Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient‐level meta‐analysis

Summary. Aim: To determine if the mode of presentation of venous thromboembolism (VTE), as deep vein thrombosis (DVT) or pulmonary embolism (PE), predicts the likelihood and type of recurrence. Methods: We carried out a patient‐level meta‐analysis of seven prospective studies in patients with a first VTE who were followed after anticoagulation was stopped. We used Kaplan‐Meier analysis to determine the cumulative incidence of recurrent VTE according to mode of presentation, and multivariable Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mode of and extent of DVT as potential risk factors for recurrence. Results: The 5‐year cumulative rate of recurrent VTE in 2554 patients was 22.6%. In 869 (36.1%) patients with PE, the 5‐year rate of any recurrence (DVT or PE) was 22.0%, and recurrence as PE was 10.6%. In 1365 patients with proximal DVT, the 5‐year recurrence rate was 26.4%, and recurrence with PE was 3.6%. The risk of recurrence as PE was 3.1‐fold greater in patients presenting with symptomatic PE than in patients with proximal DVT (HR, 3.1; 95% CI, 1.9–5.1). Patients with proximal DVT had a 4.8‐fold higher cumulative recurrence rate than those with distal DVT (HR, 4.8; 95% CI, 2.1–11.0). Conclusion: Whilst DVT and PE are manifestations of the same disease, the phenotypic expression is predetermined. Patients presenting with PE are three times more likely to suffer recurrence as PE than patients presenting with DVT. Patients presenting with calf DVT are at low risk of recurrence and at low risk of recurrence as PE.     

Prevalence and predictors for post‐thrombotic syndrome 3 to 16 years after pregnancy‐related venous thrombosis: a population‐based,cross‐sectional,case‐control study

Background:  The long‐term outcome of pregnancy‐related venous thrombosis (VT) is not known. Objectives:  To assess predictors and long‐term frequency of post‐thrombotic syndrome (PTS) after pregnancy‐related VT. Patients/Methods:  In 2006, 313 women with pregnancy‐related VT during 1990–2003 and 353 controls answered a comprehensive questionnaire that included self‐reported Villalta score as a measure of PTS. Cases were identified from 18 Norwegian hospitals using the Norwegian Patient Registry and the Medical Birth Registry of Norway. The latter was used to select as possible controls women who gave birth at the same time as a case. Thirty‐nine patients and four controls were excluded because of VT outside the lower limbs/lungs or missing Villalta scores. Two hundred and four patients had DVT in the lower limb and 70 had pulmonary embolism (PE). The control group comprised 349 women naive for VT at the time of the index pregnancy. Results:  Forty‐two per cent of cases with DVT in the lower limb, compared with 24% of cases with PE and 10% of controls, reported a Villalta score of ≥ 5. Severe PTS (Villalta score of ≥ 15) was reported among 7%, 4% and 1%. Proximal postnatal, but not antenatal, thrombosis was a strong predictor of PTS with an adjusted odds ratio of 6.3 (95% confidence interval, 2.0–19.8; P = 0.002). Daily smoking before the index pregnancy and age above 33 years at event were independent predictors for post‐thrombotic syndrome. Conclusions:  PTS is a common long‐term complication after pregnancy‐related DVT. Proximal postnatal thrombosis, smoking and higher age were independent predictors of the development of PTS.     

Long‐term outcomes of patients with cerebral vein thrombosis: a multicenter study

Summary. Background: Little information is available on the long‐term clinical outcome of cerebral vein thrombosis (CVT). Objectives and methods: In an international, retrospective cohort study, we assessed the long‐term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. Results: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient‐years. Median follow‐up was 40 months (range 6, 297 months). At the end of follow‐up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0–1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty‐four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient‐years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient‐years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). Conclusions: The long‐term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.     

Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs

Summary. Background: One in every three patients with deep vein thrombosis (DVT) in the lower limbs may have silent pulmonary embolism (PE), but its clinical relevance has not been thoroughly studied. Methods: We used the RIETE Registry data to study patients with proximal DVT and no PE symptoms, but with a systematic search for PE. We compared the outcome of DVT patients with silent PE and those with no PE. Results: Of 2375 patients with DVT, 842 (35%) had silent PE and 1533 had no PE. During the first 15 days of anticoagulation, patients presenting with silent PE had a higher incidence of symptomatic PE events than those with no PE (0.95% vs. 0.13%; P = 0.015), with a similar incidence of major bleeding (0.95% vs. 1.63%; P = 0.09). In patients with silent PE, the incidence of PE events during the first 15 days was equal to the incidence of major bleeding (eight events each), but in those with no PE the incidence of PE events was eight times lower (3 vs. 25 bleeding events). Multivariate analysis confirmed that DVT patients with silent PE had a higher incidence of symptomatic PE events during the first 15 days than those with no PE (odds ratio, 4.80; 95% CI, 1.27–18.1), with no differences in bleeding. Conclusions: DVT patients with silent PE at baseline had an increased incidence of symptomatic PE events during the first 15 days of anticoagulant therapy. This effect disappeared after 3 months of anticoagulation.     

Sex difference in risk of recurrent venous thrombosis and the risk profile for a second event

Summary Background: The risk of recurrent venous thrombosis is higher in men than in women, and this is so far unexplained. We set out to determine the influence of age, time between first and second event, type of first event, oral contraception, pregnancy and surgery. Methods: We performed a prospective follow‐up study of 474 patients with a first objective diagnosis of deep vein thrombosis, aged 18–70 years (Leiden Thrombophilia Study cohort). Results: During 3477 person‐years of follow‐up, 90 recurrences occurred. The overall incidence rates of recurrence (IRs) were 40.9 per 1000 person‐years in men and 15.8 per 1000 person‐years in women. Men with an unprovoked first event had the highest risk of recurrence, with almost one‐third experiencing a second unprovoked event within 8 years (IR 41.2 per 1000 person‐years). This risk was three‐fold lower in women [IR 14.2 per 1000 person‐years; hazard ratio 2.8 (95% confidence interval 1.4–5.7)]. Age at diagnosis had little effect on recurrence rate, and nor had time elapsed since the first event. In women, almost half of the recurrences were provoked and were mainly related to oral contraceptive use or pregnancy. Conclusions: The higher recurrence rate in men than in women is not the result of differences in the environmental or transient risk factors that we studied. The risk profile for a second thrombotic event is clearly different from that of a first.     

Clinical course of patients with symptomatic isolated superficial vein thrombosis: the ICARO follow‐up study

Essentials

• Late sequelae of isolated superficial vein thrombosis (iSVT) have rarely been investigated.
• We studied 411 consecutive outpatients with acute iSVT with a median follow‐up of three years.
• Male sex and cancer are risk factors for future deep vein thrombosis or pulmonary embolism.
• Patients without cancer appear to be at a negligible risk for death.

Summary

Background

Studies of long‐term thromboembolic complications and death following acute isolated superficial vein thrombosis (iSVT) of the lower extremities are scarce.

Objectives

To investigate the course of iSVT in the setting of an observational multicenter study.

Methods

We collected longitudinal data of 411 consecutive outpatients with acute, symptomatic, objectively diagnosed iSVT who were previously included in the cross‐sectional ICARO study. Four patients followed for < 30 days and 79 with concomitant deep vein thrombosis (DVT) or pulmonary embolism (PE) were excluded from the present analysis. The primary outcome was symptomatic DVT or PE. The safety outcomes were major bleeding and all‐cause death.

Results

The median follow‐up time was 1026 days (interquartile range 610–1796). Symptomatic DVT/PE occurred in 52 (12.9%) patients, giving annualized rates of 1.3% (95% confidence interval [CI] 0.3–3.9%) on anticoagulant treatment and 4.4% (95% CI 3.2–5.8%) off anticoagulant treatment. Male sex (adjusted hazard ratio [HR] 2.03 [95% CI 1.16–3.54]) and active solid cancer (adjusted HR 3.14 [95% CI 1.11–8.93]) were associated with future DVT/PE, whereas prior DVT/PE failed to show significance, most likely because of bias resulting from prolonged anticoagulant treatment. Three major bleeding events occurred on treatment, giving an annualized rate of 1.4% (95 CI 0.3–4.0%). Death was recorded in 16 patients (annualized rate: 1.1% [95% CI 0.6–1.7%]), and was attributable to cancer (n = 8), PE (n = 1), cardiovascular events (n = 3), or other causes (n = 4).

