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  1. Article
  2. Source: Campus Sanofi
  3. 4 Jun 2025

Acquired Thrombotic Thrombocytopenic Purpura (aTTP)

Author: Sanofi

Editorial Team

   
About TTP
Diagnosing TTP
Monitoring TTP
Resources

What is TTP?

Thrombotic thrombocytopenic purpura (TTP)—
A rare, life-threatening medical emergency

TTP is a rare, life-threatening thrombotic microangiopathy (TMA). There are approximately 3 cases per million people.1,2
The name thrombotic thrombocytopenic purpura describes the 3 main characteristics of the disease.

Illustration depicting thrombotic processes in blood vessels.

Thrombotic: characterized by the formation of microthrombi (blood clots) within a blood vessel, which clog the vessel and prevent blood circulation.

Thrombocytopenic: a lower-than-normal platelet count due to the consumption of platelets during microthrombi formation, which causes occlusion of microvasculature.

Illustration showing purpura as purple spots on the skin.

Purpura: spots of variable size on the skin or in the mucous membranes, due to small hemorrhages; they can be dark red and as small as a pinhead (petechiae) or purplish and 2 to 3 cm in diameter (ecchymosis).

Types of TTP

Acquired TTP3,4

  • aTTP, also known as immune-mediated thrombotic thrombocytopenic purpura (iTTP)
  • The most common form of TTP; approximately 95% of TTP cases are aTTP
  • Caused by autoantibody inhibition of ADAMTS13 activity.

ADAMTS13=a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13.

Hereditary TTP4,5

  • Also known as congenital TTP, inherited TTP, familial TTP, or Upshaw–Schulman syndrome
  • Very rare form of TTP; mainly detected in children
  • Caused by mutations in the ADAMTS13 gene

Primary aTTP vs secondary aTTP2,6,7

Primary aTTP

  • Primary aTTP refers to acquired autoimmune TTP for which there is no obvious underlying/precipitating cause/disease
  • Primary aTTP accounts for the majority of cases of TTP

Secondary aTTP

  • Secondary aTTP refers to acquired autoimmune TTP for which a defined underlying disorder or trigger can be identified, including connective tissue disease (eg, systemic lupus erythematosus), HIV infection, cytomegalovirus infection, and/or a specific precipitating factor (eg, pregnancy or drugs)
  • Treatment of the underlying disorder and/or removal of the underlying precipitant may be required, as well as standard TTP therapy
     

TTP causes systemic microthrombi and consequent thrombocytopenia, hemolytic anemia, and organ ischemia. These symptoms—coupled with TTP’s rarity—can cause confusion with other TMAs, making TTP a challenge to diagnose.8-10

Signs and symptoms of aTTP include1,7-10

Illustration of human skin with visible layers.

Petechiae, purpura, bruising (skin)

Headache, confusion, seizures, coma (neurological)

EKG abnormalities (cardiac)

Illustration of the human intestine.

Abdominal pain, diarrhea (gastrointestinal)

Proteinuria/hematuria (kidney)

Suspect aTTP?

The incidence of TTP is 2 to 6 per million individuals4

Rare diseases defined as <500 cases per million 11

Ultra-rare diseases defined as <20 cases per million 12

aTTP primarily affects young, healthy adults13,14

content card 1

years of age on average

of people affected are women

higher aTTP incidence in the Black population

If left untreated, TTP is rapidly fatal8,15-17

content card 4

acute mortality rate16,17

of TTP deaths occur within 24 hours of presentation8

Even with plasma exchange therapy (PEX), mortality risk persists15,16,18


Up to 20% acute mortality associated with episodes of aTTP16,18

 

9 days median time from diagnosis to death16,18

in acute phase of TTP in patients treated with PEX15,18

The burden of thrombotic thrombocytopenic purpura (TTP)

