Fact-checked by Grok 2 weeks ago

D-dimer

D-dimer is a soluble fibrin degradation product that forms when the enzyme plasmin cleaves cross-linked fibrin in blood clots during the fibrinolysis process, resulting in a unique neoantigen detectable in plasma.^[1] It consists of two D-domains of fibrinogen linked by a transglutaminase-catalyzed cross-link, distinguishing it from other fibrinogen breakdown products.^[1] The D-dimer blood test quantifies its levels to assess ongoing thrombosis and fibrinolysis, with normal concentrations typically below 0.5 mg/L fibrinogen equivalent units (FEU) in healthy adults.^[2] Clinically, the D-dimer test is valued for its high negative predictive value, particularly in ruling out deep vein thrombosis (DVT) and pulmonary embolism (PE) among patients with low or intermediate clinical pretest probability, thereby avoiding unnecessary imaging studies.^[3] Elevated levels, however, indicate potential thrombotic conditions such as disseminated intravascular coagulation (DIC), acute aortic dissection, or malignancy, though the test's low specificity necessitates confirmatory diagnostics in positive cases.^[1] It is also employed in monitoring anticoagulant therapy efficacy and prognosticating outcomes in conditions like sepsis or COVID-19, where levels exceeding 1.0 mg/L FEU correlate with increased severity.^[1] First described in the 1970s, D-dimer assays have evolved from latex agglutination methods to more sensitive quantitative immunoassays, with age-adjusted thresholds (e.g., age in years × 10 μg/L for those over 50) enhancing diagnostic accuracy in older populations.^[2] Despite its utility, factors like pregnancy, trauma, surgery, or renal impairment can falsely elevate results, underscoring the importance of integrating D-dimer testing with validated clinical scoring systems such as the Wells criteria.^[3]

Biochemistry

Formation Process

The formation of D-dimer begins with the activation of the coagulation cascade, where thrombin cleaves fibrinopeptides A and B from fibrinogen, converting it into fibrin monomers that spontaneously polymerize into protofibrils and subsequently form a soluble fibrin network.^[1] Thrombin also activates factor XIII to factor XIIIa, which catalyzes the formation of covalent cross-links between adjacent fibrin monomers, primarily via isopeptide bonds between the γ-carboxamide group of glutamine residues in the D-domains and the ε-amino group of lysine residues, thereby stabilizing the fibrin clot into an insoluble network resistant to premature degradation.^[4]^[5] Subsequent fibrinolysis involves the activation of plasminogen to plasmin, primarily by tissue plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA), which then proteolytically degrades the cross-linked fibrin clot.^[1] This degradation process releases soluble fibrin degradation products (FDPs), including the characteristic D-dimer fragment, which consists of two D-domains from adjacent fibrin monomers covalently linked by factor XIIIa, often in complex with a central E-domain (D-dimer/E complex).^[4]^[5] The D-dimer represents a neoantigen, a novel epitope exposed only after cross-linking and partial plasmin digestion, which is not present in fibrinogen or non-cross-linked fibrin degradation products.^[4] D-dimer serves as a specific biochemical marker of secondary fibrinolysis, which occurs in the context of stabilized, cross-linked fibrin clots formed during hemostasis, distinguishing it from primary fibrinolysis where plasmin directly degrades circulating fibrinogen or non-cross-linked fibrin without prior clot stabilization, thus not generating detectable D-dimer.^[1]^[5] This specificity arises because the cross-linking by factor XIIIa is essential for the formation of the stable D-domain dimer structure that survives plasmin-mediated cleavage.^[4]

Molecular Structure

D-dimer is a soluble fibrin degradation product generated from the plasmin-mediated degradation of cross-linked fibrin, specifically comprising two D-domains covalently linked by factor XIIIa-induced isopeptide bonds and associated with a central E-domain fragment.^[4]^[6] This structure arises from the outer D-domains of adjacent fibrin monomers, which are joined via cross-links between the γ-chains, forming a distinctive neoantigenic site absent in non-cross-linked fibrinogen derivatives.^[7] The molecular weight of D-dimer typically ranges from 180 to 250 kDa, depending on the extent of plasmin digestion and whether it exists as the core DD fragment or the larger DDE complex.^[8]^[9] This size reflects its derivation from the terminal fragments of the fibrin polymer, with the two D-domains (each approximately 90 kDa) connected to the E-domain (around 70 kDa).^[10] D-dimer exhibits high solubility in plasma, enabling its circulation as a detectable biomarker, in contrast to the insoluble nature of intact fibrin clots or uncross-linked fibrin monomers.^[4] The antigenic properties of D-dimer stem from the unique conformational epitope created by the γ-γ chain cross-linkage, which is specifically recognized by monoclonal antibodies in immunoassays.^[7]^[4] This cross-link, formed between lysine and glutamine residues in the γ-chains of the D-domains, ensures specificity for degradation products of polymerized fibrin rather than fibrinogen itself.^[11]

