Thrombotic Thrombocytopenic Purpura

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare and life-threatening thrombotic microangiopathy (TMA) characterized by thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and microvascular thrombosis leading to end-organ damage.1-3

cTTP results from genetic mutations of the ADAMTS13 enzyme responsible for regulating the activity of von Willebrand factor (VWF) by cleaving large and ultra-large VWF multimers into smaller subunits.1 Patients with cTTP have a severe deficiency in the ADAMTS13 enzyme which leads to increased large and ultra-large VWF multimers in the circulation causing platelet accumulation and microthrombi formation which occlude small blood vessels.1,3

Congenital thrombotic thrombocytopenic purpura illustration


Incidence/prevalence: Approximately 0.5 to 2 cases per million people.1

Population and distribution: cTTP affects men and women equally, with half of patients presenting with first episode by 2-5 years of age, and half presenting in early adulthood (often during pregnancy).4


Thrombotic thrombocytopenic purpura (TTP) can be congenital (cTTP, also referred to as hereditary TTP) or immune-mediated (iTTP, also referred to as acquired TTP).4

cTTP comprises <5% of all TTP cases, while iTTP accounts for the remaining ~95% of all TTP cases.4,5

cTTP is caused by mutations in ADAMTS13 gene, resulting in a severe ADAMTS13 deficiency (activity <10% of normal).4,6 There are more than 200 genetic mutations that have been linked to cTTP.3 Most of these mutations are compound heterozygous, and only 15 homozygous mutations have been described.7 Mutations either reduce secretion of ADAMTS13 or impair its catalytic activity resulting in a deficiency of ADAMTS13. This causes ultra large VWF multimers to remain uncleaved in the bloodstream which adhere to platelets and aggregate in the microcirculation, forming platelet-rich microthrombi.8 This can lead to acute TTP events that cause consumptive thrombocytopenia, fragmentation of circulating erythrocytes or MAHA, and eventually irreversible organ damage due to local ischemia (especially in the brain, heart, and kidneys).1,4

iTTP is an autoimmune disorder caused by auto-antibodies against endogenous ADAMTS13.4


When a TMA is suspected, platelet count, creatinine levels, and peripheral blood smear should be assessed.4 If platelet count is <30 × 109 cells/L, creatinine level <2.25 mg/dL, and schistocytes are present in peripheral blood smear, then TTP is suspected. ADAMTS13 activity assay can confirm TTP if it indicates <10% of normal ADAMTS13 activity. To differentiate between iTTP and cTTP, an anti-ADAMTS13 IgG assay is carried out, and if negative, then cTTP is suspected. cTTP can be confirmed by genetic sequence analysis.

Navigating cTTP

Long-term morbidity:
cTTP can affect many organs and systems, and can cause neurologic symptoms (like confusion, headache, focal neurological deficits, paresis, speech impairment, visual changes, encephalopathy, coma, and depression), cardiovascular symptoms (like chest pain, heart failure, hypotension, and stroke/transient ischemic attack), gastrointestinal symptoms (like abdominal pain), and/or renal symptoms (like proteinuria and microhematuria), in addition to fever and purpura, which appears as purplish bruises or pinpoint-sized dots on skin or mucous membranes.4,9

TTP manifests as acute events with short- and long-term outcomes and is associated with a significant disease burden.4,5 Quality of life and lifespan are significantly reduced compared to the general population due to serious, ongoing widespread organ damage and other comorbidities resulting from an ADAMTS13-deficient state.

Patients’ quality of life also suffers due to the treatment burden and complications.10

cTTP is associated with a 90% mortality rate if left untreated and even with treatment, the mortality rate remains high (5-16%) especially during acute episodes.9,11

Medication Resources


(ADAMTS13, recombinant-krhn)

Upcoming & Past Conferences in Hematology

  • Upcoming

  • Past

Thrombosis and Hemostasis Societies of North America (THSNA), 2024

April 4 - 6, 2024

A summit of 10 of the leading non-profit organizations in hemostasis and thrombosis, providing expertise and insight on improving patient care.