Short- and long-term implications threaten patients with aTTP

Short-term implications

Mortality

  • Untreated, aTTP has an acute mortality rate of up to 90%1-3
  • Approximately 55% to 80% of deaths among patients with aTTP occur within 2 weeks of diagnosis4-6
  • Significantly higher rates of in-hospital mortality have also been reported in patients with TTP and CV complications(19.7% vs 4.1%)7

Health-related quality of life

  • Rates of depression (10% to 73%) are considerably higher in patients following an episode of TTP, compared with both healthy individuals and reference populations8-12

Morbidity

  • Most common complications in patients hospitalized with TTP are CV complications (25%), such as stroke (10%), heart failure (8%), and acute coronary syndrome (6%)7

Economic burden

  • Short-term treatment of acute thromboembolism such as stroke, acute MI, or TIA requires multiple healthcare resources, including hospitalization with diagnostic tests (eg, CT scans), administration of thrombolytic and/or other drugs, admittance to intensive care/critical care unit, and/or ongoing specialist nursing care (eg, physiotherapy, speech therapy)13-15

An increased time at risk of microvascular thrombosis can lead to irreversible organ damage to the heart, brain, and kidneys16

Long-term implications

Mortality

  • 23-fold increase in mortality was observed in patients who did not reach a platelet recovery rate of 5 × 109/L per day by day 3 of PEX17
  • Inability to normalize platelet count over 7 days of PEX was associated with a significantly increased risk of death18

Health-related quality of life

  • Long-term outcomes are driven by the consequences of platelet aggregation, leading to systemic microvascular thrombosis7,19

Morbidity

  • Recovery following an acute episode of aTTP is not a resolution of symptoms but the beginning of a long-term morbidity burden: hypertension, stroke, and depression requiring pharmacological treatment were significantly greater for TTP survivors versus the age- and sex-matched US population8,9,20

Economic burden

  • Other long-term consequences that have been reported include neurocognitive impairment, depression, hypertension, headaches, and SLE; all require healthcare resources on an ongoing basis11,20

Long-term morbidity leads to suboptimal health-related quality of life, in both mental (anxiety, depression) and physical functioning, and potentially reduces life expectancy8-20

aTTP=acquired thrombotic thrombocytopenic purpura; CT=computed tomography; CV=cardiovascular; MI=myocardial infarction; PEX=plasma exchange; SLE=systemic lupus erythematosus; TIA=transient ischemic attack; TTP=thrombotic thrombocytopenic purpura.

The pathophysiology of thrombotic thrombocytopenic purpura (TTP)

TTP is characterized by potentially fatal systemic microthrombi1,2

TTP is caused by severely decreased activity of the ADAMTS13 enzyme. ADAMTS13 is the protease that cleaves von Willebrand factor (vWF). In patients with acquired TTP (aTTP), this deficiency is immune mediated.1

Decreased ADAMTS13 activity leads to an accumulation of ultra-large von Willebrand factor (ULvWF) multimers, which spontaneously bind to platelets and induce aggregation. This results in dangerous microthrombi that drive severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia.2

ADAMTS13=a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13.

TTP pathophysiology

An in-depth exploration of the causes of TTP and the severe consequences of the disease.

What is the pathophysiology of aTTP?

3 key mechanisms drive the pathophysiology of aTTP2

antibody

Auto antibody formation

Autoantibodies to ADAMTS13 inhibit its activity or enhance clearance of the enzyme

ADAMTS13 deficiency causes uncleaved ULvWF

ADAMTS13 (the enzyme responsible for cleaving vWF in the blood-clotting process) is deficient, leaving platelet-hyperadhesive ULvWF strands intact to circulate without being cleaved.

antibody

Microthrombi formation

ULvWF accumulates and spontaneously binds to platelets, forming microthrombi.

Normal physiology2,3

brochure

Thrombotic thrombocytopenic purpura2,3

brochure 1

Adapted from Joly B et al. Blood 2017 and Saad J & Schoenberger L 2018.

