In a plenary session, Dr. Marie Scully discussed thrombotic microangiopathies (TMAs), one of the most terrifying conditions faced by hematologists. One such TMA, Thrombotic thrombocytopenic purpura (TTP) requires time dependent diagnosis and treatment.  ADAMSTS13 is a metalloprotease enzyme that plays a critical role in breaking down von-Willebrand factor (VWF).  The importance of VWF is to maintain primary hemostasis and prevent thrombosis.  In thrombocytopenia purpura (TTP) there is a deficiency of this enzyme, which is central to the pathology to disease. 

The availability of complement inhibitors, such as eculizumab, has changed the landscape of another TMA, aHUS (atypical hemolytic uremic syndrome), and  this has translated to improved outcomes for patients with this devastating disorder.  The use of eculizumab is associated with hematologic improvement with best responses and improved prognoses with early use (within the first 7 days)..

During the lecture Dr. Scully surprised the audience with a camel…to discuss cameloids.   Camels have a unique type of antibody, single heavy chain antibodies. This peculiarity has been harnessed for the generation of nanobodies for clinical use in disorders such as TTP. The commercially available nanobody product, caplacizumab disrupts the binding of platelets to VWF. Recent phase III studies assessing  this agent have demonstrated improved time to platelet normalization and reduction in the risk of exacerbation.  No deaths were seen in either the phase II or phase III program, based on the early use of therapy. 

Rituximab is also used in TTP to remove anti-ADAMTS 13 IgG antibodies produced by B-cells.  While this agent is not going to cure the auto-immunity surrounding TTP, it may lead to normalization of ADAMSTS13 levels. Long term monitoring is necessary.  She stressed not to forget that “…it takes 10-14 days for rituximab to have effect”, and hence early use of this medication with adjunctive measures (plasma exchange, corticosteroids and if available caplacizumab) are required for best outcomes. 

When considering pregnancy related TMAs, pregnancy associated TTP may present during any stage of pregnancy, most commonly in the 3rd trimester.  What happens to the mother and baby?  Significant maternal morbidity and mortality exists, and damage to the fetus is common due to placental damage.  Plasma infusion during pregnancy in congenital TTP is critical to successful outcomes and should be considered a standard of care. 

In cases of congenital TTP, the risk of arterial events is significant after 40 years of age.  Even in patients with a normal platelet count who are not on a plasma infusion prophylactic strategy, they may very well experience significant symptoms such as headaches, lethargy, abdominal pain and proteinuria.  Plasma infusion can significantly reduce these symptoms, as well as the risk of stroke.

She left the audience with some key messages: A multifaceted approach is required for this rare condition. One needs to be able to see a clinical problem, have scientists look at it in more detail and the commercial sector to assist in developing therapeutics to improve patient outcomes.  

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