Clinical Diagnosis Of Venous Thromboembolism Research Articles

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery.

This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE. We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (≥ fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications and mortality within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis. We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I2 = 28%; moderate-quality evidence).For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I2 = 28%; moderate-quality evidence).We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I2 = 0%; moderate-quality evidence).The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis, which approached significance (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 0%; moderate-quality evidence).No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (M-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; moderate-quality evidence).No difference in mortality between the control and LMWH group was found, 3.8% and 3.9%, respectively (M-H OR 1.15, 95% CI 0.72 to 1.84; moderate-quality evidence).Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery.

This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE. We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (≥ fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications and mortality within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis. We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I2 = 28%; moderate-quality evidence).For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I2 = 28%; moderate-quality evidence).We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I2 = 0%; moderate-quality evidence).The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 0%; moderate-quality evidence).No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (M-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; moderate-quality evidence).No difference in mortality between the control and LMWH group was found, 3.8% and 3.9%, respectively (M-H OR 1.15, 95% CI 0.72 to 1.84; moderate-quality evidence).Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery.

This an update of the review first published in 2009.Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in-hospital period is well-documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in-hospital period only in preventing late onset VTE. We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (≥ fourteen days) with any LMWH agent with placebo, or other methods, or both to thromboprophylaxis during the admission period only. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed-effect model for analysis. We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with control or placebo. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria.For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out-of-hospital LMWH (Mantel Haentzel (M-H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I2 = 28%; seven studies, n = 1728; moderate-quality evidence).For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M-H OR 0.39, 95% CI 0.27 to 0.55; I2 = 28%; moderate-quality evidence).We found a similar reduction when analysis was limited to incidence in proximal DVT (M-H OR 0.22, 95% CI 0.10 to 0.47; I2 = 0%; moderate-quality evidence).The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis (M-H OR 0.30, 95% CI 0.08 to 1.11; I2 = 0%; moderate-quality evidence).No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (HM-H OR 1.10, 95% CI 0.67 to 1.81; I2 = 0%; seven studies, n = 2239; moderate-quality evidence).Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

Increased Risk of Chemotherapy-Associated Venous Thromboembolism in Elderly Patients with Cancer

Data on the relationship between aging, chemotherapy, and risk for venous thromboembolism (VTE) are controversial. We sought to evaluate the risk of chemotherapy-associated VTE in young to middle-aged (YMA) and elderly cancer patients and to analyze the VTE-free survival time in both groups. Patients with histologically confirmed diagnosis of solid malignancy receiving any type of systemic chemotherapy, no clinical diagnosis of VTE before chemotherapy initiation, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 were enrolled in this study. Of the 486 consecutive patients included in the study, 380 (78%) were classified as YMA (≤70 years of age) and 106 (22%) as elderly (>70 years of age). At a median follow-up of 1 year, the incidence of VTE events was almost two-fold greater in elderly than in YMA (11% vs. 6%). Age (≤70 years vs. >70 years (hazard ratio [HR], 2.42; 95% confidence interval [CI] 1.15-5.06; p=0.020), ECOG-PS (HR, 6.54; 95% CI 3.10-13.8; p<0.0001), and platinum-based chemotherapy (HR, 2.46; 95% CI 1.06-5.69; p=0.035) were independent risk factors for VTE. In the elderly subset, a trend toward an increased risk of VTE in patients receiving a platinum-based chemotherapy when compared with a non-platinum-containing regimen was observed (15% vs. 9.1%). The Kaplan-Meier analysis showed that elderly patients had a significantly shorter VTE-free survival time compared with younger cancer patients (log-rank test=2.0; p=0.045). Our study reports an increase incidence of VTE in elderly cancer patients treated with chemotherapy compared with the younger group, suggesting that aging is one of the most important risk factors for VTE. On the basis of the results of this study, we believe that a validated predictive model including age, ECOG-PS, and type of chemotherapy (platinum- vs. non-platinum containing regimen) would enable clinicians to target thromboprophylaxis to those patients considered to be at greatest risk.

