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The Pulmonary Embolism Severity Index (PESI) estimates the risk of 30-day mortality in patients with acute pulmonary embolism (PE). We constructed a simplified version of the PESI.The study retrospectively developed a simplified PESI clinical prediction rule for estimating the risk of 30-day mortality in a derivation cohort of Spanish outpatients. Simplified and original PESI performances were compared in the derivation cohort. The simplified PESI underwent retrospective external validation in an independent multinational cohort (Registro Informatizado de la Enfermedad Tromboembólica [RIETE] cohort) of outpatients.In the derivation data set, univariate logistic regression of the original 11 PESI variables led to the removal of variables that did not reach statistical significance and subsequently produced the simplified PESI that contained the variables of age, cancer, chronic cardiopulmonary disease, heart rate, systolic blood pressure, and oxyhemoglobin saturation levels. The prognostic accuracy of the original and simplified PESI scores did not differ (area under the curve, 0.75 [95% confidence interval (CI), 0.69-0.80]). The 305 of 995 patients (30.7%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.0% (95% CI, 0.0%-2.1%) compared with 10.9% (8.5%-13.2%) in the high-risk group. In the RIETE validation cohort, 2569 of 7106 patients (36.2%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.1% (95% CI, 0.7%-1.5%) compared with 8.9% (8.1%-9.8%) in the high-risk group.The simplified PESI has similar prognostic accuracy and clinical utility and greater ease of use compared with the original PESI.

The influence of several diseases and clinical conditions on the presence of pulmonary embolism (PE) in a large series of patients with deep venous thrombosis (DVT) in the lower extremities was analyzed prospectively. Lung scan findings from a series of 434 consecutive patients with DVT (with and without symptoms of PE) were studied and then correlated to five clinical variables: age, sex, elapsed time since clinical symptoms had appeared in the leg to diagnosis, degree of proximity of venous thrombus, and the presence or not of several risk factors that could have predisposed to thrombus development. According to scintigraphic findings, 164 patients were considered to have PE (asymptomatic in 76 of them), while 200 patients were classified as having only DVT. Lung scan was considered to be indeterminate for PE in 70 patients, and they were not included in the study. No differences were found in terms of age, sex, interval of time elapsed since onset of symptoms to diagnosis, or in the degree of proximity of the thrombus. However, several differences between groups were found when comparing the presence or absence of several predisposing factors for thrombosis: DVT developing in immobilized patients was associated with a significantly lower incidence of PE as compared with nonimmobilized patients (p = 0.005). Conversely, patients with a history of venous thromboembolism (VTE) had a significantly higher rate of embolism (31/51 vs 133/313; p = 0.01). On logistic regression analysis, a history of VTE showed a statistically significant association with more than a twofold higher risk of having PE for patients with such an antecedent. Our findings suggest that different pathophysiologic pathways could perhaps explain differences in embolic potential.

To determine the possible role of platelet-activating factor (PAF) in pulmonary embolism (PE), the reactivity of the airways to inhaled PAF, using doses ranging from 6.25 to 400 micrograms, was examined in 24 patients with a past episode of PE. Twelve of these patients had experienced acute respiratory insufficiency during the episode (with or without additional symptoms). None of the remaining 12 patients had experienced any respiratory symptoms during the PE episode. Diagnosis was established by means of a ventilation-perfusion lung scan performed when admitted to the hospital because of deep venous thrombosis (DVT) in the lower limbs. Nonspecific bronchial reactivity as measured by the response to bronchoprovocation testing with methacholine showed no significant differences between both groups. PAF caused a dose-dependent bronchoconstriction defined by at least a 35 percent decrease in specific airway conductance (SGaw) in all patients. The average dose of PAF needed to decrease SGaw 35 percent was significantly lower in patients who had had a symptomatic PE than in those with asymptomatic PE (p = 0.011). This finding suggests that patients who suffered from symptomatic PE may present a greater airway reactivity to inhaled PAF. This different behavior might explain the existence of some of the respiratory symptoms of PE, which could be attributed to PAF-related effects. However, additional studies are needed to evaluate the role of PAF in PE.

Fundamento Valorar la sospecha diagnosticade tromboembolia pulmonar (TEP) en elarea de urgencias. Pacientes Y Metodos Se analizan los casosde dos anos, y se compara el grupo A (sospechade TEP) con el grupo B (sin sospechade TEP). Resultados De 57 casos, no se sospechoTEP en 14 (25%). Hubo diferencias significativasen los signos de trombosis venosaprofunda (mayor frecuencia en el grupo A),insuficiencia cardiaca y derrame pleural(mayor frecuencia en el grupo B). Los diagnosticosalternativos fueron insuficienciacardiaca y neumonia. Conclusiones Los pacientes con TEP nosospechada no presentan un perfil clinicodiferencial. La TEP se confunde con insuficienciacardiaca y neumonia.

In a previously reported study we compared the use of a low-molecular-weight heparin (LMWH) and conventional heparin in the thromboprophylaxis of patients with hip fracture. In an attempt to establish additional factors which could aid in predicting the development of deep-venous thrombosis (DVT), we retrospectively studied several clinical and laboratory variables and found that granulocyte count on admission was higher in patients without subsequent postoperative DVT. Forty additional patients were included in a further prospective study in order to validate our previous findings. 38% of patients who developed DVT had a granulocyte count lower than 9,500/microliters, whereas only 18% of those patients with DVT had a count higher than 9,500/microliters. These figures imply a positive predictive value of 38% and a negative predictive value of 82%. We suggest that granulocytes could play a role in the development of DVT and preoperative granulocyte count may be used to detect a high-risk population for DVT after a hip fracture.