Formation of microthrombi causes2

thrombocytopenia

Severe thrombocytopenia

(often platelets <30 × 109/L)

Microangiopathic hemolytic anemia (MAHA)

characterized by the presence of schistocytes in blood smear

Organ ischemia

(lesions can occur in any organ, but they most frequently affect the heart, brain, gastrointestinal tract, and kidney)

Platelet aggregation leads to microthrombi formation, which can have fatal consequences.1,2

Signs and symptoms of aTTP

The symptoms of aTTP are driven by microthrombi, which are unpredictable and potentially fatal1,2

Microthrombi can have serious acute and chronic consequences in TTP—putting patients at risk for devastating effects and death without urgent treatment.

See the ISTH Guidelines

Microthrombi can occur in any organ with microvessels, but the most commonly affected are3

infographic

Tissue and organ damage resulting from ischemia leads to increased levels of lactate dehydrogenase (LDH), troponins (heart), and creatinine (kidney).¹,⁴

Expert Opinion About aTTP

Signs and symptoms of acquired thrombotic thrombocytopenic purpura (aTTP) include1,4,5

Illustration of human skin with visible layers.

Petechiae, purpura, bruising (skin)

Headache, confusion, seizures, coma (neurological)

EKG abnormalities (cardiac)

Illustration of the human intestine.

Abdominal pain, diarrhea (gastrointestinal)

Proteinuria/hematuria (kidney)

 of TTP episodes result in ischemia due to platelet aggregation in the microcirculation of the brain.3

The consequences of microthrombi can be severe, with TTP potentially resulting in acute thromboembolic events such as1,2,4

brain

Stroke

Myocardial infarction

Arterial thrombosis

Early death

Consequences can also be long term

See how

Identifying thrombotic thrombocytopenic purpura (TTP) among thrombotic microangiopathies (TMAs)

TMAs require urgent management, but variable presentation can make them difficult to distinguish1,2

TMA is a pathologic term used to describe occlusive microvascular or macrovascular disease, often with intraluminal thrombus formation.3 Presentation of TMAs varies widely, including but not limited to stroke, neurologic complications, severe renal failure, flu-like symptoms, and simple fatigue.4,5
This leads to the involvement of several physician specialists at the outset of patient care in clinic and hospital settings. Both—the variability of TMAs and the involvement of many specialties—pose a challenge to prompt recognition and diagnosis of TTP.4,5

Your role is crucial to the diagnosis and speed of appropriate treatment for TMAs6

In most cases, patients present at the emergency department for a nonspecific somatic complaint, and thrombocytopenia is subsequently discovered. More rarely, the results of a CBC can reveal thrombocytopenia during an appointment in a non-hospital setting.6

It is critical to suspect TMA when you see7,8:

thrombocytopenia

Thrombocytopenia

(often platelets <30 × 109/L)

Microangiopathic hemolytic anemia (MAHA)

characterized by the presence of schistocytes in blood smear

Organ failure

of varying severity

Thrombocytopenia associated with MAHA should suggest a TMA syndrome, even in the absence of organ failure.9

Important TMA lab markers6,10,11

Biological report sheet

Blood count

• Thrombocytopenia

 

• Hemolytic anemia

 

Reticulocyte count

High (>120 g/L)*

 

Hemoglobin

Low

 

Schistocytes on blood smear

Present†

A hallmark of TTP, but absence
does not rule out a diagnosis

Coombs test

Negative‡

 

Hemolysis evaluation

• Hyperbilirubinemia

 

• Haptoglobin low, even undetectable

 

 • High LDH rate§

While not diagnostic, elevated LDH
may predict organ damage

Hemostasis assessment

• Most often normal

 

• D-dimer rate may be moderately elevated

 

See all important TTP lab markers

Understanding the types of TMAs can change how you treat the patient1,12

TMAs are classified into 2 types: primary and secondary. Primary TMAs have no clear underlying cause, while secondary TMAs may be caused by a number of clinical conditions. Recognizing the underlying cause, or lack thereof, can determine treatment course.1,12