Conclusions

The long‐term risk of DVT/PE after anticoagulant discontinuation for acute iSVT is clinically relevant, especially in males and in the presence of active cancer. The risk of death appears to be negligible in patients without cancer.     

Venous thromboembolism and subsequent diagnosis of subarachnoid hemorrhage: a 20‐year cohort study

Summary. Background: Venous thromboembolism is a predictor of subsequent risk of ischemic stroke and intracerebral hemorrhage, but no data are available regarding its association with risk of subarachnoid hemorrhage. Objectives: To examine this issue, we conducted a nationwide cohort study in Denmark. Patients and methods: Between 1977 and 2007, we identified 97 558 patients with a hospital diagnosis of venous thromboembolism and obtained information on risk of subsequent subarachnoid hemorrhage during follow‐up in the Danish Registry of Patients. The incidence of subarachnoid hemorrhage in the venous thromboembolism cohort was compared with that of 453 406 population control cohort members. Results: For patients with pulmonary embolism (PE), there was clearly an increased risk of subarachnoid hemorrhage, both during the first year of follow‐up [relative risk 2.69; 95% confidence interval (CI), 1.32–5.48] and during later follow‐up of 2–20 years (relative risk 1.40; 95% CI, 1.05–1.87). For patients with deep venous thrombosis (DVT) the risk was likewise clearly increased during the first year of follow‐up (relative risk 1.91; 95% CI, 1.13–3.22), but not during later follow‐up (relative risk 1.04; 95% CI, 0.81–1.32). Conclusions: We found evidence that PE is associated with an increased long‐term risk of subarachnoid hemorrhage. The two diseases might share etiologic pathways affecting the vessel wall or share unknown risk factors.     

Family history of myocardial infarction is an independent risk factor for venous thromboembolism: the Tromsø study

Summary. Background: Recent studies indicate that arterial cardiovascular diseases and venous thromboembolism (VTE) share common risk factors. A family history of myocardial infarction (MI) is a strong and independent risk factor for future MI. Objectives: The purpose of the present study was to determine the impact of cardiovascular risk factors, including family history of MI, on the incidence of VTE in a prospective, population‐based study. Patients and methods: Traditional cardiovascular risk factors and family history of MI were registered in 21 330 subjects, aged 25–96 years, enrolled in the Tromsø study in 1994–95. First‐lifetime VTE events during follow‐up were registered up to 1 September 2007. Results: There were 327 VTE events (1.40 per 1000 person‐years), 138 (42%) unprovoked, during a mean of 10.9 years of follow‐up. In age‐ and gender‐adjusted analysis, age [hazard ratio (HR) per decade, 1.97; 95% confidence interval (CI), 1.82–2.12], gender (men vs. women; HR, 1.25; 95% CI, 1.01–1.55), body mass index (BMI; HR per 3 kg m^?2, 1.21; 95% CI, 1.13–1.31), and family history of MI (HR, 1.31; 95% CI, 1.04–1.65) were significantly associated with VTE. Family history of MI remained a significant risk factor for total VTE (HR, 1.27; 95% CI, 1.01–1.60) and unprovoked VTE (HR, 1.46; 95% CI, 1.03–2.07) in multivariable analysis. Blood pressure, total cholesterol, HDL‐cholesterol, triglycerides, and smoking were not independently associated with total VTE. Conclusions: Family history of MI is a risk factor for both MI and VTE, and provides further evidence of a link between venous and arterial thrombosis.     

