Intended for healthcare professionals

Practice Rational Testing

Investigating an incidental finding of a paraprotein

BMJ 2012; 344 doi: (Published 04 May 2012) Cite this as: BMJ 2012;344:e3033
  1. Jennifer M Bird, consultant haematologist
  1. 1Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol BS2 8ED, UK
  1. Correspondence to: jenny.bird{at}

A paraprotein can have many causes—some serious but others unlikely ever to cause any problems. This article outlines key investigations and some of the difficulties that may arise after the incidental finding of a paraprotein

Learning points

  • Raised serum globulin concentration or total protein may be the first indication of a paraprotein, but a raised globulin level is more commonly due to polyclonally raised globulins in reaction to inflammation, infection, or cancer

  • A paraprotein is detected by serum protein electrophoresis and then further characterised by immunofixation

  • Evaluate any patient with a newly detected paraprotein for symptoms or signs of myeloma or other lymphoproliferative disorder, both clinically and with investigations

  • Most patients with a newly detected paraprotein will have monoclonal gammopathy of undetermined significance (MGUS) and will never progress to a condition that requires treatment

A 61 year old man with no significant medical history is found to have an elevated total protein and globulin level after routine private health screening in relation to his employment. He is referred to his general practitioner for evaluation. He reports being “completely well” other than occasional back pain and takes no regular medications. Further investigation with serum protein electrophoresis reveals that he has a paraprotein at a concentration of 21 g/L (any measured paraprotein is an abnormal finding)

What is the next investigation?

Raised serum globulin or total protein, or both, is often the first indication of the presence of a paraprotein. The level of globulin in the serum is derived by subtracting the albumin concentration from the total protein. All globulins are produced by plasma cells in the bone marrow. When a raised globulin level is found, it is important to determine the cause of the increased production of immunoglobulin:

  • Polyclonally increased plasma cells—a reaction to several different disease processes including inflammation, infection, liver disease, and cancer

    • or

  • Monoclonal …

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