Types of TMAs1,12

Primary TMAs

  • TTP (acquired/immune-mediated and hereditary)
  • HUS (atypical/complement-mediated and Shiga toxin–producing E coli)

Secondary TMAs

  • Systemic lupus erythematosus
  • Pregnancy-associated (eg, hemolysis, elevated liver enzymes, low platelet count [HELLP] syndrome)
  • Hematopoietic progenitor cell transplantation
  • Drug-induced

The 2 primary TMAs—TTP and HUS—are often confused, but differentiating them is critical to determining appropriate treatment1,2

Historically, TTP and hemolytic uremic syndrome (HUS) were classified based on clinical findings: TTP for predominant neurologic involvement and HUS for the kidney-dominant diseases.1,13 With recent understanding of the molecular basis of TMAs, definitions have changed.1,7,8,11,13

TTP is now defined as
ADAMTS13 deficiency

(<10%)

vsHUS may be caused by Shiga toxin-producing E coli (STEC-HUS)
OR
genetic mutations in complement regulatory proteins (atypical or complement mediated HUS)

Differentiation of TTP from HUS can be confounded by kidney involvement in TTP. 25% of patients with TTP had kidney injury in the Oklahoma TTP Registry.5,14,15

Variable presentation of TMAs, potential confusion with HUS, and lack of diagnostic protocols can result in a missed or delayed diagnosis of aTTP2,16

20 %

of patients with aTTP were misdiagnosed 16
According to a retrospective review of the French Reference Centre for TMA registry (N=423).

This number may be underestimated due to the study being unable to exclude the possibility that some misdiagnosed patients may have died before their TTP diagnosis was made.16

The consequences of delayed diagnosis and treatment of TTP can be devastating, including organ failure or even death.7,11,15-17

aTTP=acquired thrombotic thrombocytopenic purpura; CBC=complete blood count; E coli=Escherichia coli; LDH=lactate dehydrogenase.
*Emphasizes the regenerative nature of anemia.
†Nonsystematic presence of schistocytes, possibly late onset, hence the importance of repeating this test several times to increase the sensitivity of the examination.16
‡Test may turn out to be slightly positive in an autoimmune environment.16 §Related to hemolysis and organ tissue damage.6

How to diagnose thrombotic thrombocytopenic purpura (TTP)

Diagnosing TTP rapidly is critical and can save a life1

When a patient presents with2

thrombocytopenia

Severe thrombocytopenia

(often platelets <30 × 109/L).

Microangiopathic hemolytic anemia (MAHA)

characterized by the presence of schistocytes in blood smear

With no identified cause

The risk of death is acute and imminent if TTP remains undiagnosed and untreated1,3,4

of untreated patients1,3,4

of the acute event if untreated1

Why TTP can be difficult to diagnose

TTP is rare and presents similarly to other thrombotic microangiopathies (TMAs), making it a challenge to diagnose. All TMAs result in thrombosis of capillaries and arterioles due to endothelial injury.5,6
A delay in diagnosing TTP can leave patients at risk for organ damage and death. The uncertainty around what’s happening to these patients can cause fear and frustration.5,7-9

It's critical to differentiate TTP from other TMAs quickly so patients can get started on appropriate treatment

Diagnosing TTP in adults: Step-by-step1,7,10-15

Presentation

Neurological symptoms

Headache and/or confusion and/or seizures and/or other cerebral abnormalities

Gastrointestinal symptoms

Abdominal pain, nausea, and diarrhea

Cardiac symptoms

Chest pain and/or hypotension and/or myocardial infarction and/or congestive heart failure and/or sudden cardiac arrest and/or other cardiac abnormalitiesChest pain and/or hypotension and/or myocardial infarction and/or congestive heart failure and/or sudden cardiac arrest and/or other cardiac abnormalities

