From the Research
Platelet reduction in Thrombotic Thrombocytopenic Purpura (TTP) occurs primarily due to excessive platelet consumption in abnormal blood clots throughout the body, as a result of ADAMTS13 enzyme deficiency or dysfunction, which is supported by the most recent study 1.
Pathophysiology of TTP
The ADAMTS13 enzyme normally breaks down large von Willebrand factor multimers. Without proper ADAMTS13 activity, these multimers accumulate in the bloodstream and spontaneously bind to platelets, causing widespread microvascular thrombosis.
- As platelets become incorporated into these microthrombi, their numbers in circulation dramatically decrease, resulting in thrombocytopenia.
- This process is further exacerbated by increased platelet activation and aggregation in response to the abnormal vascular environment.
- The mechanical stress from blood flow through partially occluded vessels can also damage platelets, further contributing to their reduction.
Diagnosis and Treatment
Treatment typically involves plasma exchange to remove the abnormal multimers and replenish ADAMTS13, along with immunosuppression in autoimmune cases, as recommended by 1 and 2.
- Prompt treatment is essential as TTP has a high mortality rate if left untreated due to widespread microvascular thrombosis affecting vital organs.
- The use of caplacizumab, a novel anti-VWF therapy, has shown promise in the management of TTP, as mentioned in 1.
- Long-term follow-up after the acute episode is critical to monitor for relapse and to diagnose and manage chronic sequelae of this disease, as emphasized in 1.