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PubMed1996

Stoichiometry of 2',5'-oligoadenylate-induced dimerization of ribonuclease L. A sedimentation equilibrium study.

Ribonuclease L is an endoribonuclease that is activated by binding of 2',5'-linked oligoadenylates. Activation of ribonuclease L also induces dimerization. Here, we demonstrate using equilibrium sedimentation that dimerization requires the binding of one 5'-monophosphate 2',5'-(adenosine)3 molecule per ribonuclease L monomer. No dimerization was observed in the absence of activator up to a protein concentration of 18 microM, indicating that unliganded enzyme is unable to dimerize or the association is very weak. In parallel with dimerization, enzymatic activity is also maximized at a 1:1 activator: ribonuclease L stoichiometry. The same stoichiometry for dimerization is observed using a nonphosphorylated activator 2'-5'-(adenosine)3. Adenosine triphosphate or RNA oligonucleotide substrates do not induce dimerization. The observed stoichiometry supports a model for ribonuclease L dimerization in which activator binds to monomer, which subsequently dimerizes.

Adenine Nucleotides↗
PubMed1997

The majority of stem cell factor exists as monomer under physiological conditions. Implications for dimerization mediating biological activity.

Soluble Escherichia coli-derived recombinant human stem cell factor (rhSCF) forms a non-covalently associated dimer. We have determined a dimer association constant (Ka) of 2-4 x 10(8) M-1, using sedimentation equilibrium and size exclusion chromatography. SCF has been shown previously to be present at concentrations of approximately 3.3 ng/ml in human serum. Based on the dimerization Ka, greater than 90% of the circulating SCF would be in the monomeric form. When 125I-rhSCF was added to human serum and the serum analyzed by size exclusion chromatography, 72-49% of rhSCF was monomer when the total SCF concentration was in the range of 10-100 ng/ml, consistent with the Ka determination. Three SCF variants, SCF(F63C), SCF (V49L,F63L), and SCF(A165C), were recombinantly expressed in Escherichia coli, purified, and characterized. The dimer Ka values, biophysical properties, and biological activities of these variants were studied. Dimerization-defective variants SCF(F63C)S-CH2CONH2 and SCF(V49L,F63L) showed substantially reduced mitogenic activity, while the activity of the Cys165-Cys165 disulfide-linked SCF(A165C) dimer was 10-fold higher than that of wild type rhSCF. The results suggest a correlation between dimerization affinity and biological activity, consistent with a model in which SCF dimerization mediates dimerization of its receptor, Kit, and subsequent signal transduction.

Amino Acid Sequence↗
PubMed1993

In vitro dimerization of HIV-2 leader RNA in the absence of PuGGAPuA motifs.

Retroviral particles contain a dimeric genome consisting of two full-length, noncovalently linked RNA molecules. Linkage of the two genomes is thought to be critical for a productive reverse transcription reaction and may increase genetic recombination rates. The molecular nature of the dimer linkage structure (DLS) is poorly understood. It was recently shown that in vitro synthesized retroviral transcripts can dimerize in the absence of protein factors. We studied in vitro dimerization of human immunodeficiency virus type 2 (HIV-2) RNA. Specific dimerization of HIV-2 RNAs was observed upon incubation at 37 degrees C in high-salt buffer. Previously, physical and biochemical studies have mapped dimer linkage structures in retroviral leader RNA close to the gag open reading frame. In this study, we found efficient dimerization of HIV-2 RNAs containing only the 5' terminal 255 nucleotides of the leader RNA. Therefore, it seems likely that multiple dimerization signals are present in retroviral leader RNA. The implications for genome dimerization and genome packaging are discussed.

Genome, Viral↗
PubMed1999

D-Dimer formation during cardiac and noncardiac thoracic surgery.

