Skip to main content

Main menu

  • Home
  • Our journals
    • Clinical Medicine
    • Future Healthcare Journal
  • Subject collections
  • About the RCP
  • Contact us

Clinical Medicine Journal

  • ClinMed Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Author guidance
    • Instructions for authors
    • Submit online
  • About ClinMed
    • Scope
    • Editorial board
    • Policies
    • Information for reviewers
    • Advertising

User menu

  • Log in

Search

  • Advanced search
RCP Journals
Home
  • Log in
  • Home
  • Our journals
    • Clinical Medicine
    • Future Healthcare Journal
  • Subject collections
  • About the RCP
  • Contact us
Advanced

Clinical Medicine Journal

clinmedicine Logo
  • ClinMed Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Author guidance
    • Instructions for authors
    • Submit online
  • About ClinMed
    • Scope
    • Editorial board
    • Policies
    • Information for reviewers
    • Advertising

Change in blood test results prior to diagnosis in multiple myeloma

Catherine Atkin, Elizabeth Sapey and Alex Richter
Download PDF
DOI: https://doi.org/10.7861/clinmed.20-2-s99
Clin Med March 2020
Catherine Atkin
AUniversity of Birmingham, Birmingham, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth Sapey
AUniversity of Birmingham, Birmingham, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alex Richter
AUniversity of Birmingham, Birmingham, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
Loading

Introduction

Multiple myeloma is a plasma cell malignancy, with one of the longest diagnostic pathways of all cancers in the UK.1 Delay in diagnosis in myeloma is associated with poorer prognosis and more advanced disease.2 End organ damage is often present at diagnosis,3 detectable on blood tests as anaemia, renal impairment and hypercalcaemia – recognition often relies on these features. Other blood test abnormalities occur, including raised total protein, or raised calculated globulin (total protein minus albumin) which reflects total immunoglobulin levels.4 Previous research suggests that some abnormalities may be present for years before diagnosis.5,6 This may allow strategies to detect these changes earlier, and prompt automated testing to reduce diagnostic delay. This research aimed to assess blood test abnormalities present at diagnosis with multiple myeloma, and change over time before diagnosis.

Methods

Data were collected for all patients diagnosed with multiple myeloma at the Queen Elizabeth Hospital Birmingham between 2007 and 2017. Patients were identified using clinical coding. Blood test results available on clinical systems up to the date of diagnosis were collated. Calculated globulin was determined for each result and compared with immunoglobulin results from the same sample using Spearman’s rank order correlation. Test results were grouped in 90-day intervals preceding date of diagnosis. Mean results for each test were calculated for each interval and change was assessed using one-way repeated measures ANOVA.

Results

Using the above criteria, 285 patients were identified. In total, 56,711 individual tests were available. Per patient, this ranged from 10 results (one full blood count) to 2,535 individual tests spanning 13 years. The most common abnormalities at diagnosis were low haematocrit (86%), anaemia (81%), raised total protein (49.8%) and raised creatinine (44.5%).

There was a statistically significant decline in mean haemoglobin over 2 years prior to diagnosis (p<0.0005). Haematocrit appeared to decline over the same time, but this was not statistically significant. There appeared to be an increase in mean corrected calcium and creatinine in the 90 days preceding diagnosis, but not before.

Calculated globulin ranged from 13 g/L to 133 g/L, and was raised in 43.8% of patients and low in 2.5%. Calculated globulin correlated well with total immunoglobulin levels (combined IgG, IgA and IgM) with a strong positive correlation (rs(73) 0.961; p<0.0005; Fig 1). However, the relationship between calculated globulin and each immunoglobulin class separately was not linear (Fig 2).

Fig 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig 1.

Correlation between calculated globulin and sum total of immunoglobulin G, immunoglobulin A and immunoglobulin M.

Fig 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Fig 2.

Correlation between calculated globulin and individual classes of immunoglobulin.

Discussion

Abnormalities that are often used to prompt testing, for instance hypercalcaemia, raised total protein and abnormal renal function, are abnormal in fewer than half of patients with myeloma at diagnosis. It is important to highlight this in education and awareness campaigns, as normal results should not prevent testing.

Haemoglobin declines over at least 2 years prior to diagnosis. A gradual unexplained fall in haemoglobin could be used to identify patients for testing.

Calculated globulin is an accurate reflection of the total immunoglobulin level. An abnormal calculated globulin may prompt testing for myeloma, but normal calculated globulin cannot rule out myeloma, due to a fall in the uninvolved classes of immunoglobulin, so cannot be used alone as a screening test.

Conflicts of interest

None declared.

  • © Royal College of Physicians 2020. All rights reserved.

References

  1. ↵
    1. Howell D
    , Smith A, Jack A, et al. Time-to-diagnosis and symptoms of myeloma, lymphomas and leukaemias: a report from the Haematological Malignancy Research Network. BMC Hematol 2013;13:9.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Kariyawasan CC
    , Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: causes and consequences of delay in diagnosis. QJM 2007;100:635–40.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Rajkumar SV
    , Dimpoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538–48.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Jolles S
    , Borrell R, Zouwail S, et al. Calculated globulin (CG) as a screening test for antibody deficiency. Clin Exp Immunol 2014;177:671–8.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Edgren G
    , Bagnardi V, Bellocco R, et al. Pattern of declining hemoglobin concentration before cancer diagnosis. Int J Cancer 2010;127:1429–36.
    OpenUrlPubMed
  6. ↵
    1. Koshiaris C
    , Van den Bruel A, Oke JL, et al. Early detection of multiple myeloma in primary care using blood tests: a case–control study in primary care. Br J Gen Pract 2018;68:e586–93.
    OpenUrlAbstract/FREE Full Text
Back to top
Previous articleNext article

Article Tools

Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Citation Tools
Change in blood test results prior to diagnosis in multiple myeloma
Catherine Atkin, Elizabeth Sapey, Alex Richter
Clinical Medicine Mar 2020, 20 (Suppl 2) s99-s100; DOI: 10.7861/clinmed.20-2-s99

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Change in blood test results prior to diagnosis in multiple myeloma
Catherine Atkin, Elizabeth Sapey, Alex Richter
Clinical Medicine Mar 2020, 20 (Suppl 2) s99-s100; DOI: 10.7861/clinmed.20-2-s99
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Introduction
    • Methods
    • Results
    • Discussion
    • Conflicts of interest
    • References
  • Figures & Data
  • Info & Metrics

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Complex care liaison preoperative assessment clinic: a 1-year review
  • The acceptability and utility of different diagnostic tests and sample types for the surveillance of trachoma in the Bijagos Islands, Guinea Bissau
  • Machine learning methods in predicting chemotherapy-induced neutropenia in oncology patients using clinical data
Show more Research

Similar Articles

Navigate this Journal

  • Journal Home
  • Current Issue
  • Ahead of Print
  • Archive

Related Links

  • ClinMed - Home
  • FHJ - Home
clinmedicine Footer Logo
  • Home
  • Journals
  • Contact us
  • Advertise
HighWire Press, Inc.

Follow Us:

  • Follow HighWire Origins on Twitter
  • Visit HighWire Origins on Facebook

Copyright © 2021 by the Royal College of Physicians