Thrombotic Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura

• Overview

  Thrombotic Thrombocytopenic Purpura (TTP) is a rare, life-threatening disorder of the blood-coagulation system which causes microscopic clots to form in small blood vessels throughout the body. Although it’s rare, TTP affects about 4 to 6 people per million each year, most often women and African-Americans. Diagnosis of TTP is made clinically, but discerning it from other thrombotic microangiopathies is often difficult.

  BloodCenter of Wisconsin, part of Versiti, pioneered the ADAMTS13 assays and is the only U.S. lab that conducts activity, inhibitor, antibody, and sequencing assays in-house. By creating a more sensitive assay, we can determine the precise level of activity of the disease, producing a more accurate diagnosis. BloodCenter also offers one of the fastest turn-around time of TTP diagnosis in the country, with average turnaround times under 24 hours.

• Approach

  Streamlined testing algorithm using tailored, evidence-based protocols.

  Versiti Diagnostic Labs’ goal is to simplify and streamline the diagnostic process, with tailored, evidence-based protocols. The experience of our team—and our desire to provide you with industry-leading service—allows us to provide more than just a test result. We practice laboratory medicine to provide specific diagnostic insights for every patient. Our expert consultation when you need it, offers a comprehensive approach to diagnosing TTP.

   ADAMTS13 is a plasma protein that regulates the interaction of platelets with von Willebrand factor. Severe deficiency of ADAMTS13 allows formation of platelet microthrombi, which in turn obstruct arterioles and capillaries, generating the clinical sequelae of TTP. In adults, severe ADAMTS13 deficiency is usually an acquired abnormality caused by autoantibody.

   The majority of adults with idiopathic TTP have a severe deficiency of ADAMTS13 with activity levels < 10%. The low levels are often due to autoantibodies that inhibit or clear ADAMTS13. Patients with idiopathic TTP usually require therapeutic plasma exchange to achieve clinical remission. Patients with idiopathic TTP and severe ADAMTS13 deficiency are more likely to respond to plasma exchange therapy than patients without severe deficiency. Persistence of ADAMTS13 deficiency or an inhibitor/antibody during clinical remission suggests an increased risk for recurrence of symptomatic TTP.

   Congenital severe ADAMTS13 deficiency is a rare autosomal recessive disorder (Upshaw-Schulman syndrome). Patients usually present as children, but adult presentations are reported, often triggered by stress events such as pregnancy. Patients are at risk for recurrent episodes of TTP. Antibody to ADAMTS13 is usually not detected, and patients generally improve with plasma transfusion therapy for ADAMTS13 replacement.

   Disease-causing mutations have been identified throughout the coding sequence of the ADAMTS13 gene. No specific mutation appears to predominate. DNA sequence analysis will confirm a diagnosis of congenital ADAMTS13 deficiency. For family members of patients with known ADAMTS13 mutations, sequencing of the appropriate exons can be used for diagnosis, carrier status or prenatal testing.