Laboratory Measurement

Assay Methods

D-dimer assays primarily detect the cross-linked fibrin degradation products using monoclonal antibodies specific to the D-dimer neoantigen, enabling quantitative or semi-quantitative measurement in plasma samples.^[4] The gold standard for D-dimer quantification is the quantitative enzyme-linked immunosorbent assay (ELISA), which provides precise measurements in ng/mL fibrinogen equivalent units (FEU) or D-dimer units (DDU) and is considered the most accurate method due to its high specificity for the D-dimer epitope.^[12]^[5] Semi-quantitative latex agglutination assays, often performed as slide tests, detect visible agglutination of latex particles coated with anti-D-dimer antibodies when mixed with patient plasma, offering a rapid but less precise alternative with results reported as positive or negative above a threshold.^[13]^[6] Automated turbidimetric and immunoturbidimetric methods, integrated into clinical chemistry analyzers, measure the increase in turbidity from antibody-antigen complexes using latex-enhanced particles, providing quantitative results with high throughput and comparability to ELISA in sensitivity.^[14]^[5] Citrated plasma is the preferred sample type for D-dimer assays, as it stabilizes coagulation factors and prevents clotting, with 3.2% sodium citrate being the standard anticoagulant.^[1]^[15] Pre-analytical factors significantly impact results; for instance, samples should be processed within 4-8 hours at room temperature or up to 24 hours at 4°C if uncentrifuged, while prolonged storage beyond 8 hours at room temperature or freezing without proper handling can lead to degradation.^[5]^[16] Hemolysis interferes with assay performance by causing falsely elevated readings in immunoturbidimetric methods due to spectral overlap and protein interference, necessitating rejection of severely hemolyzed specimens.^[17]^[18] Quantitative ELISA assays exhibit the highest sensitivity for detecting D-dimer, typically ranging from 94% to 98%, making them ideal for ruling out thrombotic conditions, though they require 1-2 hours for processing in a laboratory setting.^[19]^[20]^[21] In contrast, point-of-care (POC) tests, such as rapid latex agglutination or portable turbidimetric devices, offer turnaround times of 10-20 minutes directly at the bedside, with sensitivities comparable to lab-based methods (around 95%) but potentially lower precision in semi-quantitative formats.^[22]^[23]^[24] Lab-based automated immunoturbidimetric assays balance sensitivity (93-97%) with faster turnaround (15-30 minutes) compared to ELISA, facilitating high-volume testing in clinical laboratories.^[25]^[26]

Reference Ranges

The D-dimer test is typically reported in either fibrinogen equivalent units (FEU) or D-dimer units (DDU), where FEU measures the concentration relative to intact fibrinogen fragments while DDU specifically quantifies the D-dimer fragment; the two units are related by a conversion factor of approximately 1 FEU ≈ 2 DDU.^[27] For excluding venous thromboembolism (VTE) in low-risk patients, the standard cutoff is less than 500 ng/mL FEU or less than 250 ng/mL DDU.^[28]^[2] Reference ranges can vary based on factors such as age, pregnancy, neonatal status, and recent surgery, which elevate baseline levels compared to non-pregnant adults.^[28] In elderly patients over 50 years, an age-adjusted cutoff of age × 10 ng/mL FEU is often applied to improve specificity while maintaining sensitivity for VTE exclusion.^[2] During pregnancy, D-dimer levels progressively increase across trimesters, with first-trimester baselines ranging from approximately 100 to 1070 ng/mL FEU, rendering standard cutoffs less reliable.^[29] Neonates exhibit higher baseline D-dimer concentrations, with mean levels around 1.74 mg/L FEU (range 0.25–2.81 mg/L) in the first 28 days of life, exceeding adult normals due to immature coagulation systems.^[30] Post-surgery, D-dimer levels commonly rise and remain elevated for at least one week, often surpassing 1 mg/L FEU, reflecting activation of fibrinolysis from tissue trauma.^[31] Additionally, reference ranges may differ slightly by assay method, as variations in reagent sensitivity and calibration affect reported thresholds.^[32]

Clinical Indications

Venous Thromboembolism

D-dimer testing plays a central role in the diagnostic algorithm for venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), primarily by facilitating the exclusion of these conditions in patients with low clinical pretest probability.^[33] The test's high negative predictive value (NPV), often exceeding 95% and approaching 99% in low-risk settings, allows clinicians to safely rule out acute VTE without immediate imaging when results are negative.^[34] This approach is particularly effective in patients with a Wells score less than 2, indicating low pretest probability, where a negative D-dimer result reliably identifies those unlikely to have DVT or PE.^[1] Meta-analyses of studies from the 1990s onward have consistently demonstrated D-dimer's sensitivity for acute VTE in the range of 93-97%, making it a valuable screening tool when combined with clinical assessment.^[35] For instance, quantitative enzyme-linked immunosorbent assays (ELISA) achieve sensitivities around 96% (95% CI: 92-99%), supporting their use for exclusion purposes.^[35] However, due to lower specificity (typically 40-50%), positive results do not confirm VTE and necessitate confirmatory imaging, such as compression ultrasonography for DVT or computed tomography pulmonary angiography for PE.^[36] In clinical practice, D-dimer is integrated into validated algorithms like the Wells criteria or Geneva score, where it is reserved for low-to-moderate risk patients to avoid unnecessary radiation exposure from imaging.^[33] Guidelines from the American Society of Hematology recommend against using D-dimer as a standalone test in high pretest probability cases (e.g., Wells score ≥6 for PE), opting instead for direct imaging to expedite diagnosis.^[33] This combined strategy has been validated in prospective studies, reducing the need for imaging by up to 30% in appropriately selected populations while maintaining high safety profiles.^[37]

