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Thrombotic Thrombocytopenic Purpura (TTP)

Thrombotic Thrombocytopenic Purpura (TTP) is a life-threatening thrombotic microangiopathy caused by severe deficiency of ADAMTS13, leading to accumulation of unusually large von Willebrand factor multimers and widespread platelet-rich microthrombi

Also called

Moschcowitz Syndrome

ICD-10

M31.1

Specialty

Hematology

Onset

Acute

Reviewed

August 2026

On This Page

Overview

Thrombotic Thrombocytopenic Purpura (TTP) causes widespread formation of platelet-rich microthrombi in small blood vessels. This consumes platelets and mechanically fragments red blood cells, causing thrombocytopenia and microangiopathic hemolytic anemia. The microthrombi can also cause neurological, renal, gastrointestinal, and cardiac complications

Etiology & Risk Factors

–Thrombotic Thrombocytopenic Purpura (TTP) results from severe deficiency of the ADAMTS13 enzyme, which normally cleaves large von Willebrand factor multimers.

Acquired Thrombotic Thrombocytopenic Purpura (TTP) Usually caused by:

  • Autoantibodies against ADAMTS13

Congenital Thrombotic Thrombocytopenic Purpura (TTP)

Caused by:

  • Inherited mutations in the ADAMTS13 gene

-Risk Factors / Triggers

  • Pregnancy
  • Autoimmune disease
  • Infection
  • Certain medications
  • Malignancy
  • Transplantation
  • Some cases occur without an identifiable trigger

Pathophysiology

Severe ADAMTS13 deficiency → impaired cleavage of ultra-large von Willebrand factor multimers → excessive platelet adhesion and aggregation in small vessels → platelet-rich microthrombi → platelet consumption → thrombocytopenia → mechanical fragmentation of red blood cells passing through partially occluded vessels → schistocyte formation and microangiopathic hemolytic anemia → tissue ischemia and organ dysfunction

Clinical Presentation

Symptoms

  • Fatigue

  • Weakness

  • Headache

  • Confusion

  • Fever

  • Abdominal pain

  • Nausea

  • Vomiting

  • Dark urine

  • Reduced urine output

  • Chest pain

  • Shortness of breath

Signs

  • Petechiae

  • Purpura

  • Pallor

  • Jaundice

  • Fever

  • Neurological abnormalities

  • Renal impairment

-Classic Pentad

Historically described as:

  1. Thrombocytopenia

  2. Microangiopathic hemolytic anemia

  3. Neurological abnormalities

  4. Renal dysfunction

  5. Fever

The complete pentad is uncommon, and treatment should not wait for all five features.

History Taking

-Ask about:

  • Fatigue
  • Headache
  • Confusion
  • Seizures
  • Visual symptoms
  • Fever
  • Bleeding or bruising
  • Abdominal pain
  • Dark urine
  • Reduced urine output
  • Chest pain
  • Pregnancy
  • Autoimmune disease
  • Recent infection
  • Recent medications
  • Previous episodes of Thrombotic Thrombocytopenic Purpura (TTP)

Physical Examination

-General Examination

Look for:

  • Pallor

  • Jaundice

  • Petechiae

  • Purpura

  • Fever

-Neurological Examination

Assess for:

  • Confusion

  • Reduced consciousness

  • Focal neurological deficits

  • Seizures

  • Headache

-Cardiovascular Examination

Look for:

  • Tachycardia

  • Signs of myocardial ischemia

  • Heart failure

-Abdominal Examination

Assess for:

  • Abdominal tenderness

  • Hepatomegaly

  • Splenomegaly

Investigations

-Complete Blood Count

Typical findings:

  • Severe thrombocytopenia

  • Anemia

-Peripheral Blood Film

Characteristic findings:

  • Schistocytes

  • Polychromasia

  • Anisocytosis

-Hemolysis Screen

Typical findings:

  • ↑ LDH

  • ↑ Indirect bilirubin

  • ↓ Haptoglobin

  • ↑ Reticulocyte count

  • Hemoglobinuria may occur

Direct Antiglobulin Test

  • Usually negative

-ADAMTS13 Activity

  • Severely reduced ADAMTS13 activity, typically <10%, strongly supports Thrombotic Thrombocytopenic Purpura (TTP).