Thromboembolic complications during pregnancy and delivery

Venous thromboembolism is one of the leading cause of maternal mortality worldwide. The incidence of venous thromboembolism is estimated at 0.76 to 1.72 per 100.000 pregnancies which is four times as great as the risk in nonpregnant women. The purpose of this article is to raise awareness of this frequent problem in pregnancy and provide a practical approach for the diagnosis, management, and prevention of venous thromboembolism during pregnancy and delivery. A number of risk factors for the development venous thromboembolism have been identified. The two most important risk factors for venous thromboembolism in pregnancy are thrombophilia and previous venous thromboembolism. Deep venous thrombosis in the majority of cases occurs in the lower extremities and pelvis. As the clinical diagnosis of venous thromboembolism is unreliable, the women who are suspected of having deep venous thrombosis or pulmonary embolism should be examined promptly using imaging diagnostics. The first diagnostic method is Doppler ultrasound. Where available, individual authors recommend magnetic resonance venography, pulmonary angiography or computed tomography. Unfractionated heparin or low-molecular-weight heparin has a central place in the prevention and treatment of venous thromboembolism in pregnancy because they do not pass through the placenta, thus avoiding the risks likely to be induced by warfarin. The prevention of venous thromboembolism must focus on the patients known to be at high risk bearing in mind that the recommendations for prophylaxis, even in high-risk patients, are based on the limited data.

Deep vein thrombosis and pulmonary embolism: diagnosis, treatment and prevention

Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major public health issue, with an incidence of 1/1,000 and thousands of VTE-related deaths each year in the UK. The estimated cost of VTE and its complications to the NHS is in excess of £600 million. 1 PE is the most common cause of inpatient mortality, and is the leading cause of death in pregnant women. Common risk factors include hospitalisation, surgery, cancer and immobilisation; and in women, combined oral contraceptive use, hormone replacement therapy and pregnancy. Approximately a quarter of VTE episodes are unprovoked, that is without an identifiable precipitant. 2 Clinical features of DVT include swelling and pain, pitting oedema, increased warmth and superficial venous dilation of the lower limb. PE may present with or without symptoms of a DVT in addition to chest pain, breathlessness, haemoptysis, syncope, hypotension, tachycardia and hypoxia. Without prompt recognition and treatment, PE can lead to death in up to 30%. Clinical diagnosis of VTE can be challenging and, furthermore, clinically silent episodes are not uncommon. Integrated diagnostic strategies have been demonstrated to be safe, efficacious and cost effective. 3 These strategies employ the use of a clinical pretest probability score (Table 1) in combination with D-dimer to inform the need for further diagnostic imaging. Patients at low risk of DVT/PE with a negative Ddimer result (using a high sensitivity assay) require no further investigation. However, those identified as moderate or high probability, or with a raised D-dimer require definitive imaging to confirm or exclude the diagnosis. Non-invasive compression ultrasonography is increasingly used first line for investigation of DVT, with advantages over venography including superior safety and portability. Sensitivity can be adversely affected by operator experience and poor views may be obtained in the presence of severe obesity, gross oedema or a plaster cast. However, its sensitivity for symptomatic proximal DVT remains up to 97%. 4 Computed tomography (CT) pulmonary angiography is currently accepted as the investigation of choice for PE diagnosis 5 ; its increased resolution allows detection of PE to subsegmental levels, in addition to detection of alternate diagnoses, such as, infection or cancer. Treatment for VTE is primarily aimed at prevention of clot extension, embolisation and symptom relief, with additional long-term aims of minimising recurrence and preventing postthrombotic syndrome. 6 Anticoagulation is the mainstay of treatment and should be initiated at confirmation of diagnosis or when first suspected if there is a delay in diagnostic imaging. Thrombolysis or surgical thrombectomy/embolectomy should be reserved for selected patients with haemodynamic instability due to massive PE or critical limb ischaemia secondary to DVT. Low molecular weight heparins (LMWHs) are the preferred agents for initiation of anticoagulation due to improved efficacy, safety and ease of administration with once daily subcutaneous injection. 6 Monitoring of the anticoagulant effect is not required routinely with LMWH and rates of early mortality, recurrence and major bleeding are reduced compared to unfractionated heparin, as is the risk of heparin-induced thrombocytopenia. Warfarin should be initiated once the diagnosis of VTE is confirmed, in the absence of contraindications,

Venous thromboembolism prophylaxis in hospitalized elderly patients: Time to consider a MUST strategy