The incidence and first‐year mortality of heart failure in Belgium: a 2‐year nationwide prospective registration

Aims: The aim of this study is to determine the incidence and mortality of heart failure (HF) in Belgium. Methods: Data were prospectively collected during a 2‐year period by a nationwide network of sentinel practices. All adult patients for whom, for the first time the diagnosis of HF was clinically suspected were registered. Patients were finally included if the diagnosis of HF was confirmed after 1 month. Results: The yearly incidence of confirmed HF in the Belgian adult population was estimated to be 194 patients per 100,000 inhabitants (95% CI: 172–218). At diagnosis, the median age of the patients with confirmed HF was 79 years: 82 years for women and 76 years for men (p < 0.0001). For the population aged 55 years or more, the yearly incidence of HF was 502 (95% CI: 444–565) with no significant difference between men and women. At diagnosis, most of the patients were classified as NYHA III (50%), 27% as NYHA IV and 20% as NYHA II. Six months after the initial diagnosis, the mortality was 19% and after 12 months it was 26%. Conclusion: In Belgium, yearly 15,643 new patients of HF are diagnosed (95% CI: 13,861–17,590). HF is fatal for more than one quarter of the patients in the first year after the diagnosis.     

Burden of illness in venous thromboembolism in critical care: a multicenter observational study

PURPOSE: The frequency of clinically diagnosed venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE) in medical-surgical critically ill patients is unclear. The objectives of this study were to estimate the prevalence and incidence of radiologically confirmed DVT and PE in medical-surgical intensive care unit (ICU) patients and to determine the impact of prophylaxis on the frequency of these events. MATERIALS AND METHODS: In a retrospective observational cohort study in 12 adult ICUs, we identified prevalent cases (diagnosed in the 24 hours preceding ICU admission up to 48 hours post-ICU admission) and incident cases (diagnosed 48 hours or more after ICU admission and up to 8 weeks after ICU discharge) of upper or lower limb DVT or PE. Deep venous thrombosis was diagnosed by compression ultrasound or venogram. Each DVT was classified as clinically suspected or not clinically suspected in that the latter was diagnosed by scheduled screening ultrasonography. Pulmonary embolism was diagnosed by ventilation-perfusion lung scan, computed tomography pulmonary angiography, echocardiography, electrocardiography, or autopsy. RESULTS: Among 12,338 patients, 252 (2.0%) patients had radiologically confirmed DVT or PE and another 47 (0.4%) had possible DVT or PE. Prevalent DVTs were diagnosed in 0.4% (95% confidence interval [CI], 0.3%-0.5%) of patients and prevalent PEs were diagnosed in 0.4% (95% CI, 0.3%-0.6%). Incident DVTs were diagnosed in 1.0% (95% CI, 0.8%-1.2%) of patients, and incident PEs were diagnosed in 0.5% (95% CI, 0.4%-0.6%). Of patients with incident VTE, 65.8% of cases occurred despite receipt of thromboprophylaxis for at least 80% of their days in ICU. The median (interquartile range) ICU length of stay was similar for patients with DVT (7 [3-17]) and PE (5 [2-8]). For all patients with VTE, ICU mortality was 16.7% (95% CI, 12.0%-21.3%) and hospital mortality was 28.5% (95% CI, 22.8%-34.1%). CONCLUSIONS: Venous thromboembolism appears to be an apparently infrequent, but likely underdiagnosed problem, occurring among patients receiving prophylaxis. Findings suggest the need for increased suspicion among clinicians, renewed efforts at thromboprophylaxis, and evaluation of superior prevention strategies.     

Familial thrombophilia and lifetime risk of venous thrombosis.

BACKGROUND: We started a large multicenter prospective follow-up study to provide reliable risk estimates of venous thrombosis in families with various thrombophilic defects. OBJECTIVES: This paper describes data collected at study entry on venous events experienced before study inclusion, i.e. the baseline data. PATIENTS/METHODS: All individuals (probands, relatives) registered in nine European thrombosis centers with the factor (F)V Leiden mutation, a deficiency of antithrombin, protein C or protein S, or a combination of these defects, were enrolled between March 1994 and September 1997. As control individuals, partners, friends or acquaintances of the thrombophilic participants were included. Incidence and relative risk of objectively confirmed venous thrombotic events (VTEs) prior to entry were calculated for the relatives with thrombophilia and the controls. RESULTS: Of the 846 relatives with thrombophilia (excluding probands), 139 (16%) had experienced a VTE with an incidence of 4.4 per 1000 person years. Of the controls, 15 of the 1212 (1%) controls had experienced a VTE with an incidence of 0.3 per 1000 person years. The risk of venous thrombosis associated with familial thrombophilia was 15.7 (95% CI 9.2-26.8) and remained similar after adjustment for regional and sex-effects (16.4; 95% CI 9.6-28.0). The highest incidence per 1000 person years was found in relatives with combined defects (8.4; 95% CI 5.6-12.2), and the lowest incidence was found in those with the FV Leiden mutation (1.5; 95% CI 0.8-2.6). CONCLUSIONS: Considerable differences in the lifetime risk of VTE were observed among individuals with different thrombophilia defects.     