UNLABELLED: The ability to make therapeutic decisions regarding excessive fibrinolysis in the perioperative period is limited by the lack of availability of a near site monitor of fibrinolysis. We investigated the use of a latex agglutination D-dimer assay to detect perioperative fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. We studied 27 patients who underwent thoracic surgery requiring cardiopulmonary bypass (CPB; coronary artery bypass grafting, n = 12; valvular surgery, n = 15) and a cohort of 20 patients who underwent noncardiac thoracic surgical procedures not requiring CPB. The purpose of this investigation was to determine the relationship among alterations in the latex agglutination D-dimer assay, use of extracorporeal circulation, type of cardiac surgical procedure, and mediastinal and/or chest tube drainage (cardiac surgery only) in patients undergoing thoracic surgery. Perioperative D-dimer levels, measured by latex agglutination, had significant (P < or = 0.05) intragroup changes among patients undergoing cardiac surgery (requiring CPB) and the cohort of patients who underwent noncardiac thoracic surgery without CPB. Although intraoperative D-dimer levels were not increased in patients undergoing noncardiac thoracic surgery, postoperative levels were significantly (P < 0.05) increased (compared with preinduction). In cardiac surgery patients requiring CPB, intraoperative D-dimer formation was significantly (P < or = 0.05) increased but did not demonstrate any intragroup (coronary artery bypass grafting versus valvular surgery) differences. Finally, D-dimer levels were not associated with postoperative mediastinal and/or chest tube accumulative drainage measured at intervals up to 48 h postoperatively in patients undergoing cardiac surgery requiring CPB. Our study indicates that the latex agglutination D-dimer assay can detect excessive fibrinolysis perioperatively, and that extracorporeal circulation can significantly influence the pattern of D-dimer formation in patients undergoing thoracic surgery. IMPLICATIONS: We assessed the ability of a readily available D-dimer assay to detect excessive fibrinolysis in patients undergoing thoracic surgery with and without extracorporeal circulation. The findings demonstrate that the assay used in this investigation reflected variable amounts of fibrinolysis in patients undergoing both types of thoracic surgery.

Adult↗
PubMed2000

A new method for measuring D-dimer using immunoturbidometry: a study of 255 patients with suspected pulmonary embolism and deep vein thrombosis.

D-Dimer testing has been suggested as a non-invasive method for the exclusion of pulmonary embolism (PE) and deep vein thrombosis (DVT). In this study, we compared a new method, the Miniquant D-dimer (Biopool International, Ventura, California, USA) to other previously validated D-dimer methods used for the purpose. Patients who were undergoing a definitive diagnostic study for thromboembolism had a blood sample drawn at that time. A whole-blood D-dimer (SimpliRed; Agen Biomedical Ltd, Brisbane, Australia) test was performed, and residual plasma was frozen and later analyzed using two enzyme-linked immunosorbent assay (ELISA) methods (D-dimer Gold; Agen, and Asserachrome D-Di; Stago International, Parsippany, New Jersey, USA) and the Miniquant D-dimer. Once all samples were analyzed, the correlation and accuracy of the Miniquant was compared with the ELISA method using Spearman's regression and Dunn's multiple paired comparison. All D-dimer methods were compared with radiographic studies. The data was analyzed collectively and segregated into in-patient (n = 112) and out-patient (n = 143) populations. The Miniquant D-dimer sensitivity, specificity and negative predictive value (NPV) for all patients were 95, 21, and 94% for DVT, and 100, 26, and 100% for PE. This new D-dimer method demonstrates acceptable sensitivity in patients with PE and DVT and, based on the high NPV of this method, it can be used for the exclusion of thromboembolism.

Adult↗
PubMed2003

The relationship between acute ischaemic stroke and plasma D-dimer levels in patients developing neither venous thromboembolism nor major intercurrent illness.

