Q&A Column, 12/13

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Editor: Frederick L. Kiechle, MD, PhD

Submit your pathology-related question for reply by appropriate medical consultants. CAP TODAY will make every effort to answer all relevant questions. However, those questions that are not of general interest may not receive a reply. For your question to be considered, you must include your name and address; this information will be omitted if your question is published in CAP TODAY.

Q. Our hematology standardization committee has asked us for input on performing cell counts on tubes No. 1 and No. 4 for cerebrospinal fluid. Each site in our system has a different protocol set up with its emergency department with regard to when a count is performed on tube No. 1 after counting tube No. 4. Some sites use RBC greater than five to automatically count tube No. 1 with or without an order to not delay patient care, whereas other sites use greater than 50 or greater than 200. Is there an established guideline recommendation for the number of RBCs seen on CSF tube No. 4 before doing an additional count on tube No. 1?

A. The CAP Hematology and Clinical Microscopy Resource Committee is not aware of established guideline recommendations for this purpose.  RBC count on tube No. 1, in addition to count on tube No. 3 or No. 4, can provide useful information for distinguishing traumatic lumbar puncture from subarachnoid hemorrhage. However, this method is not entirely reliable since a decline in RBC numbers is not entirely specific for traumatic lumbar puncture. Central nervous system hemorrhage also results in xanthochromia, perhaps a better indicator of hemorrhage, although this finding can also be seen with systemic hyperbilirubinemia and conditions causing elevated CSF protein. In addition, xanthochromia may not be present until about 12 hours after a bleeding event.

The Clinical and Laboratory Standards Institute currently recommends cell count on tube No. 1 if a traumatic tap is suspected. Procedurally, the laboratory could rely on the clinician to request testing on tube No. 1 when clinically indicated or, alternatively, the laboratory could initiate this testing based on RBC results for tube No. 3 or No. 4. Members of the CAP resource committee were surveyed, and a majority of their laboratories perform cell counts as ordered by the physician (that is, tube No. 1 is performed if ordered). A few labs have criteria to cancel tube No. 1 if RBCs are not increased in tube No. 3 or No. 4 since the tube No. 1 count is unlikely to be useful for a diagnosis of subarachnoid hemorrhage. In this case, criteria for cancellation were established with input from the medical staff and reflect a very low number of RBCs in tube No. 3 or No. 4, such as <10 RBC × 106/L or lower. None of the resource committee members reported using established reflex criteria for ordering RBC count on tube No. 1 if RBCs were elevated in tube No. 3 or No. 4. This approach also seems reasonable, but the clinical laboratory and the medical staff ordering CSF testing should establish by agreement appropriate criteria for reflex testing.

1. Body Fluid Analysis for Cellular Composition; Approved Guideline, H56-A. Wayne, Pa.: Clinical and Laboratory Standards Institute; 2006.
2. Van Gijn J, Kerr RS, Rinkel GJE. Subarachnoid haemorrhage. Lancet. 2007;369: 306–318.
3. Shah KH, Edlow JA. Distinguishing traumatic lumbar puncture from subarachnoid hemorrhage. J Emerg Med. 2002;23(1):67–74.

Joan Etzell, MD
Medical Director, Sutter Health Shared Laboratory
Clinical Professor of Laboratory Medicine, UCSF School of Medicine
Chair, CAP Hematology and Clinical Microscopy Resource Committee

Q. We are looking into replacing the fibrin degradation product (FDP) with the D-dimer assay for disseminated intravascular coagulation (DIC) in our obstetric patients because we get very few requests for the FDP assay. Would the D-dimer provide our obstetricians with the same information as the FDP? We currently perform D-dimer for suspected deep vein thrombosis and pulmonary embolism.

A. D-dimer assays have largely replaced fibrin degradation product and fibrin split product assays in the evaluation of disseminated intravascular coagulation. FDP assays are typically manual latex agglutination assays that suffer from poor analytic sensitivity, variable human end point interpretation limiting reproducibility, and poor clinical specificity. In contrast, modern automated D-dimer assays have excellent low end sensitivity and good precision and can quantitate high levels accurately. Boisclair, et al., recommended that D-dimer replace FDP assays for evaluation of DIC and other hypercoagulable states.1 Bick, et al., reported that D-dimer was more sensitive and specific for DIC than FDP assays and should replace this test for that indication.2 Lehman, et al., evaluated D-dimer and found a cutoff of 8 μg/mL FEU was best for detecting overt DIC.3 In summary, D-dimer assays are felt to be superior to FDP assays for diagnosis of DIC and should replace them.

1. Boisclair MD, Ireland H, Lane DA. Assessment of hypercoagulable states by measurement of activation fragments and peptides. Blood Rev. 1990;4:25–40.
2. Bick RL, Baker WF. Diagnostic efficacy of the D-dimer assay in disseminated intravascular coagulation (DIC). Thromb Res. 1992;65(6):785–790.
3. Lehman CM, Wilson LW, Rodgers GM. Analytic validation and clinical evaluation of the STA LIATEST immunoturbidimetric D-dimer assay for the diagnosis of disseminated intravascular coagulation. Am J Clin Pathol. 2004;122(2):178–184.

Wayne L. Chandler, MD
Vice Chair, Clinical Innovation
Medical Director, Houston Methodist Diagnostic Laboratories
Medical Director, Coagulation Laboratory
Department of Pathology and Genomic Medicine, The Methodist Hospital Houston
Professor of Pathology and Laboratory Medicine, Weill Cornell Medical College
Member, CAP Coagulation Resource Committee