Introduction: Findings from the recent EXCLAIM study demonstrate that selected acutely ill medical patients with reduced mobility benefit from extended-duration enoxaparin venous thromboembolism (VTE) prophylaxis (Blood2007;110:1862). However, it is unknown whether the EXCLAIM population is representative of acutely ill medical patients admitted to hospitals worldwide. In this subanalysis, we assessed whether the EXCLAIM population was representative of the medical patients enrolled in the multinational IMPROVE (Chest2007;132:936–45) and ENDORSE (Lancet2008;371:387–94) registries known to be at risk for VTE. Methods: Using patient data from IMPROVE and ENDORSE, we applied the EXCLAIM eligibility criteria to a representative, multinational population of acutely ill medical patients at risk for VTE. The IMPROVE and ENDORSE studies assessed VTE-risk and prophylaxis use of enrolled patients according to the 2004 American College of Chest Physicians (ACCP) guidelines (Chest2004;126:338S–400S). ACCP criteria for VTE risk were met in 46% (6,907/15,156) of IMPROVE and 43% (15,487/36,351) of ENDORSE study patients (Chest2007;132:936–45; Lancet2008;371:387–94). The EXCLAIM eligibility criteria required patients to be confined to total bed rest (level 1 immobility), or bed rest with bathroom privileges (level 2 immobility) and have at least 1 of 3 predefined risk factors for VTE (i.e., age > 75 years; history of VTE; active or prior cancer). Results: EXCLAIM eligibility criteria were met in 30% (2,072/6,907) IMPROVE and 36% (5,535/15,487) ENDORSE medical patients considered at risk for VTE by ACCP. During hospitalization, ACCP-recommended prophylaxis was provided to 69% (1,426/2,072) and 46% (2,548/5,535) of EXCLAIM-eligible patients enrolled in IMPROVE and ENDORSE, respectively. Following discharge from hospital (median length of stay 5 days for US, 8 days for non-US), only 9% (153/1,719) of EXCLAIM-eligible patients in the IMPROVE study received any type of ACCP-recommended VTE prophylaxis. Conclusions: Evidence from the EXCLAIM study demonstrated that the benefit-to-risk ratio in selected hospitalized medical patients favors the use of prolonged VTE prophylaxis. This population corresponds to one in three of the representative hospitalized patients with acute medical illness enrolled in IMPROVE and ENDORSE. Data on prophylaxis use from the IMPROVE registry suggest that only 9% of such patients are currently receiving optimal VTE prophylaxis following hospital discharge.

Background: The EXtended CLinical prophylaxis in Acutely Ill Medical patients (EXCLAIM) trial was a randomized, double-blind, placebo-controlled, multicenter, international study that demonstrated a 38% relative risk reduction (RRR) for venous thromboembolism (VTE) with extended-duration enoxaparin prophylaxis compared with placebo (2.5% vs 4.0%; absolute difference [AD], −1.5% 95.8% CI −2.5 to −0.5%; P=0.002). Major bleeding occurred in 0.7% (20/2975) and 0.2% (7/2988) of patients who received enoxaparin and placebo, respectively (AD, 0.4% [CI 0.1% to 0.8%]; P=0.012). As age is a known independent risk factor for VTE, we conducted a pre-specified sub-analysis of the EXCLAIM trial to compare the efficacy and safety of extended-duration enoxaparin prophylaxis in patients >75 years old with patients ≤75 years old. Methods: EXCLAIM eligibility required a recent (≤3 days) reduction in mobility due to acute medical illness, an anticipated level 1 (total bed rest/sedentary) or level 2 (level 1 with bathroom privileges) decreased mobility, and age ≥40 years. During the latter part of the study, a protocol amendment required patients with level 2 mobility to have ≥1 of 3 additional pre-specified risk factors (i.e., active or prior cancer, history of VTE, age >75 years). Of the 7500 patients enrolled, 7415 received open-label enoxaparin 40 mg SC od for 10±4 days. Of these, 6085 were randomized to double-blind therapy (enoxaparin 40mg SC od or placebo) of 28±4 additional days duration. The incidence of VTE, the primary efficacy end point, was defined as the composite of symptomatic or asymptomatic proximal deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE), or fatal PE during the double-blind treatment period. Patients were screened for DVT with bilateral proximal lower extremity compression ultrasound at the end of randomized therapy. The incidence of major bleeding, the primary safety end point, was assessed through 48 hours after the last dose of study treatment. Results: Of the 5963 randomized patients that received at least one dose of double-blind therapy, 29.9% (1781) were >75 years of age (mean age 81.5 years) and 70.1% (4182) were ≤75 years old (mean age 61.8 years). In patients >75 years old, the incidence of VTE was 2.5% (18/725) in the enoxaparin group compared with 6.7% (50/743) in the placebo group (AD −4.2% [95.8% CI −6.5 to −2.0%]; P75 years old (0.6% vs 0.2%; AD 0.3%, 95% CI −0.2 to 0.9%; P=0.282) and significantly higher in patients ≤75 years old (0.7% vs 0.2%; AD 0.5%, 95%CI 0.1 to 0.9%; P=0.041). Though the older group had a higher death rate compared to the younger group (3.2% vs 1.6%), the survival between the treatment groups was similar within the two age groups. Without extended prophylaxis (i.e., placebo group), patients >75 years old had a significantly higher risk of VTE than those Conclusions: Despite standard-duration prophylaxis with enoxaparin for 6 to 14 days, acutely ill patients >75 years of age have a significantly higher risk of VTE in the following month, compared to patients ≤75 years of age. The risk-to-benefit ratio of extended-duration enoxaparin following standard-duration prophylaxis in acutely ill medical patients appears most favorable in patients >75 years of age.