Disseminated Intravascular Coagulation and Other Conditions

In disseminated intravascular coagulation (DIC), D-dimer levels are markedly elevated, often exceeding 10 times the upper limit of normal (typically >5,000 ng/mL FEU), reflecting the consumptive coagulopathy characterized by widespread fibrin formation and fibrinolysis.^[38] These high levels contribute to the International Society on Thrombosis and Haemostasis (ISTH) scoring system for overt DIC (revised in 2025), where an increase in fibrin-related markers like D-dimer assigns points as follows: moderate increase (>3× upper limit of normal, 2 points) or strong increase (>7× upper limit of normal, 3 points) toward a total score ≥5, indicating high diagnostic likelihood.^[39]^[40] Serial D-dimer measurements, recommended every 24–48 hours in critically ill patients, help track disease progression, treatment response, and resolution of coagulopathy by monitoring trends in fibrin turnover.^[41] Beyond DIC, D-dimer serves as a prognostic biomarker in various systemic conditions involving hypercoagulability. In sepsis, elevated admission D-dimer levels (>1–2 μg/mL) correlate with increased mortality risk (odds ratio up to 18.4) and severe outcomes like acute respiratory distress syndrome, independent of other inflammatory markers.^[42] Similarly, in trauma patients, particularly those with traumatic brain injury, high D-dimer at admission (>1,793 ng/mL) predicts in-hospital complications, such as coagulopathy and mortality, with levels serving as an independent indicator of poor prognosis.^[43] For acute aortic dissection, D-dimer exhibits high sensitivity (pooled 96%, 95% CI 91–98%) for diagnosis, enabling rule-out in low-risk cases when combined with clinical scores like the Aortic Dissection Detection Risk Score.^[44] In cancer-associated thrombosis, pretreatment D-dimer elevations (>0.5 μg/mL) are linked to higher thrombotic event rates (hazard ratio 2.22) and worse overall survival, reflecting tumor burden and endothelial activation.^[45] An emerging application of D-dimer is in assessing hypercoagulability during COVID-19, where levels ≥2,000 ng/mL predict adverse outcomes like ICU admission (odds ratio 4.27) and mortality, associated with microvascular thrombosis and organ injury.^[46] For non-diagnostic purposes, D-dimer aids risk stratification in hospitalized medical patients; incorporation into the IMPROVEDD score (adding 2 points if ≥2× upper limit of normal) identifies those at high risk for venous thromboembolism (hazard ratio 2.73), guiding decisions on extended prophylaxis beyond hospitalization.^[47] This approach enhances VTE event prediction without relying solely on clinical factors, supporting guidelines from the American Society of Hematology.^[48]

Interpretation

Negative Test Results

A negative D-dimer test result, indicating a level below the established cutoff threshold, serves as a reliable tool for excluding venous thromboembolism (VTE) in patients stratified to low clinical pretest probability, thereby minimizing the need for confirmatory imaging such as ultrasound or computed tomography pulmonary angiography. This diagnostic utility stems from the test's high sensitivity, which enables safe rule-out of acute VTE events, with the negative predictive value (NPV) approaching 100% in outpatient settings when integrated with validated clinical decision rules.^[33]^[49] The reliability of a negative result is most pronounced in acute clinical scenarios involving low pretest probability, as assessed by tools like the Wells or Geneva scores, where the absence of elevated D-dimer levels effectively rules out proximal deep vein thrombosis or pulmonary embolism. False negatives remain infrequent, with rates below 3% in appropriately selected populations, though they may arise in cases of small distal thrombi or chronic clot formations that generate insufficient fibrin degradation products to trigger detectable elevations. Standard cutoff values for negativity, typically around 500 ng/mL fibrinogen equivalent units depending on the assay, are outlined in the Reference Ranges section.^[50]^[34]^[51] When a negative D-dimer accompanies a low or negative clinical prediction score, no additional diagnostic testing for VTE is warranted, allowing clinicians to forgo anticoagulation and imaging while providing patient reassurance and optimizing resource allocation in emergency and ambulatory care environments. This combined strategy has been validated in prospective studies, confirming its safety and efficiency for excluding VTE without missed diagnoses in low-risk cohorts.^[33]^[52]

