) and 13 without any other risk factors (low-risk group) received dalteparin starting immediately after cesarean section until the patients were mobilized. Sixteen women without any other risk factors served as controls (control group). Activated partial thromboplastin times, thrombin-antithrombin complex, alpha (2)-plasmin inhibitor-plasmin complex, and activated factor X levels were not different between the high-risk and the low-risk groups. However, fibrinogen/fibrin degradation products D-dimer levels were higher in the high-risk group than in the low-risk and control groups on days 3 and 7 after cesarean section. These findings suggest that the D-dimer levels may be elevated by some risk factors and that postoperative D-dimer determinations may be useful in assessing the risk of thromboembolism during LMWH treatment after cesarean section.     

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

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

Hypercoagulability in Cushing's syndrome: prevalence,pathogenesis and treatment

Cushing's syndrome is not only accompanied by an increased prevalence of cardiovascular disease but also by a hypercoagulable state that is reflected by an increased incidence of venous thromboembolism. Overall, patients with CS have been reported to have a more than 10‐fold increased risk of developing venous thromboembolism. Moreover, the incidence of postoperative thrombosis has been shown to be comparable to the risk after major orthopaedic surgery. Hypercoagulability in CS is due to both increased production of procoagulant factors with activation of the coagulation cascade and an impaired fibrinolytic capacity, resulting in a shortened activated partial thromboplastin time and an increased clot lysis time respectively. Although these abnormalities seem to improve 1 year following successful surgery, they do not yet normalize. Therefore, sustained biochemical remission might be required to fully resolve the hypercoagulable state in CS. Considering the risk of venous thromboembolism in uncontrolled CS there may be a rationale to give patients with active CS thromboprophylaxis. So far this seems warranted following surgical interventions. However, further studies are needed to determine the optimal dosage and duration of thromboprophylaxis.     

Oral anticoagulation in venous thromboembolism: decisions based on more than mere feelings.

Although there is a very limited scientific basis for the recommendation to target the intensity of oral anticoagulation after venous thromboembolism at an international normalized ratio (INR) of 2.0-3.0, this has been widely adopted. It seems possible from the DURAC I and II trials that a slight lowering of the upper limit could further reduce the risk of major haemorrhage. The optimal duration of anticoagulation in this group of patients has been extensively investigated. For the majority of patients a treatment duration of 6 months eliminates the high risk of relatively early recurrences without yielding an increase in the incidence of major haemorrhages. Patients with a distal deep vein thrombosis and a temporary risk factor or those with poor compliance should have a shorter treatment duration, whereas further prolongation is warranted in patients with certain biochemical abnormalities or recurrent thromboembolic episodes. The optimal treatment regimen is individualized, taking into account a variety of risk factors, and re-evaluated regularly in case of prolonged therapy.     

Long-term treatment for venous thromboembolism

Anticoagulation is the corner stone of therapy for venous thromboembolism. The optimal duration of this therapy depends on the balance between the risk of recurrent thrombosis if anticoagulants are stopped, and the risk of bleeding if patients remain on treatment. The risk of recurrence is low if thrombosis was precipitated by a major reversible risk factor such as surgery. Patients with idiopathic thrombosis (no apparent risk factor) and those with persistent risk factors (eg, cancer), have a high risk of recurrence. Some hereditary (eg, protein C, protein S or antithrombin deficiency; homozygous factor V Leiden) and acquired (eg, antiphospholipid antibodies) thrombophilic states are also risk factors for recurrence. Three months of anticoagulation is recommended when the risk of recurrence is low, whereas the duration of therapy should be extended to 6 months or longer when this risk is high, depending on the balance between the risk of recurrence and the risk of bleeding in each individual patient. Heparin preparations, at doses intermediate to those used for the acute treatment of venous thromboembolism and for primary prophylaxis, are an alternative to oral anticoagulants during the maintenance phase of treatment.     

Venous thromboembolism in hospitalized inflammatory bowel disease patients: the magnitude of the problem is staggering

There is evidence that thromboembolism as a disease-specific extraintestinal manifestation of inflammatory bowel disease (IBD) is developed as the result of multiple interactions between acquired and genetic risk factors. An imbalance of procoagulant, anticoagulant, and fibrinolitic factors predisposing to thrombosis has been reported by several studies in patients with IBD. The study by Nguyen and Sam demonstrates that hospitalized IBD patients have higher prevalence of venous thromboembolism and a more than two-fold excess of mortality compared with non-IBD hospitalized patients. When the findings from this large study are combined with previous data, they suggest that thromboembolism is a significant cause of extraintestinal morbidity and mortality in IBD patients with a higher risk during hospitalization.     

