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Faulty In Vitro Clotting in Myeloma

From Heidi Lawson:

I was wondering if you had any information on why multiple myeloma (MM) patient specimens do not (at times or at all) spin down well in serum separator tubes (SST) or red top tubes. I called BD and they gave me a small excerpt of information stating that MM patients, due to myeloma proteins, inhibit the three stages of fibrin formation. Do you have any additional information that may be useful in understanding this phenomenon a little better? Thanks!

Hello, Heidi. My first thought was that the abnormally high plasma specific gravity associated with myeloma protein (M-protein) causes the gel to float, rather than position itself between the serum and the red cell layer. This has been documented in myeloma. This can be a big problem, as the surface gel particles plug instrument probes. However, my idea does not account for poor clotting in the red-stopper tube.

The material that BD sent you was excerpted from a BD Tech Talk:

BD Tech Talk, November, 2005

The BD article indicates that M-protein partially blocks thrombin’s action on fibrinogen, slowing formation of fibrin monomers. The monomers, in turn polymerize, slowly. There are two case reports that support this…

  • Panzer S, Thaler E. An acquired cryoglobulinemia which inhibits fibrin polymerization in a patient with IgG kappa myeloma. Haemostasis. 1993;23:69–76.
  • Soria J, Soria C, Samama M, Fine JM, Bousser J. Analysis of a fibrin formation abnormality in a case of multiple myeloma. Scand J Haematol 1975;15:207–18.

To resolve the problem, if you can spare the time, just let the tube stand for an hour until the slowed clotting process is complete. If the analyte you wish to measure is not heat sensitive, incubate at 37°C to speed the clotting process. Also, you can inject a small aliquot of topical thrombin into the tube. I hope this helps, and I invite our other participants to share their approach to this problem. Geo.

Comments (1)
Specimen Management
Feb 2, 2012 11:08pm

Dear George,
Clotting occurs less than 1 min,never separate

Dear George,
Clotting occurs less than 1 min,never separate serum even after 12 hours. Rinse the syringe with heparin and draw sample. I had one pt 76 yrs,further evaluation done, M band positive,bone marrow showed plasma cells confirmed multiple myeloma diagnosis. It is biological variation. Addition of thrombin cleared gelification. My question is thrombin being clot activator,why lysis. What is pathophysiology.
With regards, VILAS HIREMATH

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