Risk factors for thrombophilia in extrahepatic portal vein obstruction

Scant information exists on the role of thrombophilia in extrahepatic portal vein obstruction (EHPVO). We studied 65 patients with EHPVO, 500 with deep vein thrombosis (DVT) of the lower limbs, and 700 healthy controls referred for thrombophilia screening, including the search for gain-of-function mutations in genes encoding coagulation factor V (factor V Leiden) and prothrombin (prothrombin G20210A); antithrombin, protein C, and protein S deficiency; and hyperhomocysteinemia. At least one abnormality in the thrombophilia screening was found in 40% of patients with either EHPVO or lower limb DVT and in 13% of controls, for odds ratios of 4.0 (95% CI, 2.3-7.0) and 4.4 (95% CI, 3.3-5.9), respectively. Statistically significant associations with EHPVO were observed for the prothrombin G20210A mutation (odds ratio, 8.1; 95% CI, 3.8-17.5) and the deficiencies of antithrombin, protein C, or protein S taken together (odds ratio, 4.5; 95% CI, 1.1-18.0). The odds ratio for the prothrombin G20210A was approximately twice that for lower limb DVT. Patients with factor V Leiden had an odds ratio for EHPVO of 0.8 (95% CI, 0.1-6.4) and for lower limb DVT of 7.5 (95% CI, 4.4-13.0). The odds ratio for EHPVO in patients with hyperhomocysteinemia was 2.0 (95% CI, 0.9-4.9). At variance with lower limb DVT, oral contraceptive use was not associated with an increased risk of EHPVO. Myeloproliferative disorders were diagnosed in 35% of patients with EHPVO. In conclusion, the risk for EHPVO is increased in the presence of thrombophilia resulting from the prothrombin G20210A mutation and from the deficiencies of the naturally occurring anticoagulant proteins, but not from factor V Leiden.     

Cumulative flying time and risk of venous thromboembolism

The risk of venous thromboembolism (VTE) associated with cumulative flying time remains uncertain. In a case-control study in general practices throughout the UK, participants comprised 550 VTE cases identified from practice records and 1971 age- and gender-matched controls. Participants returned identical questionnaires asking for information including air travel details. Compared to not flying, cumulative flying time >12 h within the previous 4 weeks was associated with a threefold increase in the risk of VTE [odds ratio (OR) 2·75, 95% confidence interval (CI), 1·44-5·28]. Those who had flown >4 h in a single leg in the previous 4 weeks had twice the risk of VTE (OR 2·20, 95% CI, 1·29-3·73). These risks were no longer evident by 12 weeks and were similar to those of day-case or minor surgery (OR 5·35, 95% CI, 2·15-13·33). Equivalent risks for moderate and high-risk surgery were over 30-fold (OR 36·57, 95% CI, 13·05-102·52) and 140-fold (OR 141·71, 95% CI, 19·38-1036·01) respectively. The temporary nature of the association of cumulative and long-haul air travel with VTE suggests a causal relationship. The risks of VTE in those with a higher baseline risk due to surgery, previous VTE or obesity are further increased by air travel.     

Risk factors and short-term mortality of venous thromboembolism diagnosed in the primary care setting in the United Kingdom

