Microangiopathic Haemolytic anaemia

Related Subjects: |Microangiopathic Haemolytic anaemia |Haemolytic anaemia |Immune(Idiopathic) Thrombocytopenic Purpura (ITP) |Thrombotic Thrombocytopenic purpura (TTP) |Haemolytic Uraemic syndrome (HUS) |Thrombocytopenia |Disseminated Intravascular Coagulation (DIC)

🩸 Thrombotic microangiopathies (TMAs) are a group of disorders characterised by endothelial injury, platelet-rich microvascular thrombi, and resulting organ dysfunction. 💡 The classic laboratory clue is microangiopathic haemolytic anaemia (MAHA) with schistocytes on the blood film, usually alongside thrombocytopenia.

📘 About Microangiopathic Haemolytic Anaemia (MAHA)

🔬 MAHA is a haemolytic anaemia caused by mechanical destruction of red blood cells within the microcirculation. 🧩 Red cells are damaged as they pass through vessels narrowed by platelet-fibrin thrombi or severe endothelial injury. 🩻 The blood film shows schistocytes (red cell fragments, including “helmet cells” and triangular forms). ⚠️ MAHA is a pattern, not a final diagnosis — the urgent task is to identify the underlying cause.

🧾 Major Causes of MAHA / TMA

🚫 Important Clarification

• PNH causes complement-mediated intravascular haemolysis, but it is not a classic MAHA and does not typically cause schistocyte-driven red cell fragmentation.
• HIT causes thrombocytopenia and thrombosis, but it is not usually classified as a typical MAHA/TMA syndrome.

⚙️ Pathophysiology

• 🕸️ Endothelial injury or failure of normal antithrombotic regulation leads to formation of microvascular thrombi.
• 🩸 As red cells pass through these narrowed, thrombus-filled vessels, they are sheared and fragment into schistocytes.
• 📉 Platelets are consumed in thrombus formation, so thrombocytopenia commonly accompanies MAHA.
• 🧠🚰 Organ dysfunction reflects where the microthrombi are most active — brain in TTP, kidney in HUS, and widespread multi-organ failure in DIC.

🧑‍⚕️ Clinical Presentation

• Common features are anaemia, thrombocytopenia, and evidence of organ injury.
• 🔴 Symptoms of haemolysis: fatigue, pallor, jaundice, dark urine, tachycardia.
• 🧠 Neurological features are particularly suggestive of TTP: confusion, headache, transient focal deficits, seizures, reduced consciousness.
• 🚰 Renal impairment is particularly prominent in HUS and may present with haematuria, oliguria, hypertension, or fluid overload.
• 🩸 DIC may additionally present with bleeding, bruising, and oozing from lines or venepuncture sites because clotting factors are being consumed.
• 🤰 In pregnancy, think about HELLP, pre-eclampsia, TTP, and complement-mediated HUS.

🔍 Differential Diagnosis

• 🟣 TTP
• 🟢 Typical or atypical HUS
• ⚠️ DIC
• 📈 Malignant hypertension
• 🤰 Severe pre-eclampsia / HELLP syndrome
• 🪨 Systemic sclerosis renal crisis
• ⚙️ Mechanical haemolysis (prosthetic valves, LVAD)
• 🦟 Malaria or other infection-related haemolytic processes
• 🧪 Autoimmune haemolysis — usually DAT positive and does not give a schistocyte-predominant film

🧪 Investigations

• 📉 FBC: anaemia and thrombocytopenia.
• 🩻 Blood film: schistocytes are the key morphological clue.
• ⚡ LDH: raised due to haemolysis and tissue injury.
• 💛 Unconjugated bilirubin: raised.
• ⬇️ Haptoglobin: low or undetectable in intravascular haemolysis.
• 🧪 Reticulocyte count: usually raised, reflecting marrow response.
• 🧫 DAT (Coombs test): usually negative, helping distinguish MAHA from autoimmune haemolytic anaemia.
• 🚰 U&E / creatinine / urinalysis: assess renal involvement.
• 🧾 Clotting screen: usually normal in TTP/HUS, but prolonged PT/aPTT, low fibrinogen, and high D-dimer suggest DIC.
• 🧬 ADAMTS13 activity: severe deficiency strongly supports TTP, but treatment must not wait for the result.
• 🦠 Stool testing for Shiga toxin in diarrhoea-associated HUS.
• 🧬 Consider complement studies and specialist work-up if atypical HUS is suspected.

