104. Thrombohemorrhagic vasculitis (HUS, TTP, DIC) - etiology, pathogenesis, clinical manifestations.

Thrombohemorrhagic vasculitis (HUS, TTP and DIC) – etiology, pathogenesis, and clinical manifestations

Group of syndromes characterized by widespread microvascular thrombosis, leading to organ ischemia, hemolysis, and consumption of platelets and coagulation factors, resulting in bleeding.

I. Hemolytic uremic syndrome (HUS)

Etiology

• Typical (diarrhea -associated):
• Most common in children.
• Infection with Shiga toxin-producing E. coli (O157:H7) or Shigella dysenteriae.
• Atypical HUS:
• Complement regulatory protein mutations.
• Drugs, pregnancy, autoimmune conditions.

Pathogenesis

1. Shiga toxin enters circulation → damages endothelial cells in renal microvasculature.
2. Endothelial injury → platelet activation and aggregation → microthrombi formation.
3. RBCs are sheared passing through narrowed vessels → microangiopathic hemolytic anemia.
4. Thrombocytopenia due to consumption.

Clinical manifestations

• Triad:
• Microangiopathic hemolytic anemia.
• Thrombocytopenia.
• Acute renal failure (oliguria, hematuria, uremia ).
• Often preceded by bloody diarrhea.

II. Thrombotic thrombocytopenic purpura (TTP)

Etiology

Deficiency of ADAMTS13 enzyme (vWF- cleaving protease).

• Congenital deficiency.
• More commonly acquired: autoantibodies inhibiting ADAMTS13.

Pathogenesis

1. Reduced ADAMTS13 activity → large vWF multimers persist.
2. Excessive platelet adhesion and aggregation → widespread microthrombi in small vessels.
3. RBC fragmentation → microangiopathic hemolytic anemia.
4. Platelet consumption → thrombocytopenia.

Clinical manifestations

Pentad (classic but not always complete):

• Microangiopathic hemolytic anemia.
• Thrombocytopenia.
• Neurological symptoms (confusion, seizures).
• Fever.
• Renal dysfunction.