In this video lecture, Dr. Bentley Rodrigue discusses:
- The pathophysiology and diagnostic considerations of TTP, including reliance on clinical judgment and the PLASMIC score while awaiting ADAMTS13 testing.
- The central role of therapeutic plasma exchange in removing inhibitory antibodies and restoring ADAMTS13 activity.
- Practical guidelines and monitoring strategies, including ASFA recommendations, avoidance of prophylactic platelet transfusions, and management of treatment-related complications.
Dr. Bentley Rodrigue is an attending clinical pathologist specializing in Transfusion Medicine at the Beth Israel Deaconess Medical Center in Boston, Massachusetts. She currently serves as the Associate Medical Director for the Blood Bank and has an appointment at Harvard Medical School as an Instructor in Pathology. Her projects have focused on quality improvement and patient blood management, aiming to ensure optimal patient outcomes while promoting efficient use of resources. She thoroughly enjoys teaching, both formal courses and informal discussions, and has a passion for medical education.
(Video Lecture Summary)
Introduction and Pathophysiology
The lecture begins with an overview of thrombotic thrombocytopenic purpura (TTP) as a hematologic emergency where immediate treatment can be lifesaving. TTP results from a deficiency of ADAMTS13, which normally cleaves von Willebrand factor multimers. Without this enzyme, platelet-rich microthrombi form, leading to microangiopathic hemolytic anemia, thrombocytopenia, and potential organ injury. Although the classic pentad of symptoms is rarely seen, the combination of anemia, thrombocytopenia, and fever should prompt suspicion.
Diagnostic Considerations
ADAMTS13 activity testing confirms the diagnosis, but because it is a send-out test with long turnaround times, it is not practical for urgent decision-making. Instead, clinicians should use the PLASMIC score, which incorporates seven clinical variables, to estimate pretest probability and decide whether to begin treatment.
Role and Process of Therapeutic Plasma Exchange
Plasma exchange is the cornerstone of TTP treatment. The procedure removes patient plasma containing inhibitory autoantibodies and replaces it with donor plasma that restores ADAMTS13 activity. Rodrigue explains the mechanics of apheresis machines, vascular access requirements, and the use of continuous-flow centrifugation to separate blood components. Treatment is performed daily until platelet counts normalize, symptoms improve, and laboratory markers stabilize.
Adjunctive Therapies
While plasma exchange is lifesaving, it is not without limitations. Adjunctive therapies help support recovery and prevent relapse:
- Corticosteroids are routinely given to blunt the autoimmune attack on ADAMTS13.
- Rituximab, an anti-CD20 monoclonal antibody, is often added in refractory or relapsing disease to suppress autoantibody production.
These adjuncts are discussed in further detail in other management lectures, but Rodrigue emphasizes their importance alongside plasma exchange.
Guidelines and Best Practices
The American Society for Apheresis (ASFA) guidelines classify TTP as a Category I, Grade 1A indication for plasma exchange, underscoring its status as first-line therapy. Clinicians should send a type and screen to the blood bank early, conserve AB plasma for patients who are AB or whose type is unknown, and avoid prophylactic platelet transfusions since these can worsen thrombosis. Monitoring during treatment includes daily platelet counts, LDH levels, and surveillance for complications such as hypocalcemia from citrate anticoagulant, vascular access issues, and transfusion reactions.
Conclusion
Plasmapheresis represents a transformative therapy in the management of TTP, uniquely capable of addressing the disease’s dual mechanism—removing inhibitory antibodies and replenishing ADAMTS13. The lecture underscores the urgency of initiating plasma exchange without delay when TTP is suspected, as treatment delays directly correlate with mortality.
The procedure, while invasive and not without risks, is overwhelmingly beneficial in this context and remains the standard of care. Awareness of pitfalls, adherence to ASFA guidelines, and close patient monitoring are all essential for optimizing outcomes.