Adequate diagnostic management of suspected venous thromboembolism (VTE) in pregnant women is of great importance. The diagnostic performance of clinical decision rules and D-dimer testing is... Show moreAdequate diagnostic management of suspected venous thromboembolism (VTE) in pregnant women is of great importance. The diagnostic performance of clinical decision rules and D-dimer testing is influenced by physiological changes during pregnancy and is understudied. Recent studies have addressed these issues by developing a new clinical decision rule and raising the D-dimer level cut-off points. With imaging of suspected pulmonary embolism (PE) the radiation exposure remains a concern. Recent studies have adjusted CT settings and scan length to minimize this exposure without loss of image quality. Furthermore the first choice imaging modality of suspected PE in pregnant women remains a matter of debate in view of studies showing high inadequacy rates for both CT scanning and VQ scanning. Issues concerning the diagnostic management of VTE in pregnant women and advancements made in recent years will be discussed. Show less
Background: Knowledge of independent, baseline risk factors for catheter-related thrombosis (CRT) may help select adult cancer patients who are at high risk to receive thromboprophylaxis.... Show moreBackground: Knowledge of independent, baseline risk factors for catheter-related thrombosis (CRT) may help select adult cancer patients who are at high risk to receive thromboprophylaxis. Objectives: We conducted a meta-analysis of individual patient-level data to identify these baseline risk factors. Patients/Methods: MEDLINE, EMBASE, CINAHL, CENTRAL, DARE and the Grey literature databases were searched in all languages from 1995 to 2008. Prospective studies and randomized controlled trials (RCTs) were eligible. Studies were included if original patient-level data were provided by the investigators and if CRT was objectively confirmed with valid imaging. Multivariate logistic regression analysis of 17 prespecified baseline characteristics was conducted. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results: A total sample of 5636 subjects from five RCTs and seven prospective studies was included in the analysis. Among these subjects, 425 CRT events were observed. In multivariate logistic regression, the use of implanted ports as compared with peripherally implanted central venous catheters (PICCs), decreased CRT risk (OR, 0.43; 95% CI, 0.23-0.80), whereas past history of deep vein thrombosis (DVT) (OR, 2.03; 95% CI, 1.05-3.92), subclavian venipuncture insertion technique (OR, 2.16; 95% CI, 1.07-4.34) and improper catheter tip location (OR, 1.92; 95% CI, 1.22-3.02), increased CRT risk. Conclusions: CRT risk is increased with use of PICCs, previous history of DVT, subclavian venipuncture insertion technique and improper positioning of the catheter tip. These factors may be useful for risk stratifying patients to select those for thromboprophylaxis. Prospective studies are needed to validate these findings. Show less
Objective-The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34(+) cells is assumed to be indicative for the potential of these cells to support vascular maintenance... Show moreObjective-The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34(+) cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34(+) cells co-express KDR. Therefore, we studied whether CD34(+)/KDR+ cells are generated in the peripheral circulation. Methods and Results-Using an ex vivo flow model, we show that activated platelets enable CD34(+) cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34(+) co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34(+)/KDR+ cells, indicating that the level of circulating CD34(+)/KDR+ cells also relates to in vivo platelet activation. Conclusion-Circulating CD34(+)/KDR+ are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34(+) cells at sites of vascular injury. Therefore, the number of circulating CD34(+)/KDR+ cells may serve as a marker for vascular injury. (Arterioscler Thromb Vasc Biol. 2011;31:408-415.) Show less
OBJECTIVE The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34+ cells is assumed to be indicative for the potential of these cells to support vascular maintenance and... Show moreOBJECTIVE The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34+ cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34+ cells co-express KDR. Therefore, we studied whether CD34+/KDR+ cells are generated in the peripheral circulation. METHODS AND RESULTS Using an ex vivo flow model, we show that activated platelets enable CD34+ cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34+ co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34+/KDR+ cells, indicating that the level of circulating CD34+/KDR+ cells also relates to in vivo platelet activation. CONCLUSIONS Circulating CD34+/KDR+ are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34+ cells at sites of vascular injury. Therefore, the number of circulating CD34+/KDR+ cells may serve as a marker for vascular injury. Show less