Elevated Test Results

Elevated D-dimer levels signify active fibrinolysis, reflecting the breakdown of cross-linked fibrin in the context of thrombus formation or degradation, though this marker is inherently nonspecific and can arise from various prothrombotic states.^[1] In patients with moderate clinical pretest probability for venous thromboembolism (VTE), a positive D-dimer result typically prompts confirmatory imaging, such as compression ultrasonography for suspected deep vein thrombosis (DVT) or computed tomography pulmonary angiography for pulmonary embolism (PE).^[1] For instance, guidelines recommend proceeding directly to imaging without relying solely on D-dimer in high-risk scenarios, but in moderate-risk cases, it guides efficient triage to avoid unnecessary radiation exposure.^[53] The magnitude of elevation provides additional clinical insight; levels exceeding ten times the upper limit of normal (typically >5000 ng/mL fibrinogen equivalent units) are associated with extensive thrombosis, disseminated intravascular coagulation (DIC), or severe underlying conditions like cancer or infection, often warranting urgent evaluation and multidisciplinary management.^[54] Serial D-dimer measurements can track the resolution of thrombotic processes, with declining levels indicating successful treatment response in conditions such as VTE, while persistent elevation may signal ongoing disease activity or complications.^[55] Beyond acute diagnostics, elevated D-dimer holds prognostic significance across several settings. In acute coronary syndrome, higher levels independently predict major adverse cardiovascular events, including mortality and recurrent ischemia, aiding in risk stratification for intensified therapy.^[56] Similarly, postoperatively, markedly elevated D-dimer correlates with increased risk of VTE and other thrombotic complications, serving as a marker for closer monitoring in high-risk surgical cohorts.^[57] Disease-specific elevations, such as those seen in VTE or DIC, further underscore its role in guiding targeted interventions as detailed in clinical indications.^[1]

Limitations and Considerations

Specificity and False Positives

The D-dimer test exhibits low specificity for detecting venous thromboembolism (VTE), as elevated levels can occur in numerous non-thrombotic conditions, leading to frequent false-positive results.^[1] This nonspecificity arises because D-dimer reflects fibrin degradation products from ongoing coagulation and fibrinolysis, processes activated beyond thrombosis.^[58] Specificity typically ranges from 40% to 70%, depending on the assay method, with lower values for enzyme-linked immunosorbent assays (around 53%) compared to whole-blood assays (up to 71%).^[24] Common causes of false positives include inflammatory states such as infections and surgery, which trigger systemic coagulation activation.^[1] Malignancy and liver disease also frequently elevate D-dimer levels due to increased fibrin turnover and impaired clearance, respectively.^[58] In healthy elderly individuals, D-dimer concentrations rise with age, resulting in elevated results above conventional cutoffs (e.g., 500 μg/L FEU) in more than 50% of those over 50 years, even without thrombosis.^[59] Similarly, post-trauma elevations are common, affecting a substantial proportion of patients due to tissue injury and inflammatory responses.^[58] This low specificity diminishes the test's positive predictive value (PPV) for VTE, often below 50% in low-prevalence settings like outpatient evaluations with low pretest probability, necessitating confirmatory imaging for positive results.^[24] Consequently, D-dimer cannot serve as a standalone diagnostic tool and must be interpreted alongside clinical probability scores.^[1] To mitigate false positives, testing is generally avoided in hospitalized patients or those with high-risk non-thrombotic conditions, such as recent surgery or acute inflammation, where baseline elevations are anticipated.^[58]

Age-Adjusted and Clinical Context Adjustments

The interpretation of D-dimer levels requires adjustments based on patient age to enhance diagnostic accuracy, particularly in ruling out venous thromboembolism (VTE) in older individuals. For patients aged 50 years or older, an age-adjusted cutoff of age × 10 µg/L fibrinogen equivalent units (FEU) is recommended, compared to the standard threshold of 500 µg/L FEU for those under 50. This adjustment, validated in the ADJUST-PE multicenter study involving over 3,300 patients, allows for exclusion of pulmonary embolism in a greater proportion of cases—39.8% versus 28.2% with the conventional cutoff—while maintaining high negative predictive value (>99.7%) and sensitivity. The approach improves specificity by approximately 30% in this population by accounting for the natural age-related rise in D-dimer levels, thereby reducing unnecessary imaging studies without compromising safety.^[60]^[61] Integration of D-dimer testing with clinical pretest probability scores is essential for optimizing its utility in VTE diagnosis. Validated tools such as the Wells score or revised Geneva score stratify patients into low, moderate, or high risk categories; D-dimer testing is typically reserved for those with low or moderate pretest probability, where a negative result can reliably exclude VTE with a negative predictive value exceeding 99%. In high-risk patients, imaging is pursued regardless of D-dimer results due to the test's limited specificity in this group. This combined strategy, endorsed by the American Society of Hematology guidelines, minimizes overtesting and aligns diagnostic decisions with clinical context, improving overall efficiency in emergency and outpatient settings.^[33]^[62] Adjustments for special populations further refine D-dimer interpretation to address physiological variations. In pregnancy, D-dimer levels progressively elevate with gestational age—typically remaining below 500 µg/L FEU in the first trimester, rising to around 1,000–1,500 µg/L FEU by the third—necessitating gestational age-adjusted thresholds or alternative algorithms like the pregnancy-adapted YEARS criteria, which apply lower initial D-dimer cutoffs (e.g., 1,000 µg/L FEU if no YEARS items are present) to safely rule out VTE while avoiding radiation exposure from imaging. For patients with renal impairment, D-dimer concentrations are often higher due to decreased clearance, warranting elevated cutoffs adjusted for glomerular filtration rate; for instance, in severe chronic kidney disease (estimated GFR <30 mL/min/1.73 m²), thresholds up to 1,000–2,000 µg/L FEU may be used to preserve diagnostic performance without increasing missed diagnoses. In chronic conditions such as malignancy, autoimmune diseases, or advanced age-related comorbidities, routine D-dimer testing is generally avoided or interpreted cautiously, as persistently elevated baseline levels reduce the test's discriminatory value for acute VTE.^[63]^[64]^[65]