ADAMTS13 inhibitor testing can help identify acquired autoimmune disease.

-PLASMIC Score

The PLASMIC score can help estimate the probability of severe ADAMTS13 deficiency while awaiting definitive testing.

-Renal Function

Check:

  • Urea

  • Creatinine

  • Electrolytes

  • Urinalysis

-Renal impairment can occur but is often less severe than in hemolytic uremic syndrome.

-Coagulation Profile

Usually:

  • PT: normal

  • aPTT: normal

  • Fibrinogen: normal

This helps distinguish Thrombotic Thrombocytopenic Purpura (TTP) from disseminated intravascular coagulation.

-Cardiac Assessment

If clinically indicated:

  • ECG

  • Troponin

  • Echocardiography

Diagnosis

Diagnosis is based on:

  • Thrombocytopenia
  • Microangiopathic hemolytic anemia
  • Schistocytes
  • Elevated LDH
  • Low haptoglobin
  • Usually normal coagulation studies
  • Severe ADAMTS13 deficiency

ADAMTS13 activity <10% strongly supports the diagnosis.

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Management

Emergency Management

Start treatment immediately when Thrombotic Thrombocytopenic Purpura (TTP) is strongly suspected.

1. Plasma Exchange

Urgent therapeutic plasma exchange (TPE) is the cornerstone of treatment.

It:

  • Removes circulating ADAMTS13 autoantibodies

  • Replaces deficient ADAMTS13

  • Removes ultra-large von Willebrand factor multimers

2. Corticosteroids

Used to suppress the autoimmune process in acquired Thrombotic Thrombocytopenic Purpura (TTP).

3. Caplacizumab

A targeted therapy that inhibits the interaction between von Willebrand factor and platelets.

It is used with plasma exchange and immunosuppression in appropriate patients with acquired Thrombotic Thrombocytopenic Purpura (TTP).

4. Rituximab

An anti-CD20 monoclonal antibody used particularly for:

  • Severe or persistent disease

  • Relapsed disease

  • Prevention of relapse in selected patients

-Congenital Thrombotic Thrombocytopenic Purpura

Treatment may involve:

  • Plasma infusion

  • Recombinant ADAMTS13 replacement where available

-Supportive Care

  • Red blood cell transfusion when necessary

  • Avoid platelet transfusion unless there is serious bleeding or an urgent invasive procedure

  • Treat seizures

  • Manage renal dysfunction

  • Monitor cardiac and neurological complications

Complications

  • Stroke
  • Seizures
  • Renal impairment
  • Myocardial ischemia
  • Cardiac failure
  • Severe anemia
  • Organ ischemia
  • Relapse
  • Death if untreated

Prognosis

Untreated Thrombotic Thrombocytopenic Purpura (TTP) has a very high mortality rate. With rapid plasma exchange and modern therapies, survival has improved dramatically. Relapses can occur, particularly in acquired disease, so long-term monitoring is important.

Key Points / Clinical Pearls

  • Thrombotic Thrombocytopenic Purpura (TTP) is a medical emergency.
  • It is caused by severe ADAMTS13 deficiency.
  • The classic laboratory combination is thrombocytopenia + microangiopathic hemolytic anemia + schistocytes.
  • ADAMTS13 activity is typically <10%.
  • Coagulation studies are usually normal.
  • Urgent plasma exchange is the cornerstone of treatment.
  • Corticosteroids are used in acquired disease.
  • Caplacizumab rapidly inhibits platelet-von Willebrand factor interaction.
  • Rituximab may be used for persistent or relapsing disease.
  • Do not wait for ADAMTS13 results before starting treatment when clinical suspicion is high.
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  • MedlinePlus, National Library of Medicine (NIH). Thrombotic Thrombocytopenic Purpura: Medical Encyclopedia.