Introduction 

Viscosity is a critical physical property of fluids, defining their resistance to flow. Scientifically, it is described as the force exerted over time divided by the area, which can be measured by a viscometer and reported with newton-second per square meter (N∙s/m2 or Pa∙S) as its SI unit. At 20 °C, water exhibits a viscosity of 1 Centipoise (cP), equivalent to mPa∙S. Blood viscosity varies based on its cellular and acellular components, typically measuring 1.4-1.8 cP for normal serum/plasma and reaching 3.5-5.5 cp for whole blood (1, 2).

Causes of High Viscosity

Elevated viscosity in patient specimens can be caused by preanalytical and pathophysiological conditions. At the preanalytical stage, the inadequate or delayed mixing of anticoagulants will lead to clot formation in plasma; meanwhile, incomplete clotting will leave residual fibrinogen in serum, which can continue to form clots after centrifugation. Either issue can lead to viscous specimens. Additionally, certain pathophysiological conditions can contribute to high viscosity, including abnormal blood cell counts (e.g., seen in polycythemia vera, leukemia, thrombocythemia), irregularly shaped blood cells (as observed in sickle cell disease), or abnormally high levels of acellular components, such as hypergammaglobulinemia in multiple myeloma or Waldenstrom macroglobulinemia and cryoproteinemia with cryoglobulins or cryofibrinogens (3-5).

Impact on Laboratory Analysis 

While viscosity is not commonly tested in clinical laboratories, its influence on the accuracy of clinical analyses cannot be underestimated. Viscous specimens can pose challenges in auto-analyzers, potentially leading to inaccurate sampling or blockages in pipettes, probes, or tubing systems. Such issues can result in analytical errors and instrument malfunctions, jeopardizing patient care quality.

Lab Approaches to Handling Viscous Specimens

The approaches to addressing viscosity-related challenges depend on the underlying causes. However, in clinical practice, identifying the specific cause(s) of viscosity for each individual specimen within a limited time frame is challenging. To ensure timely and accurate results, a trial-and-error approach with all potential causes in mind is often necessary.

Here is a practical protocol for handling viscous specimens, starting from common to rare scenarios and from more feasible/practical solutions to less ones.

  1. Inspect the specimen's appearance and remove visible fibrin clots using a sticker.
  2. Recentrifuge the specimen to remove micro-clots or lipids (airfuge recommended). 
  3. If the above two steps fail, make a dilution with a manufacturer-recommended diluent at an appropriate dilution factor. Consider using wide-bore pipette tips and positive displacement pipettes for accurate volume measurement of viscous specimens.
  4. If issues persist, cryo-proteins are highly suspected. Then proceed to the following steps sequentially until the viscosity issue is resolved (6):
    1. Warm the serum or plasma specimen up to body temperature (37°C) for 30 minutes on the heat block or water bath and run immediately.
    2. If warming alone fails, transfer the warmed-up specimen to an aliquot tube and centrifuge it with glass beads. 
    3. If warming and centrifuge don’t resolve the issue, mix the warmed-up specimen and make appropriate dilution.
    4. If the results are still unobtainable, cancel the tests, recollect, and put the specimen into a 37°C heat block immediately after collection for delivery to the lab. 
  5. If all the above strategies prove ineffective, recollect venous blood and proceed with tests on blood gas analyzers (preferred if available) or point-of-care devices for applicable analytes, such as electrolytes and metabolites.
This report mainly focuses on viscous serum and plasma. For detailed guidance on handling viscous body fluids, please consult CLSI guideline C49-B, which provides information on dilution, freeze-thaw cycles, and managing hyaluronic acid to reduce specimen viscosity.

Conclusion

Handling viscous specimens in clinical chemistry requires a systematic approach that considers various potential causes and appropriate corrective measures. By following these protocols, laboratories can ensure the accuracy and reliability of clinical analyses, even for high-viscosity specimens.

REFERENCES

  1. Fahey JL, Barth WF, Solomon A. Serum Hyperviscosity Syndrome. JAMA 1965 May 10;192:464-7 as doi: 10.1001/jama.1965.03080190030008.
  2. Rosenson RS, McCormick A, Uretz EF. Distribution of blood viscosity values and biochemical correlates in healthy adults. Clin Chem 1996 Aug;42:8 Pt 1:1189-95.
  3. Perez Rogers A, Estes M. Hyperviscosity Syndrome. In: StatPearls. Treasure Island (FL): 2023.
  4. Kallemuchikkal U, Gorevic PD. Evaluation of cryoglobulins. Arch Pathol Lab Med 1999 Feb;123:2:119-25 as doi: 10.5858/1999-123-0119-EOC.
  5. Saadoun D, Elalamy I, Ghillani-Dalbin P, Sene D, Delluc A, Cacoub P. Cryofibrinogenemia: new insights into clinical and pathogenic features. Am J Med 2009 Dec;122:12:1128-35 as doi: 10.1016/j.amjmed.2009.03.040.
  6. Meng QH, Chibbar R, Pearson D, Kappel J, Krahn J. Heat-insoluble cryoglobulin in a patient with essential type II cryoglobulinemia and cryoglobulin-occlusive membranoproliferative glomerulonephritis: case report and literature review. Clin Chim Acta 2009 Aug;406:1-2:170-3. Epub 20090520 as doi: 10.1016/j.cca.2009.05.013.