History

Discovery and Early Research

The discovery of D-dimer traces back to the 1960s, when researchers began identifying fibrin degradation products (FDPs) in human serum as markers of fibrinolysis and thrombosis. In 1966, Cyril Merskey and colleagues developed a quantitative method to estimate these split products, linking elevated levels to conditions like venous thrombosis and disseminated intravascular coagulation (DIC), though the specific fragment now known as D-dimer was not yet distinguished from other FDPs. This work laid the groundwork for recognizing fibrin derivatives as clinically relevant biomarkers. By the early 1970s, efforts focused on differentiating specific FDPs, culminating in key studies that isolated D-dimer. The term "D-dimer" was introduced by P.J. Gaffney to denote the specific cross-linked fragment derived from stabilized fibrin. In a 1972 letter to The Lancet, P.J. Gaffney described methods to distinguish D-dimer from other fibrinogen and fibrin degradation products using gel filtration and electrophoresis, highlighting its origin from cross-linked fibrin rather than fibrinogen.^[66] This was further elaborated in Gaffney's 1975 paper in Clinica Chimica Acta, which characterized D-dimer's structural properties and confirmed its presence in plasma digests of stabilized fibrin via polyacrylamide gel electrophoresis.^[67] Concurrently, studies like those by Pizzo et al. in 1973 used similar electrophoretic techniques to verify D-dimer as a cross-linked γ-chain dimer fragment, distinguishing it from non-cross-linked fragments.^[68] In the early 1980s, research connected D-dimer to pathological states, particularly DIC in sepsis. Francis et al. reported elevated D-dimer levels in septic patients with DIC, using immunoassays to demonstrate its specificity for fibrin turnover over fibrinogenolysis. This period also saw biochemical confirmation of D-dimer's formation: Marder and Francis in 1983 elucidated how plasmin degrades factor XIIIa-stabilized, cross-linked fibrin to produce the stable D-dimer fragment, resistant to further proteolysis, through sequential enzymatic action involving thrombin-mediated polymerization and factor XIIIa cross-linking.^[69] These findings solidified D-dimer's role as a unique indicator of in vivo fibrin formation and degradation.

Clinical Adoption and Advancements

The adoption of D-dimer testing as a clinical tool for excluding venous thromboembolism (VTE) began in the early 1990s, following the FDA approval of the first latex agglutination-based assays, which enabled rapid detection of fibrin degradation products in plasma.^[70] These assays marked a shift from manual qualitative methods to more standardized testing, facilitating their integration into diagnostic algorithms. A pivotal validation came in 1997, when a multicenter study demonstrated that combining D-dimer testing with clinical pretest probability assessment achieved a high negative predictive value (NPV) of over 99% for ruling out deep vein thrombosis (DVT) in low-risk patients, safely reducing the need for imaging studies.^[71] Advancements in the 2000s focused on automation, with the introduction of enzyme-linked fluorescent assays (ELFA) and latex-enhanced immunoturbidimetric methods, which reduced turnaround times to 15-35 minutes compared to the 2-4 hours of earlier ELISA techniques, thereby enhancing laboratory efficiency and clinical throughput.^[24] By the 2010s, meta-analyses supported the use of age-adjusted cutoffs (e.g., age × 10 μg/L for patients over 50 years), increasing specificity in older populations without compromising sensitivity, allowing up to 30% more patients to avoid unnecessary imaging while maintaining an NPV above 97%.^[72] In the 2020s, D-dimer testing expanded beyond traditional VTE exclusion, serving as a prognostic biomarker in COVID-19 for assessing thrombosis risk and disease severity, where elevated levels correlated with higher intubation and mortality rates.^[73] Similarly, in cancer patients, serial D-dimer monitoring has been validated to predict VTE recurrence and thrombotic events during treatment, with levels above standard thresholds indicating a 2-3-fold increased risk.^[45] Looking ahead, future developments emphasize point-of-care (POC) integration, such as microfluidic platforms that deliver D-dimer results in under 15 minutes using whole blood, potentially enabling bedside VTE risk stratification in emergency settings.^[74] Additionally, combining D-dimer with biomarkers like P-selectin or thrombin generation assays shows promise for improving specificity, reducing false positives in high-prevalence populations and refining personalized anticoagulation strategies.^[4]