Common risk factors for both arterial and venous thrombosis

Arterial and venous thromboses have traditionally been viewed as distinct conditions, with differences in risk factors, pathology and treatment. However, recent epidemiological studies have suggested associations between venous thromboembolism, arterial thromboembolism (myocardial infarction and stroke) and atherosclerosis. While several biological mechanisms might contribute to these associations, common risk factors for both arterial and venous thrombosis probably play the major role. This article summarizes the evidence for shared risk factors (clinical, biochemical and haematological) that supports this conclusion. At a practical level, it is suggested that following routine treatment of venous thromboembolism with a course of anticoagulant drugs, patients should be routinely assessed not only for risk of recurrent venous thromboembolism but also for risk of arterial thromboembolism. Appropriate lifestyle advice and medication (including aspirin) should then be considered.     

Concept of hypercoagulability: a review of its development, clinical application, and recent progress

There exist multiple clinical conditions, situations, and diseases in which persons appear to be at increased risk for thromboembolic phenomena, such as venous thrombosis and pulmonary embolus. Within this group of conditions, situations, or diseases, some are more clearly linked to thromboembolism that others. Similarly, for some, there exist clear biochemical reasons to support a proposed causal mechanism. A categorization of these risk factors has been constructed, taking into account both the apparent association of the risk factor with thromboembolism and the credibility of the proposed mechanism. Forty-eight factors have been so stratified. It is predicted that both more factors will be identified and especially that mechanisms proposed will strengthen as this area of medicine is further investigated.     

Therapy insight: Vascular complications in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is associated with an increased risk of vascular complications. The most important of these complications are arterial and venous thromboembolism, which represent a significant cause of morbidity and mortality in IBD patients. Recent data suggest that thromboembolism is a disease-specific extraintestinal manifestation of IBD. The most common thrombotic manifestations in IBD are deep vein thrombosis of the leg and pulmonary emboli. It has been suggested that disease activity and the extent of colonic localization are correlated with the risk of developing thromboembolism. The occurrence of thrombosis in patients with IBD is partially attributed to the existing hypercoagulable state in IBD. Both coagulation and fibrinolysis are activated in patients with IBD; this is especially true for those with active disease. The most common risk factors for thrombophilia in IBD patients with venous thromboembolism are Leiden mutation in the gene encoding factor V, hyperhomocysteinemia, and antiphospholipid antibodies. The main genetic defects that have been established as risk factors for venous thrombosis are rather uncommon in IBD, but when present increase the risk of thromboembolism. Screening for coagulation defects seems justified only in IBD patients with a history of thrombosis or a family history of venous thromboembolic events. Antithrombotic treatment of IBD patients with venous thromboembolism is similar to that of thrombotic non-IBD patients.     

Optimal duration of anticoagulation of venous thromboembolism

The optimal duration of anticoagulation after venous thromboembolism (VTE) is determined according to the risk of recurrent VTE after stopping anticoagulant therapy and the risk of anticoagulant-related bleeding while on antivitamin K. Clinical risk factors appears to be determinant to predict the risk of recurrence whereas the influence of biochemical and morphological tests is uncertain. The risk of recurrent venous thromboembolism is low when the initial episode was provoked by a reversible major risk factor (surgery): 3 months of anticoagulation is optimal. Conversely, this risk is high when venous thromboembolism was unprovoked or associated with persistent risk factor (cancer): 6 months or more prolonged anticoagulation is warranted. After this first estimation, the duration of anticoagulation may be modulated according to the presence of additional minor risk factors (major thrombophilia, chronic pulmonary hypertension, massive pulmonary embolism): 6 months if VTE was provoked and 12 to 24 months if VTE was unprovoked. If the risk of anticoagulant related bleeding is high, the duration of anticoagulation should be shortened (3 months if VTE was provoked and 6 or 3 months if it was unprovoked). Lastly, if VTE occurred in the setting of a cancer, anticoagulation should be conducted for 6 months or more while cancer is active or on ongoing treatment. Despite an increasing knowledge of the risk factors of recurrent VTE, a number of issues remain unresolved; randomised trial comparing different duration of anticoagulation are needed.     

Update on diagnosis and anticoagulant therapy for venous thromboembolism

Venous thromboembolism (VTE) continues to be a common medical problem requiring the need for rapid treatment with anticoagulant therapy. Until the recent availability of the direct oral anticoagulants for treatment of VTE, the option for oral anticoagulation was limited to warfarin therapy. The addition of these new medications has been welcomed, but has led to added complexities in deciding the most appropriate agent for each patient based on individual risk factors. Furthermore, there are several circumstances where optimal duration of therapy is not well established. This article will focus on the diagnosis of VTE, the choice of anticoagulant and treatment duration.     