Risk factors for post‐thrombotic syndrome in patients with a first deep venous thrombosis

Summary. Background: Post‐thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). Objectives: To determine the risk of PTS after DVT and to assess risk factors for PTS. Methods: Patients were recruited from the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Consecutive patients who suffered a first DVT of the leg were included in a follow‐up study. All patients completed a questionnaire and DNA was obtained. PTS was ascertained in a structured interview using a clinical classification score. Results: The 1‐year cumulative incidence of PTS was 25% and 7% for severe PTS. Elastic compression stockings were prescribed in 1412 (85%) patients. The majority used their stockings every day. Women were at an increased risk compared with men [risk ratio (RR) 1.5, 95% confidence interval (CI) 1.3–1.8]. Similarly, obese patients had a 1.5‐fold increased risk of PTS compared with normal weight patients (RR 1.5, 95% CI 1.2–1.9), with a 1‐year cumulative incidence of 34% compared with 22%. Patients who already had varicose veins had an increased risk (RR 1.5, 95% CI 1.2–1.8) of PTS. DVT in the femoral and iliac vein was associated with a 1.3‐fold increased risk of PTS compared with popliteal vein thrombosis (RR 1.3, 95% CI 1.1–1.6). Patients over 60 years were less likely to develop PTS than patients below the age of 30 (RR 0.6, 95% CI 0.4–0.9). Malignancy, surgery, minor injury, plaster cast, pregnancy or hormone use did not influence the risk of PTS neither did factor (F)V Leiden nor the prothrombin 20210A mutation. Conclusions: PTS is a frequent complication of DVT, despite the widespread use of elastic compression stockings. Women, obese patients, patients with proximal DVT and those with varicose veins have an increased risk of PTS, whereas the elderly appeared to have a decreased risk.     

Effect of a public awareness campaign on the incidence of symptomatic objectively confirmed deep vein thrombosis: a controlled study

Summary. Background: Although there have been attempts to raise public awareness about deep vein thrombosis (DVT), their influence on identifying confirmed cases is unknown. Objective: To determine the effect and its duration of a public awareness campaign about venous thromboembolism. Patients/Methods: A campaign to raise public awareness of DVT was conducted during one year in an urban population of approximately 100 000 (pop A). A comparison urban population of approximately 1 574 000 (pop B) was not exposed to this campaign. Patients symptomatic for DVT in both populations were referred by general practitioners for a standardized compression ultrasound (CUS) of the whole leg at no charge. Positive CUS examinations documented by photographs were analyzed by an independent adjudication committee blinded to the population. Pop A was followed for 8 months after the information campaign ended. Results and Conclusions: Symptomatic objectively confirmed DVT was found in 48 of 800 subjects tested in pop A and 226 of 2384 tested in pop B. The 1‐year incidence of confirmed DVT (proximal and distal) was 46/100 000 (95% CI, 33–59) in A and 14/100 000 (95% CI, 12–16) in B (P < 0.001). The increase in pop A was due to distal DVT (36/100 000 vs. 5/100 000 in pop B, P < 0.001). The DVT rate for pop A in an 8‐month follow‐up period was 12/100 000, significantly lower than in the first 8 months of the study period (34/100 000/8 months) (P = 0.001). The public awareness campaign significantly increased the diagnosis of distal DVT. When the campaign ended, DVT rates returned to community baseline.     