The true relationship between plasma D-dimers and acute ischaemic stroke (AIS) is uncertain as previous studies investigating this have not screened for subclinical deep vein thrombosis. We addressed this as part of a study in which we screened AIS patients for venous thromboembolism (VTE). We also assessed the performance characteristics of two D-dimer assays as exclusionary tests for VTE in these patients. One hundred and two unselected AIS patients were screened for VTE using magnetic resonance direct thrombus imaging. D-dimers were analysed on days 2, 9, 14 and 21 using the VIDAS immunofluorescent assay (cut-off >or= 500 ng/ml) and the IL test D-dimer immunoturbidimetric assay (cut-off >or= 255 ng/ml). The relationship between D-dimers and AIS was examined in 52 patients neither developing VTE nor intercurrent illness. D-dimers were elevated throughout the study. Median values at the four time points were 652, 692, 737 and 686 ng/ml (VIDAS assay) and 260.5, 268.5, 273 and 283 ng/ml (IL assay). D-dimers were higher in patients aged older than 70 years, with severe stroke or with total anterior circulation infarcts: only age older than 70 years was significantly associated with D-dimer values greater than the median on univariate and multivariable analysis. Both assays were 100% sensitive for VTE. Specificities were 30% (VIDAS assay) and 34% (IL assay). Specificity was adversely affected by age older than 70 and severe versus non-severe stroke. D-dimers are elevated in the first 3 weeks post-AIS after eliminating the confounding effect of subclinical deep vein thrombosis. The VIDAS and IL assays remained sensitive tests for VTE but the specificity was low, limiting their exclusionary efficiency in these patients.

Acute Disease↗
PubMed2006

D-dimer is not a long-term prognostic marker following acute cerebral ischemia.

Recent evidence indicates a possible role of D-dimer in the early diagnosis of ischemic stroke subtypes. Whether D-dimer can also predict the long-term outcome following ischemic stroke is controversial. To define the prognostic role of D-dimer, patients hospitalized after an acute ischemic cerebrovascular event underwent D-dimer measurement (Liatest D-D; normal level < 0.50 microg/ml) on admission and were followed up for recurrent cerebrovascular events, occurrence of other cardiovascular events, and mortality. We enrolled 96 patients (mean age 74.9 years, 42 men). Mean follow-up was 61.5 months; 47 (48.5%) patients died, 23 (48.9%) because of a vascular event. There was no difference in mean D-dimer levels between dead patients and survivors (1.68 and 1.63 microg/ml, P = NS), but the mortality risk was higher with D-dimer of at least 0.50 microg/ml (odds ratio, 5.32; 95% confidence interval, 1.79-15.84). After adjustment for age and stroke subtype, the odds ratio was not significant. Mean D-dimer was similar between patients with and without a new vascular event (1.43 and 1.68 microg/ml, P = NS), and D-dimer of at least 0.50 microg/ml was not predictive of an increased risk of subsequent events. D-dimer levels measured in the acute phase after an acute cerebrovascular event probably do not predict the long-term clinical outcome.

Acute Disease↗
PubMed1992

Amino acids necessary for DNA contact and dimerization imply novel motifs in the papillomavirus E2 trans-activator.

The bovine papillomavirus E2 protein regulates viral transcription by binding as a dimer to the DNA sequence ACCGN4CGGT. The dimerization and DNA-binding properties are localized within its carboxy-terminal 85 amino acids (325-410). Utilizing random mutagenesis coupled with phenotypic selection in yeast, functionally important amino acids in the DNA-binding domain were identified. Four trans-activation defective point mutants within a short segment (amino acids 337-344) were DNA binding defective but dimeric. The mutation of a conserved tryptophan to serine also eliminated DNA binding, but loss of dimerization was implicated because addition of dimeric monoclonal antibody complemented this defect. A simple assay for E2 dimerization was developed using UV irradiation to produce an interchain cross-link within a dimer. No heterodimeric complexes were formed when pools of E2 of varying lengths were mixed, and only proteins with tryptophan at position 360 could be UV cross-linked. Peptide mapping of irradiated E2 protein localized the cross-link to an 18-amino-acid region bracketing this tryptophan. Substitutions for this tryptophan demonstrated the requirement for a hydrophobic residue at this position, but surprisingly, even alanine was functional. Replacement of this tryptophan with three polar amino acids or glycine eliminated DNA-binding activity, but addition of dimeric monoclonal antibody restored this function. The amino acids that were identified as being involved in DNA contact and dimerization imply that these functions are mediated by novel binding motifs.