Which patients with unprovoked VTE should receive extended anticoagulation? the minority

Venous thromboembolism (VTE) is associated with a long term risk of recurrence. This risk is at least in part related to the presence of major identifiable risk factors at the time of the index event. It is generally low in the presence of removable risk factors, and very high in the presence of permanent risk factors such as active cancer. This categorization is important because it drives the duration of secondary prevention treatment with anticoagulant drugs. Unfortunately, up to 40–50% of VTE events remain classified as unprovoked. This large group of patients is obviously heterogeneous, with an unpredictable risk of recurrence. Evidences from clinical trials suggest that extending secondary prevention with vitamin K antagonists (VKAs) for 1 or 2 years after an initial course of treatment in patients with unprovoked VTE does not provide additional benefit in terms of reducing the long term risk of recurrence. Prolonging indefinitely the duration of treatment would likely be effective in reducing this risk, but at the cost of unnecessarily expose the majority of patients to several complications, there including major bleeding events, and inconveniences. A number of variables have been identified to predict the individual risk of recurrence in these patients and some clinical prediction rules have been proposed. Improved patients stratification, together with a better understanding of the mechanisms underlying unprovoked VTE, should allow physicians to individually tailor the optimal duration of secondary prevention and to identify those patients (likely the minority) for whom indefinite duration of treatment is warranted.     

The optimal duration of anticoagulant treatment following pulmonary embolism

The optimal course of oral anticoagulant therapy is determined according to the risk of recurrent venous thromboembolism after stopping therapy and the risk of anticoagulant-related bleeding. Clinical risk factors appear to be important in predicting the risk of recurrence whereas the influence of biochemical and morphological tests is uncertain. The risk of recurrent venous thromboembolism is low when the initial episode was provoked by a reversible major risk factor (surgery): 3 months of anticoagulation is sufficient. Conversely, the risk is high when venous thromboembolism was unprovoked or associated with persistent risk factor (cancer): 6 months or more prolonged anticoagulation is necessary. After this first estimation, the duration of anticoagulation may be modulated according to the presence or absence of certain additional risk factors (major thrombophilia, chronic pulmonary hypertension, massive pulmonary embolism): 6 months if pulmonary embolism was provoked and 12 to 24 months if pulmonary embolism was unprovoked. If the risk of anticoagulant-related bleeding is high, the duration of anticoagulation should be shortened (3 months if pulmonary embolism was provoked and 3 to 6 months if it was unprovoked). Lastly, if pulmonary embolism occurred in association with cancer, anticoagulation should be conducted for 6 months or more if the cancer is active or treatment is on going. Despite an increasing knowledge of the risk factors for recurrent venous thromboembolism, a number of issues remain unresolved. Randomised trials comparing different durations of anticoagulation are needed.     

Thromboembolism--an important manifestation of inflammatory bowel disease

Thromboembolism is an extraintestinal manifestation and an important cause of mortality in inflammatory bowel disease (IBD). The risk of thromboembolism appears to be multifactorial and related to mucosal inflammatory activity in most patients. Various laboratory markers such as thrombin activatable fibrinolysis inhibitor (TAFI) levels have been linked with thrombophilia in IBD but no single laboratory marker has emerged with sufficient predictive value to identify patients at particular risk. Prospective multifactorial analyses will be required; in the interim, clinicians must be vigilant and address common risk factors for thromboembolism in all patients with IBD.     

The role of ethnicity,age and gender in venous thromboembolism

Venous thromboembolism, including both deep venous thrombosis and pulmonary embolism, is the leading cause of preventable in-hospital mortality. In the inexorable progress towards individualization of risk and personalized medicine, several congenital and acquired risk factors have been identified. However, the influence of some demographical variables, especially ethnicity, age and gender, has largely been under appreciated. Although the incidence of venous thromboembolism varies widely among diverse racial/ethnic cohorts, it appears globally highest in Blacks, is intermediate in Caucasians and is lowest in Asians. The incidence and prevalence of venous thromboembolism is also strongly age-related, increasing nearly 90 fold from <15 to >80 years old. Definitive data on the relative frequency of venous thromboembolism across genders is lacking. Some studies report that gender is not an independent risk factor of venous thromboembolism, while others conclude that female gender might be a protective variable. The purpose of this review is to assess the relationship between such demographic variables and venous thromboembolism.     

Venous thromboembolism prophylaxis for the medical patient: where do we stand?

Acutely ill medical patients are at moderate to high risk of venous thromboembolism: ~10 to 30% of general medical patients may develop deep vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Medical conditions associated with a high risk of venous thromboembolism include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious diseases. Predisposing risk factors in medical patients include a history of venous thromboembolism, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility, and obesity. Heparins, including unfractionated and low molecular weight, as well as fondaparinux have been shown to be effective agents in prevention of VTE in this setting. However, it has not yet been possible to demonstrate a significant effect on mortality rates in this population. In medical patients, unfractionated heparin has a higher rate of bleeding complications than low molecular weight heparin. There is no evidence for the use of aspirin, warfarin, or mechanical methods. We recommend either low molecular weight heparin or fondaparinux as safe and effective agents in the thromboprophylaxis of medical patients.