Venous thromboembolism (VTE) is the commonest cause of preventable death in hospitalized patients. Elderly patients have higher risk of VTE because of the high prevalence of predisposing co-morbidities and acute illnesses. Clinical diagnosis of VTE in the elderly patient is particularly difficult and, as such, adequate VTE prophylaxis is of pivotal importance in reducing the mortality and morbidities of VTE. Omission of VTE prophylaxis is, however, very common despite continuous education. A simple way to overcome this problem is to implement universal VTE prophylaxis for all hospitalized elderly patients instead of selective prophylaxis for some patients only according to individual's risk of VTE. Although pharmacological VTE prophylaxis is effective for most patients, a high prevalence of renal impairment and drug interactions in the hospitalized elderly patients suggests that a multimodality approach may be more appropriate. Mechanical VTE prophylaxis, including calf and thigh compression devices and/or an inferior vena cava filter, are often underutilized in hospitalized elderly patients who are at high-risk of bleeding and VTE. Because pneumatic compression devices and thigh length stockings are virtually risk free, mechanical VTE prophylaxis may allow early or immediate implementation of VTE prophylaxis for all hospitalized elderly patients, regardless of their bleeding and VTE risk. Although the cost-effectiveness of this Multimodality Universal STat (‘MUST’) VTE prophylaxis approach for hospitalized elderly patients remains uncertain, this strategy appears to offer some advantages over the traditional ‘selective and single-modal’ VTE prophylaxis approach, which often becomes ‘hit or miss’ or not implemented promptly in many hospitalized elderly patients. A large clustered randomized controlled trial is, however, needed to assess whether early, multimodality, universal VTE prophylaxis can improve important clinical outcomes of hospitalized elderly patients.

Venous thromboembolism-related mortality and morbidity in King Fahd General Hospital, Jeddah, Kingdom of Saudi Arabia

BACKGROUND:Venous thromboembolism (VTE) is a serious and underestimated potentially fatal disease with an effective prophylactic antithrombotic therapy that is usually underused.OBJECTIVES:The primary study objective is to determine the percentage of VTE patients who received prophylactic antithrombotic therapy according to ACCP guidelines. Secondary study objectives are determining prevalence of confirmed VTE mortality among all cause hospital mortalities, measuring adherence to anticoagulation treatment after discharge and number of VTE events among those patients.METHODS:During the period from first of July 2008 till 30 of June 2009, we collected all hospital deaths, all patients with confirmed VTE diagnosis at King Fahd General Hospital, Jeddah, Kingdom of Saudi Arabia. Only patients with confirmed VTE diagnosis were included in the analysis.RESULTS:Five hundred cases with clinical diagnosis of VTE were identified. Out of them 178 were confirmed to be VTE. 36.5% of them received prophylactic antithrombotic therapy. Case fatality rate was 20.8% representing 1.9% of hospital deaths. Case fatality rate was 31% and 3.1% for patients who did not receive thromboprophylaxis and patients who received it, respectively (P < 0.0001). 66.3% and 33.7% of confirmed VTE cases occurred in surgical and medical patients respectively. Only 44.1% of surgical patients and 21.7% of medical patients received prophylaxis (P < 0.01). Case fatality rate is 11% for surgical patients and 40% for medical patients (P < 0.001). Of 141 survived cases, 118 (83.7%) were adherent to anticoagulation therapy after discharge.CONCLUSIONS:VTE prophylaxis guideline is not properly implemented and extremely underutilized. Mortality from VTE is significantly higher in patients who did not receive VTE prophylaxis. In the absence of regular post-mortem practice VTE related mortality rate would be difficult to estimate and likely will be underestimated. Health authorities should enforce VTE prophylaxis guideline within the healthcare system.

