In this video lecture, Dr. Shruti Chaturvedi discusses:
- How to distinguish TTP, atypical HUS, and secondary TMAs, highlighting differences in platelet counts, renal impairment, and clinical triggers.
- The role of ADAMTS13 testing, PLASMIC and French scores, and emerging complement assays in guiding urgent diagnostic and treatment decisions.
- Why timely recognition and tailored therapy, plasma exchange for TTP, complement inhibition for aHUS, and cause-directed treatment for secondary TMAs are critical to survival.
Dr. Shruti Chaturvedi is an Associate Professor of Medicine and Research Director in the Division of Hematology at Johns Hopkins University in Baltimore, Maryland. She specializes in disorders, immune mediated thrombotic disorders and thrombotic microangiopathy. Dr. Chaturvedi’s research program is focused on establishing the epidemiology and mechanisms of long-term sequelae of thrombotic microangiopathies including thrombotic thrombocytopenic purpura and complement mediated TMA, with the goal of developing interventions to reduce morbidity and mortality in this population. Her lab has established the risk rate of stroke and cardiovascular events in TTP survivors, and the role of remission ADAMTS13 as a targetable risk factor. The other focus of her research is the role of complement activation and genetic variations in complement genes in thrombotic disorders including antiphospholipid syndrome with the goal of translating discoveries into diagnostic tools and effective therapies. She published over 100 papers and book chapters and her work has been supported by the National Institutes of Health, Hemostasis and Thrombosis Research Society and American Society of Hematology.
(Video Lecture Summary)
Introduction
In this video, Dr. Shruti Chaturvedi, associate professor of hematology at Johns Hopkins, discusses how to differentiate thrombotic thrombocytopenic purpura (TTP) from other causes of thrombotic microangiopathy (TMA). Using case-based examples, she outlines diagnostic steps, clinical decision tools, and evolving assays that guide timely treatment.
Diagnostic Framework
The first step in approaching a suspected TMA is to confirm the presence of thrombocytopenia, anemia, hemolysis, and schistocytes on peripheral smear. Once TMA is established, the clinician must distinguish between TTP, atypical hemolytic uremic syndrome (aHUS), and secondary TMAs. This distinction is essential because untreated TTP is rapidly fatal, aHUS responds to complement inhibition, and secondary TMAs require treatment of the underlying trigger.
Clinical Features
While presentations overlap, there are distinguishing features:
TTP: More severe thrombocytopenia and frequent neurologic involvement.
aHUS: Greater renal impairment and often severe hypertension.
Secondary TMA: Triggered by pregnancy, infection, malignancy, transplantation, autoimmune disease, or drugs, with variable complement involvement. The classic “pentad” of TTP (anemia, thrombocytopenia, renal impairment, neurologic changes, fever) is rarely seen and should not delay treatment.
Diagnostic Tools
ADAMTS13 activity <10% remains the gold standard for TTP, though results are often delayed. Prediction tools like the French Score and PLASMIC Score help triage patients for empiric plasma exchange when rapid ADAMTS13 testing is unavailable. Complement dysregulation testing can support aHUS diagnosis, but many assays lack sensitivity or timeliness. Novel approaches such as the modified Ham assay and its bioluminescent variant offer rapid, sensitive ways to identify complement-mediated TMAs and may expand clinical utility.
Special Considerations in Pregnancy
Diagnosing TTP during pregnancy is challenging because preeclampsia, HELLP syndrome, aHUS, and catastrophic antiphospholipid syndrome can mimic its presentation. Timing, laboratory patterns, and progression postpartum provide important clues. For instance, preeclampsia and HELLP rarely occur before 20 weeks and improve with delivery, while TTP can arise in any trimester and persists after delivery.
Conclusion
Dr. Chaturvedi emphasizes that timely recognition of TMA subtypes is critical. Clinicians should rapidly identify TMA, use ADAMTS13 testing and predictive scores when available, and tailor treatment: plasma exchange for TTP, complement inhibition for aHUS, and underlying cause management for secondary TMAs. Emerging assays promise to further refine diagnostic speed and accuracy, ultimately improving patient outcomes.