References

[1]
D-Dimer Test - StatPearls - NCBI Bookshelf
Jun 22, 2025 · D-dimer is a byproduct of the blood clotting and breakdown process, serving as a marker of ongoing coagulation and fibrinolysis.
[2]
115188: D-Dimer - Labcorp
Elevated D-dimer levels are observed in all diseases and conditions with increased coagulation activation, eg, thromboembolic disease, DIC, acute aortic ...Missing: significance | Show results with:significance
[3]
D-Dimer Test: MedlinePlus Medical Test
Apr 11, 2024 · A D-dimer test is used to check if you may have a blood clot. The test helps to find out if you need more tests to check for blood clotting disorders.
[4]
D-dimer antigen: current concepts and future prospects | Blood
The D-dimer antigen is a unique marker of fibrin degradation that is formed by the sequential action of 3 enzymes: thrombin, factor XIIIa, and plasmin.
[5]
D-dimer: Preanalytical, analytical, postanalytical variables, and ...
The first step of D-dimer formation involves the thrombin-catalyzed conversion of fibrinogen into fibrin monomers ( Figure 1 ). Human fibrinogen is a soluble ...
[6]
Widely Used Types and Clinical Applications of D-Dimer Assay
Mar 25, 2016 · D-dimer analysis is critical for the diagnosis of deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation.The Coagulation System · D-Dimer · Central Laboratory AssaysMissing: composition properties
[7]
Measurement of crosslinked fibrin degradation products - PubMed
Aug 30, 1983 · ... antigenic determinant on D dimer, a specific fragment resulting from the degradation of crosslinked fibrin ... gamma-gamma chains, to ...
[8]
Monoclonal antibodies with equal specificity to D-dimer and high ...
D-dimer is the smallest product of fibrin degradation (MW 180 kDa), it is relatively stable and considered to be a final product of fibrin lysis. It consists ...
[9]
Reinfusion of peritoneal fluid elevates the level of plasma D‐dimer ...
Feb 14, 2024 · Considering that D‐dimer is the smallest product of fibrin degradation, with a molecular weight of 190 kDa, D‐dimer passes through capillary ...
[10]
Schematic diagram of D-dimer formation as a risk factor for the...
The structure of D-dimer is either a 180-or 195-kDa molecule of two D domains or a 340-kDa molecule of two D domains and one E domain of the original ...<|control11|><|separator|>
[11]
https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0038-1665263
[12]
An ideal choice for D-Dimer quantification - Helena Biosciences
The current gold standard methodology for quantification of D-dimer is to use an ELISA method, however this is time–consuming and requires a dedicated analyser.
[13]
Heterogeneity in the reported values and methodologies for ...
Other methods for determining DD levels include quantitative latex agglutination, semi-quantitative agglutination latex and whole blood agglutination assays ...
[14]
Comparison of quantitative immunoturbidimetric and ... - PubMed
The purposes of this study were to compare 2 D-dimer assays, a quantitative immunoturbidimetric and a semiquantitative latex agglutination assay.Missing: ELISA automated
[15]
Assessing the Reliability of D-Dimer Measurement in EDTA Plasma
Background: D-dimer determined in citrated plasma is a well-established and efficient biomarker, particularly for ruling out venous thromboembolism.
[16]
D-dimer - Test Details
Detects elevated levels of cross-linked fibrin derivatives associated with disseminated intravascular coagulation (DIC), deep vein thrombosis, pulmonary ...Missing: definition significance
[17]
Effect of hemolysis on D-dimer testing measured with the Improgen kit
Aug 10, 2025 · This study was designed to reveal the value of hemolysis affecting D-dimer in our laboratory. In this study, hemolysate samples obtained by both ...
[18]
Hemolysis interference in 10 coagulation assays on an instrument ...
Mar 19, 2020 · Normal plasma and hemolyzed blood as well as pooled samples were stored at −70°C prior to analysis. The origin of the hemolysate and normal ...2.1 Hemolysis Interference · 3 Results · 3.2 Clot Assays<|control11|><|separator|>
[19]
The accuracy of the enzyme-linked immunosorbent assay D-dimer ...
The 9 studies that used a traditional rather than a rapid ELISA method gave a pooled sensitivity estimate of 0.94 (95% CI: 0.88, 0.97) and a sensitivity of 0.45 ...
[20]
Normal d-dimer levels in emergency department patients suspected ...
Only 2 of 547 had PE despite a normal d-dimer. The sensitivity of the d-dimer ELISA for acute PE was 96.4% (95% confidence interval [CI]: 87.5% to 99.6%), ...
[21]
Review: Of the various D-dimer assays, negative ELISA results are ...
Mar 9, 2020 · Semiquantitative rapid ELISA, 90% (83 to 98), 39% (29 to 50) ; Qualitative rapid ELISA, 93% (87 to 99), 46% (35 to 57) ; Quantitative latex, 86% ( ...
[22]
Comparison of D-dimer point of care test (POCT) against current ...
D-dimer turnaround time decreased by 83%. A further recent analysis of laboratory times done in 2013 demonstrates that POC D-dimer results remain 62% quicker.
[23]
Are the latest point-of-care D-dimer devices ready for use in general ...
We evaluated clinical performance of five novel point-of-care (POC) D-dimer devices with a capillary finger stick feature for predicting venous thromboembolism ...
[24]
Review of D‐dimer testing: Good, Bad, and Ugly - Wiley Online Library