American Society of Hematology (ASH), 2023

December 9 - 12, 2023

The premier global congress from the world's largest professional society serving both clinicians and scientists working in malignant and classical hematology.

Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] & Advate® [Antihemophilic Factor (Recombinant)]

  • Clinical Outcomes of Noninhibitor Patients with Hemophilia A Switching from Prophylaxis with Factor VIII to Emicizumab: a Meta-analysis of Real-world Evidence Studies
  • Identifying Ideal Individuals for PK-guided Dosing: Recreational Risks and Elevated Breakthrough Bleeding

Vonvendi® [von Willebrand factor (recombinant)]

  • Real-world Use of Recombinant Von Willebrand Factor in People with Clinically Severe Congenital Von Willebrand Disease: Interim Analysis of ATHN 9, A Natural History Study for People with Severe VWD

American Thrombosis and Hemostasis Network Data Summit (ATHN Data Summit), 2023

October 19 - 20, 2023

Annual meeting discussing important research areas of hemophilia, health equity, thrombosis, Von Willebrand disease, rare blood disorders, and data management.

Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] & Advate® [Antihemophilic Factor (Recombinant)]

  • Risk of Intracranial Hemorrhage in US Patients With Hemophilia A: Real-World Retrospective Cohort Study Using the ATHNdataset

Academy of Managed Care Pharmacy Nexus (AMCP Nexus), 2023

October 16 - 19, 2023

Annual event with more than 2,500 members and non-members of the AMCP to engage on the latest innovations and most intentional networking in managed care pharmacy.

Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] & Advate® [Antihemophilic Factor (Recombinant)]

  • Cost Outcomes of Noninhibitor Patients With Hemophilia A Switching From Prophylaxis With Factor VIII to Emicizumab: a Meta-analysis of Real-world Evidence Studies in the United States

International Society on Thrombosis and Haemostasis (ISTH), 2023

June 24 - 28, 2023

Global congress featuring the world’s leading experts on thrombosis, hemostasis and vascular biology presenting the most recent advances, the latest science, and the newest clinical applications designed to improve patient care.

European Hematology Association (EHA), 2023

June 8 - 15, 2023

An immersive hematology event discussing cutting-edge approaches to diagnosis and treatment, including clinical and translational research, for medical professionals, national hematology societies, patient groups, medical industry and media worldwide.



Listen to podcasts focused on Congenital Thrombotic Thrombocytopenic Purpura (cTTP).


Miesbach-Disease Pathogenesis (Role of ADAMTS13)

Learn about the pathophysiology of Congenital Thrombotic Thrombocytopenic Purpura (cTTP), including the role of ADAMTS13, and how its deficiency translates into symptoms of cTTP.

Miesbach-Disease Pathogenesis (Role of ADAMTS13)
Speaker: Professor Wolfgang Miesbach and Dr. Friedrich Overkamp

Management of TTP Manifestations (Kidney Failure)

A podcast about the pathophysiology, diagnosis, and management of renal complications related to Thrombotic Thrombocytopenic Purpura (TTP).

Management of TTP Manifestations (Kidney Failure)
Speaker: Professor Paul Brinkkotter and Dr. Friedrich Overkamp



Watch videos focused on Thrombotic Thrombocytopenic Purpura, including Congenital Thrombotic Thrombocytopenic Purpura (cTTP).

Pathophysiology of Thrombotic Thrombocytopenic Purpura

Learn about the pathophysiology of Congenital Thrombotic Thrombocytopenic Purpura (cTTP), including the role of ADAMTS13 and the resulting clinical presentation of the disease.

Additional Resources


Find materials to help foster a deeper understanding of Congenital Thrombotic Thrombocytopenic Purpura (cTTP).

The history of cTTP

Discover the history of Congenital Thrombotic Thrombocytopenic Purpura (cTTP) from 1924 to today.