Prolonged thromboprophylaxis with Low Molecular Weight heparin for abdominal or pelvic surgery

Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low-molecular weight heparin (LMWH) administered during the in-hospital period is well documented, but the optimal duration of thromboprophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominal surgery benefit from prolongation of the thromboprophylaxis to 1 month after surgery. No systematic review on prolonged thromboprophylaxis after major abdominal or pelvic surgery has been published. To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 1 month after abdominal or pelvic surgery with thromboprophylaxis administered during the in-hospital period only in preventing late VTE. Electronic searches were performed January 2008 in the Medline, Embase, Lilacs, and the Cochrane Central Register of Controlled Trials. Abstract books from major congresses addressing thromboembolism were hand searched, as were reference lists from studies of relevance. We assessed both randomised and non-randomised controlled clinical trials comparing prolonged thromboprophylaxis with any anti-thrombotic agent with placebo and/or thromboprophylaxis during the admission period only. The patient population in the trials were patients undergoing abdominal or pelvic surgery. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (ascending bilateral venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral CT scan or autopsy). Studies exclusively reporting on clinical diagnosis of VTE, without objective confirmation were excluded. The identification of studies and data extraction were performed by the authors. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcome were defined as bleeding complications and mortality within 3 months after surgery. The search exclusively detected trials evaluating prolonged thromboprophylaxis with LMWH as compared to control or placebo. 133 studies were found in the searches, of which only 4 were found eligible for inclusion, and 129 were excluded. The incidence of overall VTE after major abdominal or pelvic surgery was 14.3% (95% confidence interval 11.2% - 17.8%) in the control group as compared to 6.1% (95% CI 4.0% - 8.7%) in the patients receiving out-of-hospital LMWH. This difference was statistically significant, Peto Odds Ratio 0.41 (95% CI 0.26 -0.63), P < 0.0005. Prolonged thromboprophylaxis with LMWH was also associated with a statistically significant reduction of even the incidence of symptomatic VTE from 1.7% (95% CI 0.8% - 3.4%) in the control group to 0.2 % (95% CI 0.0% - 1.2%) in patients receiving prolonged thromboprophylaxis, Peto Odds ratio 0.22 (95% CI 0.06 -0.80), P = 0.02. The respective incidence of bleeding in the control and LMWH group were 3.7% (95% CI 2.4% -5.5%) and 4.1% (95% CI 2.7% - 6.0%), Peto Odds ratio 1.11 (95% CI 0.62 - 1.97), P = 0.73. There was no significant heterogeneity detected as regards to outcome parameters reported in the included trials. Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery.

Extensive evaluation of the instrumentation laboratory IL test D-Dimer immunoturbidimetric assay on the ACL 9000 determines the D-Dimer cutoff value for reliable exclusion of venous thromboembolism.

The clinical diagnosis of venous thromboembolism (VTE), which includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), is often difficult and requires a number of imaging tests plus clinical assessment. It is now accepted that pretest clinical probability of disease plus a sensitive, quantitative D-Dimer assay can be used to reliably exclude VTE. In design of diagnostic strategies for VTE it is recommended that the D-Dimer assay be evaluated for sensitivity and specificity in well-designed, blinded studies using a cohort of patients for whom the assay will ultimately be used. Therefore we evaluated the IL Test D-Dimer on the ACL 9000 automated coagulation analyzer for its sensitivity and specificity in the diagnosis of VTE. A total of 512 patients admitted to the emergency department of Providence Hospital with suspected VTE were included in the dataset. Our aim was to find the clinically meaningful IL Test D-Dimer cutoff value, which would give us 100% sensitivity and the highest possible specificity for exclusion of VTE. Patients were categorized clinically into low, medium, or high pretest probability and had computed tomographic and/or ventilation-perfusion scans for investigation of PE and ultrasound studies for suspected DVT, with the laboratory blinded to the clinical findings. Of the 511 patients, 28 (5.4%) had confirmed VTE (PE and/or DVT) based on imaging and clinical studies. Applying receiver operating characteristic curve (ROC) analysis, we determined from our study that a cutoff value of 237 ng/mL IL Test D-Dimer gave a 100% sensitivity with a specificity of 38% for detection of VTE. The findings demonstrate that a diagnostic strategy using the IL Test D-Dimer assay as a first-line test in combination with pretest probability is safe and can be used in patients with suspected VTE. In conclusion, patient analysis results indicating low or moderate pretest probability for VTE and a negative IL Test D-Dimer (cutoff value of 237 ng/mL) assay result on the ACL 9000 reliably exclude VTE (both PE and DVT). We expect that inclusion of the rapid IL Test D-Dimer assay for assessment of suspected VTE in the emergency department at Providence will result in improved patient diagnosis and therapy, reduction in unnecessary radiological investigations, and lowering of overall costs associated with investigation of patients suspected of having VTE disease.

