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D-dimer
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<h2 id="principles">Principles</h2> <p><a href="/facts/Coagulation/vnfEevM0">Coagulation</a>, the formation of a blood clot or <a href="/facts/Thrombus/vH6FDIQG">thrombus</a>, occurs when the proteins of the <a href="/facts/Coagulation_cascade/vnfEevM0">coagulation cascade</a> are activated, either by contact with a damaged blood vessel wall and exposure to collagen in the tissue space (intrinsic pathway) or by activation of <a href="/facts/Factor_VII/cAFLoqTS">factor VII</a> by <a href="/facts/Tissue_factor/8qSycULo">tissue activating factors</a> (extrinsic pathway). Both pathways lead to the generation of <a href="/facts/Thrombin/sU9x3MeH">thrombin</a>, an enzyme that turns the soluble blood protein <a href="/facts/Fibrin/BFar47y5">fibrinogen</a> into fibrin, which aggregates into protofibrils. Another thrombin-generated enzyme, <a href="/facts/Factor_XIII/vjwf9Nb9">factor XIII</a>, then crosslinks the fibrin protofibrils at the D fragment site, leading to the formation of an insoluble gel that serves as a scaffold for blood clot formation.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> </p><p>The circulating enzyme <a href="/facts/Plasmin/bfLCyyPt">plasmin</a>, the main enzyme of <a href="/facts/Fibrinolysis/moYzJ5Gx">fibrinolysis</a>, cleaves the fibrin gel in a number of places. The resultant fragments, "high molecular weight polymers", are digested several times more by plasmin to lead to intermediate and then to small polymers (<a href="/facts/Fibrin_degradation_product/czslkV6E">fibrin degradation products</a> or FDPs). The cross-link between two D fragments remains intact, however, and these are exposed on the surface when the fibrin fragments are sufficiently digested. The structure of D-dimer is either a 180 <a href="/facts/Unified_atomic_mass_unit/IMATU3vf">kDa</a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> or 195 kDa<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> molecule of two D domains, or a 340 kDa<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> molecule of two D domains and one E domain of the original fibrinogen molecule.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> The <a href="/facts/Biological_half-life/7nB2JtMr">half-life</a> of D-dimer in blood is approximately 6 to 8 hours.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> </p><p>D-dimers are not normally present in human blood plasma, except when the coagulation system has been activated, for instance, because of the presence of <a href="/facts/Thrombosis/8Y3wh2UX">thrombosis</a> or <a href="/facts/Disseminated_intravascular_coagulation/CuWaSKQW">disseminated intravascular coagulation</a>. The D-dimer assay depends on the binding of a <a href="/facts/Monoclonal_antibody/4rUBWB87">monoclonal antibody</a> to a particular <a href="/facts/Epitope/PL0oBuGh">epitope</a> on the D-dimer fragment. Several detection kits are commercially available; all of them rely on a different monoclonal antibody against D-dimer. For some of these, the area of the D-dimer to which the antibody binds is known. The binding of the antibody is then measured quantitatively by one of various laboratory methods.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> </p> <h2 id="indications">Indications</h2> <p>D-dimer testing is of clinical use when there is a suspicion of <a href="/facts/Deep_venous_thrombosis/vX7cGv8J">deep venous thrombosis</a> (DVTl), <a href="/facts/Pulmonary_embolism/LPjKCPba">pulmonary embolism</a> (PE) or <a href="/facts/Disseminated_intravascular_coagulation/CuWaSKQW">disseminated intravascular coagulation</a> (DIC).<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a><a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p><p>For DVT and PE, there are possible various scoring systems that are used to determine the <i>a priori</i> clinical probability of these diseases; the best-known is the <a href="/facts/Deep_vein_thrombosis/vX7cGv8J">Wells score</a>.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> </p> <ul><li>For a high score, or pretest probability, a D-dimer will make little difference and <a href="/facts/Anticoagulant/cARpjm0G">anticoagulant</a> therapy will be initiated regardless of test results, and additional testing for DVT or pulmonary embolism may be performed.