Thrombotic Microangiopathies: Recent Advances and Research Trends

Thrombotic Microangiopathies (TMA) refer to a group of disorders characterized by systemic or localized endothelial injury, leading to microvascular thrombosis. These conditions include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and other secondary forms related to infections, medications, or autoimmune diseases.

Pathophysiology

The hallmark of TMA is endothelial damage resulting in platelet aggregation and microvascular thrombosis. Key mechanisms include:

• Deficiency or inhibition of ADAMTS13, leading to excessive von Willebrand factor-mediated platelet aggregation.
• Complement dysregulation contributing to atypical HUS.
• Microvascular occlusion causing end-organ damage in the kidney, brain, and heart.

Clinical Features

Common symptoms associated with TMA include:

• Thrombocytopenia with purpura and bleeding tendencies.
• Microangiopathic hemolytic anemia with schistocytes.
• Neurological symptoms such as confusion or seizures.
• Renal dysfunction manifesting as proteinuria or acute kidney injury.

Recent Advances in Diagnosis

Recent research has highlighted the importance of ADAMTS13 activity assays in distinguishing TTP from other TMAs. Additionally, complement genetics analysis aids in the identification of atypical HUS.

Therapeutic Trends

Newer therapies have emerged, including:

• Caplacizumab for acquired TTP, targeting von Willebrand factor.
• Complement inhibitors such as eculizumab for atypical HUS.
• Advancements in plasma exchange protocols for improved patient outcomes.

Future Directions

Ongoing research in gene therapy and monoclonal antibodies aims to provide more targeted treatments with fewer side effects.