The enzyme deficiency that causes Thrombotic Thrombocytopenic Purpura (TTP) is ADAMTS13. Specifically, a severe deficiency or absence of ADAMTS13 activity leads to the disease.
Understanding ADAMTS13 and TTP
TTP is a rare blood disorder characterized by the formation of small blood clots throughout the body. These clots can block small blood vessels, leading to organ damage and potentially life-threatening complications. The critical link between ADAMTS13 and TTP lies in the enzyme's function.
The Role of ADAMTS13
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is responsible for cleaving von Willebrand factor (VWF), a large protein involved in blood clotting. VWF circulates in the blood in long strings. ADAMTS13 cuts these strings into smaller pieces.
- Normal Function: When ADAMTS13 functions properly, it cleaves large VWF multimers into smaller, less active forms. This prevents excessive clot formation.
- In TTP: When ADAMTS13 is deficient or absent, large, uncleaved VWF multimers accumulate in the bloodstream. These large multimers are excessively sticky and promote the formation of widespread microthrombi (small blood clots).
Causes of ADAMTS13 Deficiency
The deficiency in ADAMTS13 can arise from two main causes:
- Acquired TTP: This is the more common form and is caused by the development of autoantibodies that target and inhibit ADAMTS13. These autoantibodies effectively block the enzyme's activity, leading to the accumulation of large VWF multimers.
- Congenital TTP: This is a rare, inherited form caused by genetic mutations in the ADAMTS13 gene. These mutations result in a non-functional or poorly functioning ADAMTS13 enzyme.
Summary
In essence, while TTP is a disorder of blood clotting, the underlying enzymatic cause is a severe deficiency or absence of ADAMTS13 activity, whether due to acquired autoantibodies or inherited genetic mutations. The lack of functional ADAMTS13 leads to the accumulation of abnormally large VWF multimers, which drive the formation of microthrombi characteristic of TTP.
