Management of superficial vein thrombosis

Superficial vein thrombosis (SVT) is less well studied than deep vein thrombosis (DVT), because it has been considered to be a minor, self‐limiting disease that is easily diagnosed on clinical grounds and that requires only symptomatic relief. The most frequently involved sites of the superficial vein system are the lower limbs, especially the saphenous veins, mostly in relation to varicosities. Lower‐limb SVT shares the same risk factors as DVT; it can propagate into the deep veins, and have a complicated course with pulmonary embolism. Clinical diagnosis may not be accurate, and ultrasonography is currently indicated for both confirmation and evaluation of SVT extension. Treatment aims are symptom relief and prevention of venous thromboembolism (VTE) in relation to the thrombotic burden. SVT of the long saphenous vein within 3 cm of the saphenofemoral junction (SFJ) is considered to be equivalent to a DVT, and thus deserving of therapeutic anticoagulation. Less severe forms of lower‐limb SVT not involving the SFJ have been included in randomized clinical trials of surgery, compression hosiery, non‐steroidal anti‐inflammatory drugs, unfractionated heparin, and low molecular weight heparins, with inconclusive results. The largest randomized clinical trial available, on 3004 patients with lower‐limb SVT not involving the SFJ, showed that fondaparinux 2.5 mg once daily for 6 weeks is more effective than placebo in reducing the risk of the composite of death from any cause and symptomatic VTE (0.9% versus 5.9%). Further studies are needed to define the optimal management strategies for SVT of the lower limbs and other sites, such as the upper limbs.     

The effectiveness of anticoagulant and antiplatelet agents in preventing venous thromboembolism during stroke rehabilitation: a historical cohort study

OBJECTIVE: To determine the effectiveness of anticoagulant and antiplatelet agents in preventing venous thromboembolism (VTE) during stroke rehabilitation. DESIGN: Historical cohort study. SETTING: Acute inpatient rehabilitation hospital. PARTICIPANTS: Consecutive patients (N=1506) with ischemic and hemorrhagic stroke admitted for rehabilitation. INTERVENTIONS: Documented use of anticoagulants (warfarin or anticoagulant doses of heparin), heparin in prophylactic doses, and antiplatelet agents. MAIN OUTCOME MEASURE: Occurrence of deep vein thrombosis detected by ultrasound or venography or pulmonary embolism detected by ventilation perfusion scan, spiral computed tomography, or pulmonary angiography. RESULTS: Fifty-eight VTE events occurred (3.9% incidence or 1.36 events per 1000 patient days), with higher risk in patients with severe stroke. Only therapeutic anticoagulation had a statistically significant protective effect for VTE risk in univariate analysis (odds ratio [OR]=.44; 95% confidence interval [CI],.20-.98). After adjusting for multiple medication use and other factors, including age, stroke onset to admission interval, length of rehabilitation stay, cause of stroke, and admission National Institutes of Health Stroke Scale score, therapeutic anticoagulation gave strong protection against VTE (OR=.37; 95% CI,.15-.88), followed by heparin (OR=.48; 95% CI,.23-.98) but not by antiplatelet agents (OR=.79; 95% CI,.40-1.57). No medications were associated with significant bleeding complications. CONCLUSIONS: Use of therapeutic anticoagulants or prophylactic heparin prevented VTE in stroke patients during inpatient rehabilitation.     

A randomized double‐blind study of low‐molecular‐weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum)

