From the Guidelines
Thrombotic Thrombocytopenic Purpura (TTP) is primarily caused by a severe deficiency of the ADAMTS13 enzyme, which can be either acquired or congenital, leading to the accumulation of large von Willebrand factor multimers and the formation of microthrombi in small blood vessels. The cause of TTP can be identified using the PLASMIC score, which takes into account the platelet count, combined hemolysis variable, absence of active cancer, absence of stem-cell or solid-organ transplant, mean corpuscular volume, international normalized ratio, and creatinine levels 1. Some key points to consider in the diagnosis of TTP include:
- The role of ADAMTS13 enzyme deficiency, which can be either acquired or congenital
- The use of the PLASMIC score to rapidly assess adults with thrombotic microangiopathies
- The importance of distinguishing TTP from other forms of thrombotic microangiopathy, such as antiphospholipid syndrome and complement-mediated TMA
- The need for prompt treatment, including plasma exchange therapy and immunosuppressive medications, to prevent morbidity and mortality 1. In clinical practice, it is essential to consider the underlying cause of TTP and to tailor treatment accordingly, taking into account the patient's individual risk factors and clinical presentation.
From the Research
Cause of Thrombotic Thrombocytopenic Purpura (TTP)
The cause of TTP is primarily attributed to:
- Autoantibodies against the von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS-13 2, 3, 4, 5, 6
- Severe deficiency of plasma ADAMTS-13 activity (< 10 IU/dL-1) with or without detectable inhibitory autoantibodies against ADAMTS-13 2
- ADAMTS13 gene mutations causing the hereditary form of TTP 4, 5, 6
- Acquired deficiency of ADAMTS-13 due to the presence of an autoantibody, representing a specific subset of microangiopathic haemolytic anaemias (MAHA) 5
Pathophysiology of TTP
The pathophysiology of TTP involves:
- Formation of microthrombi in the high shear environment of the microvasculature due to the deficiency of ADAMTS-13 3, 4, 6
- Microvascular occlusion, microangiopathic hemolytic anemia (MAHA), and organ ischemia resulting from the formation of microthrombi 3, 4
- VWF-platelet aggregation and microvascular thrombosis due to the deficiency of ADAMTS-13 6