Introduction In the EXCLAIM study, extended-duration enoxaparin prophylaxis reduced the relative risk of VTE in acutely ill medical patients by 44% compared with placebo, following standard-duration prophylaxis (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.0011). We assessed the benefits of extended-duration enoxaparin prophylaxis in subgroups of acutely ill medical patients with the most prominent primary diagnoses enrolled in EXCLAIM. Methods Patients enrolled in EXCLAIM had: recent reduced mobility (≤3 days) due to a medical illness, age ≥40 years, and anticipated level 1 (total bed rest or sedentary without bathroom privileges) or level 2 (level 1 with bathroom privileges) reduced mobility with further risk factors. Eligible patients received enoxaparin 40mg SC once-daily for 10±4 days, and were then double-blind randomized and received enoxaparin 40mg SC once-daily (n=2013) or placebo (n=2027) for a further 28±4 days. Asymptomatic DVT were diagnosed by bilateral compression ultrasound after completion of the randomized treatment. Suspected cases of symptomatic DVT or PE were confirmed by objective tests. Fatal PE were confirmed by autopsy where possible. Univariate logistic regressions were conducted to estimate treatment effects in patient subgroups. The primary safety endpoint was major bleeding. Results Baseline characteristics were similar between treatments within each primary diagnosis subgroup, and the considered primary diagnoses accounted for >80% of the enrolled population. The reduced VTE incidence associated with extended-duration enoxaparin prophylaxis was consistent across subgroups of patients with different primary diagnoses (Table). The incidence of major bleeding was generally higher in patients receiving extended-duration prophylaxis (Table). Table: VTE and major bleeding in patient subgroups receiving extended-duration vs standard-duration prophylaxis/placebo Primary diagnosis Incidence of VTE (%)* Odds Ratio [95% CI]** Incidence of Major Bleeding (%)*** Odds Ratio [95% CI] Extended Enox Standard Enox/Placebo Extended Enox Standard Enox/Placebo *N=3347 evaluable patients; **Alpha adjustment for an interim analysis; ***N=4040 treated patients Heart failure, NYHA class III or IV 3.1 4.7 0.64 [0.29–1.39] 0.0 0.2 N/A Acute respiratory insufficiency 2.2 3.7 0.60 [0.27–1.34] 0.6 0.2 3.15 [0.33–30.4] Post ischemic stroke 2.1 8.3 0.24 [0.06–0.91] 0.6 0.0 N/A Acute infection without septic shock 3.6 5.3 0.66 [0.36–1.22] 0.8 0.2 5.16 [0.60–44.3] Conclusion Extended enoxaparin prophylaxis consistently reduced VTE risk in acutely ill medical patients with the most prominent primary diagnoses compared with placebo following standard-duration prophylaxis. Major bleeding was generally higher in the extended-duration enoxaparin arm, but rates of bleeding were low. These findings are consistent with the primary findings of the EXCLAIM study which demonstrated the clinical benefit of the extended-duration enoxaparin regimen.

Introduction The EXCLAIM study has shown that in acutely ill medical patients who have received a standard 10-day period of prophylaxis with enoxaparin, extended-duration prophylaxis with enoxaparin for 4 weeks reduces the relative risk of the primary composite endpoint of asymptomatic proximal deep-vein thrombosis (DVT), symptomatic DVT or pulmonary embolism (PE), and fatal PE by 44% compared with placebo (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.0011). We assessed the consistency of these results using the composite efficacy endpoint recently proposed for venous thromboembolism (VTE) prophylaxis studies by the European Committee for Medicinal Products for Human Use (CHMP) which, in addition, takes all-cause mortality into account. Methods Patients enrolled in the EXCLAIM study had a recent reduced mobility (≤3 days) due to a medical illness, were aged 40 years or older, and had anticipated level 1 (total bed rest or sedentary without bathroom privileges) or level 2 (level 1 with bathroom privileges) reduced mobility with further risk factors. Eligible patients received enoxaparin 40mg SC once-daily for 10±4 days. Patients were then double-blind randomized and received either enoxaparin 40mg SC once-daily or placebo for a further 28±4 days. Asymptomatic DVT were diagnosed by bilateral compression ultrasound after completion of the randomized treatment period. Suspected cases of symptomatic DVT or PE were confirmed by objective tests. Fatal PE were confirmed by autopsy where possible. Data were analyzed using the CHMP-recommended composite efficacy endpoint of proximal DVT, adjudicated PE and all-cause mortality. Results Eligible patients enrolled at 370 sites in 20 countries received standard-duration prophylaxis with enoxaparin. Of these, 4114 patients were double-blind randomized and 4040 received extended-duration prophylaxis with enoxaparin (n=2013) and placebo (n=2027), respectively. Extended-duration enoxaparin reduced the relative risk of the CHMP composite endpoint by 26% compared with placebo (5.8% vs 7.9%; RR 0.74; 95% CI 0.58–0.95; p=0.018). Conclusion The significant reduction in the incidence of the primary efficacy endpoint associated with the use of extended-duration enoxaparin compared with placebo, following standard duration enoxaparin, was consistent when applying both the pre-defined EXCLAIM and the CHMP-recommended composite endpoints, the latter of which included all-cause mortality in addition to proximal DVT and adjudicated PE.