Summary. Background: Optimal doses and duration of low‐molecular‐weight heparin (LMWH) for the treatment of superficial vein thrombosis (SVT) are still uncertain. Objectives: To compare the efficacy and safety of different doses and durations of LMWH parnaparin for symptomatic lower limb SVT. Patients and methods: Outpatients with at least a 4‐cm‐long SVT of long or short saphenous veins or their collaterals were randomized to receive parnaparin either 8500 UI once daily ( o.d.) for 10 days followed by placebo for 20 days (group A) or 8500 UI o.d. for 10 days followed by 6400 UI once daily (o.d.) for 20 days (group B) or 4250 UI o.d. for 30 days (group C) in a double‐blind fashion in 16 clinics. Primary outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE) and relapse and/or symptomatic or asymptomatic SVT recurrence in the first 33 days with 60 days follow‐up. Results: Among 664 patients, primary outcome occurred in 33/212 (15.6%), 4/219 (1.8%) and 16/217 (7.3%) subjects in groups A, B and C, respectively (B vs. A: absolute risk reduction [ARR]: 13.7%, 95% confidence intervals [CI]: 8–18.9 P < 0.001; B vs. C: ARR: 5.5%; 95% CI: 1.6–9.4 P = 0.011; C vs. A: ARR: 8.2%, 95% CI: 2–14 P = 0.012). During days 0–93, the event rate was higher in group A (22.6%) than either in group B (8.7%; P = 0.001) or C (14.3%, P = 0.034). No major hemorrhages occurred. Conclusions: An intermediate dose of parnaparin for 30 days is superior to either a 30‐day prophylactic dose or a 10‐day intermediate dose for lower limb SVT treatment.     

Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients

Summary.  Background:  Cancer patients with venous thromboembolism (VTE) are at high risk of recurrent VTE despite standard anticoagulation. To date, very little published literature is available to guide the treatment of cancer patients with recurrent VTE. Objectives:  To evaluate the benefit and risk of low molecular weight heparin (LMWH) dose escalation in cancer patients with recurrent VTE. Patients and methods:  This was a retrospective cohort study of consecutive cancer outpatients referred for management of a symptomatic, recurrent VTE while receiving an anticoagulant. Confirmed episodes of recurrent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH, or initiation of therapeutic dose LMWH in patients who were taking a vitamin K antagonist (VKA). All patients were followed for a minimum of 3 months after the index recurrent VTE unless they died during this period. Results:  Seventy cancer patients with a recurrent VTE despite ongoing anticoagulation were included. At the time of the recurrence, 67% of patients were receiving LMWH, and 33% were receiving a VKA. A total of six patients [8.6%; 95% confidence interval (CI) 4.0–17.5%] had a second recurrent VTE during the 3-month follow-up period, at an event rate of 9.9 per 100 patient-years (95% CI  2.0–17.8%). Three patients (4.3%; 95% CI  1.5–11.9%), or 4.8 per 100 patient-years (95% CI  0.0–10.3%) of follow-up, had bleeding complications. The median time between the index recurrent VTE to death was 11.4 months (range, 0–83.9 months). Conclusions:  Cancer patients with recurrent VTE have a short median survival. Escalating the dose of LMWH can be effective for treating cases that are resistant to standard, weight-adjusted doses of LMWH or a VKA.     

Prevalence and risk factors of non-fatal venous thromboembolism in the active population of the VITA Project

Summary.  Cost-effective strategies for the identification of subjects at risk of venous thromboembolism (VTE) in the active population are still lacking. Our objectives were to identify risk factors for venous thromboembolism in active subjects. We analyzed data from a population-based sample of 15 055 Caucasians aged 18–65 years randomly selected from the census list of the township of Vicenza, Italy. A validated methodology was used to retrospectively identify subjects with previous VTE. Body mass index (BMI), smoking, oral contraceptive use, previous superficial vein thrombophlebitis (SVT) and familial history of VTE, all at the age of first thrombosis, were ascertained by direct interview and by review of available medical records. Ninety-two deep vein thromboses [prevalence: 61.1/10 000, 95% confidence interval (CI) 49.2–74.9], three upper deep vein thrombosis (prevalence: 1.9/10 000, 95% CI 0.4–5.8) and 21 pulmonary embolism (prevalence: 13.9/10 000, 95% CI 8.6–21.3) were identified. After age and sex adjustment, clinically identifiable risk factors were: history of SVT [odds ratio (OR) = 6.8], oral contraceptive use (OR = 4.7), family history of VTE (OR = 4.5), smoking (OR = 1.7) and BMI above the third tertile (OR vs. mid-tertile 2.9). While previous SVT and BMI were associated with VTE in all circumstantial situations (surgery/trauma, pregnancy or idiopathic VTE), for oral contraceptive use, positive family history and smoking the degree of association varied significantly depending on the situation. Non-fatal VTE affects 0.7% of the subjects belonging to an active population, 56% of cases being potentially preventable. In 30% of VTE cases, at least two easily recognizable risk factors are present. Clinical assessment of risk factors remains the mainstay of VTE prevention.     

