Thrombotic Microangiopathies: Definition and Classification

Thrombotic microangiopathies (TMA) are a group of disorders characterized by endothelial injury, leading to thrombosis in small blood vessels and subsequent organ dysfunction. They are associated with microangiopathic hemolytic anemia (MAHA) and thrombocytopenia.

Classification of TMA

Primary TMA

• Thrombotic Thrombocytopenic Purpura (TTP) - Caused by ADAMTS13 deficiency leading to uncontrolled von Willebrand factor-mediated platelet aggregation.
• Atypical Hemolytic Uremic Syndrome (aHUS) - Due to genetic mutations in the complement pathway leading to persistent complement activation and endothelial damage.

Secondary TMA

• Shiga Toxin-Associated Hemolytic Uremic Syndrome (ST-HUS) - Caused by shiga toxin-producing bacteria like E. coli O157:H7.
• Drug-Induced TMA - Associated with certain chemotherapy agents, immunosuppressants, and antibiotics.
• Infection-Related TMA - Triggered by infections such as HIV and sepsis.

Pathophysiology

TMA involves endothelial injury leading to platelet activation and microvascular thrombi formation. The consumption of platelets and destruction of red blood cells result in thrombocytopenia and hemolytic anemia.

Clinical Features

• Anemia and thrombocytopenia
• Neurological manifestations (especially in TTP)
• Renal dysfunction (prominent in HUS)
• Hypertension

Diagnosis and Treatment

Diagnosis is based on laboratory findings of MAHA, thrombocytopenia, and organ involvement. ADAMTS13 levels help differentiate TTP from other TMAs. Management involves plasmapheresis for TTP, complement inhibitors for aHUS, and supportive care in other cases.