Introduction EXCLAIM showed a 44% reduction of the relative risk of venous thromboembolism (VTE) with extended-duration enoxaparin prophylaxis compared with placebo, following standard-duration prophylaxis in acutely ill medical patients (2.8% vs 4.9%; RR 0.56; 95% CI 0.39–0.80; p=0.001). We retrospectively assessed the effects of degree of reduced mobility and prespecified risk factors on the incidence of VTE in EXCLAIM. Methods EXCLAIM eligibility required a recent (≤3 days) reduction in mobility due to acute medical illness, an anticipated level 1 (total bed rest/sedentary; no bathroom privileges) or level 2 (level 1 with bathroom privileges) decreased mobility, and age ≥40 years. During the latter part of the study, a protocol amendment required patients with level 2 mobility to have ≥1 of 3 additional prespecified risk factors (history of cancer, history of VTE, age >75 years). Enrolled patients received enoxaparin 40mg SC od for 10±4 days. Randomized patients received double-blind therapy (enoxaparin 40mg SC od or placebo) for 28±4 additional days. Patients were screened for deep vein thrombosis with bilateral proximal lower extremity compression ultrasound after randomized therapy. A blinded committee adjudicated cases of suspected VTE and major bleeding. Results Of patients evaluable for VTE (pre- and post-amendment; n=4995), 42% had level 1 mobility. 43% with level 2 mobility met the amended eligibility criteria. The incidence of VTE was 3.2%. Treatment effects on VTE incidence and major bleeding rates were consistent within mobility groups, regardless of the presence of prespecified risk factors (Table). In patients with level 1 mobility, those with ≥1 prespecified risk factors had a higher VTE incidence than those without (4.8% vs 2.6%; p=0.007). In patients with level 2 mobility, those with ≥1 risk factors had a higher VTE incidence than those without (4.6% vs 1.9%; p Table: Effect of level of reduced mobility and prespecified risk factors on incidence of VTE and major bleeding in patients receiving extended-duration prophylaxis or placebo, following standard-duration prophylaxis Level of mobility and number of prespecified risk factors Extended-duration enoxaparin Extended-duration placebo p-value for interaction* *Non-significant p-value denotes consistent treatment effect among subgroups; n=5963 for assessment of bleeding VTE (%) Level 1 - no risk factors 2.1 3.0 0.36 Level + ≥1 risk factor 2.7 6.8 Level 2 - no risk factors 1.9 2.0 Level 2 + ≥1 risk factor 3.5 5.6 Major bleeding (%) Level 1 - no risk factors 0.4 0.0 1.00 Level 1 + ≥1 risk factor 0.6 0.0 Level 2 - no risk factors 0.8 0.4 Level 2 + ≥1 risk factor 0.8 0.4 Conclusion After acutely ill medical patients with reduced mobility received standard-duration VTE prophylaxis, the presence of prespecified risk factors was associated with an increased incidence of VTE, independent of the level of reduced mobility. The treatment effects of extended-duration prophylaxis with enoxaparin compared with placebo were consistent among subgroups.

Background Acutely ill medical patients at risk for venous thromboembolism (VTE) should receive VTE prophylaxis. However, factors perceived by physicians to increase patients’ risk of bleeding may influence VTE prophylaxis practices. In this analysis from The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE), we examined whether perceived risk factors for bleeding had a significant influence on physicians’ prescribing of in-hospital prophylaxis in acutely ill medical patients. Methods Patients aged ≥18 years and hospitalized ≥3 days with an acute medical illness have been enrolled consecutively since July 2002. Risk factors considered were: severe renal failure, known bleeding disorder, hemorrhagic stroke, thrombocytopenia, bacterial endocarditis, active gastroduodenal ulcer, NSAID use, hepatic failure, age, immobility and alcoholism. Factors associated with different prescription rates of prophylaxis compared with rates in patients without these factors were identified and included in a multiple logistic regression model (significance at p100, 50–100, 20–50 and