BACKGROUND: Venous thromboembolism (VTE) manifesting as deep vein thrombosis (DVT) and pulmonary embolism (PE) remains a common vascular disease with high mortality and morbidity. Our aim was to study the clinical spectrum of VTE, assess its incidence in the general population, and evaluate potential risk factors. METHODS: Prospective cohort study with nested case-control analysis using the General Practice Research Database (1994-2000). Venous thromboembolism was newly diagnosed in 6550 patients. Cases were compared with a random sample of 10,000 controls and frequency-matched by age, sex, and year. RESULTS: The incidence rate of VTE was 74.5 per 100,000 person-years. Overweight, varicose veins, inflammatory bowel disease, cancer, and oral corticosteroid use were associated with a greater risk of VTE. Ischemic heart disease, heart failure, and cerebrovascular diseases were associated with an increased risk of PE but not with DVT. Venous thromboembolism was strongly associated with fractures (odds ratio [OR], 21.3; 95% confidence interval [CI], 15.7-28.9) and surgery (OR, 25.0; 95% CI, 14.4-43.5). In women, the risk of VTE was 1.9 (95% CI, 1.5-2.3) among those receiving opposed hormone therapy (in which the woman takes estrogen throughout the month and progesterone for 10-14 days later in the month) and 1.9 (95% CI, 1.4-2.5) among those taking oral contraceptives. Cancer and cerebrovascular diseases presented a greater relative risk of fatal PE compared with nonfatal PE. CONCLUSIONS: Overweight, varicose veins, cancer, inflammatory bowel disease, fractures, surgery, and use of oral corticosteroids, oral contraceptives, and opposed hormone therapy were independent risk factors for both DVT and PE. The magnitude of the association with some risk factors varied between DVT and PE, as well as between fatal and nonfatal PE.     

Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry

BACKGROUND: There is little information on the clinical outcome of patients with upper-extremity deep vein thrombosis (DVT). METHODS: RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute DVT or pulmonary embolism (PE). In this analysis, we analyzed the demographic characteristics, treatment, and 3-month outcome of all patients with DVT in the arm. RESULTS: Of the 11,564 DVT patients enrolled, 512 patients (4.4%) had arm DVT. They presented less often with clinically overt PE (9.0% vs 29%; odds ratio, 0.24; 95% confidence interval [CI], 0.18 to 0.33) than those with lower-limb DVT, but their 3-month outcome was similar. Of the 512 patients with arm DVT, 196 patients (38%) had cancer and 228 patients (45%) had catheter-related DVT. During follow-up, those with cancer DVT had an increased incidence of major bleeding (4.1% vs 0.9%; odds ratio, 4.4; 95% CI, 1.2 to 21), recurrent venous thromboembolism (6.1% vs 2.8%; odds ratio, 2.2; 95% CI, 0.91 to 5.6; p = 0.04), and death (22% vs 3.5%; odds ratio, 7.8; 95% CI, 4.0 to 16). Thirty patients had the composite event of recurrent DVT, symptomatic PE, or major bleeding. They were significantly older, more often had cancer, and presented more frequently with symptomatic PE on hospital admission. On multivariate analysis, only cancer patients with arm DVT had an increased risk for the composite event (odds ratio, 3.0; 95% CI, 1.4 to 6.4). CONCLUSIONS: At presentation, patients with arm DVT have less often clinically overt PE than those with lower-limb DVT, but their 3-month outcome is similar. Among patients with arm DVT, those with cancer have the worse outcome.     

High levels of factor IX increase the risk of venous thrombosis

Elevated plasma levels of factor VIII (> 150 IU/dL) are an important risk factor for deep vein thrombosis (DVT). Factor VIII is the cofactor of factor IXa in the activation of factor X. The risk of thrombosis in individuals with an elevated factor IX level is unknown. This study investigated the role of elevated factor IX levels in the development of DVT. We compared 426 patients with a first objectively diagnosed episode of DVT with 473 population controls. This study was part of a large population-based case-control study on risk factors for venous thrombosis, the Leiden Thrombophilia Study (LETS). Using the 90th percentile measured in control subjects (P(90) = 129 U/dL) as a cutoff point for factor IX levels, we found a 2- to 3-fold increased risk for individuals who have factor IX levels above 129 U/dL compared with individuals having factor IX levels below this cutoff point. This risk was not affected by adjustment for possible confounders (age, sex, oral contraceptive use, and high levels of factor VIII, XI, and vitamin K-dependent proteins). After exclusion of individuals with known genetic disorders, we still found an odds ratio (OR) of 2.5 (95% confidence interval [CI]: 1.6-3.9). The risk was higher in women (OR: 2.6, CI: 1.6-4.3) than in men (OR: 1.9, CI: 1.0-3.6) and appeared highest in the group of premenopausal women not using oral contraceptives (OR: 12.4, CI: 3.3-47.2). These results show that an elevated level of factor IX is a common risk factor for DVT. (Blood. 2000;95:3678-3682)     

No association between pulmonary embolism or deep vein thrombosis and the -455G/A beta-fibrinogen gene polymorphism.