</li> <li>For a moderate or low score, or pretest probability: <ul><li>A negative D-dimer test will virtually rule out thromboembolism:<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> the degree to which the D-dimer reduces the probability of thrombotic disease is dependent on the test properties of the specific test used in the clinical setting: most available D-dimer tests with a negative result will reduce the probability of thromboembolic disease to less than 1% if the pretest probability is less than 15-20%. Chest computed tomography (CT angiography) should not be used to evaluate <a href="/facts/Pulmonary_embolism/LPjKCPba">pulmonary embolism</a> for persons with negative results of a D-dimer assay.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> A low pretest probability is also valuable in ruling out PE.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a></li> <li>If the D-dimer reads high, then further testing (<a href="/facts/Medical_ultrasonography/Ju5BFuuV">ultrasound</a> of the leg veins or lung <a href="/facts/Scintigraphy/tkaKjAEH">scintigraphy</a> or <a href="/facts/CTPA/GRk4hkYY">CT scanning</a>) is required to confirm the presence of <a href="/facts/Thrombus/vH6FDIQG">thrombus</a>. <a href="/facts/Anticoagulant/cARpjm0G">Anticoagulant</a> therapy may be started at this point or withheld until further tests confirm the diagnosis, depending on the clinical situation.</li></ul></li></ul> <p>In some hospitals, they are measured by laboratories after a form is completed showing the probability score and only if the probability score is low or intermediate. This reduces the need for unnecessary tests in those who are high-probability.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> Performing the D-dimer test first can avoid a significant proportion of imaging tests and is less invasive. Since the D-dimer can exclude the need for imaging, <a href="/facts/Specialty_(medicine)/4eQo5Tz7">specialty</a> <a href="/facts/Professional_organizations/CGgApQAM">professional organizations</a> recommend that physicians use D-dimer testing as an initial diagnostic.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a><a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a><a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a><a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> </p> <h2 id="interpretation">Interpretation</h2> <h3>Reference ranges</h3> <p>The following are <a href="/facts/Reference_range/IqNt7ELQ">reference ranges</a> for D-dimer:<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> </p> <table><tbody><tr><th>Units</th><th>Nonpregnant adult</th><th>First <a href="/facts/Pregnancy/vEKYGpep">trimester</a></th><th>Second trimester</th><th>Third trimester</th></tr><tr><td>mg/L or μg/mL</td><td>< 0.5</td><td>0.05 - 0.95</td><td>0.32 - 1.29</td><td>0.13 -1.7</td></tr><tr><td>μg/L or ng/mL</td><td>< 500</td><td>50 - 950</td><td>320 - 1290</td><td>130 - 1700</td></tr><tr><td>nmol/L</td><td>< 2.7</td><td>0.3 - 5.2</td><td>1.8 - 7.1</td><td>0.7 - 9.3</td></tr></tbody></table> <p>D-dimer increases with age. It has therefore been suggested to use a cutoff equal to patient’s age in years × 10 μg/L (or x 0.056 nmol/L) for patients aged over 50 years for the suspicion of venous thromboembolism (VTE), as it decreases the <a href="/facts/False_positive/jkC44hML">false positive</a> rate without substantially increasing the <a href="/facts/False_negative/jkC44hML">false negative</a> rate.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a><a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> </p><p>An alternative measurement of D-dimer is in fibrinogen equivalent units (FEU). The molecular weight of the fibrinogen molecule is about twice the size of the D-dimer molecule, and therefore 1.0 mcg/mL FEU is equivalent to 0.5 mcg/mL of d-dimer.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> </p> <h3>Thrombotic disease</h3> <p>Various kits have a 93 to 95% <a href="/facts/Sensitivity_and_specificity/pzc9qfdz">sensitivity</a> (true positive rate). For hospitalized patients, one study found the <a href="/facts/Sensitivity_and_specificity/pzc9qfdz">specificity</a> to be about 50% (related to false positive rate) in the diagnosis of thrombotic disease.<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> </p> <ul><li><a href="/facts/False_positive/jkC44hML">False positive</a> readings can be due to various causes: <a href="/facts/Liver/Rtp4Fk2b">liver</a> disease, high <a href="/facts/Rheumatoid_factor/cjdWSsgn">rheumatoid factor</a>, <a href="/facts/Inflammation/Ura86MIy">inflammation</a>, <a href="/facts/Cancer/PVW6n1D0">malignancy</a>, <a href="/facts/Physical_trauma/PJ7CbnMQ">trauma</a>, <a href="/facts/Pregnancy/vEKYGpep">pregnancy</a>, recent <a href="/facts/Surgery/fG8tWf5Y">surgery</a> as well as advanced age.