Amino Acid Sequence↗
PubMed2005

An evaluation of rapid D-dimer assays for the exclusion of deep vein thrombosis.

We evaluated the performance of eight d-assays for the exclusion of deep vein thrombosis (DVT); Biopool AutoDimer, Biopool MiniQuant, bioMèrieux MDA D-Dimer, VIDAS, Dade Behring D-Dimer Plus, Trinity Biotech AMAX, NycoCard D-dimer and IL Test D-Dimer. The assays were evaluated both as stand-alone tests, and in combination with pretest probability (PTP). D-dimer assays and PTP assessment were performed on 410 patients presenting to the emergency department with suspected acute DVT. DVT was diagnosed in 76 of 410 patients (18.5%) by compression ultrasound or other imaging techniques, as required. Receiver operator characteristics analysis established optimum cut-off values and these were compared with manufacturer's cut-off values where provided. As stand-alone tests, the assays varied immensely regarding cut-off value, negative predictive value (NPV 93-100%) and specificity (0-67%). At least one patient with confirmed DVT had a low d-dimer level by each method: to achieve 100% sensitivity it would be necessary to reduce cut-off values to levels below clinical usefulness. When low d-dimer was used in combination with PTP, six of eight methods achieved > or =98% NPV, with a diagnosis of DVT excluded in 16-44% of patients without the requirement for diagnostic imaging. The highly variable diagnostic performance of these d-dimer assays means that some assays are unsuitable for certain diagnostic strategies. However, our data suggest that the combination of sensitive D-dimer assays with an assessment of PTP may be used to exclude a diagnosis of DVT.

Fibrin Fibrinogen Degradation Products↗
PubMed2005

Determinants of plasma D-dimer levels in a traveling population.

BACKGROUND: Plasma D-dimer measurement is a widely used diagnostic test for assessing individuals with suspected venous thromboembolism (VTE). Whilst a negative test is helpful in ruling out thrombosis, the significance and determinants of an elevated plasma D-dimer level in otherwise healthy subjects are poorly understood. OBJECTIVES: To determine the association between recognized risk factors for VTE and plasma D-dimer levels in an adult population. SUBJECTS AND METHODS: Blood samples for measurement of plasma D-dimer levels were obtained from 1000 adults aged <70 years who were participating in a study investigating the incidence of VTE in long distance air travellers. The relationship between D-dimer levels and selected risks factors for VTE including thrombophilia status was investigated. RESULTS: The median (Inter-quartile range) D-dimer level was 243 ng mL(-1) (175-345). Multivariate analysis showed that plasma D-dimer levels were positively associated with increasing age, larger body mass index, female gender, the use of hormone therapy, thrombophilia state, and the presence of co-morbid conditions. CONCLUSION: Plasma D-dimer levels vary markedly between individuals and are associated with known risk factors for VTE, including the presence of thrombophilia conditions. The potential role for the measurement of plasma D-dimer as a marker for thrombosis risk requires further investigation.

Age Factors↗
PubMed2006

Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review.