Klok, F.A.; Romeih, S.; Westenberg, J.J.M.; Kroft, L.J.M.; Huisman, M.V.; Roos, A. de 2011
Venous thromboembolism (VTE) is a disease that causes high morbidity and mortality in the population. At present the first-line imaging test for a suspected pulmonary embolism (PE) is computed... Show moreVenous thromboembolism (VTE) is a disease that causes high morbidity and mortality in the population. At present the first-line imaging test for a suspected pulmonary embolism (PE) is computed tomography (CT) pulmonary angiography, and ultrasonography is widely used for the diagnosis of deep-vein thrombosis (DVT). Although these modalities are proven to be safe and accurate, unresolved issues remain, such as whether CT scanning in patients with a suspected PE should be extended to the legs. Another issue is the diagnosis of recurrent DVT. Magnetic resonance imaging (MRI) offers a number of advantages in the imaging of VTE. Recent developments of scanning protocols with shorter acquisition times, sometimes complemented by navigator gating or making use of endogenous contrast, offer new perspectives for the use of MRI. This review provides an overview of state of the art MRI techniques for the diagnosis of PE and DVT. Furthermore, the use of new contrast agents such as fibrin labeling to detect thrombi are addressed. Show less
In recent years new oral anticoagulants have been evaluated in the prevention of venous thromboembolism (VTE) after elective hip or knee arthroplasty, atrial fibrillation to prevent ischemic stroke... Show moreIn recent years new oral anticoagulants have been evaluated in the prevention of venous thromboembolism (VTE) after elective hip or knee arthroplasty, atrial fibrillation to prevent ischemic stroke and in the treatment of acute VTE. While two oral anticoagulants, dabigatran and rivaroxaban, have become available for the prevention of VTE in orthopaedic surgery, other indications still are under evaluation or await approval. There are also areas where these novel drugs have not yet been evaluated. These include patients with acute VTE and cancer, pregnant patients with acute VTE and patient with either rheumatic heart valve disease or artificial heart valves. Finally, in acute care settings, where anticoagulant reversibility is critical, such as during and after coronary artery bypass surgery or acute PCI setting in patients with high bleeding risk, novel intravenous anticoagulant drugs with either short half life or specific antidotes may have added value. This article will focus on these unresolved issues. Show less
Langevelde, K. van; Tan, M.; Sramek, A.; Huisman, M.V.; Roos, A. de 2010
Venous thromboembolism (VTE) is a disease that causes high morbidity and mortality in the population At present the first-line imaging test for a suspected pulmonary embolism (PE) is computed... Show moreVenous thromboembolism (VTE) is a disease that causes high morbidity and mortality in the population At present the first-line imaging test for a suspected pulmonary embolism (PE) is computed tomography (CT) pulmonary angiography and ultrasonography is widely used for the diagnosis of deep-vein thrombosis (DVT) Although these modalities are proven to be safe and accurate unresolved issues remain such as whether CT scanning in patients with a suspected PE should be extended to the legs Another Issue is the diagnosis of recurrent DVT Magnetic resonance imaging (MRI) offers a number of advantages in the imaging of VTE Recent developments of scanning protocols with shorter acquisition times sometimes complemented by navigator gating or making use of endogenous contrast offer new perspectives for the use of MRI This review provides an overview of state of the art MRI techniques for the diagnosis of PE and DVT Furthermore the use of new contrast agents such as fibrin labeling to detect thrombi are addressed Show less
Background To our knowledge, studies evaluating the quality of life (QoL) in patients with a history of acute pulmonary embolism (PE) are not available, even though QoL is a key outcome component... Show moreBackground To our knowledge, studies evaluating the quality of life (QoL) in patients with a history of acute pulmonary embolism (PE) are not available, even though QoL is a key outcome component of medical care and a predictor of disease-specific prognosis Methods As part of a large follow-up study, the Short Form 36 (SF-36) was presented to consecutive patients who had survived one or more episodes of acute PE The results of all nine subscales of the SF-36 were compared with sex- and age-adjusted Dutch population norms Single and multivariate analyses were performed to identify independent determinants of the QoL in our study population Results The SF-36 was completed by 392 patients Except for the health change subscale, patients had substantially lower QoL than population norms on all eight remaining subscales After multivariate analysis, the hint. interval between the last thromboembolic episode and study inclusion was inversely related to QoL, and significant determinants of poor QoL were prior PE, age, obesity, active malignancy, and cardiopulmonary comorbid conditions Regression models that included all identified significant determinants proved to be quite modest predictors for QoL in the individual patient Awareness of illness, coping mechanisms, and self-management behavior might be additional important indicators of QoL in our study population but require further investigation Conclusion We identified several PE- and non-PE-related determinants of QoL in patients with a history of acute PE, which is impaired compared with sex- and age-adjusted population norms QoL after acute PE should be studied more extensively and added as a standard measure to outcome studies CHEST 2010, 138(6) 1432-1440 Show less