Background Although clinical studies have not shown a significant difference between the risk of bleeding in acutely ill medical patients receiving pharmacologic venous thromboembolism (VTE) prophylaxis and those receiving placebo, fear of bleeding may lead physicians to withhold pharmacologic prophylaxis for patients who should receive it. We therefore aimed to determine the incidence of, and risk factors for in-hospital bleeding in hospitalized acutely ill medical patients in IMPROVE, an international, observational registry. Methods Patients aged ≥18 years, hospitalized ≥3 days with an acute medical illness have been enrolled consecutively since July 2002. Exclusion criteria: therapeutic antithrombotics/thrombolytics at admission, major surgery or trauma during 3 months prior to admission, and VTE treatment within 24 hours of admission. Patients bleeding immediately before, or at admission were excluded from this analysis. Factors present at admission and associated with increased risk of in-hospital bleeding (defined as major or clinically significant nonmajor [Büller et al. N Engl J Med2003;349:1695–702]) were identified by univariate analysis (p Results Data were from 5960 patients enrolled up to 31 March 2005 in 49 hospitals (12 countries). In-hospital bleeding occurred in 170 (2.9%) patients: 68 (1.1%) major and 102 (1.7%) clinically significant nonmajor bleeding. Independent risk factors for in-hospital bleeding are shown in the Table. In-hospital prophylaxis with low-molecular-weight and unfractionated heparin were not independently associated with an increased risk of bleeding when added to the analysis (p=0.51 and 0.38, respectively). In patients with 0, 1, 2 or ≥3 of these risk factors, the incidences of major in-hospital bleeding were 0.1%, 0.4%, 1.2% and 5.2%, respectively. Conclusions In this unselected patient population, the rate of major in-hospital bleeding was low (1.1%) and similar to that in the MEDENOX study (1.0%), a major clinical study of VTE prophylaxis. Factors that we identified will be valuable for predicting the risk of in-hospital bleeding in acutely ill medical patients. Table. Factors predictive of an increased risk of in-hospital bleeding in acutely ill medical patients Factor Odds ratio 95% confidence interval Active gastroduodenal ulcer 5.38 2.90–10.00 Bleeding disorder 4.54 2.02–10.19 Hepatic failure 3.34 1.80–6.19 Serum creatinine >1.5 mg/dL 2.29 1.63-3.21 Current cancer 2.08 1.43-3.03 Central venous catheter 2.00 1.31-3.05 ICU/CCU stay 1.92 1.23-3.02 Immobile ≥ 4 days 1.75 1.24-2.46 Ischemic heart disease 1.57 1.02-2.40

Background Despite consensus group recommendations indicating that medical patients should receive appropriate venous thromboembolism (VTE) prophylaxis, prophylaxis practices remain poorly characterized. This analysis of IMPROVE, a prospective study of acutely ill medical patients, describes in-hospital prophylaxis practices prior to the publication of updated VTE prevention guidelines by the American College of Chest Physicians. Methods Patient recruitment began in July 2002. Patients ≥18 years old, and hospitalized for ≥3 days with an acute medical illness are enrolled consecutively. Exclusion criteria are: therapeutic antithrombotics/thrombolytics at admission; major surgery or trauma during 3 months prior to admission; and VTE treatment begun within 24 hours of admission. Results Data were from 4315 patients (32% from USA) enrolled up to 30 June 2004 in 37 hospitals in 11 countries (76% with 3-month follow-up data). Patients are 50% female, median (IQR) age 69 (50–80) years, median length of hospital stay 8 (5–14) days, median weight 68 (58–80) kg, and 40% were immobile for ≥3 days (median length of immobility 7 [4–14] days, including immobility immediately prior to admission). In-hospital VTE prophylaxis was received by 41% of patients (Table 1). Of patients with no risk factors (44%), one risk factor (40%), or ≥2 risk factors (16%), 25%, 49%, and 67% received prophylaxis, respectively. 12% of IMPROVE patients would have been eligible for inclusion in the MEDENOX study. Of these, only 52% received prophylaxis in hospital. Prophylaxis was provided to 6% of patients during the 3-month follow-up period, and continued in 11% of patients after discharge. Conclusions Only 41% of IMPROVE patients received VTE prophylaxis, with considerable variation in types and regimens of prophylaxis used. While MEDENOX showed the benefits of VTE prophylaxis (enoxaparin 40 mg) in acutely ill medical patients, only half of MEDENOX-eligible patients received prophylaxis. Table 1. Use of in-hospital VTE prophylaxis (N=4315) VTE prophylaxis Patients receiving VTE prophylaxis, % ROW, rest of world; *Excluding elastic stockings and aspirin ≥1 type of VTE prophylaxis* 41 LMWH - USA (Q12h, Qd) 7 (5, 1) LMWH- ROW (Q12h, Qd) 31 (29, 2) UFH - USA (Q12h, Q8h) 28 (15, 11) UFH - ROW (Q12h, Q8h) 6 (5, 0) Intermittent pneumatic compression (USA, ROW) 6 (19, 0) Aspirin (USA, ROW) 4 (7, 3) Elastic stockings (USA, ROW) 6 (3, 8)