Hyperfibrinogenaemia has been reported to be associated with deep vein thrombosis (DVT). However, whether or not the "fibrinogen-raising"-455G/A polymorphism of the beta-fibrinogen gene is associated with DVT is uncertain and there are no data on whether this polymorphism is associated with pulmonary embolism (PE). We have studied relationships between the -455G/A beta-fibrinogen gene polymorphism and the occurrence of PE and/or DVT (n = 339) (PE only, n = 76; DVT only, n = 216; PE and DVT, n = 47). There was no difference between the -455A allelic frequencies for the control (n = 190) and patient groups - PE, 0.187 and 0.171, respectively [P = 0.6087, chi test; odds ratio (OR), 1.12; 95% confidence interval (CI), 0.72-1.74]; DVT, 0.187 and 0.171, respectively (P = 0.5408, chi test; OR, 1.11; 95% CI, 0.78-1.59). This also applied when only Caucasian individuals were considered - PE allelic frequencies, 0.192 and 0.193, respectively (P = 0.9764, chi test; OR, 0.99; 95% CI, 0.62-1.60); DVT allelic frequencies, 0.192 and 0.186, respectively (P = 0.8404, chi test; OR, 1.04; 95% CI, 0.71-1.51). While the results should be interpreted with caution as the frequency of the -455A allele is rare, the -455A allele of the beta-fibrinogen gene does not appear to be associated with an increased risk of PE or DVT.     

Risk factors for deep vein thrombosis in older patients: a multicenter study with systematic compression ultrasonography in postacute care facilities in France

OBJECTIVES: To identify risk factors for deep vein thrombosis (DVT) in older patients with restricted mobility or functional disability.
DESIGN: Cross-sectional.
SETTING: Forty-two postacute care departments in France.
PARTICIPANTS: Eight hundred twelve patients aged 65 and older.
MEASUREMENTS: Twenty-two predefined characteristics were investigated, including medical and surgical risk factors, dependence in six basic activities of daily living (ADLs) rated using the Katz index, mobility, the reported value of the Timed Up and Go Test, and pressure ulcers. All patients underwent lower limb ultrasonography on the day of the cross-sectional study.
RESULTS: DVT was found in 113 patients (14%, 33 proximal DVTs (4%) and 80 isolated distal DVTs (10%)). A positive trend was found in the odds of DVT for higher values on the Timed Up and Go Test for patients who were not bedridden or confined to a chair ( P =.007). In two-level multivariable analysis adjusting for prophylaxis against venous thromboembolism, independent risk factors for DVT were aged 80 and older (adjusted odds ratio (aOR)=1.71, 95% confidence interval (CI)=1.05–2.79), previous history of venous thromboembolism (aOR=2.03, 95% CI=1.06–3.87), regional or metastatic-stage cancer (aOR=2.71, 95% CI=1.27–5.78), dependence in more than three ADLs (aOR=2.18, 95% CI=1.38–3.45), and pressure ulcers (aOR=1.85, 95% CI=1.05–3.24).
CONCLUSION: Severe dependence in basic ADLs and higher Timed Up and Go Test score are associated with greater odds of DVT in older patients in postacute care facilities in France.     

Measurement of a newly developed thrombomodulin addition activated partial thromboplastin time assay in patients with deep venous thrombosis.

We developed a simple assay using rabbit thrombomodulin (TM) based on an activated partial thromboplastin time method, which detected the response to TM in plasma coagulation. We call it thrombomodulin addition clotting time (TACT). The anticoagulant response to TM was calculated by dividing the clotting time with TM by the clotting time with buffer solution. Results were expressed as TACT ratio, which indicates the degree of inhibition of plasma clotting by TM. Using this assay, we measured the TACT ratio in 80 patients with deep-vein thrombosis (DVT) and in 126 controls matched to the patients according to age and sex. A significant difference in the TACT ratio was observed between patients with DVT (mean 1.874) and controls (mean 1.956) (p < 0.001). Twenty- three patients (29%) had TACT ratios below the 10th percentile (1.757) of distribution of control subjects (odds ratio: 3.5; 95% confidence interval (CI): 1.7-7.2). After excluding subjects with a deficiency of protein C, protein S and antithrombin III, we found an odds ratio for DVT of 3.4 (95% CI: 1.6-7.2). These data suggest that natural anticoagulant deficiencies do not influence the TACT ratio, and our case-control study may show that the plasma of patients with DVT has a low response to TM.     