Association between asymptomatic deep vein thrombosis detected by venography and symptomatic venous thromboembolism in patients undergoing elective hip or knee surgery

BACKGROUND: Venography is commonly used to compare the efficacy of different thromboprophylaxis strategies for preventing deep vein thrombosis (DVT) in patients undergoing total hip replacement (THR) or total knee replacement (TKR). METHODS: We explored the relation between asymptomatic DVT and symptomatic venous thromboembolism (VTE) in patients undergoing THR or TKR treated with standard doses of enoxaparin (30 mg b.i.d. or 40 mg o.d.) by comparing the incidence of asymptomatic DVT in venographic studies with the incidence of symptomatic VTE in studies where venography was not performed. RESULTS: In 10 venographic studies involving 5796 patients, the incidence of asymptomatic DVT after THR was 13.2% [95% CI, 12.2-14.2%] and after TKR was 38.1% (95% CI, 35.5-40.8%). In two studies involving 3500 patients who did not undergo venography, the 90-day incidence of symptomatic VTE after THR was 2.7% (95% CI, 2.1-3.4%) and after TKR was 1.8% (95% CI, 0.9-2.7%). For every symptomatic VTE in THR studies where venography was not performed there were five asymptomatic DVTs in the venographic studies; for TKR, the ratio was 1:21. The incidence of asymptomatic DVT and the symptomatic VTE/asymptomatic DVT ratio was influenced by the venogram reading committee (Gothenburg vs. Hamilton: total DVT after THR, 19.5% vs. 8.7%, P < 0.0001; for TKR, 42.7% vs. 27.2%, P < 0.0001). CONCLUSIONS: Comparisons across trials show a consistent relation between asymptomatic venographic DVT in patients undergoing elective THR or TKR surgery and symptomatic VTE in patients not undergoing venography. Differences exist in the strength of the relation depending on the type of surgery and the venogram reading committee.     

Management of primary care patients with suspected deep vein thrombosis: use of a therapeutic dose of low-molecular-weight heparin to avoid urgent ultrasonographic evaluation

BACKGROUND: Out of hospital management of patients with suspected deep vein thrombosis (DVT) can be problematic. The accuracy of clinical prediction rules in the primary care setting may be inadequate, D-dimer testing may not be available, and the cost-effectiveness of urgent ultrasonographic evaluation is uncertain. OBJECTIVE: The purpose of this study was to determine the efficacy and safety of an empiric single therapeutic dose of low-molecular weight heparin (LMWH) in the time interval preceding ultrasound investigation in patients presenting to primary care physicians (PCPs) for suspicion of DVT. METHODS: Consecutive patients with suspected DVT who presented to the office of a PCP outside regular thrombosis center working hours were enrolled. All eligible patients received a single therapeutic dose of LMWH (100 anti-Xa IU kg(-1) weight) and were scheduled to undergo clinical and instrumental evaluation at the thrombosis center the morning after. Clinical events were documented after a 3-month follow-up. RESULTS: A total of 534 consecutive patients with suspected DVT were included in this study; of these 102 patients had subsequent diagnosis of DVT. We detected no episodes of pulmonary embolism, major bleeding, or death during the 18-h window between the administration of LMWH and objective evaluation. Of the 432 patients in whom diagnosis of DVT was subsequently excluded, only three (0.7%; CI: 0.2-2.0%) developed venous thromboembolic events during the 3-month follow-up period. CONCLUSIONS: Empiric treatment with a single therapeutic dose of LMWH is effective and safe for outpatients with suspected DVT initially managed in a primary care setting. This strategy has the potential to reduce the need for urgent diagnostic imaging.     