BACKGROUND: The reported diagnostic accuracy of the D-dimer test for exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE) varies. It is unknown to what extent this is due to differences in study design or patient groups, or to genuine differences between D-dimer assays. METHODS: Studies evaluating the diagnostic accuracy of the D-dimer test in the diagnosis of venous thromboembolism were systematically searched for in the MEDLINE and EMBASE databases up to March 2005. Reference lists of all included studies and of reviews related to the topic of the present meta-analysis were manually searched for other additional potentially eligible studies. Two reviewers independently extracted study characteristics using standardized forms. RESULTS: In total, 217 D-dimer test evaluations for DVT and 111 for PE were analyzed. Several study design characteristics were associated with systematic differences in diagnostic accuracy. After adjustment for these features, the sensitivities of the D-dimer enzyme-linked immunofluorescence assay (ELFA) (DVT 96%; PE 97%), microplate enzyme-linked immunosorbent assay (ELISA) (DVT 94%; PE 95%), and latex quantitative assay (DVT 93%; PE 95%) were superior to those of the whole-blood D-dimer assay (DVT 83%; PE 87%), latex semiquantitative assay (DVT 85%; PE 88%) and latex qualitative assay (DVT 69%; PE 75%). The latex qualitative and whole-blood D-dimer assays had the highest specificities (DVT 99%, 71%; PE 99%, 69%). CONCLUSIONS: Compared to other D-dimer assays, the ELFA, microplate ELISA and latex quantitative assays have higher sensitivity but lower specificity, resulting in a more confident exclusion of the disease at the expense of more additional imaging testing. These conclusions are based on the most up-to-date and extensive systematic review of the topic area, including 184 articles, with 328 D-dimer test evaluations.

Data Collection↗
PubMed1996

Requirements for kissing-loop-mediated dimerization of human immunodeficiency virus RNA.

Sequences from the 5' end of type 1 human immunodeficiency virus RNA dimerize spontaneously in vitro in a reaction thought to mimic the initial step of genomic dimerization in vivo. Dimer initiation has been proposed to occur through a "kissing-loop" interaction involving a specific RNA stem-loop element designated SL1: the RNA strands first interact by base pairing through a six-base GC-rich palindrome in the loop of SL1, whose stems then isomerize to form a longer interstrand duplex. We now report a mutational analysis aimed at defining the features of SL1 RNA sequence and secondary structure required for in vitro dimer formation. Our results confirm that mutations which destroy complementarity in the SL1 loop abolish homodimer formation, but that certain complementary loop mutants can heterodimerize. However, complementarity was not sufficient to ensure dimerization, even between GC-rich loops, implying that specific loop sequences may be needed to maintain a conformation that is competent for initial dimer contact; the central GC pair of the loop palindrome appeared critical in this regard, as did two or three A residues which normally flank the palindrome. Neither the four-base bulge normally found in the SL1 stem nor the specific sequence of the stem itself was essential for the interaction; however, the stem structure was required, because interstrand complementarity alone did not support dimer formation. Electron microscopic analysis indicated that the RNA dimers formed in vitro morphologically resembled those isolated previously from retroviral particles. These results fully support the kissing-loop model and may provide a framework for systematically manipulating genomic dimerization in type 1 human immunodeficiency virus virions.

Base Sequence↗
PubMed1995

Characterization of elements determining the dimerization properties of RelB and p50.

Members of the Rel/NF-kappa B family of transcription factors share a region of approximately 300 amino acids which mediates dimerization and sequence-specific binding to DNA. Here we report a detailed characterization of the dimerization domain of RelB. The structural core sufficient to form stable Rel/NF-kappa B dimeric complexes consists of about 110 residues. The dimerization and DNA binding properties of more than 50 RelB mutants were analyzed by using p50 and p52 as partners. We present evidence that amino acids of a conserved element in the dimerization domain play a role in the recognition of a kappa B DNA target sequence. The analysis of hybrid molecules with dimerization domains containing different parts of p50 and RelB allowed us to identify some important structural elements determining homo- and heterodimerization properties. Furthermore, we were able to rescue the dimerization-defective mutant RelB-N287D by the introduction of a counteracting mutation intramolecularly (cis), and also intermolecularly (trans) by a mutation in the NF-kappa B dimerization partner p50. Correspondingly, a dimerization defective p50 mutant was effectively rescued by RelB-N287D.

Amino Acid Sequence↗
PubMed2003

Role of fibrin D-dimer testing in emergency medicine.