Apr 26, 2017 · These assays have a rapid turnaround time and can be performed on single samples. ... A D-dimer with high sensitivity (eg ELISA) will miss few ...
[25]
Diagnostic accuracy of four different D-dimer assays: A post-hoc ...
Feb 6, 2021 · The YEARS study is a prospective, multicentre, cohort outcome study evaluating 3462 patients with suspected PE in which four different D-dimer assays were ...
[26]
Evaluation of a new quantitative highly sensitive D‐dimer assay for ...
This new assay fulfills the requirements needed for the exclusion of VTE. It is quantitative and operator independent, its sensitivity is as high as that of the ...
[27]
D-Dimer Tests in the Emergency Department: Current Insights - PMC
Nov 11, 2021 · FEU (340 kD) and DDU (195 kD) may be used interchangeably, considering that FEU is roughly two times the mass of one DDU.What Is The D-Dimer? · D-Dimer And Sepsis · D-Dimer And Covid-19<|control11|><|separator|>
[28]
https://www.mayoclinic.org/tests-procedures/d-dimer-test/about/pac-20399777
[29]
The clinical significance of D-dimer concentrations predicting ... - NIH
Aug 8, 2025 · A study investigating reference ranges for D-dimer and fibrinogen during pregnancy reported values between 167 and 721 ng/mL for the first ...Missing: neonates elderly post-
[30]
The D-dimer reference intervals in healty term newborns - PubMed
Mean D-dimer levels of infants aged 1-28 days was 1.74 ± 1.88 mg/L (reference range; 0.25-2.81 mg/L). D-dimer levels were between 2.44 and 2.45 mg/L, 1.71-1.76 ...
[31]
D-Dimer in the Diagnosis of Deep Vein Thrombosis Following Total ...
This study indicates that D-dimer levels are always elevated for a week postoperatively following total hip or knee arthroplasty in the absence of a DVT.
[32]
Variability in D-dimer reporting revisited - PMC - PubMed Central
Nov 7, 2020 · There is an extraordinary variation in reported data for D-dimer testing of the same homogeneous samples in different laboratories using different methods.
[33]
American Society of Hematology 2018 guidelines for management ...
Nov 27, 2018 · The ASH guideline panel recommends against using a positive D-dimer alone to diagnose DVT in a population with high prevalence/PTP (≥50%). (See ...
[34]
D-Dimer: Reference Range, Interpretation, Collection and Panels
Oct 15, 2025 · D-dimer is the degradation product of crosslinked (by factor XIII) fibrin. It reflects ongoing activation of the hemostatic system.Interpretation · Background · Indications/applicationsMissing: biochemical | Show results with:biochemical
[35]
Variation in the diagnostic performance of D-dimer for suspected ...
Meta-analysis of these studies showed that D-dimer had a sensitivity (95% CI, p for heterogeneity) of 96% (92–99, p = 0.047) and specificity of 51% (38–53 ...
[36]
The Role of D-dimer in Diagnosing Pulmonary Embolism
Feb 1, 2024 · The modern enzyme-linked and latex-based d-dimer assays have a pooled sensitivity of 97% (95% CI, 96-98%) and specificity of 41% (36 to 46%) ...
[37]
Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical ...
Nov 27, 2019 · Pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP)
[38]
Characteristics of emergency patients with markedly elevated D ...
May 8, 2020 · In our study, the emergency patients with D-dimer levels higher than 10 times of the upper normal limit mainly due to sepsis, malignancy, ...Missing: threshold | Show results with:threshold
[39]
Disseminated Intravascular Coagulation - StatPearls - NCBI Bookshelf
This score includes platelet count, fibrin markers such as D-dimer, PT, and fibrinogen level, with a score over 5 indicating a high likelihood for overt DIC.
[40]
Systematic review of the prognostic utility of D-dimer, disseminated ...
Dec 9, 2020 · The present review suggests the presence of higher levels of D-dimer in those with worse prognosis, there may be an overdiagnosis of DIC in the course of the ...
[41]
D-Dimer as a Prognostic Factor in a Tertiary Center Intensive ... - NIH
Jul 21, 2022 · D-dimer is a small protein fragment produced during fibrinolysis. High D-dimer levels were shown to have prognostic impact in critically ill patients.
[42]
Plasma D-dimer levels are a biomarker for in-hospital complications ...
Oct 27, 2023 · Overall, elevated D-dimer levels at admission were associated with adverse outcomes and may predict poor prognosis in patients with TBI.
[43]
The diagnostic value of D-dimer in acute aortic dissection: a meta ...
Nov 27, 2021 · The results of the meta-analysis showed that the pooled sensitivity was 0.96 (95% CI 0.91–0.98), the pooled specificity was 0.70 (95% CI 0.57– ...
[44]
Association of D-dimer level with thrombotic events, bleeding, and ...
Mar 2, 2024 · Increases in D-dimer levels were associated with a higher risk of thrombotic events, such as VTE and cerebral infarction/TIA/SEE, during cancer treatment.
[45]
COVID-19 Organ Injury Pathology and D-Dimer Expression Patterns
Jul 24, 2025 · While hypercoagulability—often signaled by elevated D-dimer—has been thoroughly investigated, the concurrent pathological findings across organs ...
[46]
The IMPROVEDD VTE Risk Score: Incorporation of D-Dimer into the ...
The IMPROVE score is a validated venous thromboembolism (VTE) assessment tool to risk stratify hospitalized, medically ill patients based on clinical variables.
[47]