How we manage venous thromboembolism during pregnancy

During pregnancy, physiologic and anatomic changes can complicate the diagnosis of venous thromboembolism (VTE) as well as the management of patients with a high risk of or established VTE. As in nonpregnant subjects, clinical diagnosis of VTE by itself is unreliable and accurate objective testing is essential. Few diagnostic studies of VTE have been performed in pregnant women and, therefore, approaches are largely extrapolated from those used in nonpregnant subjects with modifications to limit the radiation exposure and overcome the limitations of diagnostic testing in pregnancy. Therapy of established VTE during pregnancy consists of therapeutic doses of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH), generally given throughout pregnancy subcutaneously and for 4 to 6 weeks after childbirth. A key unresolved issue includes the optimum dosing of LMWH therapy. Maternal warfarin can be safely used after childbirth because it is safe to use in the breast-fed infant of a mother receiving warfarin. Finally, pregnant women with prior VTE (with or without a hypercoagulable state) have an increased risk of recurrent venous thrombosis. A recent study has demonstrated that for women with a single episode of prior VTE, many can be managed without anticoagulants. However, for many, anticoagulant therapy with prophylactic UFH or LMWH is a reasonable option.

POSTOPERATIVE THROMBOTIC COMPLICATIONS: Venous Thromboembolism: Deep-Vein Thrombosis and Pulmonary Embolism

Autopsy findings indicate that 73% of pulmonary emboli diagnosed at autopsy were not detected clinically.70 The clinical diagnosis of venous thromboembolism is unreliable, and the first manifestation of the disease may be fatal pulmonary embolism. Patients may be totally asymptomatic, or they may have symptoms such as dyspnea, tachypnea, or chest pain, which may be dull and centrally located or pleuritic in nature. Patients often will have hypoxemia, and may initially also have hypocapnia secondary to hyperventilation. Wheezing may occur as a result of the release of emboli-associated inflammatory mediators such as serotonin. Patients may also have nonspecific signs, such as tachycardia or signs of right ventricular strain on ECG or on echocardiogram. The chest radiograph is often normal. At the other end of the spectrum is the patient who presents with sudden-onset cardiovascular collapse and pulseless electrical activity. It is well known that surgery predisposes patients to venous thromboembolism. Less appreciated is the fact that they are at risk, not only in the immediate postoperative period, but even as late as 1 month postoperatively.11, 55 Deep vein thrombosis (DVT) and pulmonary embolism represent two aspects of the same disease process. Treatment and duration of treatment are usually the same in both instances. Because diagnosis and treatment both confer significant risks to the patient, there has been an ongoing search to determine the optimal strategy for confirming, or excluding the diagnosis. Several factors have to be considered in the diagnostic work-up, such as the role of history and physical examination, and how it influences the final diagnosis. Laboratory data and other diagnostic tests should be evaluated for their sensitivity and specificity, cost-effectiveness, availability, expertise required in their interpretation, ease of performing, and patient comfort. Advances have occurred in the field of anticoagulation with the introduction of low molecular weight heparins (LMWHs). Anticoagulation carries significant risks. The low therapeutic index of oral anticoagulants requires careful long-term monitoring, which in itself poses problems, and results in significant costs and inconvenience to patients. The role of inferior vena caval filters and surgical intervention also have associated significant costs and risks. The identification and stratification of patients at risk for venous thromboembolism is of paramount importance in order to institute effective prophylaxis and treatment. Most patients who die from pulmonary embolism do so within 30 minutes of the acute event—too soon for anticoagulation to be effective.27 Despite numerous studies attesting to the efficacy and safety of prophylaxis, it is still underused.16

Hospital-based approach to the management of venous thromboembolism.