Risk factors for recurrent thrombosis: prospective study of a cohort of Japanese systemic lupus erythematosus

Not only antiphospholipid antibodies (aPLs) but also other factors should be considered in assessing the risk of thrombosis development in patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPLs). The kinds of risk factors, including past history of thrombotic event (PHTE), hypertension, hypercholesterolemia, diabetes mellitus (DM), obesity, and smoking, in conjunction with aPLs, that contribute to the development of new thrombotic events in patients with SLE and aPLs were studied prospectively over a 5-year observation period. One-hundred and sixty-six Japanese patients with SLE (55 patients with aPLs and 111 patients without aPLs) were examined and followed up for 5 years. Five major risk factors for ischemic coronary disease and stroke according to the Framingham heart cohort study were evaluated objectively in these patients. A significant difference was seen for 4 factors: past history of thrombotic event (PHTE; odds ratio: 101.93; 95% confidence interval: 12.29-845.22; p < 0.0001), hypertension (odds ratio: 8.87; 95% CI: 2.58-30.53; p < 0.001), DM (odds ratio: 5.42; 95% CI: 1.44-20.46; p < 0.05), and lupus anticoagulant (LAC; odds ratio: 47.41; 95% CI: 5.88-382.03, p < 0.0001) as aPLs, when the incidence of these risk factors was compared between patients with and without new thrombotic events. Furthermore, PHTE (odds ratio: 30.19, 95% CI: 1.33-683.13), hypertension (odds ratio: 15.44; 95% CI: 1.77-134.80), and LAC (odds ratio: 14.11; 95% CI: 0.48-412.42) showed higher odds ratios than DM (odds ratio: 11.53; 95% CI: 0.83-159.94) on multivariate logistic analysis as well as analysis of the combination of risk factors, suggesting that these are important risk factors for the development of new thrombotic events in patients with SLE and aPLs.     

Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy

BACKGROUND: In patients with venous thromboembolism (VTE), identifying clinical risk factors for recurrence during the initial 3 months of anticoagulant therapy and knowledge of the time course of recurrence may help clinicians decide about the frequency of clinical surveillance and the appropriateness of outpatient treatment. METHODS: Analysis of a randomized controlled trial database involving 1021 patients with VTE (750 with deep vein thrombosis [DVT] and 271 with pulmonary embolism [PE]) who were followed up for 3 months after the start of anticoagulant therapy. All patients received initial treatment with unfractionated heparin or a low-molecular-weight heparin (reviparin) and a coumarin derivative starting the first or second day of treatment, with a target international normalized ratio of 2.0 to 3.0. RESULTS: Four independent clinical risk factors for recurrent VTE were identified: (1) cancer (odds ratio [OR], 2.72; 95% confidence interval [CI], 1. 39-5.32), (2) chronic cardiovascular disease (OR, 2.27; 95% CI, 1. 08-4.97), (3) chronic respiratory disease (OR, 1.91; 95% CI, 0.85-4. 26), and (4) other clinically significant medical disease (OR, 1.79; 95% CI, 1.00-3.21). Older age was associated with a decreased risk for recurrent VTE (OR, 0.76; 95% CI, 0.64-0.92). Previous VTE, sex, and idiopathic VTE were not risk factors for recurrence. In patients with DVT or PE, there was no significant difference in the rates of recurrent nonfatal VTE (4.8% vs 4.1%; P =.62), major bleeding (2.9% vs 2.2%; P =.53), and non-VTE death (6.4% vs 7.8%; P =.45), but recurrent fatal PE was more frequent in patients with PE than DVT (2. 2% vs 0%; P<.01). There was a clustering of recurrent VTE episodes during the initial 2 to 3 weeks after the start of treatment. CONCLUSIONS: During the initial 3 months of anticoagulant therapy, recurrent VTE is more likely to occur in patients with cancer, chronic cardiovascular disease, chronic respiratory disease, or other clinically significant medical disease. Patients with PE are as likely to develop recurrent VTE as those with DVT; however, recurrence is more likely to be fatal in patients who initially present with PE. Arch Intern Med. 2000;160:3431-3436.     

