Microangiopathic Haemolytic Anaemia (MAHA) – and When to Worry

Microangiopathic Haemolytic Anaemia (MAHA) – and When to Worry

1. What is MAHA?

Microangiopathic haemolytic anaemia (MAHA) is a serious form of haemolytic anaemia in which red blood cells are destroyed mechanically as they pass through small blood vessels.

• Unlike immune haemolysis, MAHA is not caused by antibodies
• Instead, it results from physical damage within the circulation

Analogy: Red blood cells moving through damaged vessels are like cars driving over spikes—they become fragmented as they pass through.

2. Pathophysiology (“Cheese Slicer” Effect)

The hallmark of MAHA is the presence of schistocytes (fragmented red cells) on a blood film.

• Caused by:
  • Fibrin strands in small vessels
  • Narrowed or obstructed microcirculation
• These act like a wire cheese slicer, shearing red cells under pressure

Key consequence:

• Intravascular haemolysis → release of haemoglobin → jaundice and organ stress

3. Epidemiology

• MAHA is uncommon, but not rare in critical care settings
• Occurs across all age groups depending on cause:
  • Children: more often HUS
  • Adults: more often TTP, DIC, malignancy, pregnancy, hypertension
• Often presents in acutely unwell or hospitalised patients

4. Causes

MAHA is not a single disease, but a manifestation of underlying pathology, usually involving endothelial injury or microthrombi.

A. Thrombotic Microangiopathies (TMAs)

Thrombotic Thrombocytopenic Purpura (TTP)

• Due to deficiency of ADAMTS13 enzyme
• Leads to large von Willebrand factor multimers → platelet clumping
• Causes:
  • MAHA
  • Thrombocytopenia
  • Organ ischaemia (brain, kidneys)

Note. TTP is a medical emergency

Haemolytic Uraemic Syndrome (HUS)

• Often follows E. coli (Shiga toxin) infection
• Toxin damages renal microvasculature

Classic triad:

• MAHA
• Thrombocytopenia
• Acute kidney injury (AKI)

More common in children

B. Disseminated Intravascular Coagulation (DIC)

• Triggered by:
  • Sepsis
  • Trauma
  • Cancer
• Mechanism:
  • Widespread activation of clotting
  • Formation of fibrin “mesh” in vessels

Results in:

• Red cell destruction (MAHA)
• Consumption of clotting factors → bleeding risk

C. Severe Hypertension

• “Malignant hypertension” damages vessel walls
• Leads to:
  • Endothelial injury
  • Narrowed vessels → shear stress

D. Pregnancy-Related / HELLP Syndrome

• Severe form of pre-eclampsia

Features:

• Haemolysis (MAHA)
• Elevated liver enzymes
• Low platelets

Requires urgent obstetric management

E. Infections

• Severe infections (sepsis) can trigger MAHA via DIC
• Certain pathogens directly damage vessels

Includes:

• Bacterial toxins (e.g. E. coli)
• Viral haemorrhagic fevers (e.g. Ebola, Marburg, Hantavirus)

F. Drugs and Medical Treatments

• Chemotherapy agents
• Immunosuppressants (e.g. tacrolimus, ciclosporin)
• Post-transplant complications

G. Malignancy

• Advanced cancers may:
  • Release pro-coagulant substances
  • Cause microvascular obstruction

5. Risk Factors

• Severe infection or sepsis
• Pregnancy (especially pre-eclampsia)
• Uncontrolled hypertension
• Cancer
• Recent transplant
• Use of certain drugs (chemotherapy, immunosuppressants)
• Genetic or autoimmune predisposition (e.g. TTP)

6. Symptoms

Symptoms relate to anaemia, thrombocytopenia, and organ damage:

General

• Fatigue
• Weakness
• Shortness of breath

Haemolysis-related

• Jaundice (yellowing of skin/eyes)
• Dark urine

Low platelets

• Easy bruising
• Petechiae
• Bleeding

Organ involvement

• Confusion, strokes, or other neurological symptoms (especially TTP)
• Reduced urine output (acute kidney injury (AKI), especially HUS)
• Fever (often in infection-related cases)

7. Diagnosis

Blood tests

• Anaemia (low haemoglobin)
• Thrombocytopenia (low platelets)

Key diagnostic features

• Blood film: schistocytes (fragmented red cells)
• Elevated:
  • LDH (cell breakdown marker)
  • Indirect bilirubin
• Reduced haptoglobin

Additional tests (depending on suspected cause)

• ADAMTS13 activity (TTP)
• Coagulation profile (DIC)
• Kidney function tests
• Infection screening

8. Treatment

Treatment is urgent and cause-specific.

TTP

• Emergency plasma exchange
• Immunosuppression (e.g. steroids)

HUS

• Supportive care (fluids, dialysis if needed)
• Manage complications

DIC / Sepsis

• Treat underlying infection
• Support coagulation system

Hypertension

• Controlled reduction of blood pressure

Drug-induced

• Stop the offending drug

HELLP / Pregnancy-related

• Stabilisation
• Delivery of the baby is often required

9. When to Worry

MAHA is always medically significant because it signals a potentially life-threatening process.

Seek urgent medical attention if there is:

• Sudden severe fatigue
• Unexplained bruising or bleeding
• Yellowing of skin or eyes
• Reduced urine output
• Confusion or neurological symptoms
• Fever with any of the above

10. Outlook (Prognosis)

• Depends heavily on the underlying cause and speed of treatment
• TTP: fatal if untreated, but survival is high with rapid treatment
• HUS: often good recovery in children, but kidney damage can occur
• DIC: prognosis depends on underlying illness (often severe)