Paraprotein Pathway

Publication: 22/11/2021  
Next review: 22/11/2024  
Best Practice Document
ID: 7248 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2021  


This Best Practice Document is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Paraprotein Pathway

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Paraproteins are abnormal immunoglobulins produced by clonal plasma cells. They can be complete immunoglobulin (IgA, IgG, IgM, IgD, IgE) or part of the immunoglobulin structure (usually light chains). Paraproteins are measured by protein electrophoresis of serum. Light chains can be measured in serum and can sometimes be found in urine (Bence Jones protein).

Immunoglobulin levels may sometimes be raised but without the presence of a monoclonal paraprotein - this indicates an inflammatory state and does not require referral to haematology.

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Haematological diseases associated with a paraprotein

Paraproteins are found in a range of haematological conditions, some of which require urgent investigations and treatment while others require only intermittent monitoring.

Key haematological diagnosis to consider include:

  1. MGUS 
  2. Myeloma and plasmacytoma
  3. Amyloidosis
  4. B cell lymphoma including CLL and Waldenström's macroglobulinemia

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Investigations and management

If you suspect a new diagnosis of myeloma or when a new paraprotein has been identified

  1. Check full blood count, renal function and calcium
  2. Assess patient for symptoms including bone pain and specifically back pain

Emergency situations:

  1. Symptoms of hyperviscosity (e.g. headache, blurred vision, thrombosis) should be discussed urgently with the on-call haematology SpR.
  2. Symptoms of malignant spinal cord compression should be discussed urgently with the on-call clinical oncology SpR

2ww referral to haematology if paraprotein present plus one or more of the following criteria:

  1. High paraprotein level: (not total immunoglobulin, but the monoclonal component only).  The level considered ‘high’ depends on the isotype:
    1. IgG >15g/L
    2. IgA >10g/L
    3. IgM >10g/L
    4. Any level of IgD or IgE
  2. Serum free light chain ratio >100 or <0.01
  3. Haemoglobin <100 g/L
  4. Calcium >2.75 mmol/L
  5. Creatinine > 177 mmol/L or eGFR <40 ml/min or rapid and unexplained deterioration in renal function
  6. New or unexplained bone pain
  7. Peripheral neuropathy not explained by other conditions / medications
  8. Lymphadenopathy or hepatosplenomegaly
  9. Nephrotic range proteinuria (also requires renal referral)

Routine referral to haematology if new paraprotein is identified but the above criteria are not met.

  • Patients with uncomplicated MGUS will be offered a telephone appointment in the MGUS clinic.
  • All other patients will be offered a myeloma clinic appointment

If further advice is needed then please use the haematology advice and guidance service.


Record: 7248
Clinical condition:
Target patient group:
Target professional group(s): Primary Care Doctors
Secondary Care Doctors
Adapted from:

Evidence base


Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

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