The Wells rule and D‐dimer for the diagnosis of isolated distal deep vein thrombosis

Summary. Background: Pretest clinical probability with the Wells rule and D‐dimer have been widely investigated for the diagnosis of symptomatic proximal deep vein thrombosis (DVT) of the lower limbs, but they have not been formally tested for symptomatic isolated distal DVT diagnosis. Objective: To evaluate the diagnostic accuracy of the Wells rule and D‐dimer for isolated distal DVT. Design, Setting, and Patients: This was a single‐center, cross‐sectional study including 873 consecutive outpatients with suspected DVT, in whom pretest clinical probability determination, D‐dimer determination (STA Liatest; cut‐off of < 500 ng mL^?1) and complete compression ultrasonography of both lower limbs were performed. Results: The isolated distal DVT prevalence was 12.4% (90/725). The sensitivity of the Wells rule for isolated distal DVT was 47% (95% confidence interval [CI] 36–57%), the specificity was 74% (95% CI 70–77%), and the negative and positive predictive values were 91% (95% CI 88–93%) and 20% (95% CI 15–26%), respectively. Patients with isolated distal DVT had higher D‐dimer levels than patients without DVT (1759 ± 1576 vs. 862 ± 1079 ng mL^?1, P = 0.0001). D‐dimer was negative in 13 patients with isolated distal DVT. D‐dimer sensitivity and specificity for isolated distal DVT were 84% (95% CI 75–91%) and 50% (95% CI 46–54%), respectively, with a negative predictive value of 96% (95% CI 93–98%). In patients with low pretest clinical probability, the D‐dimer negative predictive value was 99% (95% CI 95–100%). Conclusion: In clinically suspected DVT with negative proximal compression ultrasonography, pretest clinical probability with the Wells rule has a low diagnostic accuracy for isolated distal DVT. D‐dimer has a better negative predictive value, but alone it does not exclude isolated distal DVT. In patients with low pretest clinical probability, D‐dimer had a negative predictive value of > 95% for isolated distal DVT.     

Clinical outcomes after peripheral blood stem cell donation by related donors: a Dutch single‐center cohort study

BACKGROUND: Relatives donating peripheral blood stem cells (PBSCs) may be accepted for donation on less strict criteria than unrelated donors. We evaluated the occurrence of adverse events during procedure and follow‐up, with a special focus on donors who would have been deferred as unrelated donors. STUDY DESIGN AND METHODS: All 268 related PBSC donors at our center (1996‐2006) were included. Data were retrospectively collected from medical reports and standard follow‐up. Health questionnaires were sent from 2007. Medical outcomes of donors, deferrable or eligible according to international criteria for unrelated donation, were compared. RESULTS: Forty donors (15%) would have been deferred for unrelated donation. Short‐term adverse events occurred in 2% of procedures. Questionnaires were returned by 162 (60%) donors on average 7.5 years after donation, bringing total person‐years of follow‐up to 1278 (177 in deferrable donors). Nine malignancies and 14 cardiovascular events were reported. The incidence rate of cardiovascular events in eligible donors was 6.5 (95% confidence interval [CI], 2.5‐12.3) per 1000 person‐years compared to 44.9 (95% CI, 17.4‐85.2) in deferrable donors; incidence rates of malignancies were 4.6 (1.4‐9.6) and 24.0 (6.0‐53.9) per 1000 person‐years, respectively, in eligible and deferrable donors. All incidence rates were within the range of age‐ and sex‐matched general population. No autoimmune disorders were reported. CONCLUSION: In both the eligible and the deferrable related donors treated with granulocyte–colony‐stimulating factor there are few short‐term and long‐term problems. The occurrence of post‐PBSC cardiovascular events and malignant disease in related donors appears to be within the range of the general population.     

Incidence and cumulative recurrence rates of venous thromboembolism in the Taiwanese population