🚨 Red Flags

• MAHA + thrombocytopenia + neurological symptoms = treat as TTP until proven otherwise.
• MAHA + thrombocytopenia + AKI after bloody diarrhoea = think HUS.
• MAHA + thrombocytopenia + abnormal clotting = think DIC.
• Pregnancy + MAHA + transaminitis + thrombocytopenia = urgent obstetric/haematology review.

💊 Management

• 🎯 Treat the underlying cause urgently — MAHA is a syndrome, not a final diagnosis.
• 🔄 TTP: start urgent plasma exchange immediately; add steroids, and specialist centres may use caplacizumab and rituximab.
• 🟢 Typical HUS: usually supportive care — fluid balance, blood pressure control, and dialysis if required.
• 🧬 Complement-mediated HUS: urgent specialist input; complement inhibition (for example eculizumab/ravulizumab) may be indicated.
• ⚠️ DIC: treat the trigger (e.g. sepsis, trauma, malignancy) and support coagulation abnormalities with appropriate blood products when needed.
• 📈 Malignant hypertension: controlled blood pressure reduction and organ support.
• 🩸 Red cell transfusion may be needed for severe symptomatic anaemia.
• 🚫 Platelet transfusion is generally avoided in TTP unless there is life-threatening bleeding or an invasive procedure is essential.

📚 References

• Diagnostic Approach to Microangiopathic Haemolytic Disorders
• How to Approach a Patient With TMA
• ISTH Guidelines for Thrombotic Thrombocytopenic Purpura

📖 Cases – Microangiopathic Haemolytic Anaemia (MAHA)

• Case 1 – Thrombotic Thrombocytopenic Purpura (TTP) ⚡:
  A 35-year-old woman presents with fever, confusion, petechiae, and jaundice. Bloods: Hb 7.5 g/dL, platelets 25 × 10⁹/L, LDH markedly raised, haptoglobin low. Blood film: schistocytes. Creatinine is mildly elevated.
  Diagnosis: MAHA due to TTP.
  Management: Immediate plasma exchange, steroids, urgent haematology involvement, and ADAMTS13 testing without delaying treatment.
  Teaching point: In practice, the key triad is MAHA + thrombocytopenia + organ injury. The historic pentad is neither required nor usually complete.
• Case 2 – Haemolytic Uraemic Syndrome (HUS) 🧒:
  A 6-year-old boy develops pallor, abdominal pain, haematuria, and oliguria one week after bloody diarrhoea. Bloods: Hb 6.9 g/dL, platelets 30 × 10⁹/L, creatinine 280 µmol/L. Blood film: schistocytes.
  Diagnosis: MAHA due to typical HUS.
  Management: Supportive care, careful fluid management, blood pressure control, and dialysis if required.
  Teaching point: HUS is typically renal-predominant, especially after Shiga toxin exposure.
• Case 3 – Disseminated Intravascular Coagulation (DIC) 🩸:
  A 58-year-old man in septic shock develops bruising and oozing from venepuncture sites. Bloods: Hb 8.2 g/dL, platelets 40 × 10⁹/L, PT and aPTT prolonged, fibrinogen low, D-dimer high. Blood film: schistocytes are present.
  Diagnosis: MAHA due to sepsis-associated DIC.
  Management: Treat the sepsis urgently, support organ failure, and use blood products as clinically indicated.
  Teaching point: Abnormal clotting studies point away from isolated TTP/HUS and towards DIC.

🩺 Teaching Point: Think MAHA when you see anaemia + thrombocytopenia + schistocytes. Then ask: brain? → TTP, kidney? → HUS, clotting abnormal? → DIC. This “pattern recognition first” approach is what makes these cases safer at the bedside.