Background We examined data from acutely ill medical patients enrolled in The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) to determine factors that are independently associated with an increased risk of bleeding during hospitalization. Methods Patients ≥18 years old, hospitalized for ≥3 days with an acute medical illness have been enrolled consecutively since July 2002. Exclusion criteria are: therapeutic antithrombotics/thrombolytics at admission; major surgery or trauma during 3 months prior to admission; and venous thromboembolism (VTE) treatment within 24 hours of admission. Patients with bleeding immediately prior to, or at admission were excluded from this analysis. Factors considered were: age, ICU stay, reduced creatinine clearance, severe infection, cerebrovascular stroke, cancer, diabetes, severe renal failure, hypertension, lower limb paralysis, bleeding disorders, hemorrhagic stroke, thrombocytopenia, gastro-duodenal ulcer, hepatic failure, central venous catheter at admission, hormonal therapy for cancer, platelet count, BMI, immobility, and length of hospital stay. Factors increasing the risk of bleeding were identified by univariate analysis ( P ≤ 0.20) and included in a multiple logistic regression model. Factors with significance of P ≤0.05 were retained in the model. Bleeding events were defined as major or clinically significant non-major according to published criteria (Buller HR et al. N Engl J Med. 2003;349:1695–702). Results . Data were from 2816 patients enrolled up to 30 June 2004 in 34 hospitals in 10 countries. Patients were: 48% female, mean age 64 years, mean weight 72 kg, mean length of hospital stay 12 days, and 37% were immobile for ≥ 3 days (median duration of immobility 6 days, including immobility immediately prior to admission). Only 89 (3.2%) patients had in-hospital bleeding: 1.2% major, 1.9% clinically significant non-major, 0.1% unspecified. Factors that were independently associated with an increased risk of bleeding (major or non-major) in acutely ill medical patients are shown in Table 1. Conclusion Only 3.2% of acutely ill medical patients in IMPROVE had in-hospital bleeding. Major bleeding (1.2%) was similar to that observed in a major clinical trial on VTE prophylaxis, MEDENOX (1.0%; Samama et al. N Engl J Med. 1999;341:793– 800). Advanced age, contrary to the belief of many physicians, was not independently associated with an increased risk of bleeding. Final results will be presented with adjustment for the influence of VTE prophylaxis and antiplatelet drugs. Table 1. Factors independently associated with an increased risk of bleeding in acutely ill medical patients | Factor | OR | 95% CI | |:----------------------------------------------------------------------:| ---- | ---------- | | *compared with creatinine clearance >60 mL/min (normal renal function) | | Bleeding disorder | 8.38 | 3.53–19.90 | | Active gastro-duodenal ulcer | 4.26 | 1.86–9.76 | | Hepatic failure | 2.97 | 1.26–6.96 | | Creatinine clearance

Introduction Patients who are underweight or obese are often excluded from clinical trials of venous thromboembolism (VTE) treatment. Thus, recommendations based on evidence from these trials may not be optimal for patients at these two extremes of body weight. The Registro Informatizado de la Enfermedad TromboEmbólica (RIETE), initiated in March 2001, is a multicenter, observational registry gathering data on treatment practices and clinical outcomes in patients with objectively confirmed, symptomatic, acute VTE. The aim of this analysis was to examine the influence of body weight on clinical outcomes of patients with VTE. Methods Patients with objectively confirmed, symptomatic, acute VTE are consecutively enrolled into the RIETE registry. Patients are excluded if they are participating in a therapeutic clinical trial or are not available for 3-month follow-up. For this analysis, data from patients in the following ranges of body weight were examined: 100 kg. Results As of December 2003, 6128 patients with acute VTE were enrolled from 94 participating centers. Of these, 122 (2%) weighed 100 kg. Patient characteristics are presented in table 1. Incidences of recurrent VTE, bleeding complications (fatal, major, or minor), or fatal PE were similar between groups. However, the incidence of the composite endpoint of VTE recurrence and/or major bleeding was higher in patients 100 kg and 50–100 kg groups. Conclusion Although there were no differences in the incidences of recurrent VTE, bleeding complications or fatal PE between groups, patients with VTE, weighing Table 1. Patient characteristics Patients, n(%) 100 kg NSAIDs, nonsteroidal anti-inflammatory drugs; *p1.2 mg/dL), recent surgery (65 years 78 (64) 3678 (63) 48 (27)‡ NSAIDs 14 (11)* 373 (6.4) 11 (6.7) Corticosteroids 18 (15)† 463 (7.9) 11 (6.1) Cancer 43 (35)‡ 1194 (20) 21 (12)† Immobility ≥4 days 53 (43)‡ 1575 (27) 44 (25) Previous VTE 16 (13) 987 (17) 47 (26)†

We suggest that real-time B-mode US should be considered as the method of choice in patients with suspected DVT, mainly in those cases (as in pregnant women) in whom extrinsic compression may induce false-positive results with the remainder noninvasive methods

We have prospectively studied a series of 121 consecutive patients with venous thromboembolism (38 with pulmonary embolism, 83 with venous thrombosis of the lower extremities) searching for recurrences of pulmonary embolism despite adequate heparin therapy. A baseline ventilation-perfusion lung scan was obtained initially in every patient, whether the original diagnosis was pulmonary embolism or venous thrombosis. Repeat chest roentgenograms and lung scans were obtained routinely at eight days of heparin treatment. The primary trial endpoints were a finding of a clinically apparent recurrent pulmonary embolism, or laboratory evidence of subclinical pulmonary embolism. Eight items of clinical and laboratory information were recorded at admission and then correlated with the lung scan results. Recurrences were seen in seven of 38 patients with an original diagnosis of pulmonary embolism, and in five of 83 patients admitted because of venous thrombosis (p = 0.034). Recurrences were also more frequent in patients with a free-floating thrombus on venography (p = 0.014). The risk of new defects in patients with venous thrombosis and without free-floating thrombus was 3.05 percent, venous thrombosis with free-floating thrombus, 13.33 percent; patients with pulmonary embolism without free-floating thrombus, 11.42 percent; and with free-floating thrombus, 38.67 percent. Venography seems thus mandatory in patients with pulmonary embolism, as it recognizes a subgroup of patients at a high risk of recurrences.