Summary. Background: Little information is available on the epidemiology of venous thromboembolism (VTE) in Asian populations. Objectives: To investigate VTE incidence, VTE cumulative recurrence rates and risk factors for VTE recurrence among the adult Taiwanese population. Methods: This population‐based cohort study used the Taiwanese National Health Insurance claims databases to identify 5347 adult patients (2463 men, 46.1%) with VTE diagnosed in 2001 and 2002. We calculated the crude incidence of VTE and its recurrence. We also conducted a nested case–control study (n = 3576) among this population to estimate the association between VTE recurrence and exposure to potential VTE risk factors by conditional logistic regression. Results: The crude incidence of VTE was 15.9 per 100 000 person‐years, and its recurrence rate was 5.1% per person‐year. During 11 566 person‐years of follow‐up, the cumulative rates of VTE recurrence at 6, 12, 24, 36 and 47 months were 6.7%, 9.4%, 12.4%, 13.9%, and 14.4%, respectively. By conditional logistic regression, histories of VTE [adjusted odds ratio (OR) 1.71, 95% confidence interval (CI) 1.32–2.16] or malignant neoplasm (adjusted OR 1.64, 95% CI 1.26–1.99), major extremity trauma (adjusted OR 2.76, 95% CI 1.82–4.52), serious neurologic diseases (adjusted OR 1.43, 95% CI 1.12–1.84) or undergoing major surgery (adjusted OR 4.57, 95% CI 1.72–12.50) were associated with higher risks of VTE recurrence. Conclusions: The incidence of VTE is lower in the Taiwanese population than in Caucasians. Most VTE recurrences occur within 12 months, but they continue to occur beyond 1 year. The VTE recurrences are associated with malignancy, history of VTE, and major surgery after a previous VTE.     

The effects of cause of death classification on prognostic assessment of patients with pulmonary embolism

Summary. Background: Although previous studies have provided evidence that the majority of deaths following an acute pulmonary embolism (PE) directly relate to the PE, more recent registries and cohort studies suggest otherwise. Methods: We assessed the cause of death during the first 30 days after the diagnosis of acute symptomatic PE in a consecutive series of patients. We also assessed the prognostic characteristics of the simplified Pulmonary Embolism Severity Index (sPESI) and cardiac troponin I (cTnI) obtained at the time of PE diagnosis. Results: During the first 30 days after diagnosis, 127 of the 1291 patients died (9.8%; 95% confidence interval [CI], 8.2–11.5). Sixty patients (4.6%; 95% CI, 3.5–5.8) died from definite or possible PE, and 67 (5.2%; 95% CI, 4.0–6.4) died from other causes (cancer 25, infection 18, hemorrhage 7, heart failure 7, chronic obstructive pulmonary disease 5, renal failure 1, seizures 1, unknown 3). The sPESI predicted all‐cause (odds ratio [OR], 5.97; 95% CI, 1.74–20.54; P < 0.01) and PE‐associated mortality (OR, 8.79; 95% CI, 1.12–68.79; P = 0.04). cTnI only predicted PE‐associated mortality (adjusted OR, 2.39; 95% CI, 1.25–4.57; P < 0.01). For all‐cause mortality, the sPESI low‐risk strata had a negative predictive value of 98.8% (95% CI, 97.4–100) in comparison with 91.3% (95% CI, 88.9–93.6) for the cTnI. Conclusions: Within the first 30 days after the diagnosis of acute symptomatic PE, death due to PE and death due to other causes occur in a similar proportion of patients. As cTnI only predicted PE‐associated mortality, low‐risk sPESI had a higher negative predictive value for all‐cause mortality compared with cTnI.     

Risk factors for venous thrombosis in medical inpatients: validation of a thrombosis risk score.

BACKGROUND/OBJECTIVES: The occurrence of and risk factors for venous thrombosis (VT) complicating hospital admission in unselected medical inpatients have not been widely studied. PATIENTS and METHODS: In a 400-bed teaching hospital we identified all cases of VT complicating hospital admission between September 2000 and September 2002 using discharge codes and chart review. Controls were randomly selected adult inpatients frequency matched to cases for medical service. RESULTS: The incidence of VT complicating hospital admission was 7.6 per 1000 admissions. On average, VT was diagnosed on the fifth hospital day. The median age of the 65 cases and 123 controls was 68 years and 45% were men. Cases had a 4-fold higher death rate than controls [95% confidence interval (CI) 1.9, 8.8]. At admission, trauma within 3 months, leg edema, pneumonia, platelet count > 350 x 10(3) mm(-3) and certain cancers were associated with risk of VT. Age, body mass index, and acute myocardial infarction were not associated with VT risk. One of three published VT risk models was able to risk stratify patients and was associated with a 2.6-fold increased risk of VT (95% CI 1.3, 5.5). Use of VT prophylaxis did not differ in cases and controls; prophylaxis was used < 1/3 of hospital days in 52% of patients. CONCLUSIONS: VT was common among medical inpatients. Of the risk factors identified, elevated platelet count has not been previously reported. Only one of three published risk scores was associated with risk of inpatient VT. Future study should improve upon risk prediction models for in-hospital VT among medical patients.     

