D-dimer is a protein structure at the core of fibrin (polymerized fibrinogen) and is one of the last of the fibrin split products to be released during fibrinolysis. Thus tests for D-dimer indicate that intravascular clotting and fibrinolysis has occurred, but do not necessarily indicate the source and extent of thrombosis. An elevated result is totally non-specific in identifying the site of clotting. A D-dimer in the normal range simply means that intravascular clotting/fibrinolysis is not occurring at the time the sample was drawn.

The Laboratory at LMC offers a quantitative assay. We have discontinued the older and less sensitive latex agglutination technique. Our test is performed on our new Diagnostica Stago instruments, using their quantitative reagent. It is the most commonly used of the rapid turnaround D-dimer quantitative tests, and correlates well with ELISA reference methods. It is available 24/7 and on a STAT basis.

The most misunderstood concept in using the D-dimer in VTE is that it does not diagnose this disease. It is used, rather, as a test of exclusion of VTE. Our particular test has a negative predictive value of approximately 95%. That is, if the test result is normal (<0.5 ng/ml), it is highly unlikely that the patient’s symptoms are due to VTE, especially with a "low degree of clinical suspicion". Thus, it’s best use is to help avoid additional and more expensive tests to rule out this condition. A normal (or negative) D-dimer result will also decrease time spent in the hospital or ER setting. If the D-dimer is elevated, additional consideration may be warranted to confirm or rule out VTE as well as other sources of intravascular clotting.

The D-dimer test is part of a DIC panel which includes: PT/PTT, Fibrinogen, Platelet Count, D-dimer, and peripheral RBC morphology looking for schistocytes.

D-dimer is often elevated in this condition. However, it is not generally considered a helpful part of the diagnostic panel.

Activation of the coagulation system occurs during the active phase of chronic inflammatory bowel disease. Elevated D-dimer results have been used to indicate that the disease is, indeed, active rather than quiescent.

Pre-eclampsia: 

Elevation of D-dimer levels into the abnormal ranges often parallels the development of pre-eclampsia.

Both oral anti-coagulants and heparin therapy will cause D-dimer levels to decrease. Therefore, a normal D-dimer does not exclude recurrent thrombosis in patients receiving these anti-coagulants.

William Armstrong, M. D

C. DIFFICILE TESTING:

Some Traditional Controversies Resolved

Based on personal experience, most clinical microbiologists have always felt that repeat C. difficile toxin assays within a seven-day period rarely provide any meaningful results that alter therapy or clinical management. This is more intuitive after an initial positive result since most published data confirm that "test of cure" studies are poor predictors of subsequent relapse and that patients should not be considered therapeutic failures until they have received at least six days of appropriate therapy. But studies have now indicated that tests repeated within seven days of an initial negative result eventuate in a shift from negative to positive well less than 1% of the time. Of course, no test is perfect; and repeat testing may rarely be indicated in highly suspicious cases.

In order to reduce unnecessary and potentially misleading results, LMC’s Microbiology Laboratory thinks that a no-repeat-testing-within-seven-days rule is appropriate for C. difficile toxin assays. If a physician has reason to think that an initial negative result may have been a false negative, repeat tests will be accepted upon physician consultation with the laboratory staff.

In the past, occasional Infection Control Practitioners have suggested the usefulness of C. difficile test in asymptomatic patients in an effort to identify and isolate carriers with the purpose of preventing the spread of C. difficile-associated nosocomial disease. Some have even suggested treating the carrier state. These practices are to be strongly discouraged since asymptomatically colonized patients actually have very little risk of developing or transmitting clinical disease. Furthermore, transmission of infection to other patients is associated with ongoing diarrhea and not with the mere presence of toxin in the stool. Finally, testing patients to identify and treat carriers in an effort to eradicate the carrier-state is not justified since neither Vancomycin nor Flagyl have been demonstrated to be reliably efficacious for this purpose. For these reasons, the Microbiology Lab will reject specimens for C. difficile toxin testing from asymptomatic patients or patients with formed stools.

In summary, published data support laboratory policies for rejection of repeat stool specimens within 7 days of an initial specimen, and for rejection of formed stools for C. difficile toxin testing. If you have any concerns or questions concerning these new policies, please contact the Microbiology Laboratory (791-2408) or Dr. Kitt McMaster.

(posted 5/14/03)