A 60-year old male with no significant past medical history has been treated in your ICU for 21 days for severe staphylococcal sepsis and multi-organ failure, for which he is receiving linezolid.
He requires continuous renal replacement therapy (CRRT) and, despite therapeutic heparin to facilitate this, his filter keeps clotting. His platelet count has reduced from 154 x 106/L to 56 x 106/L from day 18 to day 21.
a) List the four most likely differential diagnoses for the thrombocytopenia. (20% marks)
b) Discuss your investigation for the thrombocytopenia. (40% marks)
c) Outline your immediate management of this problem. (40% marks)
a)
i. Linezolid
ii. Consumption coagulopathy (from clotting on renal replacement therapy)
iii. Pseudothrombocytopenia (i.e., platelet clumping)
iv. Sepsis induced including DIC
v. Heparin induced (HIT or HITTS)
vi. TTP/HUS (less likely)
b)
Exclude pseudothrombocytopaenia
Increased consumption
Decreased production
a. Drugs, sepsis, alcohol, bone marrow suppression
c)
Additional Examiners’ Comments:
Most candidates passed but there was overall a knowledge gap on the management of this clinical problem
Possible differentials for thrombocytopenia? There is a vast array. Observe:
Decreased platelet production
|
Increased platelet destruction
|
Pseudothrombocytopenia
|
Dilution of platelets
Sequestration
|
In order to simplify one's answer, one may be able to narrow this range to the causes which are relevant to the critically septic patient on dialysis. This exact list is also offered in the discussion section of Question 4 from the second paper of 2001, which offers an essentialy identical scenario.
In brief:
This is a more manageable list.
One would organise the following investigations in order to work through it:
The links point to brief explanatory notes for these tests, which one may find in the local chapter on thrombocytopenia.
The following list of generic steps applies to thrombocytopenia of any cause:
Minimise platelet destruction
Maximise platelet production
Protect the patient from complications of thrombocytopenia
Stasi, Roberto. "How to approach thrombocytopenia." ASH Education Program Book 2012.1 (2012): 191-197.
UpToDate: Approach to the adult patient with thrombocytopenia.
Casonato, A., et al. "EDTA dependent pseudothrombocytopenia caused by antibodies against the cytoadhesive receptor of platelet gpIIB-IIIA." Journal of clinical pathology 47.7 (1994): 625-630.
Castro, Christine, and Mark Gourley. "Diagnostic testing and interpretation of tests for autoimmunity." Journal of Allergy and Clinical Immunology 125.2 (2010): S238-S247.
Arepally, Gowthami M., and Thomas L. Ortel. "Heparin-induced thrombocytopenia." New England Journal of Medicine 355.8 (2006): 809-817.
Chong, B. H., J. Burgess, and F. Ismail. "The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia." Thrombosis and haemostasis 69.4 (1993): 344-350.