Renal impairment

Hematuria and proteinuria; creatinine <2 mg/dL; typically not severe

1/4

Neurological symptoms

Headache and/or confusion and/or seizures and/or other cerebral abnormalities

Gastrointestinal symptoms

Abdominal pain, nausea, and diarrhea

Cardiac symptoms

Chest pain and/or hypotension and/or myocardial infarction and/or congestive heart failure and/or sudden cardiac arrest and/or other cardiac abnormalitiesChest pain and/or hypotension and/or myocardial infarction and/or congestive heart failure and/or sudden cardiac arrest and/or other cardiac abnormalities

Renal impairment

Hematuria and proteinuria; creatinine <2 mg/dL; typically not severe

1/2

Diagnosing aTTP?

Learn about scoring systems

Important TTP lab markers

The presence of schistocytes on the blood smear is the morphologic hallmark of the disease, but the absence of schistocytes does not rule out TTP.2,16

Although serum creatinine is typically <2.0 mg/dL at presentation, the Oklahoma TTP-HUS Registry reported kidney injury 25% of the time.2,15

While not diagnostic, elevated LDH may be predictive of severe organ damage, and elevated troponin may indicate cardiovascular risk.1,2

ADAMTS13 activity <10% confirms a TTP diagnosis and supports TTP treatment, but ADAMTS13 levels of 10% to 20% do not rule out TTP. TTP management will rely on clinical judgment.2,7,13

ADAMTS13 <10% confirms TTP. Test as soon as possible when TMA is suspected.2,7,13


LDH=lactose dehydrogenase; MAHA=microangiopathic hemolytic anemia; TMA=thrombotic microangiopathy; TTP=thrombotic thrombocytopenic purpura.

Guidelines for diagnosing and treating thrombotic thrombocytopenic purpura (TTP)

The International Society on Thrombosis and Haemostasis (ISTH) published guidelines are the first comprehensive, evidence-based, international guidelines on the diagnosis, treatment, and management of TTP.1

See the ISTH Guidelines

Most recent publication

The ISTH Guidelines for Diagnosis and Treatment were published July 2020.

About ISTH

With more than 5000 members across 100 countries, the ISTH is the leading thrombosis and hemostasis–related professional organization in the world.2

Why the ISTH Guidelines were developed

Diagnosing and treating TTP can be complicated.1

  • The rarity of TTP—and its similar presentation to other TMAs—can make recognition a challenge  
  • Management of TTP varies among healthcare professionals (HCPs)
  • Treatment recommendations in TTP have evolved

ISTH created the guidelines as a comprehensive, uniform, international resource to inform the diagnosis and management of TTP1

The ISTH Guidelines can aid HCPs—both those with limited experience with TTP and those considered experts in TTP—in making a TTP diagnosis and following an appropriate treatment strategy.

These include1

  • Emergency/critical care physicians
  • Hematologists
  • Nephrologists
  • Neurologists
  • Transfusion medicine specialists
  • Hospitalists
  • Policy makers

The ISTH has created the first evidence-based guidelines to support rapid TTP diagnosis and treatment.

The prognosis of thrombotic thrombocytopenic purpura (TTP) can be unpredictable1,2

Patients can experience refractory disease or recurrence of their TTP (exacerbation or relapse), highlighting the need for vigilant monitoring3,4

The risks and effects of TTP extend beyond the first acute events that patients experience.5-7

Here are some of the various ways TTP can affect your patients after diagnosis and treatment.

TTP episode

Even with plasma exchange therapy (PEX), mortality risk persists8-10

acute mortality associated with episodes of aTTP9,10

Refractory TTP

Occurs when patients do not have a clinical response after 5 sessions of PEX. Clinical response is defined as sustained platelet count ≥150 × 109/L and LDH <1.5 times ULN and no clinical evidence of new or progressive organ injury.4

Refractory TTP can indicate poor prognosis for survival3

of aTTP patients experience unpredictable refractoriness

TTP exacerbation

A platelet count decrease after a clinical response and before a clinical remission. A clinical exacerbation is defined as platelet count decrease to <150 × 109/L (with other causes of thrombocytopenia excluded), with or without clinical evidence of new or progressive ischemic organ injury, within 30 days of stopping plasma exchange or anti-vWF therapy.4

TTP exacerbation is a threat to patient recovery

of patients have ≥1 TTP episode within 30 days of stopping plasma exchange*
*Retrospective review of French Reference Centre for TMA registry (N=388).