A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer

BACKGROUND: The optimal thromboprophylactic dosage regimen of low-molecular-weight heparins in high-risk general surgery remains debatable. OBJECTIVES: We performed a randomized, double-blind study to compare the efficacy and safety of nadroparin 2850 IU (0.3 mL) and enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism (VTE) after colorectal surgery for cancer. Patients and methods: Patients undergoing resection of colorectal adenocarcinoma were randomized to receive once daily either 2850 IU nadroparin or 4000 IU enoxaparin s.c. for 9 +/- 2 days. The primary efficacy outcome was the composite of deep vein thrombosis (DVT) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism up to day 12. The main safety outcome was major bleeding. A blinded independent committee adjudicated all outcomes. RESULTS: Out of 1288 patients analyzed, efficacy was evaluable in 950 (73.8%) patients. The VTE rate was 15.9% (74/464) in nadroparin-treated patients and 12.6% (61/486) in enoxaparin-treated patients, a relative risk of 1.27 (95% confidence interval; CI: 0.93-1.74) that did not met the criterion for non-inferiority of nadroparin. The rate of proximal DVT was comparable in the two groups (3.2% vs. 2.9%, respectively), but that of symptomatic VTE was lower in nadroparin-treated patients (0.2% vs. 1.4%). There was significantly (P = 0.012) less major bleeding in nadroparin- than in enoxaparin-treated patients (7.3% vs. 11.5%, respectively). CONCLUSION: Compared with those receiving enoxaparin 4000 IU, patients treated with nadroparin 2850 IU showed a higher incidence of asymptomatic distal DVT, but a lower incidence of symptomatic VTE. Nadroparin treatment was safer in terms of bleeding risk.     

Superficial vein thrombosis and recurrent venous thromboembolism: a pooled analysis of two observational studies

Summary. Background: The management strategies for symptomatic isolated superficial vein thrombosis (SVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) have yet to achieve widespread consensus. Concerns have been raised regarding the usefulness of prescribing anticoagulant treatments to all patients with isolated SVT. Determining the isolated SVT subgroups who have the highest risks of venous thromboembolism (VTE) recurrence (composite of DVT, PE, and new SVT) may facilitate the identification of patients who are likely to benefit from anticoagulant treatment. Design and methods: We performed a pooled analysis on individual data from two observational, multicenter, prospective studies, to determine predictors for VTE recurrence and their impact in an unselected population of symptomatic isolated SVT patients. Results: One thousand and seventy‐four cases of symptomatic isolated SVT were followed up at 3 months. VTE recurrence was observed in 3.9% of the patients; 16.2% of the patients did not receive anticoagulants, and 0.6% experienced a VTE recurrence. Cancer, personal history of VTE and saphenofemoral/popliteal involvement significantly increased the risk of subsequent VTE or DVT/PE in univariate analyses. Only male sex significantly increased the risk of VTE or DVT/PE recurrence in multivariate analyses. Twelve per cent of the patients had cancer or saphenofemoral junction involvement, and were at higher risk of DVT/PE recurrence than patients without those characteristics (4.7% vs. 1.9%, P = 0.06). Conclusions: In patients with symptomatic SVT, only male sex significantly and independently increased the risk of VTE recurrence. Cancer or saphenofemoral junction involvement defined a population at high risk for deep VTE recurrence. Some SVTs might be safely managed without anticoagulants.     