American Society of Hematology 2018 guidelines for management ...
d-dimer, a by-product of fibrin degradation, is a biomarker for increased VTE risk in medical inpatients. A modified version of the IMPROVE VTE risk score, ...
[48]
A Latex D-Dimer Reliably Excludes Venous Thromboembolism
In patients with a low or moderate pretest probability, the sensitivity, negative predictive value, and negative likelihood ratio were 97%, 99%, and 0.07, ...
[49]
Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism
Nov 15, 2012 · When the likelihood of DVT is low, a negative d-dimer assay result excludes DVT. Likewise, a low pretest probability with a negative d-dimer ...
[50]
Effectiveness of D-Dimer as a Screening Test for Venous ...
The D-dimer has been shown to be highly sensitive (>95%) in excluding acute VTE at the cutoff value of 500 μg FEU/l, at least in patients with LCP or ICP.
[51]
Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical ...
Feb 15, 2022 · DVT is considered excluded if clinical pretest probability is low and the D-dimer test is negative. If clinical pretest probability is moderate ...Methods · Patient Enrolment And Care... · Results<|control11|><|separator|>
[52]
How we manage a high D-dimer - PMC - NIH
Besides VTE, D-dimer may be high due to physiologic conditions, including aging, pregnancy, and strenuous physical activity. In addition, several disorders have ...What Is D-Dimer? · Conditions Associated With... · Venous Thromboembolism
[53]
The clinical significance of ultra-high D-dimer levels - PMC
Plasma D-dimer measurements are routinely obtained in clinical practice to diagnose venous thromboembolism (VTE) owing to the test's high degree of sensitivity, ...
[54]
Guidance for the treatment of deep vein thrombosis and pulmonary ...
Anticoagulation options for acute VTE include unfractionated heparin, low molecular weight heparin, fondaparinux and the direct oral anticoagulants (DOACs).
[55]
Prognostic Value of D-dimer in patients with acute coronary ... - NIH
May 7, 2021 · This study aimed to investigate the prognostic value of D-dimer in ACS patients treated by percutaneous coronary intervention (PCI).
[56]
Postoperative D-dimer levels predict venous thromboembolisms ...
An elevated D-dimer level at 7 days after surgery is an independent predictor of VTE in patients undergoing ACLR. The postoperative D-dimer level is a more ...
[57]
A Test in Context: D-Dimer - JACC
Generation of D-dimer requires the sequential activity of 3 enzymes: thrombin, activated factor XIII (factor XIIIa), and plasmin (Figure 1). The process ...
[58]
How we manage a high D-dimer | Haematologica
Oct 26, 2023 · Quantitative ELISA have a high sensitivity (>95%) but a low specificity for VTE and thus are principally used for exclusion purposes. For this ...
[59]
Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism
Mar 19, 2014 · Elderly patients may have the greatest potential benefit of the use of the age-adjusted cutoff. In patients 75 years or older, the proportion of ...
[60]
Impact of the Age-Adjusted D-Dimer Cutoff to Exclude Pulmonary ...
May 3, 2021 · Of the 1421 patients with a nonhigh PTP and negative D-dimer using the AADD cutoff left untreated, 20 had suspected VTE. Objective testing ...
[61]
Diagnosing VTE: Guidelines from the American Society of Hematology
Dec 1, 2019 · Pretest probability using the Wells, Geneva, or Constans score determines the need for diagnostic testing for VTE. • A d-dimer test alone ...
[62]
Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected ...
Mar 20, 2019 · This patient met one YEARS criterion (pulmonary embolism was considered to be the most likely diagnosis) and had a d-dimer level of 1480 ng per ...
[63]
The diagnostic performance of renal function-adjusted D-dimer ... - NIH
In patients with mild to moderate renal impairment, the use of the validated age-adjusted D-dimer threshold should be preferred, whereas in patients with severe ...Table 1 · Figure 1 · Figure 2
[64]
Reference Levels of Plasma D-dimer for Normal Pregnant and Their ...
Nov 20, 2024 · The mean D-dimer levels in the healthy pregnancy group were 0.56 mg/L in early pregnancy, 1.08 mg/L in mid-pregnancy, 1.48 mg/L in late ...
[65]
https://www.imrpress.com/journal/CEOG/51/11/10.31083/j.ceog5111256/htm
[66]
https://doi.org/10.1016/S0140-6736(72)92994-7
[67]
https://doi.org/10.1016/0009-8981(75)90345-8
[68]
The Role of D-dimer Testing in Clinical Hematology and Oncology
The first D-dimer assay to receive approval from the US Food and Drug Administration (FDA) was based on the agglutination of latex beads coated with monoclonal ...Missing: 1990s | Show results with:1990s
[69]
https://doi.org/10.1111/j.1749-6632.1983.tb23260.x
[70]
Diagnostic accuracy of conventional or age adjusted D-dimer cut-off ...
We found no association between the sensitivity and specificity of D-dimer testing and the prevalence of venous thromboembolism in the study ...
[71]
D-dimer as a biomarker for disease severity and mortality in COVID ...
Jul 10, 2020 · D-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital ...
[72]
Point-of-Care Platform for Diagnosis of Venous Thrombosis by ...
Dec 21, 2022 · Our platform is able to deliver accurate and cost-effective results for both TG and D-dimer assays when using undiluted plasma in under 15 min.Missing: prospects | Show results with:prospects