Ventilation-perfusion lung scans were done in 70 patients admitted because of an iliofemoral deep vein thrombosis (DVT), and diagnosed by venography. Eighteen items of clinical and laboratory information were measured to predict the presence of lung scan abnormalities consistent with asymptomatic pulmonary embolism. Eighteen patients had perfusion defects in the lung scan that were classified as "high probability of pulmonary embolism", while the lung scan was normal in 32 patients. Patients with an idiopathic DVT were at high risk of pulmonary embolism, but those with a postoperative DVT had a low embolic risk. In patients with a postoperative DVT two factors predicted pulmonary embolism: those patients who developed symptomatic DVT after an operation but had a normal lung scan showed higher platelet counts than their preoperative levels. Conversely, it they developed a pulmonary embolism their platelet count dropped from their preoperative levels.

Serum total thyroxine, triiodothyronine, and thyrotropin response to thyro tropin-releasing hormone (TRH-TSH test) were measured in 126 consecutive patients admitted with atrial fibrillation: 33 patients with an acute arterial limb embolism (Group I), 31 patients with an acute embolic stroke (Group II), and 62 patients without any arterial occlusion (Group III). A blunted TRH-TSH test, suggestive of thyrotoxicosis, was found in 5 patients in Group I, 8 patients in Group II, and 2 patients in Group III. The diagnosis of hyperthyroidism was confirmed in 8 patients (by repeated TRH-TSH test and scintigraphy): 4 pa tients in Group I (12.1%) and 4 patients in Group II (12.9%). All of them had a nonvalvular atrial fibrillation. Thyrotoxicosis should not be recognized in 6 of them if TRH-TSH test was not performed, because peripheral hormone levels were normal. Five of these 8 patients with thyrotoxicosis had reversion to sinus rhythm after treatment with carbimazole, either spontaneously or after car dioversion. This outcome prevented prolongation of anticoagulant therapy for an indefinite time.

A prospective study has been made of the incidence of changes in transaminase levels, hyperkalaemia and thrombocytopenia in three groups of patients: 89 consecutive patients with venous thrombosis receiving therapeutic heparinization, 49 patients admitted because of hip fracture and receiving prophylactic low-dose conventional heparin, and 43 patients admitted because of hip fracture and randomly allocated to receive low molecular weight heparin. Laboratory measurements were made on admission and 8 days after commencing heparin. Only two patients on high-dose heparin developed thrombocytopenia. Increased transaminases were frequent with conventional heparin (18% and 32% of patients on high-dose heparin developed abnormal AsT and AlT values, respectively compared with 14% and 17% patients on low dose therapy). In contrast, only one patient on low molecular weight heparin developed abnormal AlT activity. Hyperkalaemia was uncommon in patients on any form of heparin therapy, and severe hyperkalaemia occurred in only one patient.

Objectives The purpose of this study was to investigate the survival effects of inferior vena cava filters in patients with venous thromboembolism (VTE) who had a significant bleeding risk. Background The effectiveness of inferior vena cava filter use among patients with acute symptomatic VTE and known significant bleeding risk remains unclear. Methods In this prospective cohort study of patients with acute VTE identified from the RIETE (Computerized Registry of Patients With Venous Thromboembolism), we assessed the association between inferior vena cava filter insertion for known significant bleeding risk and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, and VTE rates through 30 days after the initiation of VTE treatment. Propensity score matching was used to adjust for the likelihood of receiving a filter. Results Of the 40,142 eligible patients who had acute symptomatic VTE, 371 underwent filter placement because of known significant bleeding risk. A total of 344 patients treated with a filter were matched with 344 patients treated without a filter. Propensity score–matched pairs showed a nonsignificant trend toward lower risk of all-cause death for filter insertion compared with no insertion (6.6% vs. 10.2%; p = 0.12). The risk-adjusted PE-related mortality rate was lower for filter insertion than no insertion (1.7% vs. 4.9%; p = 0.03). Risk-adjusted recurrent VTE rates were higher for filter insertion than for no insertion (6.1% vs. 0.6%; p Conclusions In patients presenting with VTE and with a significant bleeding risk, inferior vena cava filter insertion compared with anticoagulant therapy was associated with a lower risk of PE-related death and a higher risk of recurrent VTE. However, study design limitations do not imply a causal relationship between filter insertion and outcome.

In a randomized, prospective, double-blind trial, the effect of conventional low-dose heparin (5,000 units every 8 hours) was compared with that of a low molecular weight fragment (2165 LMWH, Kabi Vitrum AB, starting 2,500 units 2 hr before surgery, and then 5,000 units subcutaneously every morning for 9 days). A total of 90 patients admitted because of hip fracture fulfilled the inclusion criteria and were analyzed for development of pulmonary embolism and deep vein thrombosis: 46 patients were included in the low molecular weight heparin (LMWH) group, and 44 in the conventional heparin group. Two and three, respectively, died before diagnostic tests were performed. In the remaining patients a ventilation-perfusion lung scan was performed 8 days after intervention. In the first 57 patients studied a bilateral ascending venography was performed on the ninth day only if clinical symptoms suggested a deep venous thrombosis. Because of the rate of venous thrombosis detected in those patients was unexpectedly low, venography was requested in the remaining 33 patients, even if the screening tests were negative. Pulmonary embolism occurred in six patients, all in the LMWH group. Deep vein thrombosis occurred in 14 patients in the LMWH group and in six patients in the conventional heparin group. Both differences are statistically significant. Mortality did not differ between the groups, nor did haemorrhagic complications. Our findings suggest that, in patients with hip fracture, LMWH is not useful at the dosage used.