OBJECTIVES: Systemic values of the fibrinolytic plasma marker fibrin D-dimer are raised in a variety of acute clinical conditions. D-dimer values can now be rapidly determined and used to aid diagnosis in emergency medicine. However, despite clinical guidelines, inappropriate and unnecessary measurement of D-dimer values is a significant clinical problem. An understanding of the pathophysiological basis and limitations of the value of D-dimer values may help reduce this problem. This review discusses the pathophysiology of the fibrinolytic system. The currently used assays, clinical indications, and limitations of D-dimer measurement are reviewed. Finally, the potential future clinical indications for measurement of D-dimer values in emergency medicine are discussed. METHODS: Literature on D-dimer was identified from Medline, along with cross referencing from the reference lists of major articles on the subject RESULTS: and conclusions: Systemic D-dimer values aids diagnosis, and is potentially a prognostic indicator, in a variety of clinical conditions in emergency medicine. However, it has limited specificity in patients with comorbid conditions. Although, currently, there is no standard D-dimer assay, immunoturbidimetric assays are the most suitable for use in emergency medicine

Biomarkers↗
PubMed2004

Do normal D-dimer levels reliably exclude cerebral sinus thrombosis?

BACKGROUND AND PURPOSE: Cerebral sinus thrombosis (CST) needs to be considered in the differential diagnosis of all patients with acute headache. Early diagnosis is essential because early treatment may prevent morbidity and may even be life-saving. Definite exclusion, however, needs advanced neuroradiologic diagnostics, which are not readily available in many hospitals. Because measurement of D-dimers has been demonstrated to be helpful in excluding thromboembolic disease, our aim was to investigate whether D-dimers would be also sensitive enough to exclude CST. METHODS: We undertook a prospective multicenter study over a 2.5-year period including all patients who came to the emergency departments with symptoms suggestive of CST. All patients were diagnosed either by magnetic resonance venography, spiral computed tomography scan venography, or intra-arterial digital subtraction angiography. D-dimer levels were measured at admission and analyzed by the same method in all patients. RESULTS: A total of 343 patients were included. CST was diagnosed in 35 patients, of whom 34 had D-dimers above the cutoff value (>500 microg/L). From the 308 patients not having CST, D-dimers were elevated in 27. Sensitivity of D-dimers was 97.1%, with a negative predictive value of 99.6%. Specificity was 91.2%, with a positive predictive value of 55.7%. D-dimers were positively correlated with the extent of the thrombosis and negatively correlated with the duration of symptoms (Spearman rank correlation coefficients 0.76, -0.58, respectively). CONCLUSIONS: D-dimer measurement is useful in patients with suspected CST. Normal D-dimers make the presence of CST very unlikely.

Adult↗
PubMed1996

Deep vein thrombosis in stroke. The use of plasma D-dimer level as a screening test in the rehabilitation setting.

BACKGROUND AND PURPOSE: Venous thromboembolism is a leading cause of morbidity and mortality during the acute recovery period after stroke. This study investigated the utility of plasma D-dimer level as a diagnostic test for deep vein thrombosis (DVT) in patients hospitalized for stroke rehabilitation. METHOD: Plasma samples were drawn from 105 nonambulatory rehabilitation patients with recent ischemic or hemorrhagic stroke and assayed for D-dimer with an enzyme-linked immunosorbent method. Samples were drawn within 24 hours of venous duplex ultrasound (VDU) screening for DVT. Optimal discriminant analysis was used to determine whether plasma D-dimer level, age, sex, days after stroke onset, stroke etiology. National Institutes of Health Stroke Scale score, and ambulatory status could correctly classify patients' DVT status. RESULTS: Fourteen of 105 patients had DVT identified by VDU scan. Of all attributes, only D-dimer level had significant ability to discriminate between patients with or without DVT (P < .0001). The optimal cut point for predicting DVT was D-dimer = 1591 ng/mL, resulting in 79% sensitivity, 78% specificity, 35% positive predictive value, and 96% negative predictive value. Reducing the D-dimer cut point to 1092 ng/mL improved both sensitivity and negative predictive value to 100% but reduced specificity to 66% and positive predictive value to 31%. CONCLUSIONS: A D-dimer level < or = 1092 ng/mL can exclude the presence of DVT in stroke rehabilitation patients. When a D-dimer level > 1092 ng/mL occurs, further diagnostic testing is necessary to confirm DVT. Plasma D-dimer level is a simple and inexpensive screening test for DVT during stroke rehabilitation.

