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Disease Profile

Thrombotic thrombocytopenic purpura, acquired

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Purpura, thrombotic thrombocytopenic; TTP; Moschowitz syndrome;

Categories

Blood Diseases

Summary

Thrombotic thrombocytopenic purpura (TTP), acquired is a blood disorder characterized by low platelets (i.e., thrombocytopenia), small areas of bleeding under the skin (i.e., purpura), low red blood cell count, and hemolytic anemia. TTP causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and decrease or stop blood flow to organs such as the brain, kidneys, and heart. Complications may include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems. Hemolytic anemia can lead to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.[1][2][3] Acquired TTP usually begins in adulthood, but can affect children. An episode of TTP usually occurs suddenly and lasts for days or weeks, but it may continue for months. Relapses (or flareups) can occur in up to 60 percent of people who have the acquired TTP.[2] Acquired TTP is caused when a person's body mistakingly makes antibodies that block the activity of the ADAMTS13 enzyme. THe ADAMTS13 enzyme normally helps control the activity of certain blood clotting factors. Treatment includes plasma exchange and in some cases may also include corticosteroid therapy or rituximab.[1][2][3][4]

Symptoms

The signs and symptoms of thrombotic thrombocytopenic purpura, acquired (acquired TTP) may include:[1][2]

  • Purplish bruises on the skin or mucous membranes (such as in the mouth). These bruises, called purpura, are caused by bleeding under the skin
  • Pinpoint-sized red or purple dots on the skin. These dots, called petechiae, often are found in groups and may look like a rash.Bleeding under the skin causes petechiae.
  • Paleness or jaundice (a yellowish color of the skin or whites of the eyes)
  • Fatigue (feeling very tired and weak)
  • Fever
  • A fast heart rate or shortness of breath.
  • Nausea or vomiting
  • Headache, speech changes, confusion, coma, stroke, or seizure
  • A low amount of urine, or protein or blood in the urine

Acquired TTP usually presents as severe low red blood cell count due to destruction of red blood cells (microangiopathic hemolytic anemia or MAHA) and low platelet count (thrombocytopenia) in a previously healthy individual.[1][2] Due to earlier diagnosis and improved treatments, fewer people with acquired TTP become critically ill. TTP affects the central nervous system and/or gastrointestinal system in over 1/3 of cases. Kidneys may also be damaged by TTP, but severe kidney damage is no longer common. Other organs such as the heart may be affected, but the lungs are rarely affected.[1]

Diagnosis

Thrombotic thrombocytopenic purpura, acquired (acquired TTP) is diagnosed by medical history, a thorough physical exam, and blood tests. Medical history suggestive of TTP might include having had certain diseases or conditions, such as cancer, HIV, lupus, or recent infections (or recent pregnancy), all of which can be triggers for the onset of TTP. Certain medications, quinine, chemotherapy and procedures like bone marrow transplants may also trigger the onset of acquired TTP. Physical exam would look for the signs and symptoms of acquired TTP. Blood tests will measure platelet and red and white blood cell counts, rule out other causes of anemia, and check kidney function. Special blood test assays can be used to check the level of activity of the ADAMTS13 enzyme and for the presence of the ADAMTS13 antibody inhibitor.[1][2]

Treatment

The main treatment for people with thrombotic thrombocytopenic purpura, acquired (acquired TTP) is daily plasma exchange (PEX or plasmaphoresis).[1][2][4] PEX removes antibodies (proteins) from the blood that damage the ADAMTS13 enzyme and replaces the ADAMTS13 enzyme.[1] Corticosteroids are usually given in addition to PEX. Some doctors may also give rituximab, but others use this medication only in cases that are not responding to treatment well or are more severe. Both corticosteroids and rituximab help slow or stop the making of the antibody which is attacking the ADAMTS13 enzyme, but both medications can have serious long term side effects. PEX is recommended to be continued daily until the platelet count has returned to normal. Once the person continues to be stable, corticosteroids will be decreased over a 2-3 week period. Since relapses can occur, doctors will continue to check for signs of TTP, especially during the first several years after an episode.[2][4]

In about 10% of cases, acquired TTP does not respond well to these treatments. Other medications including certain chemotherapy drugs may be tried, or the doses of the corticosteroids may be increased. As medical researchers continue to learn more about the antibodies that attack the ADAMTS13 enzyme, new treatments are being developed.[2][4]

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

  • Caplacizumab(Brand name: Cablivi) Manufactured by Ablynx NV
    FDA-approved indication: February 2019, caplacizumab (Cablivi) was approved for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
    National Library of Medicine Drug Information Portal

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
    • Genetics Home Reference (GHR) contains information on Thrombotic thrombocytopenic purpura, acquired. This website is maintained by the National Library of Medicine.
    • The National Heart, Lung, and Blood Institute (NHLBI) has information on this topic. NHLBI is part of the National Institutes of Health and supports research, training, and education for the prevention and treatment of heart, lung, and blood diseases.
    • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

      In-Depth Information

      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Thrombotic thrombocytopenic purpura, acquired. Click on the link to view a sample search on this topic.

        Selected Full-Text Journal Articles

          References

          1. George JN and Cuker A. Acquired TTP: Clinical manifestations and diagnosis. UpToDate. November 25 2015; https://www.uptodate.com/contents/acquired-ttp-clinical-manifestations-and-diagnosis.
          2. Explore Thrombotic Thrombocytopenic Purpura. National Heart, Lung, and Blood Institute. February 1 2016; https://www.nhlbi.nih.gov/health/health-topics/topics/ttp/.
          3. Wun T. Thrombotic Thrombocytopenic Purpura. Medscape Reference. June 20 2016; https://emedicine.medscape.com/article/206598-overview.
          4. Tersteeg C, Verhenne S, Roose E, Schelpe AS, Deckmyn H, De Meyer SF, and Vanhoorelbeke K. ADAMTS13 and anti-ADAMTS13 autoantibodies in thrombotic thrombocytopenic purpura current perspectives and new treatment strategies. Expert Rev Hematol. 2016; 9(2):209-21. https://www.ncbi.nlm.nih.gov/pubmed/26581428.

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