Clinical Pearls & Morning Reports
Published November 9, 2023
Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). In less than 5% of cases, such ADAMTS13 deficiency is genetic, causing congenital TTP. TTP is a life-threatening emergency that requires immediate treatment. Read the NEJM Case Records here.
Q: What is the function of the ADAMTS13 enzyme?
A: ADAMTS13 is a plasma protease synthesized in the liver that cleaves von Willebrand factor. Most cases of TTP are caused by an autoantibody to ADAMTS13 that prevents this cleavage. When the cleavage does not occur, platelet microthrombi form in small vessels in multiple anatomical sites, causing the clinical manifestations of TTP.
Q: Is reduced ADAMTS13 activity specific for TTP?
A: Although a mild decrease in ADAMTS13 activity can be seen with aging and certain medical conditions (e.g., liver disease, inflammatory conditions, or pregnancy), a severe decrease in ADAMTS13 activity (to a level of <10%) is characteristic of TTP.
A: The decision to initiate the best available therapy — therapeutic plasma exchange — often must be made before the results of diagnostic laboratory testing have been received. Therapeutic plasma exchange not only permits the transfusion of a high volume of ADAMTS13 in donor plasma but also removes the circulating antibody inhibitor in more than 95% of patients with autoimmune TTP. Plasma transfusion may be started before the initiation of therapeutic plasma exchange as a temporizing measure. For both immediate and postdischarge treatment of TTP, therapeutic plasma exchange must be accompanied by immunosuppression. Glucocorticoid therapy is typically started alongside therapeutic plasma exchange. The administration of rituximab within 3 days after presentation is associated with better clinical outcomes—specifically, fewer days of treatment with therapeutic plasma exchange, fewer hospital days overall, a higher ADAMTS13 activity level, a lower inhibitor level, and a lower risk of relapse. The lifetime risk of relapse is at least 20%, even in patients who receive rituximab therapy.
A: Therapeutic plasma exchange is associated with procedural risks and considerable use of health care resources. In deciding whether therapeutic plasma exchange should be started immediately, before the results of ADAMTS13 testing are available, the PLASMIC score is particularly instructive. Developed in 2017, the PLASMIC score is based on seven components: a platelet count (P) of less than 30,000 per microliter; the presence of hemolysis (L) as indicated by the laboratory value for indirect bilirubin, reticulocytes, or haptoglobin; the presence of active cancer (A) in the past 12 months, in the absence of stem-cell or solid-organ transplantation (S); a mean corpuscular volume (M) of less than 90 fl; an international normalized ratio (I) of less than 1.5; and a creatinine level (C) of less than 2.0 mg per deciliter. All these components can be assessed with the initial history taking, physical examination, and routine laboratory testing. Therapeutic plasma exchange is typically considered when the PLASMIC score is 5 or greater, indicating at least intermediate risk of TTP.