An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study

BACKGROUND: Little information is available concerning risk factors for venous thromboembolism (VTE) in nonhospitalized patients. PARTICIPANTS AND METHODS: An epidemiologic case-control study of deep vein thrombosis (DVT) risk factors was conducted in 1272 outpatients by general practitioners. The case population (636 patients presenting with DVT) was paired with the control population (636 patients presenting with influenzal or rhinopharyngeal syndrome) according to sex and age. Deep vein thrombosis was to be documented by at least 1 objective test. Risk factors were classified into "intrinsic" ("permanent") and "triggering" ("transient") factors and were evidenced using univariate analysis. RESULTS: In the medical population, defined as patients who had not undergone surgery or application of a plaster cast to the lower extremities within the 3 weeks preceding inclusion (494 cases and 494 controls), intrinsic factors such as history of VTE, venous insufficiency, chronic heart failure, obesity, immobile standing position, history of more than 3 pregnancies, and triggering factors such as pregnancy, violent effort, or muscular trauma, deterioration of general condition, immobilization, long-distance travel, and infectious disease were significantly more frequent in the case patients than in the controls (odds ratio, >1; P<.05). In the overall population, additional risk factors were cancer, blood group A, plaster cast of the lower extremities, and surgery. In both populations, the number of risk factors per patient was greater in the case patients than in the controls. CONCLUSION: Several risk factors for DVT were identified in medical outpatients presenting with DVT, and their comprehension may improve appropriateness and efficiency of the different methods available for thromboprophylaxis. Arch Intern Med. 2000;160:3415-3420.     

Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives

BACKGROUND: Conflicting data are available on air travel as a risk factor for venous thromboembolism. To our knowledge, there are no studies investigating whether individuals with thrombophilia and those taking oral contraceptives are more likely to develop venous thromboembolism during flights than those without these risk factors. PARTICIPANTS AND METHODS: The study sample consisted of 210 patients with venous thromboembolism and 210 healthy controls. DNA analysis for mutations in factor V and prothrombin genes and plasma measurements of antithrombin, protein C, protein S, total homocysteine levels, and antiphsopholipid antibodies were performed. RESULTS: In the month preceding thrombosis for patients, or the visit for controls, air travel was reported by 31 patients (15%) and 16 controls (8%), with an oddsratio of 2.1 (95% confidence interval, 1.1-4.0). Thrombophilia was present in 102 patients (49%) and 26 controls (12%), and oral contraceptives were used by 48 patients and 19 controls (61% and 27% of those of reproductive age, respectively). After stratification for the presence of air travel and thrombophilia, the odds ratio for thrombosis in individuals with both risk factors was 16.1 (95% confidence interval, 3.6-70.9). Stratification for the presence of air travel and oral contraceptive use gave an odds ratio of 13.9 (95% confidence interval, 1.7-117.5) in women with both risk factors. CONCLUSIONS: Air travel is a mild risk factor for venous thromboembolism, doubling the risk of the disease. When thrombophilia or oral contraceptive use is present, the risk increases to 16-fold and 14-fold, respectively, indicating a multiplicative interaction.     