TTP relapse

A new episode of TTP after achieving clinical remission.† A clinical relapse is defined as platelet count decrease to <150 × 109/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury and a confirmed documentation of severe ADAMTS13 deficiency.4

ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13.

†Clinical remission is defined as sustained clinical response with no plasma exchange and no anti-vWF therapy for ≥30 days or attainment of ADAMTS13 remission.

TTP exacerbation is a threat to patient recovery11

reported relapse rate in studies of TTP7

Monitor patients closely. Make them aware of the potential for recurrence (exacerbation or relapse) and educate on symptoms and triggers so they know to reach out immediately.


ULN = upper limit of normal.

The long-term impact of thrombotic thrombocytopenic purpura (TTP)

Patients can experience the effects of TTP long after their first episodes

The consequences of TTP can lead to many long-term complications and health risks. Approaching TTP with a long-term mindset can help ensure comprehensive care for your patients.1-3

Microthrombi may result in long-term neurocognitive decline in patients with TTP1

63% of patients with TTP have neurological signs and symptoms during their first event, including2-4

  • Coma
  • Focal neurological signs
  • Seizures
  • Stroke
  • Seizures
  • Stroke

In these patients, studies have shown4

Persistent neurological impairment during remission (49%)

  • Disorientation
  • Loss of concentration
  • Dizziness
  • Lack of balance
  • Headache
  • Diplopia

Significant impairment in memory domains

(direct, backward, and deferred memory) vs the general population

Higher prevalence of relapse in TTP

vs those without neurological symptoms (41% vs 8%)

Patients with TTP may have increased risk of stroke after recovery5

Stroke during the median observation follow-up period (3.08 years) after recovery from TTP occurred in 13.1% of patients, which is five-fold higher than the expected prevalence from an age- and sex-matched reference population.

Stroke risk is common after recovery from TTP and is associated with ADAMTS13 levels

Low ADAMTS13 activity after recovery from an acute episode is associated with an increased risk of
ischemic stroke during the follow-up period (P=0.007).

0 %

of patients with >70% ADAMTS13 levels experienced stroke (0/22)

27.6 %

of patients with >70% ADAMTS13 levels experienced stroke (0/22)

Patients with TTP reported decreased quality of life1,4

TTP affects patients’ quality of life over the long term, owing to exacerbations, relapses, and sustained neurocognitive defects. Patients’ responses across health-related quality of life measures suggest that living with TTP is a considerable emotional burden.

Clinical anxiety and depression are serious risks for patients with TTP4

40 %

of patients with >70% ADAMTS13 levels experienced stroke (0/22)

20 %

of patients with >70% ADAMTS13 levels experienced stroke (0/22)

It’s important to monitor the physical and mental health of your patients with TTP.1,4,5

TTP resources for you

The International Society on Thrombosis and Haemostasis (ISTH) TTP Guideline

The ISTH TTP Guidelines are the first evidence-based, international guidelines on the diagnosis, treatment, and management of TTP. The guidelines emphasize the importance of diagnosis through clinical assessment or risk assessment tools, such as the French or PLASMIC score. Clinical assessment can help predict the likelihood of severe ADAMTS13 deficiency in a patient with suspected TTP and guide treatment decisions.1

Inform your approach to thrombotic thrombocytopenic purpura (TTP) treatment by understanding key clinical considerations and therapeutic options.

See the ISTH Guidelines

Expert Opinion About aTTP

MAT-AE-2200643-V1-Nov-22  

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