Huisman, M.V.; Quinlan, D.J.; Dahl, O.E.; Schulman, S. 2010
Background-Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically... Show moreBackground-Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically important efficacy and bleeding outcomes of these 2 new agents versus low-molecular-weight heparin (enoxaparin) is lacking. Methods and Results-We separately pooled efficacy and safety data from 6 phase III randomized trials (18 405 participants) comparing equivalent durations of treatment with enoxaparin (40 mg once daily [od] or 30 mg twice daily) versus dabigatran (220 mg od) or versus rivaroxaban (10 mg od) after hip or knee arthroplasty. Odds ratios (OR) for individual outcomes were calculated for each trial and were pooled using the Mantel-Haenszel method. Compared with dabigatran, enoxaparin had a similar risk of symptomatic venous thromboembolism plus all-cause mortality (0.9% versus 1.1%; OR, 0.76; 95% confidence interval [CI], 0.44 to 1.31; I-2=76%) and bleeding (5.0% versus 5.6%; OR, 0.90; 95% CI, 0.71 to 1.15; I-2=0%). Compared with rivaroxaban, enoxaparin had a 2-fold higher risk of symptomatic venous thromboembolism plus all-cause mortality (1.2% versus 0.6%; OR, 2.04; 95% CI, 1.32 to 3.17; P<0.001; number needed to treat, 167; I-2=0%) but demonstrated a significant lower risk of bleeding (2.5% versus 3.1%; OR, 0.79; 95% CI, 0.62 to 0.99; P=0.049; number needed to harm, 167; I-2=0%). Conclusions-In patients undergoing hip or knee arthroplasty, enoxaparin and dabigatran showed similar rates of efficacy and bleeding. Enoxaparin was less effective than rivaroxaban but had a lower risk of bleeding. These results may have important implications for the choice of prophylactic agent in major joint arthroplasty. (Circ Cardiovasc Qual Outcomes. 2010;3:652-660.) Show less
BACKGROUND Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically... Show moreBACKGROUND Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically important efficacy and bleeding outcomes of these 2 new agents versus low-molecular-weight heparin (enoxaparin) is lacking. METHODS AND RESULTS We separately pooled efficacy and safety data from 6 phase III randomized trials (18 405 participants) comparing equivalent durations of treatment with enoxaparin (40 mg once daily [od] or 30 mg twice daily) versus dabigatran (220 mg od) or versus rivaroxaban (10 mg od) after hip or knee arthroplasty. Odds ratios (OR) for individual outcomes were calculated for each trial and were pooled using the Mantel-Haenszel method. Compared with dabigatran, enoxaparin had a similar risk of symptomatic venous thromboembolism plus all-cause mortality (0.9% versus 1.1%; OR, 0.76; 95% confidence interval [CI], 0.44 to 1.31; I²=76%) and bleeding (5.0% versus 5.6%; OR, 0.90; 95% CI, 0.71 to 1.15; I²=0%). Compared with rivaroxaban, enoxaparin had a 2-fold higher risk of symptomatic venous thromboembolism plus all-cause mortality (1.2% versus 0.6%; OR, 2.04; 95% CI, 1.32 to 3.17; P<0.001; number needed to treat, 167; I²=0%) but demonstrated a significant lower risk of bleeding (2.5% versus 3.1%; OR, 0.79; 95% CI, 0.62 to 0.99; P=0.049; number needed to harm, 167; I²=0%). CONCLUSIONS In patients undergoing hip or knee arthroplasty, enoxaparin and dabigatran showed similar rates of efficacy and bleeding. Enoxaparin was less effective than rivaroxaban but had a lower risk of bleeding. These results may have important implications for the choice of prophylactic agent in major joint arthroplasty. Show less
Introduction: Microparticles (MPs) carrying active tissue factor (TF) have been detected in the plasma of cancer patients in particular in those presenting with acute deep vein thrombosis (DVT) or... Show moreIntroduction: Microparticles (MPs) carrying active tissue factor (TF) have been detected in the plasma of cancer patients in particular in those presenting with acute deep vein thrombosis (DVT) or pulmonary embolism (PE). Experimental studies in mice have revealed that circulating MPs carrying TF contribute to thrombus formation. Aim: To study whether unselected patients with an acute confirmed PE have elevated TF activity in the MP fraction (MP-TF activity). Materials and Methods: Plasma MP-TF activity was measured in 159 non-selected patients with clinically suspected PE and in 48 healthy controls as previously described. Blood was collected at time of inclusion. The diagnosis of acute PE was confirmed in 54 patients and excluded in 105 patients. Results: Median MP-TF activity in 159 patients with clinically suspected PE was 