This is a prospective study of 108 patients in two distinct groups undergoing real-time ultrasonography (US) and ascending conventional venography within the same day. The two patient groups consisted of the following: Those patients evaluated because of suspicion of deep venous thrombosis of lower limbs (69 patients) and those at high risk for venous thrombosis (19 patients with a recent hip fracture, 20 with a suspected pulmonary embolism). In the diagnosis group 48 patients had venographic evidence of thrombosis. The predictive value of abnormal findings from real-time US was 97%, and that of a negative study was 75%. Thus, real-time US may have a role as a diagnostic procedure, to be fol lowed by x-ray venography in patients with negative US results. By contrast, real-time US is far less sensitive as a screening test in patients without clinical evidence of thrombosis. Only 3 of 9 patients with thrombosis were detected, with a 50% sensitivity for proximal vein thrombosis. Therefore, the use of real-time US for screening high-risk patients must be limited to very high risk patients in whom other tests are ineffective (as in hip surgery).

AT-III activity has been evaluated in 675 patients with different kinds of hepatic disease.In 300 patients with hepatic chronic disease, AT-III levels showed a good correlation with prothrombin time as well as same diagnostic value. Survival in this group of patients was directly related to AT-III values.In 75 patients with acute liver disease, persistent low AT-III values correlated with clinical evolution of fulminans hepatitis.In 200 patients with cholestatic syndrome, evaluation of AT-III levels had no value for differential diagnosis of neither obstacle’s localization nor benign or neoplastic process.In 100 patients, suffering from cancer, without and with hepatic metastasis, AT-III values decreased in terminal states only.

The presence of peptic ulcer disease implies a high risk of bleeding in patients on heparin therapy. We reviewed our experience with 166 consecutive patients admitted because of venous thromboembolism. Of these 166 patients, 29 were referred for upper gastrointestinal endoscopy in order to detect the presence of any lesion that might contraindicate heparin therapy. A gastric ulcer was found in 10 patients, a duodenal ulcer in 11, and gastric erosions with signs of bleeding in 3 patients. Given the unexpectedly high frequency of ulcer in these patients, an upper gastrointestinal endoscopy was routinely performed early in the course of admission in 50 consecutive patients with venous thromboembolism. A gastric ulcer was found in 5 patients (10%), a duodenal ulcer in 7 (14%), and erosions in 2. Five of these patients had an unsuspected ulcer. A case can be made for prophylactic antiulcer therapy for all patients placed on anticoagulants for venous thromboembolism. Upper gastrointestinal endoscopy is indicated in patients with ulcer symptoms, in those with a previous history of peptic ulcer disease, and perhaps, in patients developing occult blood in the stools while on treatment with anticoagulants.

SummaryIn a previous report we found an inverse correlation between pre-operative platelet count (PlC) levels and the risk of post-operative pulmonary embolism in patients undergoing hip surgery. In the present study, we prospectively evaluated the prognostic significance of pre-operative PlC levels on survival in 180 consecutive patients undergoing surgery for colorectal cancer. Other major clinicopathological parameters studied were age, gender, Dukes’ stage, duration of surgery, pre-operative haemoglobin levels and transfusion requirements.There were no significant differences in mean pre-operative PlC levels according to tumor stage. Thirty-three patients (18%) died during follow-up (3-23 months, median: 13 months). Univariate analysis (Kaplan-Meier estimates) showed that advanced tumor stage (p

Background: The most common complication of intravenous therapy is infusion phlebitis. This study was done to prospectively assess its frequency in a series of consecutive patients who will undergo surgery, and to identify which variables may predict an increased risk for phlebitis. Patients and Methods: 400 consecutive patients who will undergo surgery in a general surgery department were included. Only the first catheter, inserted the day before surgery, was taken into account. Eighteen variables (from the infusion, the catheter and from the patient) were prospectively evaluated for their contribution to the occurrence of phlebitis. Results: 60/400 patients (15%) developed phlebitis, and most of them needed insertion of a further catheter. The univariate analysis showed that patients who developed phlebitis were older, and their pre-operative levels of both blood haemoglobin and neutrophil cound were significantly higher than those in patients who did not develop phlebitis. However, the multivariate analysis only confirmed the association with blood haemoglobin levels: the risk of phlebitis sharply increased in the patients with the highest haemoglobin levels. As to the influence of time on phlebitis development, there was a significant decrease in the day-specific risk, from the 5th day on. Comments: In our series, blood haemoglobin levels were found to be the only variable associated to a higher risk of phlebitis. Besides, in contrast with the recommendations by the Centers for Disease Control, no significant increase in the day-specific risk of phlebitis was found. Thus, a guideline to select the type of catheter to be inserted in an individual patient is suggested.

To the Editor. —We have read the article by Rodzynek et al1dealing with the diagnostic value of antithrombin III (AT III) determinations and the aminopyrine breath test in patients with liver diseases. We are pleased that these workers confirm the findings we reported earlier. In 1984, we reported, as did Rodzynek et al1in 1986, that the decrease in AT III levels in patients with cirrhosis of the liver was greater than in patients with aggressive hepatitis and persistent hepatitis.2,3The decrease in AT III levels was more marked in patients with cirrhosis of the liver and ascites than in patients with compensated cirrhosis of the liver. Also, AT III levels proved to be a more sensible and specific marker for cirrhosis of the liver than prothrombin time.4 From these data, we conducted a survival study in cirrhotic patients, trying to correlate the decrease of AT