In this video lecture, Dr. Marie Scully discusses:
- The clinical and laboratory hallmarks of TTP, including thrombocytopenia, microangiopathic hemolytic anemia, and organ involvement.
- The role and limitations of clinical scoring systems, and the importance of ADAMTS13 testing in confirming diagnosis.
- Why delayed diagnosis increases mortality and complications, and the critical role of blood film review and early referral.
Dr. Marie Scully is a Consultant Haematologist at University College London Hospitals (UCLH), currently acting as the clinical lead for haemostasis and thrombosis, having spent ten years as the clinical lead for blood transfusion. She has considerable experience in within complex tertiary cases within obstetrics, neurosurgery, intensive care and haematooncology associated haemostasis and thrombosis complications. Her particular area of interest is acquired haemostasis and platelet disorders, specifically Immune Thrombocytopenic Purpura (ITP). She runs specialist ITP and TTP clinics and works on obstetric haematology, as part of a team that specialises in treating varied and complex thrombosis, acquired and inherited bleeding disorders.
(Video Lecture Summary)
Introduction
In this lecture, Dr. Marie Scully provides an overview of the diagnosis of thrombotic thrombocytopenic purpura (TTP). She situates TTP within the broader category of thrombotic microangiopathies (TMAs), emphasizing that it is a rare but life-threatening medical emergency requiring rapid recognition and intervention.
Diagnostic Features of TMA and TTP
The diagnosis of TMA relies on two key laboratory findings: thrombocytopenia and microangiopathic hemolytic anemia. These are typically confirmed by blood film review, which may show fragmented red cells, anemia, reduced platelet counts, and polychromasia.
In addition to laboratory findings, TTP has characteristic clinical features, with microvascular thrombosis affecting the brain, heart, and kidneys. These thrombi are specifically composed of platelets and von Willebrand factor, reflecting the underlying defect in ADAMTS13 function.
Differential Diagnosis
Professor Scully highlights the broad differential diagnosis for TMAs, which includes malignancy and its treatments, autoimmune conditions, pregnancy-related complications, infection, malignant hypertension, disseminated intravascular coagulation (DIC), and hemolytic uremic syndrome (HUS). Distinguishing TTP from these conditions is essential because timely treatment alters survival outcomes.
Pathophysiology and Role of ADAMTS13
Normal hemostasis involves ADAMTS13 cleaving ultra-large von Willebrand factor multimers into smaller units that regulate platelet adhesion. In TTP, the absence of ADAMTS13, either inherited or immune-mediated, prevents this process. As a result, large multimers persist, capturing platelets and driving microvascular thrombosis.
This pathophysiology underscores why thrombocytopenia in TTP reflects platelets being consumed in the wrong location rather than an absolute deficiency.
Diagnostic Tools: Scoring Systems and Limitations
Two clinical scoring systems, the French score and the PLASMIC score, aim to predict severe ADAMTS13 deficiency. While useful, Professor Scully cautions that these are retrospective models and not always reliable in real-world practice. They may assist in estimating likelihood, but definitive diagnosis hinges on ADAMTS13 testing.
ADAMTS13 Testing and Prognostic Implications
ADAMTS13 activity testing is the most important laboratory parameter to confirm TTP and distinguish it from other TMAs. Registry data from the UK demonstrate that ADAMTS13 testing has both high sensitivity and specificity compared with secondary causes of TMA.
Importantly, delays in diagnosis and treatment of more than 24 hours significantly increase mortality, neurological complications, and hospital length of stay. Reviewing blood films promptly in thrombocytopenic patients and sending ADAMTS13 samples at first suspicion are therefore essential steps.
Practical Laboratory Evaluation
Basic laboratory work-up should include a full blood count, reticulocyte count, blood film, lactate dehydrogenase (LDH), coagulation screen (typically normal in TTP), B12 and folate levels, liver and kidney function tests, and troponin. These help differentiate TTP from other TMAs and provide baseline information for management.
Conclusion
TTP is rare but life-threatening, requiring urgent recognition and treatment. Blood film review remains critical in any patient with new thrombocytopenia, and early ADAMTS13 testing should be prioritized. She emphasizes the central role of collaboration between hematologists and laboratory scientists at presentation, and closes by underscoring the need for continued education to ensure timely diagnosis.