Acute venous thromboembolism in patients with recent major bleeding. The influence of the site of bleeding and the time elapsed on outcome

BACKGROUND: Patients with major bleeding who subsequently develop clinically apparent venous thromboembolism (VTE) present a particularly difficult therapeutic dilemma. METHODS: RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We retrospectively studied those who had experienced recent major bleeding (<30 days prior to VTE) to assess the influence of the site of bleeding and the time elapsed to VTE on their 3 month outcome. RESULTS: Of 12,294 patients enrolled up to July 2005, 306 (2.5%) had recent major bleeding: gastrointestinal (GI) tract, 116 (38%); intracranial, 94 (31%); other, 96 (31%). During the study period, 19 patients [6.2%; 95% confidence interval (CI) 3.5-8.9] with recent bleeding rebled (eight died): 13 of them (68%) during the first 2 weeks. Multivariate analysis confirmed that patients with recent GI bleeding had an increased risk for both major rebleeding (hazard ratio 2.8; 95% CI 1.4-5.3) and death (hazard ratio 1.9; 95% CI 1.2-3.1) compared to those with no recent bleeding. Those who bled in other sites had an increased risk only for death (hazard ratio 2.0; 95% CI 1.2-3.3). An elapsed time of <2 weeks from bleeding to the index VTE event was also associated with an increased risk for major rebleeding (hazard ratio 2.4; 95% CI 1.2-5.0) and death (hazard ratio 2.8; 95% CI 1.8-4.5). CONCLUSION: The incidence of new bleeding or death depends on the site of prior bleeding and the time elapsed until VTE. This information may help to identify the best therapeutic approach for these high-risk patients.     

Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months

BACKGROUND: The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. AIM: To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. METHODS: In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. RESULTS: Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. CONCLUSION: The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.     

Conservative perioperative anticoagulation management in patients with chronic venous thromboembolic disease: a cohort study

Summary. Background: Guidelines for perioperative warfarin management in patients with venous thromboembolic disease (VTE) are largely based on expert opinion. Objectives: To assess the effectiveness and safety of a conservative perioperative anticoagulation strategy in patients with VTE on chronic warfarin therapy. Our center uses a conservative bridging approach for chronic VTE patients consisting of withholding warfarin for 5 days preoperatively, with prophylactic low‐molecular‐weight heparin (LMWH) post‐procedure only if patients are admitted to hospital. Patients/Methods: We performed a single‐center retrospective cohort study. During the study period (1997–2011) there were 634 procedures in 416 patients that were reviewed for postoperative outcomes at 30 and 90 days. Results: Of the 634 procedures, 156 procedures (24.6%) were completed as inpatients. Pre‐ and post‐procedure LMWH bridging was used in 15 (2.4%) and 152 (24.0%) of all procedures, respectively. The 30‐day VTE incidence was 0.32% (95% confidence interval [CI] 0.087–1.14), all non‐fatal DVTs. The 30‐day incidence of major and total bleeding events was 1.26% (95% CI 0.64–2.47) and 3.00% (95% CI 1.93–4.63), respectively. The all‐cause mortality rate was 0.32% (95% CI 0.087–1.14) at 30 days; two patients died from arterial thrombosis events. Conclusions: A randomized controlled trial is needed to provide definitive conclusions but a conservative bridging approach appears promising.     

Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis

BACKGROUND: Limited data exist on the risk of pregnancy-associated venous thromboembolism (VTE) in women with a history of VTE. Objective: To evaluate the risk of recurrent pregnancy-associated thrombosis in women with previous VTE in a large retrospective cohort study. PATIENTS AND METHODS: One hundred and fifty-nine women with at least one pregnancy (293 pregnancies in total) after a VTE were included into the study. The patients underwent a standardized interview on their history of thrombosis and pregnancy-associated complications. RESULTS: Eight recurrent events occurred during 197 pregnancies without thrombosis prophylaxis. The probability of VTE during pregnancy without thrombosis prophylaxis was 6.2% (95% confidence interval 1.6-10.9%). The risk was constant over the whole period of pregnancy. Of the eight women with VTE during pregnancy four had heterozygous FV:R506Q, two in combination with hyperhomocysteinemia. No VTE occurred during 87 pregnancies with thrombosis prophylaxis. In the postpartum period 15 VTEs occurred, two of 83 (2.4%) after pregnancy termination, one of 53 (1.9%) after miscarriage, three of 10 (30%) after stillbirth and nine of 138 (6.5%) after live birth. CONCLUSIONS: Without thrombosis prophylaxis the risk for recurrent symptomatic VTE is substantial during the whole period of pregnancy in women with previous VTE. The majority of events occurred after delivery, reflecting the very high risk during the postpartum period. Prospective and comparative trials to ascertain efficacy and safety of prophylactic heparin are urgently needed.     

