Thrombotic microangiopathy (TMA) is a pathological condition characterized by thrombocytopenia, microangiopathic haemolytic anaemia, and injury to multiple organs due to small-vessel thrombus formation.

The kidney is commonly affected because of extensive glomerular circulation involvement, resulting in acute kidney injury (AKI). Early recognition and treatment are essential because untreated TMA can rapidly progress to severe organ dysfunction and death.

Major primary thrombotic microangiopathies include:

• Thrombotic thrombocytopenic purpura (TTP)

• Complement-mediated atypical haemolytic uraemic syndrome (aHUS)

Epidemiology

TMA is an uncommon but potentially life-threatening disorder. It may occur as a primary disease caused by genetic or autoimmune abnormalities or as a secondary complication of other conditions.

The incidence varies depending on the underlying cause. TTP is rare but represents a medical emergency requiring urgent treatment.

Risk factors

Risk factors include:

• Autoimmune diseases

• Systemic lupus erythematosus

• Malignant hypertension

• Pregnancy-related disorders

• Certain medications

• Infections

• Malignancies

• Transplantation

• Complement pathway abnormalities

Pathophysiology

TMA develops due to endothelial injury and formation of platelet-rich microvascular thrombi.

This causes:

• Reduced blood flow through small vessels

• Mechanical destruction of red blood cells

• Platelet consumption

• Tissue ischemia

In the kidney, microvascular obstruction damages glomerular capillaries, causing:

• Reduced filtration

• Proteinuria

• Haematuria

• Acute kidney injury

Clinical presentation

Patients may present with:

Haematological manifestations

• Haemolysis

• Anaemia

• Thrombocytopenia

Kidney manifestations

• Acute kidney injury

• Reduced urine output

• Increased serum creatinine

Other organ manifestations

• Pancreatitis

• Hepatitis

• Seizures

• Confusion or neurological symptoms

• Diarrhoea, vomiting, and abdominal pain

• Digital gangrene

Diagnostic criteria

TMA is suspected when there is:

• Thrombocytopenia

• Evidence of microangiopathic haemolytic anaemia

• Evidence of organ injury, especially kidney involvement

Differential diagnosis

Conditions that should be considered include:

1. Thrombotic thrombocytopenic purpura (TTP)

2. Atypical haemolytic uraemic syndrome (aHUS)

3. Disseminated intravascular coagulation (DIC)

4. Severe malignant hypertension

5. Systemic lupus erythematosus-associated nephritis

6. Acute kidney graft rejection

7. Drug-induced microangiopathy

8. Severe infections causing sepsis-associated organ injury

Investigations

Recommended investigations include:

• ADAMTS13 activity testing

  • Activity greater than 10% makes TTP less likely

• Complete blood count

• Peripheral blood smear

• Kidney function tests

• Kidney biopsy where indicated

• HIV serology

• Bacterial cultures and serological testing where infection is suspected

• ANA

• Anti-double stranded DNA antibodies

• Antiphospholipid antibodies

• Anti-Scl70 antibodies

Management

Management aims to:

• Identify and treat the underlying cause

• Prevent irreversible organ damage

• Correct the underlying microvascular process

Non-pharmacological treatment

Measures include:

• Close monitoring in a high-dependency or intensive care setting when severe

• Supportive management of kidney failure

• Management of complications such as fluid overload and electrolyte abnormalities

• Dialysis when indicated

Pharmacological treatment

Treatment depends on the cause.

Primary thrombotic microangiopathies

Thrombotic thrombocytopenic purpura

Plasma exchange should be initiated urgently while awaiting confirmation of ADAMTS13 results.

Plasma exchange should continue until TTP is excluded or clinical improvement occurs.

Immunosuppressive therapy may be required depending on specialist assessment.

Complement-mediated atypical haemolytic uraemic syndrome

Management requires specialist-directed therapy targeting complement activation pathways.

Referral

Urgent referral is required for:

• Suspected TTP

• Severe thrombocytopenia

• Acute kidney injury

• Neurological symptoms

• Rapid clinical deterioration

• Need for plasma exchange

Complications

Potential complications include:

• Acute kidney injury

• End-stage kidney disease

• Stroke

• Seizures

• Multi-organ failure

• Death

Prognosis

The outcome depends on:

• Speed of diagnosis

• Underlying cause

• Time to initiation of treatment

• Degree of kidney and other organ involvement

Early recognition and prompt plasma exchange in TTP significantly improve survival.

Prevention

Preventive strategies include:

• Early diagnosis of underlying diseases

• Monitoring high-risk patients

• Avoidance of causative medications where possible

• Regular follow-up after transplantation

• Prompt treatment of infections and autoimmune disorders