Predictors of the post‐thrombotic syndrome with non‐invasive venous examinations in patients 6 weeks after a first episode of deep vein thrombosis

Summary. Background: Post‐thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) affecting a large number of patients. Because of its potential debilitating effects, identification of patients at high risk for the development of this syndrome is relevant, and only a few predictors are known. Objectives: To assess the incidence and potential predictors of PTS. Methods: We prospectively followed 111 consecutive patients for 2 years after a first episode of objectively documented DVT of the leg. With non‐invasive venous examinations, residual thrombosis, valvular reflux, calf muscle pump function and venous outflow resistance were assessed at 6 weeks, 3 months, 6 months, 1 year, and 2 years. The Clinical, Etiologic, Anatomic, and Pathophysiologi classification was used to record the occurrence and severity of PTS. Regression analysis with area under the receiver operating characteristic (ROC) curve was performed to identify potential predictors. Results: The cumulative incidence of PTS was 46% after 3 months, and the incidence and severity did not increase further. Men appeared to be at increased risk as compared with women (risk ratio [RR] 1.4, 95% confidence interval [CI] 0.9–2.2), as were patients over 50 years as compared with younger patients (RR 1.4%, 95% CI 0.9–2.1). Patients with thrombosis localized in the proximal veins at diagnosis had an increased risk of PTS as compared with patients with distal thrombosis (RR 2.3%, 95% CI 1.0–5.6). PTS developed in 32 of 52 patients (62%) with residual thrombosis in the proximal veins 6 weeks after diagnosis, as compared with 17 of 45 patients (38%) without residual proximal thrombosis, leading to a 1.6‐fold increased risk (95% CI 1.0–2.5). The presence of valvular reflux in the superficial veins was also a predictor at 6 weeks, with a 1.6‐fold increased risk as compared with patients without superficial reflux (95% CI 1.1–2.3). A multivariate analysis of these predictors yielded an area under the ROC curve of 0.72 (95% CI 0.62–0.82). Conclusions: PTS develops in half of all patients within 3 months, with no further increase being seen up to 2 years of follow‐up. Male sex, age over 50 years, proximal localization of the thrombus at entry, residual proximal thrombosis and superficial valvular reflux at 6 weeks seem to be the most important predictors of PTS in patients with a first episode of DVT. Duplex scanning 6 weeks after diagnosis appears to be clinically useful for the identification of patients at risk of PTS.     

Treatment of upper‐extremity deep vein thrombosis

Summary. Background: Upper extremity deep vein thrombosis (DVT) can result in fatal pulmonary embolism if not treated. Patients with malignancy may be at particularly high risk. Heparin or low‐molecular‐weight heparin followed by warfarin has been used as standard treatment for lower extremity DVT. However, a paucity of studies exist reporting the efficacy and safety of these regimens in patients with upper extremity DVT. We studied the effectiveness and safety of treatment with dalteparin sodium followed by warfarin and also dalteparin sodium monotherapy for 3 months in patients with confirmed upper extremity DVT. Methods: Consecutive patients with confirmed upper extremity DVT received daily dalteparin sodium for 5–7 days followed by warfarin therapy for 3 months (phase I) or dalteparin sodium monotherapy for 3 months (phase II). The primary outcome measure was the incidence of new symptomatic venous thromboembolism during the 3‐month follow‐up period. The outcome measure of safety was the incidence of major and minor bleeding. Results: Of 631 consecutive patients screened, 74 were eligible and 67 enrolled. No patients receiving either phase I (0%; 95% CI, 0–12%) or phase II (0%; 95% CI, 0–9%) therapy had venous thromboembolism on 3‐month follow‐up. One patient (4%; 95% CI, 0–18%) receiving phase I therapy experienced major bleeding. Five patients died during the follow‐up period; none were attributed to pulmonary embolism. Conclusions: Patients with upper extremity DVT may be treated safely with either dalteparin sodium followed by warfarin or dalteparin sodium monotherapy for 3 months with a good prognosis.