Incidence of air travel-related pulmonary embolism at the Madrid-Barajas airport

BACKGROUND: Prolonged air travel and the associated immobilization are risk factors for venous thromboembolism. The occurrence of pulmonary thromboembolism (PTE) under these circumstances is referred to as economy class syndrome. We assessed the incidence of symptomatic PTE in passengers on long-haul flights arriving at Madrid-Barajas Airport, Madrid, Spain, and the association with the number of flight hours. METHODS: We retrospectively reviewed cases of PTE among international travelers arriving at Madrid-Barajas Airport between January 1995 and December 2000. Patients presenting with symptoms of deep venous thrombosis but without symptoms of PTE were excluded. Pulmonary thromboembolism was identified using an algorithm of diagnostic tests. The incidence of PTE and the association with flight duration was assessed. RESULTS: The average number of passengers per year who arrived at the airport on flights originating abroad in the period analyzed was 6 839 222. Sixteen cases of PTE were detected over the 6-year period. All patients with travel-associated PTE had flight durations of greater than 6 hours. The overall incidence of PTE was 0.39 per 1 million passengers (95% confidence interval [CI], 0.20-0.58). On flights that lasted between 6 and 8 hours, the incidence was 0.25 per 1 million passengers (95% CI, 0-0.75), while on flights longer than 8 hours, the incidence was 1.65 per 1 million passengers (95% CI, 0.81-2.49) (P<.001). CONCLUSIONS: Air travel is a risk factor for PTE, and the incidence of PTE increases with the duration of the air travel. However, the low incidence of PTE among long-distance passengers, similar to that observed in other international airports, does not justify social alarm.     

Risk of venous thrombosis in carriers of the prothrombin G20210A variant and factor V Leiden and their interaction with oral contraceptives

BACKGROUND AND OBJECTIVES: The prothrombin G20210A mutation and factor V Leiden have been found to be associated with an increased risk of venous thrombosis, but the reported prevalences of the prothrombin gene variant both in the normal population and in patients with deep venous thrombosis (DVT) vary greatly in the literature. Moreover, the influence of oral contraceptives (OC) on thrombotic events in patients with the prothrombin G20210A variant has not been well established. In this study we evaluate both circumstances. DESIGN AND METHODS: A case-control study was run on 229 patients with DVT and 246 healthy controls. The patients' history of thrombosis and acquired thrombotic risk factors, especially OC, were recorded. Prothrombin G20210A mutation, factor V Leiden, antithrombin, heparin II cofactor, plasminogen and proteins C and S were evaluated. RESULTS: Seven and a half percent of the patients and 2.9% of the controls were carriers of the prothrombin mutation, while 12.2% of the patients and 1.6% of the controls had factor V Leiden. Among the 229 DVT patients there were 130 patients with clinically suspected thrombophilia (first thrombotic event occurring before the age of 45 years or positive family history of thrombosis or recurrent venous thrombosis). Ten percent of these 130 patients were carriers of the prothrombin G20210A mutation and 18.5% had the factor V Leiden mutation. The odds ratios (OR) for DVT risk were: 2.4 (95% CI, 1.0-6.3) for the total DVT patients and 5.2 (95% CI, 1.4-19.5) for the patients with clinically suspected thrombophilia with the prothrombin mutation. The risk of thrombosis was 6.9 (95% CI, 2.3-20.6) for the DVT patients and 14.3 (95% CI, 3.3-64.6) for the patients with clinically suspected thrombophilia with factor V Leiden. Fifty-five percent of the patients with combined congenital defects (prothrombin mutation G20210A plus another congenital defect) had recurrent thrombosis. In women receiving OC the risk of DVT was 3.5 (95% CI, 1.5-8.2) that of the patients not receiving OC. When women with combined defects were also taking OC, the risk of thrombosis increased significantly. INTERPRETATION AND CONCLUSIONS: The prevalence of the prothrombin G20210A mutation in the healthy population in our study is similar to that observed in other southern European countries. The prothrombin G20210A mutation does not by itself seem to be a high thrombotic risk factor. However, when it is present together with other thrombotic risk factors, the predicted risk of thrombotic events increases. The use of OC by women with the prothrombin G20210A variant or FV Leiden, either alone or combined with other thrombotic risk factors, was associated with a significant increase in the risk of venous thrombosis.     

Hepatitis E virus antibody prevalence among persons who work with swine.

