Congenital
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

Epidemiology

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

Pathophysiology

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

Diagnosis

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

Mortality:
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

Adzynma

(ADAMTS13, recombinant-krhn)

Medication Resources

Adzynma

(ADAMTS13, recombinant-krhn)

Medication Resources

Adzynma

(ADAMTS13, recombinant-krhn)

Podcasts

 

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

 

TTP Pathophysiology and Classification

Learn about the pathophysiology of Thrombotic Thrombocytopenic Purpura (TTP), classification into different types, the role of ADAMTS13, and how its deficiency translates into symptoms of cTTP.

TTP Pathophysiology and Classification
Speaker: Dr. Wolfgang Miesbach, University Hospital in Frankfurt, Germany
0s

TTP Overview and Long-Term Manifestations

An introduction to cTTP and its long-term manifestations in different organ systems.

TTP Overview and Long-Term Manifestations
Speaker: Dr. X. Long Zheng, University of Kansas Medical Center, Kansas City, KS, US
0s

TTP Cardiovascular Complications

A podcast about how multiple organs can be affected by congenital and immune TTP, with a focus on cardiovascular complications.

TTP Cardiovascular Complications
Speaker: Dr. Shruti Chaturvedi, Johns Hopkins University, Baltimore, MD, US
0s

TTP Renal Complications

A podcast about the pathophysiology, diagnosis, and management of renal complications related to TTP.

TTP Renal Complications
Speaker: Dr. Paul Brinkkotter, University Hospital in Cologne, Germany
0s

Videos

 

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.

Upcoming & Past Conferences in Hematology

  • Upcoming

  • Past

Academy of Managed Care Pharmacy Nexus (AMCP Nexus), 2024

October 14 - 17, 2024 | Link to Event

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.

American Thrombosis and Hemostasis Network Data Summit (ATHN Data Summit), 2024

October 22 - 23, 2024 | Link to Event

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

American Society of Hematology (ASH), 2024

December 7 - 12, 2024 | Link to Event

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

Bleeding Disorders Conference (BDC), 2024

September 12 - 14, 2024

The National Bleeding Disorders Foundation (formally NHF)’s Annual Bleeding Disorders Conference brings the bleeding disorders community together for educational sessions, networking opportunities, and exhibits.

International Society on Thrombosis and Haemostasis (ISTH), 2024

June 22 - 26, 2024

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.

  • Global Prevalence of Anticoagulant Reversal for Major Bleeding and Urgent Surgery in Patients with Atrial Fibrillation and Venous Thromboembolism: A Systematic Review of Data from 38 Countries

Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] & Advate® [Antihemophilic Factor (Recombinant)] & "other FVIII replacement therapies"

  • Physical Activity Engagement and Health-Related Quality Of Life in Patients with Hemophilia A Receiving Either Octocog Alfa Or Rurioctocog Alfa Pegol Versus Other FVIII Replacement Therapies
  • Clinical Outcomes in Patients with Hemophilia A Receiving Octocog Alfa or Rurioctocog Alfa Pegol Versus Other FVIII Replacement Therapies: Insights From The Ahead, CHESS II, and CHESS PAEDS Studies
  • The Impact of Recombinant Factor VIII Products on Inhibitor Development in Previously Untreated and Previously Treated Children with Hemophilia A: A Systematic Review

Ceprotin® [Protein C Concentrate (Human)]

  • High-Concentration Protein C Concentrate: In Vitro and In Vivo Feasibility Studies
  • Pharmacokinetics of Protein C in Neonates with Severe Congenital Protein C Deficiency
  • Pharmacokinetics of Protein C Concentrate After Intravenous and Subcutaneous Administration in Göttingen Minipigs

Obizur® [Antihemophilic Factor (Recombinant), Porcine Sequence]

  • Evaluation of Factor VIII Population Pharmacokinetics and Exposure-Response to Support Dosing of Recombinant Porcine Factor VIII in Patients with Acquired Hemophilia A

TAK-330 (4-factor prothrombin complex concentrate [4F-PCC])

  • A Phase 3 Trial of TAK-330 (4-Factor Prothrombin Complex Concentrate [4F-PCC]) vs Standard-Of-Care 4F-PCCs for FXa Inhibitor-Induced Anticoagulation Reversal Before Urgent Surgery/Invasive Procedure

Prothromplex® (Human Prothrombin Complex)

  • Safety Assessment of Prothromplex®, a 4-Factor Prothrombin Complex Concentrate, Focused on Heparin-Related Adverse Events

Professional Society for Health Economics and Outcomes Research (ISPOR), 2024

May 5 - 8, 2024

Leading global conference discussing how to establish, incentivize, and share value sustainable for health systems, patients, and technology developers.

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