A previously well 54 year old man presents with confusion. On examination a rash is noted (see photograph below). Temperature is 37.10 C. The initial blood results are provided on the next page.

Venous biochemistry

Test

Value

Normal Range

Sodium

135 mmol/L

135 -145

Potassium

3.8 mmol/L

3.5 - 4.5

Urea*

18 mmol/L

2.9 - 8.2

Creatinine*

177  mol/L

70 -120

Bilirubin*

45  mol/L

<20

Haematology

Test

Value

Normal Range

Hb*

99 G/L

135 -180

WBC

10.8 x 109/L

4.0 -11.0

Platelets*

26 x 109/L

140 - 400

Blood film:      Schistocytes

Coagulation

Test

Value

Normal Range

PT

10 sec

9 -12

APTT

29 sec

24 - 39

Fibrinogen

3.0 G/L

1.7 - 4.5

 

a)          What is the most likely diagnosis? Provide 3 reasons.

b)         What definitive treatment needs to be instituted urgently?

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College Answer

a)          What is the most likely diagnosis? Provide 3 reasons.

TTP

Reasons: Low platelets, renal dysfunction, presence of schistocytes suggestive of MAHA and neurological symptoms.

b)         What definitive treatment needs to be instituted urgently?

Plasma exchange

Discussion

Thrombotic thrombocytopenic purpura is discussed in greater detail elsewhere.

Characteristic features of TTP are as follows:

  • Anaemia
  • Thrombocytopenia
  • Microangiopathic haemolytic anaemia
  • Schistocytosis
  • Neurological symptoms
  • Fever
  • Renal failure

The presence or raised bilirubin suggests that intravascular hameolysis is taking place, and the presence of serious renal failure lends itself to the idea that a haemolytic-uremic syndrome may also be in play here. Those two have been together in the same category before (TTP/HUS). Nowadays, TTP and HUS and HELLP are all recognised as a spectrum of thrombotic microangiopathies.

The definitive treatment for it is plasma exchange, aiming to remove the ADAMTS-13 inhibitor while replacing the missing ADAMTS-13 protein with FFP.

Not much else can be added to this brief answer, the third in a three-part question, which is valued at ten points in total (thus one has 3.333 minutes to dedicate to it).

 

References

References

George, James N. "Thrombotic thrombocytopenic purpura." New England Journal of Medicine 354.18 (2006): 1927-1935.

Peyvandi, Flora, et al. "von Willebrand factor cleaving protease (ADAMTS‐13) and ADAMTS‐13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura." British journal of haematology 127.4 (2004): 433-439.

Tsai, Han-Mou. "Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura." Journal of the American Society of Nephrology 14.4 (2003): 1072-1081.

Oh's Intensive Care manual:

Chapter 97 (pp. 993)  Therapeutic  plasma  exchange  and  intravenous  immunoglobulin  therapy  by Ian  Kerridge,  David  Collins  and  James  P  Isbister

Kakishita, Eizo. "Pathophysiology and treatment of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)."International journal of hematology 71.4 (2000): 320-327.

Noris, Marina, and Giuseppe Remuzzi. "Hemolytic uremic syndrome." Journal of the American Society of Nephrology 16.4 (2005): 1035-1050.