Thrombotic thrombocytopenia (TTP) is a life threatening disorder characterized by clotting in small blood vessels resulting in reduced blood supply to end organs such as the central nervous system and kidneys and is associated with thrombocytopenia and microangiopathic haemolytic anaemia.

Originally, it was characterized by a pentad of thrombocytopenia, microangiopathic haemolytic anaemia, neurological signs, renal impairment and fever.  However, the presence of the pentad is not necessary for the diagnosis.

TTP is due to a marked deficiency of ADAMTS13 activity either due to congenital deficiency or development of autoantibodies against this protease.  ADAMTS13 is also known as von Willebrand factor cleaving protein and is normally produced in the liver.  As the name suggests, it cleaves ultra large von Willebrand multimers which would otherwise cause spontaneous aggregation of platelets in small blood vessels.  This results in narrowed vessels and causes tearing of red cells leading to microangiopathic haemolytic anaemia, consumption of platelets and end organ ischaemia.  Acquired TTP may be associated with pregnancy, malignancy, autoimmune diseases, drugs but most of the time the underlying cause is unknown. 

Clinical signs and symptoms may be variable and due to thrombocytopenia and organs involved such as bruising or bleeding, fever, fluctuating neurological status, abdominal pain, chest pain, renal impairment and jaundice.  

TTP is a medical emergency and treatment should be started as soon as possible.  Treatment is with plasma exchange using either fresh frozen plasma or cryodepleted plasma both of which contains replacement ADAMTS13.  Platelet transfusion is generally contraindicated.

 

References

1.    Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. British journal of haematology. 2012;158(3):323-35.
2.    Crawley JTB, Scully MA. Thrombotic thrombocytopenic purpura: basic pathophysiology and therapeutic strategies. ASH Education Program Book. 2013 December 6, 2013;2013(1):292-9.