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a></li> <li><a href="/facts/False_negative/jkC44hML">False negative</a> readings can occur if the sample is taken either too early after thrombus formation or if testing is delayed for several days. Additionally, the presence of anti-coagulation can render the test negative because it prevents thrombus extension. The anti-coagulation medications <a href="/facts/Dabigatran/qEzkkvr4">dabigatran</a> and <a href="/facts/Rivaroxaban/lhH7t8rv">rivaroxaban</a> decrease D-dimer levels but do not interfere with the D-dimer assay.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a></li> <li>False values may be obtained if the specimen collection tube is not sufficiently filled (false low value if underfilled and false high value if overfilled). This is due to the dilutional effect of the anticoagulant (the blood must be collected in a 9:1 blood to anticoagulant ratio).</li> <li>Likelihood ratios are derived from sensitivity and specificity to adjust pretest probability.</li></ul> <p>In interpretation of the D-dimer, for patients over age 50, a value of (patient's age) × 10 μg/L may be abnormal.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a><a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> </p> <h2 id="history">History</h2> <p>D-dimer was originally identified, described and named in the 1970s (<a href="https://www.sciencedirect.com/sdfe/pdf/download/eid/1-s2.0-026894999390039X/first-page-pdf">Fibrinolysis, Dr P J Gaffney</a>) and found its diagnostic application in the 1990s.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> </p> <h2 id="external-links">External links</h2> <ul><li><a href="http://labtestsonline.org/understanding/analytes/d-dimer/tab/test">D-dimer</a> - Lab Tests Online</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Asakura, Hidesaku; Ogawa, Haruhiko (2020). "COVID-19-associated coagulopathy and disseminated intravascular coagulation". International Journal of Hematology. 113 (1): 45–57. doi:10.1007/s12185-020-03029-y. ISSN 0925-5710. PMC 7648664. PMID 33161508. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Khan, Faizan; Tritschler, Tobias; Kahn, Susan R; Rodger, Marc A (2021). "Venous thromboembolism". The Lancet. 398 (10294): 64–77. doi:10.1016/s0140-6736(20)32658-1. ISSN 0140-6736. PMID 33984268. S2CID 234497047. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Khan, Faizan; Tritschler, Tobias; Kahn, Susan R; Rodger, Marc A (2021). "Venous thromboembolism". The Lancet. 398 (10294): 64–77. doi:10.1016/s0140-6736(20)32658-1. ISSN 0140-6736. PMID 33984268. S2CID 234497047. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Ponti, G; Maccaferri, M; Ruini, C; Tomasi, A; Ozben, T (2020). "Biomarkers associated with COVID-19 disease progression". Critical Reviews in Clinical Laboratory Sciences. 57 (6): 389–399. doi:10.1080/10408363.2020.1770685. ISSN 1040-8363. PMC 7284147. PMID 32503382. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284147" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284147</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Ponti, G; Maccaferri, M; Ruini, C; Tomasi, A; Ozben, T (2020). "Biomarkers associated with COVID-19 disease progression". Critical Reviews in Clinical Laboratory Sciences. 57 (6): 389–399. doi:10.1080/10408363.2020.1770685. ISSN 1040-8363. PMC 7284147. PMID 32503382. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284147" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284147</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Asakura, Hidesaku; Ogawa, Haruhiko (2020). "COVID-19-associated coagulopathy and disseminated intravascular coagulation". International Journal of Hematology. 113 (1): 45–57. doi:10.1007/s12185-020-03029-y. ISSN 0925-5710. PMC 7648664. PMID 33161508. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Khan, Faizan; Tritschler, Tobias; Kahn, Susan R; Rodger, Marc A (2021). "Venous thromboembolism". The Lancet. 398 (10294): 64–77. doi:10.1016/s0140-6736(20)32658-1. ISSN 0140-6736. PMID 33984268. S2CID 234497047. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Asakura, Hidesaku; Ogawa, Haruhiko (2020). "COVID-19-associated coagulopathy and disseminated intravascular coagulation". International Journal of Hematology. 113 (1): 45–57. doi:10.1007/s12185-020-03029-y. ISSN 0925-5710. PMC 7648664. PMID 33161508. