73-year-old female with a background of rheumatoid arthritis has been admitted to your ICU with a history of acute shortness of breath and a fluctuating conscious state. She has been having severe headaches for the last three weeks.

The following investigations were obtained:

Parameter

Patient Value

Normal Adult Ran e

Haemoglobin

76

1 15 - 160

White Cell Count

23.8 x 10

4.0 - 1 1.0

Platelets

198 x 10 IL

150 - 450

Blood Film

2% Plasma cells and rolueaux formation

Parameter

Patient Value

Normal Adult Range

Sodium

137 mmol/L

135 - 145

Potassium

4.3 mmol/L

3.2 -4.5

Chloride

106 mmol/L

100 - 1 10

Bicarbonate

25 mmol/L

22 - 27

Urea

15.0 mmol/L*

3.0 - 8.0

Creatinine

280 umol/L*

70 - 120

Total Calcium

2.75 mmol/L*

2.15 - 2.60

Phosphate

1.3 mmol/L

0.7 — 1.4

Albumin

26 g/L*

33 — 47

Globulins

92.3 g/L*

25 — 45

a) Give the diagnosis. (20% marks)

b) What urgent treatment is indicated? (10% marks)

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College Answer

a)

  • Hyperviscosity syndrome secondary to multiple myeloma.

b)

  • Plasmapheresis.

Discussion

a)

This looks like a hyperviscosity syndrome due to hypergammaglobulinaemia, a complication of Waldenström's macroglobulinemia or (less likely) multiple myeloma or plasmacytoma.

Features of this presentation which suggest hyperviscosity:

  • Acute shortness of breath, which suggests heart failure
  • A fluctuating conscious state, which suggests cerebrovascular disease
  • Severe headaches,  which suggests cerebrovascular disease
  • Leukocytosis, which suggests haematological malignancy
  • An elevated globulin level
  • An elevated plasma cell count, which suggests plasmacytoma or Waldenström's macroglobulinemia

Other clinical features of symptomatic hyperviscosity include:

  • Constitutional symptoms: fatigue, malaise, and shortness of breath.
  • Haemorrhagic symptoms:  gingival or mucosal bleeding, or epistaxis.
  • Blurred vision due to central retinal vein occlusion
  • Headaches due to increased intracranial pressure (due to venous occlusion)
  • Fundoscopy reveals dilated, tortuous retinal veins, as well as flame-shaped haemorrhages.
  • Stroke, seizures, coma (usually, venous cerebral infarction)
  • Renal failure
  • Aggravated heart failure (more difficult to pump the viscous blood)
  • Priapism

Even though multiple myeloma is quoted by the college, Waldenström's macroglobulinemia is the disorder where clinically significant hyperviscosity occurs most frequently, according to this article by Mehta et al (2003). This is because Waldenström's macroglobulinemia is characterised by the excess production of IgM, which is a massive molecule. However, numerous other causes of plasmacytosis exist:

  • MGUS
  • Multiple myeloma
  • Waldenström's macroglobulinemia
  • Solitary plasmacytoma
  • Systemic AL amyloidosis
  • POEMS syndrome
  • Adenocarcinoma of the colon
  • Pulmonary tuberculosis
  • Cirrhosis of the liver
  • Aplastic anaemia
  • Syphilis
  • Leprosy
  • Varicella zoster infection
  • Serum sickness
  • Primary infection and reactivation of Epstein–Barr virus
  • Acute respiratory infections
  • Parvovirus B19 infection
  • Rubella
  • Hepatitis virus A infection

b) Plasmapheresis is the usual urgent treatment for this. You centrifuge away the monoclonal badness and replace with nice clean albumin.

References

References

Mehta, Jayesh, and Seema Singhal. "Hyperviscosity syndrome in plasma cell dyscrasias." Seminars in thrombosis and hemostasis. Vol. 29. No. 05. Copyright© 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.:+ 1 (212) 584-4662, 2003.