Venous thromboembolism and the risk of subsequent symptomatic atherosclerosis

BACKGROUND: Recently, we reported an association between asymptomatic carotid atherosclerosis and venous thromboembolism (VTE) of unknown origin. We hypothesized that patients with VTE of unknown origin would be at a higher risk of developing symptomatic atherosclerosis than patients with VTE induced by known risk factors. METHODS: To examine this hypothesis, we studied 1,919 consecutive patients followed prospectively after their first VTE episode. The primary outcome was non-fatal and fatal symptomatic atherosclerotic disease in patients with VTE of unknown origin as compared to those with secondary VTE. An independent committee assessed all study outcomes, and adjusted hazard ratios (HR) were calculated using the Cox's proportional hazards model. RESULTS: After a median follow-up of 48 and 51 months, respectively, at least one symptomatic atherosclerotic complication was detected in 160 of the 1,063 patients (15.1%) with VTE of unknown origin, and in 73 of the 856 (8.5%) with secondary VTE. After adjusting for age and other risk factors of atherosclerosis, the HR for symptomatic atherosclerotic complications in patients with VTE of unknown origin compared to those with secondary VTE was 1.6 (95% confidence intervals; CI: 1.2-2.0). When the analysis was restricted to patients without previous symptomatic atherosclerosis, the HR became 1.7 (95% CI: 1.1-2.4). CONCLUSIONS: Patients with VTE of unknown origin have a 60% higher risk of developing symptomatic atherosclerotic disease than do patients with secondary venous thrombosis.     

Bridging therapy in patients on long-term oral anticoagulants who require surgery: the Prospective Peri-operative Enoxaparin Cohort Trial (PROSPECT)

BACKGROUND: The peri-operative management of patients on oral anticoagulants (OACs) is a common clinical problem. Our aim was to determine the incidence of major bleeding during peri-operative administration of treatment-dose enoxaparin and the impact of the extensiveness of the procedure on the risk of bleeding. METHODS: We performed a prospective cohort study of 260 patients at 24 North American sites on OACs for atrial fibrillation or a history of deep vein thrombosis (DVT) requiring invasive or surgical procedures whose treating physician felt that bridging therapy was required. Warfarin was withheld, and once-daily s.c. enoxaparin (1.5 mg kg(-1)) was given peri-operatively. Patients were followed for 28 days after OAC was therapeutic. RESULTS: Major bleeding was observed in nine of 260 patients (3.5%, 95% CI: 1.6-6.5). The bleeding risk varied markedly by extensiveness of procedure: the incidence of major bleeding for invasive procedures, minor surgery and major surgery was 0.7% (95% CI: 0.02-3.7), 0% (95% CI: 0-5.0), and 20.0% (95% CI: 9.1-35.7), respectively. There were five thromboembolic events in total (1.9%, 95% CI: 0.6-4.4). There were four arterial events (2.3%, 95% CI: 0.6-5.7) in 176 patients with atrial fibrillation, and one venous event (1.0%, 95% ci: 0.03-5.7) in 96 patients with prior DVT/ CONCLUSIONS: Bridging therapy with once-daily therapeutic-dose enoxaparin administered primarily in an outpatient setting has a low incidence of major bleeding for patients undergoing invasive procedures and minor surgery. Further studies are needed to optimize the bridging strategy for patients undergoing major surgery.     

Venous thromboembolism and mortality after hip fracture surgery: the ESCORTE study.

