January 7th - LBJ - TTP

So, remember that mnemonic in First Aid - "FATRN" - Fever, Anemia, Thrombocytopenia, Renal Failure, Neurologic Changes - Well it's good for med school memorization, but not applicable to TTP in the real world.  Remember - before the treatment for TTP was perfected, those patients did have Renal Failure and Altered Mental Status - but we see that not too often now because we treat patients beforehand - if you do see these in a patient it is late stage disease!!

So when do you think of TTP on Boards?  Whenever you see the combination of a Microangiopathic Hemolytic Anemia (MAHA) And Thrombocytopenia.  What Makes a MAHA? - fibrin deposition that shears the RBC cells causing fragments, ie schistocytes.  These patients will have a low haptoglobin and a high LDH with a Normal Coombs Test.  However, do not wait for these lab tests to diagnose.  As stated before patients can get Neurologic Disease - anywhere from forgetfullness, delerium to seizures.  Don't wait for this to diagnose.  Renal Failure is late stage.  Don't have to have this to diagnose. So the take home:

TTP + MAHA will be TTP (or even HUS) or some other causes listed below...

There are two forms of TTP - idiopathic and acquired. Acquired is usually due to medications - ticlopidine, clopidogrel, cyclosporine, mitomycin C.  Almost all patients with TTP regardless of the cause have a deficiency of ADAMTS13 - which usually cleaves vWF.  If you can't cleave vWF - you get large aggregates that cause a thrombotic state.  ADAMTS13 is not involved in HUS. 

So, If you suspect TTP, look for schistocytes on the smear. If there are at least "occasional" on the smear (i.e. more than 2 per hpf) then they are significant. If you see this with thrombocytopenia, consider treatment immediately...

Before treatment was perfected, mortality was >90%. If TTP/HUS is suspected (and you are sure it's not another condition listed below) then treat with plasma exhange.  If you can't get the Line or there is no availability to do plasma exchange, then transfuse FFP in the meantime.  Some will even give steroids in the interim.  No matter what the platelets are, do not transfuse, as you will cause more clotting.  Monitor treatment with LDH Levels. 

What else can cause Schistocytes (i.e a MAHA) that you need to know for Boards, and how to tell Apart:
TTP: As per this article
HUS: Can present like TTP, more likely in young patients, almost all will have some renal insufficiency
DIC: Will have MAHA and TCP, But PT and PTT are elevated, unlike with TTP/HUS where they are       normal        
HELLP - MAHA + TTP But Patient will be pregant and have elevated liver enzymes
Malfunctioning Valve Prosthesis: - Usually does NOT cause Thrombocytopenia but will have MAHA.        PT and PTT are normal unless there is an underlying disorder or patient is on warfarin for the valve!
Malignant HTN - Can tell by the BP Reading.  Also, Thrombocytopenia is uncommon with this

Just a bit more on HUS: There are two forms - in children this is usually triggered by antecedent bacterial enteritis, especially E. Coli. Within a week of the infection, patients can get renal failure, MAHA and TCP.  In adults there are forms of HUS after bone marrow transplant and chemotherapy.  Sometimes it is hard to distinguish TTP/HUS - so even when HUS is considered, plasma exhange may be used "just in case" TTP is going on.