The primary goal of venous thromboembolism (VTE) management is to prevent fatal pulmonary embolism (PE). It has long been recognized that venous thrombi in the deep veins of the legs are the source of more than 90% of fatal pulmonary emboli [1,2]. Thrombi that develop in the proximal deep leg veins (i.e. the iliofemoral system) are particularly prone to embolize. One of the great challenges confronting clinicians in hospital-based practice is that the clinical diagnosis of VTE is not speci~c. VTE is clinically suspected in approximately 600,000 patients each year, but is con~rmed in only one third [3]. Further increasing the diagnostic challenge, a clinical diagnosis of VTE is not sensitive [4]. Only one in three patients with clinically signi~cant VTE are clinically suspected (Figure 1). Even physicians who are aware of the dangers of VTE must struggle to identify high-risk patients and to make a ~rm diagnosis. The potential public health impact of VTE is considerable, with the potential for overuse of diagnostic tests, on the one hand, and high morbidity and mortality, on the other. Clearly, the identi~cation of high-risk patients and the institution of effective preventive strategies are vital in the comprehensive management of VTE[5]. The odds of acute proximal DVT vary widely from 1:2000 in the general population to 1:3 in hospitalized patients with VTE signs and symptoms (e.g., calf or thigh pain, leg swelling, unexplained dyspnea; Table 1). While VTE signs and symptoms are generally not suf~ciently speci~c to form a basis for treatment decisions, they are suf~cient to justify an order for objective tests. Because a majority of patients with VTE do not have clinical signs or symptoms, including patients with proximal thrombi involving the iliofemoral system (i.e., those most likely to embolize) and patients who die from PE [6], a high index of suspicion must be maintained in hospitalized patients. Particular attention should be given to patients with recognized VTE risk factors (Table 2).

Imaging Venous Thromboembolism with Emphasis on Ultrasound, Chest CT, Angiography and Echocardiography

IntroductionThe clinical diagnosis of venous thromboembolism (VTE) is dif ficult and sometimes unreliable. Pulmonary angiography and contrast venography are used as reference tests for pulmonary embolism (PE) and deep vein thrombosis (DVT), respectively.1,2 However, due to the invasive nature of these reference tests, the optimal and clinically acceptable diagnosis of VTE remains a matter of some debate. Until recently, standard diagnostic strate gy in suspected pulmonary embolism (PE) consisted of a lung perfusion scan, followed by venous ultrasound (VUS), if a lung perfusion scan did not produce a definitive diagnosis. Eventually pulmonary angiography was performed.3,4 In clinical practice this strategy has rarely been respected because it required many pulmonary angiographic examinations. Diagnostic managemen was often halted prematurely without performing pulmonary angiography and, thus, without final confirmation or exclusion o PE.5-7 In addition, suspected DVT is often managed only on the basis of single VUS examination, which, unfortunately, has a rel atively low sensitivity when used to visualize the vasculature below the knee.8 This chapter focuses on newer, noninvasive diagnostic tests that permit direct imaging of venous thromboemboli. While the place of those tests in diagnostic algorithms remains to be fully determined, they may already be helpful in simplifying the diagnostic management of patients in many clinical situations including those patients at high-risk of venous thromboem bolism. These patients represent a non-homogeneous group such as patients with recent major surgery, serious medical dis eases, or a concomitant history of VTE or thrombophilia According to a recent consensus statement, screening for VTE is technically possible, but, in the presence of effective prophy laxis, neither was demonstrated to be necessary or cost effec tive.9 Therefore, the main effort should be focused on effective diagnostic management of those patients who present with symptoms and/or signs suggestive of VTE.

Deep vein thrombosis and pulmonary emboli in neurosurgical patients: a review.

This review examines the incidence, natural history, diagnosis, prophylaxis, and management of deep vein thrombosis (DVT) and pulmonary embolism (PE) in neurosurgical patients. Recent studies estimate the incidence of postoperative DVT detected by fibrinogen scanning in neurosurgical patients to be 29% to 43%. Specific factors that enhance the risk of venous thromboembolism include previous DVT, surgery, immobilization, advanced age, obesity, limb weakness, heart failure, and lower extremity trauma. Clinical diagnosis of venous thromboembolism is unreliable but can be augmented by noninvasive screening tests such as iodine-125-fibrinogen scanning, Doppler ultrasonography, and impedance plethysmography. As prophylactic measures, mini-dose heparin and external pneumatic compression of the legs have decreased the incidence of DVT in clinical studies of neurosurgical patients. However, no prophylactic measure has been convincingly shown to prevent PE in neurosurgical patients. Thrombi involving the popliteal, deep femoral, and iliac veins appear most likely to cause significant PE. Anticoagulation therapy constitutes standard management of DVT and PE; however, in neurosurgical patients the potential for precipitating intracranial or intraspinal hemorrhage may necessitate vena caval interruption. This appears to be an effective alternative to anticoagulation.