A 45-year-old woman presents with seizures, after having had a fluctuating level of consciousness and fever. Her admission tests revealed:
|
Test |
Value |
Normal range |
|
Haemoglobin |
100 |
115-160 g/L |
|
White blood cells |
6.9 |
4.0-11.0 x10^9/L |
|
Platelets |
64 |
140-400x10^12/L |
|
International Normalised Ratio |
1.1 |
0.8 – 1.3 |
|
APTT |
38 |
24-35 seconds |
|
Fibrinogen |
3.6 |
2.0-5.0 g/L |
|
Na |
142 |
135-145 mmol/L |
|
K |
4.8 |
3.5-5.5 mmol/L |
|
Glucose |
6.8 |
3.6-7.7 mmol/L |
|
Urea |
18.9 |
2.5-8.3 mmol/L |
|
Creatinine |
0.21 |
0.05-0.11 mmol/L |
|
Lactate De-Hydrogenase |
540 |
120-250 IU/L |
What is the most likely diagnosis, and what other investigations would you order to help confirm the diagnosis? What do you expect the results of these investigations to show?
This woman has anaemia with an elevated LDH (suggestive of haemolysis), thrombocytopenia without evidence of DIC or other significant coagulation problems, renal insufficiency, fluctuating neurological abnormalities and fever. These are the “pentad” of features of the syndrome of Thrombotic Thrombocytopenic Purpura (also known as TTP-Haemolytic Uraemic Syndrome). Further tests are required to confirm the diagnosis (some by excluding significant negatives which require dramatically different treatment). Sepsis is less likely because of the normal white cell count and the presence of thrombocytopenia without evidence of DIC. Peripheral blood film should confirm a microangiopathic (i.e. red cell fragmentation) anaemia, confirm thrombocytopenia, and exclude a toxic appearance of the white cells (as they are normal in number). Haemolysis screen should demonstrate an elevated bilirubin and a reduced haptoglobin concentration, but a negative Coombs test. Urinalysis should be near normal and should exclude an active sediment. Microscopy and culture of appropriate samples (eg. urine and blood, and/or lumbar puncture to exclude meningitis) should exclude active infection. A CT scan of the head should also be performed to exclude intracranial pathology as the cause for the seizures.
The abnormalities and characteristic historical features are:
The college correctly points out that these are the features of TTP. However, with the available test results, one cannot rule out other thrombotic microangiopathies.
What other investigations would you order to help confirm the diagnosis?
Well. A good article from 2013 offers a thorough discussion of the labratory features.
A systematic approach to the confirmation of the diagnosis of TTP would include the following:
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.
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.
Kappler, Shane, Sarah Ronan-Bentle, and Autumn Graham. "Thrombotic Microangiopathies (TTP, HUS, HELLP)." Emergency Medicine Clinics of North America (2014).
Veyradier, A., and D. Meyer. "Thrombotic thrombocytopenic purpura and its diagnosis." Journal of Thrombosis and Haemostasis 3.11 (2005): 2420-2427.
Beckford, M. D., and M. D. Shah. "Thrombotic Thrombocytopenic Purpura: A Review of the Disease Entity, its Clinical and Laboratory Features, and Management Strategies." The Medicine Forum. Vol. 12. No. 1. 2011.