Anemia (60%)
Anemia is normochromic normocytic.
Rouleaux formation is common. This is an aspecific finding, due to increased levels of paraproteins, globulins, and fibrinogen.

Presence of rouleaux (stacking of red cells) in the smear of the peripheral blood in a patient with multiple myeloma (courtesy of Dr. Michael G. Bayerl - Hematopathology, Penn State Hershey Medical Center):



In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2.
Blood. 2010 Nov 4;116(18):3635-44.
Maes K, Nemeth E, Roodman GD, Huston A, Esteve F, Freytes C, Callander N, Katodritou E, Tussing-Humphreys L, Rivera S, Vanderkerken K, Lichtenstein A, Ganz T.


Leukopenia (15%)

Rare cases of multiple myeloma and MGUS are associated with a neutrophilic leukemoid reaction. This is due to the synthesis of G-CSF by the clonal plasma cells. Plasma G-CSF is increased.

Chronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid reactions.
Br J Haematol. 2015 Nov;171(3):400-10.
Bain BJ, Ahmad S.

This study tries to identify findings that distinguish chronic neutrophilic leukemia (CNL) from the leukemoid reaction associated with plasma cell disorders, and it concludes that the most important diagnostic finding of CNL is the clonality of the myeloid cells, and the presence of molecular genetic abnormalities such as mutations in CSF3R, the gene encoding the G-CSF receptor. Features such as toxic granulation, Dohle bodies, and the neutrophil alkaline phosphatase (NAP) score do not aid in the differential diagnosis.


Thrombocytopenia (15%)


Elevated BUN, creatinine

Differential diagnosis of renal failure:

                     URINE       URINE
                    ALBUMIN   LIGHT CHAINS
   Myeloma kidney      +          +++
   LCDD                +           +
   Amyloidosis        +++          +



Hypercalcemia (30%)





Normally, 93% of plasma consists of water (which contains the sodium), and 7% of it consists of solids (proteins + lipids). Since the plasma water is often diluted before the measurement (in order to reduce the volume of blood needed for analysis), the increase in the fraction of proteins results in a greater dilution and factitiously low serum sodium concentration.


Decreased anion gap


Elevated ESR


Elevated serum beta2-microglobulin


Paraproteinemia - See "Diagnosis"


Elevated plasma viscosity



M components with antibody activity

M components with antibody activity. Anti-smooth muscle, anti-thyroglobulin and anti-streptolysin-O activity in five M component sera.
Ann Clin Res. 1971 Apr;3(2):86-97.
Wager O, Räsänen JA, Haltia K, Wasastjerna C.

Human monoclonal immunoglobulins that bind the human acetylcholine receptor.
Eur J Immunol. 1987 Dec;17(12):1867-9.
Eng H, Lefvert AK, Mellstedt H, Osterborg A.
These authors screened 149 monoclonal Ig samples and found that 14 (9%) reacted with the human acetylcholine receptor (AChR). The anti-AChR binding of the M components was restricted to the F(ab')2 fragment. Despite the presence of anti-AChR antibodies, none of the patients had symptoms of myasthenia gravis.

Hypoglycemia due to an insulin binding antibody in a patient with an IgA-kappa myeloma.
J Clin Endocrinol Metab. 2007 Jun;92(6):2013-6.
Halsall DJ, Mangi M, Soos M, Fahie-Wilson MN, Wark G, Mainwaring-Burton R, O'Rahilly S.
This is the first report of a patient with an IgA-kappa myeloma with spontaneous hypoglycemia due to monoclonal anti-insulin antibodies. The authors used polyethylene glycol precipitation and gel filtration chromatography to demonstrate high-molecular weight insulin immunoreactivity in the patient's plasma. This was characterized as an insulin binding IgA-kappa paraprotein. The hypoglycemia was associated with high-plasma insulin levels, and it was probably due to delayed clearance of insulin.



Vitamin deficiency

Myeloma and pernicious anemia.
Am J Med Sci. 1978 Jan-Feb;275(1):93-8.
Perillie PE.
This study describes 4 cases of pernicious anemia associated with multiple myeloma.

Prevalence and significance of vitamin D deficiency in multiple myeloma patients.
Br J Haematol. 2008 May 15.
Badros A, Goloubeva O, Terpos E, Milliron T, Baer MR, Streeten E.




Hyperammonemia: an unusual presenting feature of multiple myeloma.
Indian J Med Sci. 2005 Jan;59(1):24-7.
Shah AS, Shetty N, Jaiswal S, Mehta BC.
This is a case report of a 76 year old lady with altered mental status due to hyperammonemia. She had no evidence of liver disease, and work-up showed multiple myeloma. Treatment of myeloma resulted in a reduction of serum ammonia levels and improvement in her mental status. Hyperammonemia should be included in the differential diagnosis of altered mental status in multiple myeloma, along with the other more common causes, such as hypercalcemia and hyperviscosity.

Hyperammonemia and encephalopathy in patients with multiple myeloma.
Am J Hematol. 2007 May;82(5):414-5.
Talamo G, Cavallo F, Zangari M, Barlogie B, Lee CK, Pineda-Roman M, Kiwan E, Krishna S, Tricot G.




Elevated levels of serum prolactin in patients with advanced multiple myeloma.
Neuroimmunomodulation. 2001;9(4):231-6.
Gadó K, Rimanóczi E, Hasitz A, Gigler G, Tóth BE, Nagy GM, Pálóczi K, Domján G.
These authors measured serum prolactin levels of 56 patients with multiple myeloma, and found that patients with advanced disease had a significant increase in prolactin concentration, while patients in stages I and II and control subjects had normal values. In a patient, serial determinations of the serum prolactin levels clearly showed an increase of the prolactin concentration during the disease progression.

Positive pregnancy tests in a nongravid, premenopausal woman due to hCG beta-chain production by multiple myeloma.
Am J Clin Pathol. 2005 Jul;124(1):108-12.
Slone SP, Ahmed Z, Cole LA, Elin RJ, Martin AW, Herzig RH, Herzig GP, Miller JJ.
nongravid, premenopausal woman receiving chemotherapy for multiple myeloma had a positive pregnancy test. This was found to be related to human chorionic gonadotropin (hCG) originated from myeloma. Immunohistochemical stains showed that MM cells expressed hCG.

Patients with myeloma can have hyperamylasemia, due to the ectopic production of amylase by myeloma cells. It can be caused by macroamylase, an immunoglobulin-amylase complex.

Amylase: a disease activity index in multiple myeloma?
Leuk Lymphoma. 2006 Jan;47(1):151-4.
Pinelli M, Bindi M, Rosada J, Scatena P, Castiglioni M.
This is a case report of a patient with lambda-light chain multiple myeloma who had hyperamylasemia of the salivary type. The authors review the literature of ectopic production of amylase by myeloma cells, and they conclude that these cases are associated with high tumor mass, extensive bone destruction, extra-medullary disease,  and poor prognosis.



Giampaolo Talamo, M.D.