BACKGROUND: Recent changes in the management of hip fracture surgery patients may have modified the epidemiology of postoperative complications. OBJECTIVES: We performed an observational study of a cohort of patients undergoing hip fracture surgery to update the epidemiological data on this population. The primary study outcome was the incidence of confirmed symptomatic venous thromboembolism (VTE) [defined as deep vein thrombosis, pulmonary embolism (PE), or both] at 3 months. Overall mortality at 1, 3 and 6 months was also evaluated. Patients/methods: Consecutive patients aged at least 18 years hospitalized in French public or private hospitals (531 centers) undergoing hip fracture surgery were recruited prospectively during 2 months in 2002 and a follow-up at 6 months. Predictive factors for VTE at 3 months and for death at 6 months were also analyzed. RESULTS: Data from 6860 (97.3%) of the 7019 recruited patients were included in the analysis. The median age was 82 years. Low molecular weight heparins were administered perioperatively in 97.6% of patients; 69.5% received this treatment for at least 4 weeks. The actuarial rate of confirmed symptomatic VTE at 3 months was 1.34% (85 events, 95% CI: 1.04-1.64). There were 16 PEs (actuarial rate: 0.25%), three of which were fatal. Overall, 1006 (14.7%) patients were dead at 6 months. Cardiovascular disease was the most frequent cause of death (270 patients; 26.8%). CONCLUSIONS: The current rate of postoperative VTE is low, but overall mortality remains high. Indeed, hip fracture patients belong to a vulnerable group of old people with comorbid diseases and a high risk of postoperative morbidity and mortality. An interdisciplinary approach could be the challenge to improve short and long-term outcome.     

Low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism: meta-analysis of the randomized comparisons with oral anticoagulants

Summary. Background: The management of venous thromboembolism (VTE) requires an initial treatment with unfractionated heparin (UFH) or low‐molecular‐weight heparin (LMWH), followed by oral anticoagulants (OA) for at least 3 months. OA treatment however, requires laboratory monitoring of anticoagulation, carries a definite risk of bleeding, and may be contraindicated in some patients. As an alternative to vitamin K antagonists, subcutaneous LMWH has been proposed and evaluated in randomized clinical trials, but they are all small studies that lack the power to establish if these two treatment modalities are equivalent in efficacy or safety. Objectives: The objective of this review was to evaluate the efficacy (VTE recurrence) and safety (bleeds and deaths) of long‐term treatment of VTE with LMWH compared with OA. A secondary endpoint was to evaluate the effect of LMWH on cancer mortality. Methods: Computerized searches of MedLine and EmBase were performed. In addition, randomized clinical trials were located through personal communication with colleagues, and through the manual scanning of meeting proceedings and reference lists of relevant studies. When necessary, the authors of the selected papers were called to obtain additional information. Two reviewers (AI and FG) reviewed and extracted data independently using a standard form. The primary analysis was performed for efficacy and safety endpoints on an intention‐to‐treat basis for the study period of randomized treatment. A meta‐regression analysis was used to investigate the relationship between daily dose and clinical outcome. Results: Seven studies that fulfillled our predefined criteria were identified, for a total of 1379 patients. When all studies were combined, a statistically non‐significant reduction in the risk of VTE (OR 0.66; 95% confidence interval [CI] 0.41, 1.07) and in the risk of major bleeding (OR 0.45; 95% CI 0.18, 1.11) in favor of LMWH treatment was found. No difference in total mortality (OR 1.19; 95% CI 0.78, 1.83) or in cancer‐related mortality was observed between the LMWH and the OA treatment. Conclusions: The results of this meta‐analysis indicate that a 3‐month course of LMWH is as effective and safe as a corresponding period of OA treatment, and may thus be considered as a valuable alternative option for patients in whom OA treatment appears contraindicated or problematic.     