72 fM Xa/min [range 32-6657] fM Xa/min and higher than in healthy controls (66 [range 28-183] fM Xa/min; P<0.05). There was no significant difference (P=0.169) in MP-TF activity between patients with confirmed PE (median 84.5 fM Xa/min [range 36-2149]) and patients without PE (72 fM Xa/min [range 32-6657]) fM Xa/min). In the 159 patients with clinically suspected PE we observed in an exploratory analysis higher MP-TF activity levels in patients with active cancer (median 137 fM Xa/min [range 36-6657]) and cardiovascular disease (median 131.5 fM Xa/min [range 45-2149]) than in patients without these disorders (P=0.0004 and P=0.014, respectively). Conclusion: In patients presenting with clinically suspected PE plasma MP-TF activity was not associated with confirmed PE. (C) 2010 Elsevier B.V. All rights reserved. Show less
Dogan, H.; Kroft, L.J.M.; Huisman, M.V.; Geest, R. van der; Li, Y.; Lamb, H.J.; Roos, A. de 2010
OBJECTIVE. The purpose of this article is to determine the independent predictors of right ventricular (RV) dysfunction in patients with acute pulmonary embolism (PE) and to assess the relationship... Show moreOBJECTIVE. The purpose of this article is to determine the independent predictors of right ventricular (RV) dysfunction in patients with acute pulmonary embolism (PE) and to assess the relationship between RV ejection fraction (EF) and PE load. SUBJECTS AND METHODS. Breath-hold CT of the chest was performed for 64 patients with PE (33 men and 31 women; mean [+/- SD] age, 58.6 +/- 16.5 years). In addition, ECG-synchronized cardiac CT was performed to determine the RV and left ventricular (LV) EFs. PE load was determined using the Qanadli obstruction index. Multivariable regression analysis was performed to determine independent predictors of RV dysfunction (defined as EF < 35%). In addition, the relationship between RV EF and PE load was assessed by receiver operating characteristic (ROC) curves. RESULTS. RV dysfunction was independently predicted by a PE load greater than 50% (odds ratio, 40.17; 95% CI, 4.22-382.67) and an LV EF less than 45% (odds ratio, 31.18; 95% CI, 2.00-487.09; p < 0.05 for both). Curve analysis revealed that a PE load greater than 50% had a sensitivity of 82% and a specificity of 85% to identify an RV EF less than 35%. Conversely, an RV EF less than 35% had a sensitivity of 93% and a specificity of 67% to predict a PE load greater than 50%. CONCLUSION. RV dysfunction (defined as RV EF < 35%) in patients with acute PE is highly sensitive to define a PE load greater than 50%. Furthermore, RV dysfunction is independently predicted by an obstruction index greater than 50% or an LV EF less than 45%. Assessment of RV function by ECG-synchronized CT may become useful for guiding therapy. Show less
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism (PE) with an estimated incidence of 0.5 to 1.5% in the Netherlands, depending on the... Show moreChronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism (PE) with an estimated incidence of 0.5 to 1.5% in the Netherlands, depending on the aetiology of the PE. The underlying pathophysiological mechanism is largely unknown and may be caused by (recurrent) emboli or primarily by a characteristic arteriopathy of the pulmonary arteries. Patients with CTEPH present with nonspecific symptoms predominantly caused by right heart failure and up to 40% have no prior history of venous thromboembolism (VTE). The diagnostic approach of CTE PH aims at assessing the location and extent of the embolic obstruction to establish the operability and prognosis of the patients. A heart catheterisation for invasive pressure measurements is obligatory for the final diagnosis. CTEPH is associated with a poor prognosis if left untreated. The preferred treatment is pulmonary endarterectomy. In certain patients with inoperable disease or with persistent or recurrent pulmonary hypertension after surgery, pharmacotherapy might be beneficial. Show less
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism (PE) with an estimated incidence of 0.5 to 1.5% in the Netherlands, depending on the... Show moreChronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism (PE) with an estimated incidence of 0.5 to 1.5% in the Netherlands, depending on the aetiology of the PE. The underlying pathophysiological mechanism is largely unknown and may be caused by (recurrent) emboli or primarily by a characteristic arteriopathy of the pulmonary arteries. Patients with CTEPH present with nonspecific symptoms predominantly caused by right heart failure and up to 40% have no prior history of venous thromboembolism (VTE). The diagnostic approach of CTEPH aims at assessing the location and extent of the embolic obstruction to establish the operability and prognosis of the patients. A heart catheterisation for invasive pressure measurements is obligatory for the final diagnosis. CTEPH is associated with a poor prognosis if left untreated. The preferred treatment is pulmonary endarterectomy. In certain patients with inoperable disease or with persistent or recurrent pulmonary hypertension after surgery, pharmacotherapy might be beneficial. Show less