Prevalence of antibody and risk factors to hepatitis E virus (HEV) infection were determined in a cross-sectional study of 2 group-matched populations: swine farmers (n=264) and persons without occupational exposure to swine (n=255) in Moldova, a country without reported cases of hepatitis E. The prevalence of HEV infection was higher among swine farmers than among the comparison group (51.1% vs. 24.7%; prevalence ratio, 2.07; 95% confidence interval [CI], 1.62-2.64). In multivariate analysis, HEV infection was associated with an occupational history of cleaning barns or assisting sows at birth (odds ratio [OR], 2.46; 95% CI, 1.52-4.01), years of occupational exposure (OR, 1.04 per year; 95% CI, 1.01-1.07), and a history of drinking raw milk (OR, 1.61; 95% CI, 1.08-2.40). HEV infection was not associated with civilian travel abroad or having piped water in the household. The increased prevalence of HEV infection among persons with occupational exposure to swine suggests animal-to-human transmission of this infection.     

Hyperlipidaemia and venous thromboembolism in patients lacking thrombophilic risk factors

To ascertain the potential contribution of serum lipids to the development of deep vein thrombosis (DVT), a case-control study was conducted in 143 DVT patients lacking thrombophilic risk factors and in 194 age- and sex-matched controls. DVT patients showed significantly higher body mass indices (BMI), and triglyceride levels than did controls (P < 0.001 and P = 0.045 respectively). Using multivariate analysis, BMI was the only variable which remained statistically different, thus the risk of DVT was associated with obesity (odds ratio = 2.49). These results were confirmed when additional control for fibrinogen and plasminogen activator inhibitor type 1 (PAI-1) was carried out in a subgroup of cases and controls. When idiopathic (n = 39) and secondary (n = 104) patients with DVT were compared, the former showed a higher mean age, a higher proportion of men, and higher cholesterol levels. Age, sex and total cholesterol were statistically different by multivariate analysis. After age was dichotomized as >or= 50 years and cholesterol >or= 5.69 mmol/l, all three variables constituted independent risk factors for idiopathic DVT, with odds ratios of 2.73 for ages >or= 50 years; 3.72 for men and 2.67 for cholesterolaemia >or= 5.69 mmol/l. Obesity thus constitutes an independent risk factor for DVT, possibly in part mediated through triglyceride, fibrinogen and PAI-1 effects on haemostasis. In addition, cholesterolaemia levels of >or= 5.69 mmol/l constitute an independent risk factor for idiopathic DVT.     

Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors

BACKGROUND: The recurrence rate after deep vein thrombosis (DVT) is high and the risk factors for recurrent thromboembolic events have only been investigated on a small scale. OBJECTIVES: To estimate the cumulative incidence of recurrent venous thromboembolic events after a first or a second DVT and to identify possible risk factors for recurrent venous thromboembolism. METHODS: We prospectively followed up 738 consecutive patients with an objectively verified symptomatic DVT for 3.7 to 8.8 years. Medical records and death certificates for all patients were reviewed during follow-up and recurrent DVT and pulmonary embolism were registered. RESULTS: The 5-year cumulative incidence of recurrent venous thromboembolic events was 21.5% (95% confidence interval [CI], 17.7%-25.4%) after a first DVT and 27.9% (95% CI, 19.7%-36.1%) after a second DVT. The 5-year cumulative incidence of fatal pulmonary embolism was 2.6% (95% CI, 1.1%-4.1%) after a first DVT. Proximal DVT (relative risk [RR], 2.40; 95% CI, 1.48-3.88; P<.001), cancer (RR, 1.97; 95% CI, 1.20-3.23; P<.001), and history of a venous thromboembolism (RR, 1.71; 95% CI, 1.16-2.52; P<.01) predicted an independently increased risk of recurrent events in multivariate survival analysis. Postoperative DVT (RR, 0.27; 95% CI, 0.13-0.55; P<.001) and a long duration of oral anticoagulation therapy (RR, 0.95; 95% CI, 0.92-0.98; P<.01) involved a smaller risk of recurrent events. Sex, age, initial antithrombotic therapy, or immobilization did not affect the risk of a recurrent event. CONCLUSIONS: The recurrence rate after a symptomatic DVT is high. Patients with proximal DVT, diagnosed cancer, short duration of oral anticoagulation therapy, or a history of thromboembolic events had a higher risk of recurrent events, while patients with postoperative DVT had a lower recurrence rate. This knowledge could help identify patients who might benefit most from prolonged prophylactic treatment in various risk situations.     