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Ponti, G; Maccaferri, M; Ruini, C; Tomasi, A; Ozben, T (2020). "Biomarkers associated with COVID-19 disease progression". Critical Reviews in Clinical Laboratory Sciences. 57 (6): 389–399. doi:10.1080/10408363.2020.1770685. ISSN 1040-8363. PMC 7284147. PMID 32503382. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284147" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284147</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Asakura, Hidesaku; Ogawa, Haruhiko (2020). "COVID-19-associated coagulopathy and disseminated intravascular coagulation". International Journal of Hematology. 113 (1): 45–57. doi:10.1007/s12185-020-03029-y. ISSN 0925-5710. PMC 7648664. PMID 33161508. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Ponti, G; Maccaferri, M; Ruini, C; Tomasi, A; Ozben, T (2020). "Biomarkers associated with COVID-19 disease progression". Critical Reviews in Clinical Laboratory Sciences. 57 (6): 389–399. doi:10.1080/10408363.2020.1770685. ISSN 1040-8363. PMC 7284147. PMID 32503382. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284147" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284147</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Velavan, Thirumalaisamy P.; Meyer, Christian G. (25 April 2020). "Mild versus severe COVID-19: laboratory markers". International Journal of Infectious Diseases. 95: 304–307. doi:10.1016/j.ijid.2020.04.061. PMC 7194601. PMID 32344011. Retrieved 25 April 2020. <a href="https://www.ijidonline.com/article/S1201-9712(20)30277-0/fulltext#%20" target="_blank">https://www.ijidonline.com/article/S1201-9712(20)30277-0/fulltext#%20</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Asakura, Hidesaku; Ogawa, Haruhiko (2020). "COVID-19-associated coagulopathy and disseminated intravascular coagulation". International Journal of Hematology. 113 (1): 45–57. doi:10.1007/s12185-020-03029-y. ISSN 0925-5710. PMC 7648664. PMID 33161508. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Kogan AE, Mukharyamova KS, Bereznikova AV, Filatov VL, Koshkina EV, Bloshchitsyna MN, Katrukha AG (July 2016). "Monoclonal antibodies with equal specificity to D-dimer and high-molecular-weight fibrin degradation products". Blood Coagulation & Fibrinolysis. 27 (5): 542–50. doi:10.1097/MBC.0000000000000453. PMC 4935535. PMID 26656897. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935535" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935535</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Olson JD, Cunningham MT, Higgins RA, Eby CS, Brandt JT (August 2013). "D-dimer: simple test, tough problems". Archives of Pathology & Laboratory Medicine. 137 (8): 1030–8. doi:10.5858/arpa.2012-0296-CP. PMID 23899057. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Olson JD, Cunningham MT, Higgins RA, Eby CS, Brandt JT (August 2013). "D-dimer: simple test, tough problems". Archives of Pathology & Laboratory Medicine. 137 (8): 1030–8. doi:10.5858/arpa.2012-0296-CP. PMID 23899057. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Asakura, Hidesaku; Ogawa, Haruhiko (2020). "COVID-19-associated coagulopathy and disseminated intravascular coagulation". International Journal of Hematology. 113 (1): 45–57. doi:10.1007/s12185-020-03029-y. ISSN 0925-5710. PMC 7648664. PMID 33161508. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>Lippi G, Cervellin G, Franchini M, Favaloro EJ (November 2010). "Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future". J Thromb Thrombolysis. 30 (4): 459–71. doi:10.1007/s11239-010-0460-x. PMID 20213258. S2CID 23806848. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>Asakura, Hidesaku; Ogawa, Haruhiko (2020). "COVID-19-associated coagulopathy and disseminated intravascular coagulation". International Journal of Hematology. 113 (1): 45–57. doi:10.1007/s12185-020-03029-y. ISSN 0925-5710. PMC 7648664. PMID 33161508. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>Asakura, Hidesaku; Ogawa, Haruhiko (2020). "COVID-19-associated coagulopathy and disseminated intravascular coagulation". International Journal of Hematology. 113 (1): 45–57. doi:10.1007/s12185-020-03029-y. ISSN 0925-5710. PMC 7648664. PMID 33161508. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648664</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>Ponti, G; Maccaferri, M; Ruini, C; Tomasi, A; Ozben, T (2020). "Biomarkers associated with COVID-19 disease progression". Critical Reviews in Clinical Laboratory Sciences. 57 (6): 389–399. doi:10.1080/10408363.2020.1770685. ISSN 1040-8363. PMC 7284147. 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