Mathilde Nijkeuter

Accuracy of clinical decision rule, D‐dimer and spiral computed tomography in patients with malignancy, previous venous thromboembolism, COPD or heart failure and in older patients with suspected pulmonary embolism

Summary.  Background: The diagnostic work‐up of patients with suspected pulmonary embolism (PE) has been optimized and simplified by the use of clinical decision rules (CDR), D‐dimer (DD) testing and spiral computed tomography (s‐CT). Whether this strategy is equally safe and efficient in specific subgroups of patients is evaluated in this study. Methods: A diagnostic strategy including a CDR, DD test and s‐CT was evaluated in patients with malignancy, previous venous thromboembolism (VTE), chronic obstructive pulmonary disease or heart failure and in older patients. PE was ruled out by either an unlikely CDR and a normal DD or a s‐CT negative for PE. The safety of these tests was assessed by the 3‐month incidence rate of symptomatic VTE in those without PE at baseline. The efficiency was evaluated by calculating the numbers needed to test for the different subgroups. Results: The venous thromboembolic incidence rate after the combination of an unlikely CDR and a normal DD varied from 0% (95% CI: 0–7.9%) in the 482 patients older than 75 years of age to 2% (95% CI: 0.05–10.9%) in the 474 patients with a malignancy. For s‐CT these incidences varied from 0.3% to 1.8%. The number needed to test in order to rule out one patient from PE with the studied strategy was highest in cancer patients and in the elderly patients (approximately 10). Conclusion: It appears to be safe to rule out PE by either the combination of an unlikely CDR and a normal DD or by a negative s‐CT in various subgroups of patients with suspected PE. However, the clinical usefulness of the CDR in combination with the DD as the initial step in the diagnostic process varied among these patient groups.

The Importance of Clinical Probability Assessment in Interpreting a Normal d-Dimer in Patients With Suspected Pulmonary Embolism

BACKGROUND The d-dimer test is widely applied in the diagnostic workup of patients with suspected pulmonary embolism (PE). The objective of this study was to investigate how often the d-dimer test fails when clinical probability is not taken into account. METHODS We used data collected in 1,722 consecutive patients with clinically suspected PE to analyze the 3-month venous thromboembolism (VTE) rate in all patients with a normal d-dimer concentration and separately for patients who have a normal d-dimer concentration with an unlikely or likely clinical probability for PE, as assessed by the Wells clinical decision rule. RESULTS The 3-month VTE rate in all patients with a normal d-dimer concentration (n = 563) was 2.3% (95% confidence interval [CI], 1.4 to 3.9%). In the patients with an unlikely probability of PE (n = 477), VTE was confirmed in 1.1% of the patients with a normal d-dimer concentration (95% CI, 0.4 to 2.4%). In those patients with a likely clinical probability of PE (n = 86), VTE was confirmed in 9.3% of the patients with a normal d-dimer concentration (95% CI, 4.8 to 17.3%). The difference in VTE incidence between patients with unlikely and likely clinical probabilities of PE was significant (p < 0.001). CONCLUSIONS Our findings indicate that it is of utmost importance to first examine the patient and assess the clinical probability, after which the d-dimer concentration can be taken into account, in order to prevent physicians from being influenced by a normal d-dimer test result when they evaluate the clinical probability of PE. Patients with a likely clinical probability should undergo further testing, regardless of the d-dimer test outcome.

A simple diagnostic strategy in hospitalized patients with clinically suspected pulmonary embolism

Objectives.  Diagnostic strategies in patients with suspected pulmonary embolism have been extensively studied in outpatients; their value in hospitalized patients has not been well established. Our aim was to determine the safety and clinical utility of a simple diagnostic strategy in hospitalized patients with suspected pulmonary embolism.

D-dimer Testing in Patients with Suspected Pulmonary Embolism and Impaired Renal Function

BACKGROUND Determination of pretest probability and D-dimer tests are the first diagnostic steps in patients with suspected pulmonary embolism, which can be ruled out when clinical probability is unlikely and D-dimer level is normal. We evaluated the utility of D-dimer testing in patients with impaired renal function. METHODS D-dimer tests were performed in consecutive patients with suspected pulmonary embolism and an unlikely clinical probability. Creatinine levels were assessed as clinical routine. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. Correlation between D-dimer level and renal function and proportions of patients with normal D-dimer in different categories of estimated glomerular filtration rate (eGFR) were assessed. Different categories of decreasing eGFR were defined as: normal renal function (eGFR >89 mL/min), mild decrease in eGFR (eGFR 60-89 mL/min), and moderate decrease in eGFR (eGFR 30-59 mL/min). RESULTS Creatinine levels were assessed in 351 of 385 patients (91%). D-dimer levels significantly increased in 3 categories of decreasing eGFR (P = .027 and P = .021 for moderate renal impairment compared with mild renal impairment and normal renal function, respectively). Normal D-dimer levels were found in 58% of patients with eGFR >89 mL/min, in 54% with eGFR 60-89 mL/min, and in 28% with eGFR 30-59 mL/min. CONCLUSIONS The specificity of D-dimer testing in patients with suspected pulmonary embolism and decreased GFR is significantly decreased. Nonetheless, performing D-dimer tests is still useful because computed tomography scanning can be withheld in a significant proportion of these patients.

Plasma levels of microparticle-associated tissue factor activity in patients with clinically suspected pulmonary embolism

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 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.

High D-dimer levels increase the likelihood of pulmonary embolism.

Objective.  To determine the utility of high quantitative D‐dimer levels in the diagnosis of pulmonary embolism.