Venous thrombosis after long-haul flights

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Prophylaxis against venous thromboembolism in hospitalized medical patients: an evidence-based and practical approach

To discuss the evidence regarding the efficacy and safety of anticoagulant prophylaxis against deep vein thrombosis (DVT) in hospitalized medical patients; to understand barriers to implementation of prophylaxis and how they can be overcome; and to have a practical approach as to which patients should and should not receive anticoagulant prophylaxis. The frequency of DVT in hospitalized medical patients, in the absence of prophylaxis varies from 10-15%. Autopsy studies have shown that pulmonary embolism (PE) is associated with 5-10% of deaths in hospitalized patients. With appropriate use of anticoagulant prophylaxis, there is a 57% reduction in the risk for symptomatic PE (relative risk [RR] 0.43, 95% CI 0.26-0.71), a 62% reduction in the risk for fatal PE (RR 0.38, 95% CI 0.21-0.69), and a 53% reduction in the risk for symptomatic DVT (RR 0.47, 95% CI 0.22-1.00). Anticoagulant prophylaxis is also associated with a non-significant increased risk for major bleeding (RR 1.32, 95% CI 0.73-2.37). Risk factors for DVT and bleeding in medical patients may help to identify patients in whom anticoagulant prophylaxis is indicated or contraindicated but validated risk stratifications schemes are lacking. Among hospitalized medical patients, randomized trials have established an acceptable therapeutic benefit-to-risk ratio of anticoagulant prophylaxis to reduce the incidence of clinically silent and symptomatic venous thromboembolism, including a reduction in the incidence of fatal PE. Additional research is needed to develop a validated risk stratification model for hospitalized medical patients that can help identify patients who would benefit most from anticoagulant prophylaxis.     

Venous thromboembolism in travellers: can we identify those at risk?

To assess the prevalence of clinical and laboratory risk factors in patients who develop venous thromboembolism following travel. The design was a case series of 58 consecutive patients presenting with venous thromboembolism within 30 days of travel. The setting was a major metropolitan teaching hospital and an affiliated private practice. The main outcome measures were prevalence of clinical and laboratory risk factors for venous thromboembolism, time to presentation, mode and duration of travel. Forty-eight [83%; 95% confidence interval (CI), 71-91%] of 58 patients developed venous thromboembolism following air travel. Thirty-four (59%; 95% CI, 45-71%) patients had travelled for more than 8 h and most patients were diagnosed with venous thromboembolism within 1 week of completing their journey. Pulmonary embolism occurred in 24 patients (41%; 95% CI, 29-55%), proximal deep vein thrombosis in 23 patients (40%; 95% CI, 27-53%), calf vein thrombosis in four patients (7%; 95% CI, 2-17%), and superficial thrombophlebitis in seven patients (12%; 95% CI, 5-23%). At least one clinical or laboratory risk factor (other than travel) was found in 49 patients (84%; 95% CI, 73-93%) and two or more risk factors were found in 30 patients (52%; 95% CI, 38-65%). The most common risk factors were oestrogens (24%; 95% CI, 14-37%), a past history of thrombosis (24%: 95% CI, 14-37%), and factor V Leiden (24%: 95% CI, 14-37%). These retrospective uncontrolled data suggest that at least one clinical or laboratory risk factor is present prior to travel in more than 80% of patients who develop venous thromboembolism within 30 days of travel. In most cases these risk factors can be identified by the clinical history alone, without recourse to laboratory testing. Whether patients with known risk factors for venous thromboembolism prior to travel should be targeted with specific thromboprophylaxis requires randomized evaluation.