Management of patients with suspected deep vein thrombosis in the emergency department: combining use of a clinical diagnosis model with D-dimer testing

The management of patients presenting to hospital Emergency Departments with suspected deep vein thrombosis is problematic since urgent diagnostic imaging is at times unavailable. We evaluated the accuracy of a rapidly available D-dimer test and the potential of combining D-dimer testing with an explicit clinical model to improve the management of patients with suspected deep vein thrombosis. Two hundred and fourteen patients with suspected deep vein thrombosis presenting to the Emergency Departments of two tertiary care institutions were enrolled in this prospective cohort study. Patients were evaluated by an Emergency Physician who determined the pre-test probability for deep vein thrombosis to be either low, moderate, or high using an explicit clinical model. Patients were managed according to their pre-test probability category by specific algorithms that in all cases included venous ultrasound imaging within 24 h and a 90-day follow-up for the development of thromboembolic complications. Patients also underwent fingerstick SimpliRED(R) whole blood agglutination D-dimer testing; however, D-dimer results did not influence subsequent patient management. D-dimer had a sensitivity of 82.5% and a specificity of 84.9% for the diagnosis of deep vein thrombosis. The observed negative predictive value of D-dimer was 96.9% (95% CI, 93.0% to 99.1%) overall, and 100% (95% CI, 96.3% to 100%) in low probability patients, 94.1% (95% CI, 83.8% to 98.8%) in moderate probability patients, and 86.7% (95% CI, 59.4% to 98.3%) in high probability patients. SimpliRED(R) D-dimer has a high negative predictive value and may be useful in excluding the diagnosis in patients at low pre-test probability for deep vein thrombosis.     

Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis: a population study based on 23 796 consecutive autopsies

BACKGROUND: The relationship between atherothrombotic disease and venous thromboembolism (VTE) remains unclear. PATIENTS AND METHODS: In a cohort of 23,796 consecutive autopsies, performed using a standardized procedure and representing 84% of all in-hospital deaths between 1970 and 1982 in an urban Swedish population, we investigated the relationship between verified arterial thrombosis and VTE, with the hypothesis that patients with thrombosis in major artery segments have increased odds of VTE. RESULTS: We found an increased risk of VTE in patients with arterial thrombosis (Odds ratio; OR adjusted for gender and age 1.4, 95% confidence interval; CI 1.3-1.5) (P < 0.001). Patients with cervico-cranial and peripheral artery thrombosis had an excess risk even when controlling for age and major concomitant diseases. A negative association between coronary thrombosis and VTE in the univariate analysis (OR 0.7; 95% CI 0.6-0.8) (P < 0.001), was less pronounced in the multivariate analysis (OR 0.8; 95% CI 0.7-1.0) (P = 0.016). CONCLUSIONS: A positive association between atherothrombosis and VTE was confirmed, except in patients with coronary thrombosis, where IHD as competing death cause is a possible confounder. Our findings indicate a potential for directed prevention, but may also imply similarities in etiology.     

Management of suspected pulmonary embolism (PE) by D-dimer and multi-slice computed tomography in outpatients: an outcome study

OBJECTIVES: A prospective outcome study designed to evaluate a simple strategy for the management of outpatients with suspected pulmonary embolism (PE), based on clinical probability, D-dimer, and multi-slice computed tomography (MSCT). METHODS: A cohort of 432 consecutive patients admitted to the emergency department with suspected PE was managed by sequential non-invasive testing. Patients in whom PE was ruled out were not given anticoagulants, but were followed-up for 3 months. RESULTS: Normal D-dimer and low-intermediate clinical probability ruled out PE in 103 patients [24% (95% CI 20-28)]. Seventeen patients had normal D-dimer, but high clinical probability and proceeded to MSCT. All patients proved negative for PE. A total of 329 (76%) patients underwent MSCT examination. Pulmonary embolism was diagnosed in 93 patients [21.5% (95% CI 18-26)] and was ruled out by negative MSCT in 221 patients [51% (95% CI 46-56)]. MSCT scans were determined as inconclusive in 15 (4.5%) patients. No patient developed objectively verified venous thromboembolism (VTE) during the 3-month follow-up period. However, the cause of death was adjudicated as possibly related to PE in two patients, resulting in an overall 3-month VTE risk of 0.6% (95% CI 0-2.2%). The diagnostic algorithm yielded a definite diagnosis in 96.5% of the patients. CONCLUSIONS: This simple and non-invasive strategy combining clinical probability, D-dimer, and MSCT for the management of outpatients with suspected PE appears to be safe and effective.