Alternative diagnosis other than pulmonary embolism as a subjective variable in the Wells clinical decision rule: not so bad after all

PTS of the upper extremity in children should consider this normal variation, and a difference of 2% should not be viewed as clinically significant. In addition, our data show that many children also have superficial veins apparent on visual inspection. Therefore, the Vein Prominence Scale used in this study should be modified to reflect that a finding of grade 1 or 2 visible veins unilaterally may be an unreliable indicator of PTS affecting the upper extremity. Arm pain appeared to be a rare complaint in healthy children (with only 2% having reports of pain), although it is a common symptom in patients with a history of DVT likely to have PTS [6]. This study is limited by the fact that one investigator took all themeasurements, sowewere unable to test the reliability of the Vein Prominence Scale. In addition, our scale was arbitrarily developed,basedonour experience assessingpatientswithDVT orwithCVCsat risk of havingunderlyingDVT [10]. Finally,we did not correlate our findings with similar examination of the children s lower extremities. Nevertheless, this is the first study reporting the normal variation in PTS measurements among childrenof variousages, race/ethnicities andweights.The results should help provide a framework for clinical care and for the design and execution of future studies in children and adults at risk of upper venous system DVT and PTS.

Clinically suspected acute recurrent pulmonary embolism: A diagnostic challenge

It is unknown whether strategies validated for diagnosing pulmonary embolism (PE) are valid in patients with a history of PE. It was the objective of this study to investigate whether a diagnostic algorithm consisting of sequential application of a clinical decision rule (CDR), a quantitative D-dimer test and computed tomography (CT) safely ruled out a clinical suspicion of acute recurrent PE. Data were obtained from a diagnostic outcome study of patients suspected of PE. Acute recurrent PE was ruled out by an unlikely probability of PE (CDR score </= 4 points) combined with a normal D-dimer test (</= 500 ng/ml) or by a normal CT in all other patients. The primary outcome was the incidence of acute recurrent venous thromboembolism during three months of follow-up in patients with normal tests and not treated with anticoagulants. Of 3,306 patients suspected of acute PE, 259 patients (7.8%) had a history of PE of whom 234 were not treated with anticoagulants. The probability of PE was unlikely in 82 of 234 patients (35%), and 42 had a normal D-dimer test (18%), excluding recurrent PE. None of these patients had a thrombotic event during follow-up (0%, 95%CI: 0-6.9). A CT was indicated in all other patients (192) and ruled out recurrent PE in 127 patients (54%). Only one patient with a negative CT had a fatal recurrent PE during follow-up (0.8%; 95%CI: 0.02-4.3). In conclusion, this prospective study demonstrates the safety of ruling out a clinical suspicion of acute recurrent PE by a simple diagnostic algorithm in patients with a history of PE.

Incidence of diagnosis of subsegmental pulmonary emboli using multidetector row and single-detector row computed tomography.

M. NI JK EUT ER ,* J . M . KWAKKEL -VAN ERP , M. J . H . A . KRU IP , M. SOHNE ,§ H . R . B Ü LLER ,§ F . W. G . LEEBEEK and M. V . HUISMAN* ON BEHALF OF THE CH R IST OP HE R S T UD Y INVEST IGATORS *Department of General Internal Medicine-Endocrinology, Leiden University Medical Center, Leiden; Department of Pulmonology, Rijnstate Hospital, Arnhem; Department of Hematology, Erasmus University Medical Center, Rotterdam; and §Department of Vascular Medicine, Amsterdam Medical Centre, Amsterdam, the Netherlands

Diagnosing pulmonary embolism in pregnancy: Is there a role for D-dimer as a stand-alone test?

To the Editor: Giacomini and colleagues (1) conclude their interesting review of decision tools for life support by questioning to what extent such tools affect actual decisions taken because the effect of the various types of document (guidelines, recommendations, etc.) has not been well evaluated. The reality of end-of-life choices in an intensive care unit (ICU) is a complex mosaic, and it is by no means easy to formulate an answer to this question. However, one aspect—one fragment of the mosaic—that may be worth noting emerges from two different European studies on end-of-life decisions. Both studies, one Scandinavian (2) and the other Italian (3), have highlighted a significant degree of ignorance of the existence of guidelines in such a critical area of ICU practice. The first study showed that 29% of physicians had no knowledge of any written guidelines on triage and the withholding and withdrawal of intensive care. Nevertheless, the study found that ICU physicians generally act in broad conformity with guidelines, despite having little familiarity with actual documents. The second study found that only 3% of ICU physicians referred to international guidelines on triage and the withholding and withdrawal of intensive care, and most (56%) were unaware of the existence of such guidelines. Data of this kind cannot fail to raise questions about the effect of life-support decision tools on actual clinical practice; it is perhaps not simply an issue of how users interpret and apply these tools but, first and foremost, a question of whether such tools are effective in reaching their intended recipients (ICU physicians) and, therefore, whether they are capable of promoting any real cultural growth on these matters, even before being suitable tools for helping and informing clinical activity. If we are to avoid the proliferation of brief, pragmatic schemas for decision making—attractive as they may be, but equally simplistic and lacking in ethical consideration—we need to identify strategies that can be effective in “intercepting” or getting through to physicians. Indubitably, guidelines and recommendations still have a valid role (3), but I believe that only a continuous and methodic program of training and education is capable of influencing attitudes and modifying practice. End-of-life decision making and care must be maintained and given more importance in the training curricula of ICU physicians (4), but end-of-life ethics must also become a specific area of competency, which needs to be improved and updated. On this subject, it is astonishing that in Italy, even after the recent reform of the regulations on specialization training in anesthesia and intensive care (5), these topics have no more than an extremely marginal role in the curriculum. The author has not disclosed any potential conflicts of interest.