🩸 Chapter 89: Thrombotic Microangiopathies (TMA)

TTP vs HUS · ADAMTS13 deficiency · Shiga toxin (ST-HUS) · Atypical HUS (complement-mediated) · Plasma exchange (PLEX) · Eculizumab · MAHA + thrombocytopenia · Differential diagnosis · Avoid platelet transfusion in TTP

🔍 Core Concepts: Thrombotic Microangiopathies

📌 TTP (Thrombotic Thrombocytopenic Purpura)
Pentad: thrombocytopenia, MAHA, neurological symptoms, renal impairment, fever. ADAMTS13 deficiency (activity <10%). Treatment: plasma exchange (PLEX) + steroids + rituximab.
🦠 ST-HUS (Shiga Toxin HUS)
Typical HUS: diarrhoea (E. coli O157:H7), triad: AKI, thrombocytopenia, MAHA. Supportive care, hydration. PLEX not beneficial. Avoid antibiotics (increase toxin release).
🧬 aHUS (Atypical HUS)
Complement dysregulation (CFH, CFI, MCP mutations). No diarrhoea, recurrent. Treatment: eculizumab (anti-C5 monoclonal antibody). PLEX may be used.
💊 Drug-induced TMA
Quinine, calcineurin inhibitors (cyclosporine, tacrolimus), gemcitabine. Stop drug. PLEX may help if immune-mediated.
🩺 Diagnosis
Schistocytes on smear, low platelets, elevated LDH, low haptoglobin, negative Coombs test. ADAMTS13 activity <5-10% confirms TTP. Stool PCR for Shiga toxin.
⚠️ Contraindications
Platelet transfusion in TTP (may exacerbate thrombosis) — only if life-threatening bleeding. Avoid in ST-HUS unless bleeding.

🩺 Stepwise Approach: Suspected TMA

1
Recognise clinical syndrome
Thrombocytopenia + microangiopathic haemolytic anaemia (MAHA) — schistocytes, elevated LDH, low haptoglobin. Exclude DIC (normal PT/PTT, fibrinogen).
2
Differentiate TTP vs HUS
Neurological symptoms prominent in TTP; renal failure dominant in HUS. History of diarrhoea → ST-HUS. No diarrhoea → TTP or aHUS. Send ADAMTS13 activity, stool Shiga toxin PCR.
3
Initiate plasma exchange (PLEX) urgently if TTP suspected
Do not wait for ADAMTS13 result. PLEX daily until platelet count normalises and LDH normalises. Steroids (methylprednisolone) adjunct. Rituximab for refractory/relapsing.
4
ST-HUS management
Supportive care: IV fluids (early hydration may protect kidneys), avoid antibiotics (increase Shiga toxin release), avoid PLEX (not beneficial). Dialysis if needed.
5
aHUS management
Eculizumab (anti-C5) — blocks terminal complement. PLEX may be used if eculizumab not available. Monitor for meningococcal infection (vaccinate before, give prophylaxis).
6
Avoid platelet transfusion
Platelets contraindicated in TTP (may worsen thrombosis) unless life-threatening haemorrhage. Transfuse only if bleeding.