Cerebrovascular Disorders↗
PubMedDate not supplied

ELISA D-dimer measurement for the clinical suspicion of pulmonary embolism in the emergency department: one-year observational study of the safety profile and physician's prescription.

OBJECTIVES: To validate the safety profile of a rapid ELISA D-dimer as the first diagnostic step in the clinical suspicion of pulmonary embolism (PE) in outpatients admitted to an emergency department (ED), and to retrospectively evaluate the appropriateness of the physician's prescription. DESIGN AND SETTING: An observational study of all patients admitted to the ED of an urban university teaching hospital with signs and symptoms justifying the prescription of a rapid ELISA D-dimer measurement (Vidas; Biomerieux; France) as the first line diagnostic test for PE. Acute PE was established or excluded according to an appropriate combination of the D-dimer concentration, the lung scintigraphy, the spiral computerized tomography (spiral CT), the venous ultrasonography, and the arteriography in case of uncertain results. All patients with D-dimer values under the cut-off point of 500 ng/ml were followed up after 6 months. RESULTS: 395 patients were studied. A normal D-dimer concentration < 500 ng/ml was found in 179 patients (45% of the cohort). The retrospective analysis showed that none of these patients were found to have a high pre-test clinical probability. None of these 179 patients received anticoagulation nor displayed a PE event during a 6-month period (negative predictive value 100%; 95% CI, 98.0 to 100%; sensitivity 100%; 95% CI, 90.3 to 100%). Among the 216 patients (55%) with D-dimer values above 500 ng/ml, PE was confirmed in 32 cases, for a prevalence of the disease of 8.1%. Eighty-six patients (22%) had no additional testing in spite of positive D dimer values > 500 ng/ml, pointing out a 22% rate of inappropriate use of the D-dimer measurement. CONCLUSION: This observational study confirms that a normal rapid ELISA D-dimer value (< 500 ng/ml) used as a first diagnostic step in ruling out the diagnosis of PE is a safe clinical practice when the pre-test clinical probability is low or intermediate. Nevertheless, the low prevalence rate of the disease (8.1%) suggests a potential overused and inappropriate prescription.

Adolescent↗
PubMed2002

Significance of a plasma D-dimer test in patients with primary pulmonary hypertension.

BACKGROUND: D-dimer, a degradation product of fibrin, has been increasingly used as a marker or prognostic factor in various thrombotic diseases. OBJECTIVE: To assess the significance of a d-dimer test in patients with primary pulmonary hypertension (PPH). PATIENTS AND METHODS: Fourteen patients with PPH (12 women and 2 men) aged 25 to 68 years (mean +/- SD age, 50 +/- 14 years) entered the study. Plasma d-dimer was determined by Miniquant assay (Biopool International; Venture, CA) 3 +/- 5 months after the disease onset, and patients were followed up for 1 year. We compared the d-dimer levels to the demographic, clinical, and hemodynamic data of the patients. RESULTS: D-dimer levels were positively correlated with New York Heart Association classification (r = 0.59, p = 0.01) and pulmonary artery pressure (r = 0.43, p = 0.03) and were negatively correlated with oxygen saturation (r = - 0.45, p = 0.03) and 6-min walk distance (r = - 0.49, p = 0.04). One-year survival was also negatively correlated with d-dimer (point-biserial r = - 0.71, p = 0.004), with a higher d-dimer value associated with poorer survival. No significant correlations were found between d-dimer values and sex, age, diffusing capacity of the lung for carbon monoxide, or cardiac index. CONCLUSION: D-dimer levels may have a role in the evaluation of patients with PPH. This simple, noninvasive test may be helpful for identifying patients who are at a higher risk for severe disease.

Adult↗