In this video lecture, Dr. Marie Scully discusses:
- How normal pregnancy physiology changes lab thresholds and complicates the differential diagnosis of TMAs.
- The distinguishing features, timing, and urgency of TTP versus preeclampsia/HELLP and complement-mediated HUS, including the role of ADAMTS13 testing.
- Management approaches for congenital and immune TTP in pregnancy, including ADAMTS13 replacement, maternal-fetal monitoring, and selected use of immunosuppression, plasma exchange, and caplacizumab.
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
Dr. Marie Scully explores the complexities of thrombotic thrombocytopenic purpura (TTP) in the context of pregnancy. She begins by emphasizing how normal pregnancy alters laboratory parameters, complicating the diagnosis of thrombotic microangiopathies (TMAs).
Physiologic Considerations in Pregnancy
Pregnancy itself frequently produces mild thrombocytopenia: around 10% of pregnancies have platelet counts below 150 × 10^9/L, with most being benign gestational thrombocytopenia (>75,000/µL). Smaller proportions are due to immune thrombocytopenia, and 20–30% are associated with hypertensive disorders of pregnancy. Renal physiology is also altered. Creatinine levels are lower in pregnancy so acute kidney injury is diagnosed by a doubling from baseline. LDH values follow non-pregnant reference ranges.
Diagnosing Thrombotic Microangiopathy in Pregnancy
Thresholds for concern differ from the non-pregnant state. A platelet count <100,000/µL, hemoglobin <10 g/dL, and LDH >1.5× the upper limit of normal should raise suspicion. Blood smear findings remain crucial: schistocytes with polychromasia, anemia, and thrombocytopenia, plus evidence of maternal end-organ injury (neurologic, renal, cardiac).
Differential Diagnosis: TMAs in Pregnancy
Several pregnancy-related conditions can mimic TMA. Preeclampsia (~1 in 20 pregnancies) and HELLP (~1 in 1000) are most common. Other contributors include autoimmune disorders, abruption, hemorrhage, and DIC. Importantly, TTP and complement-mediated HUS are the only TMAs that may present at any stage, from the first trimester through postpartum and both are medical emergencies. Unlike preeclampsia/HELLP, which usually resolve after delivery, TTP and HUS often persist and must be closely monitored.
Role of ADAMTS13 Testing
Routine labs and blood film form the foundation of evaluation, but ADAMTS13 testing is critical when TTP is suspected. TTP is typically associated with ADAMTS13 activity <20%, while other TMAs including HUS usually show >20%. Most cases of TTP present late in the third trimester or postpartum. In pregnancy overall, immune TTP is more common than congenital, though congenital TTP often manifests later.
Congenital TTP and Pregnancy
For congenital TTP (cTTP), timing of diagnosis and enzyme replacement therapy are key. Pre-diagnosis, the risk of intrauterine fetal death is high. With diagnosis and regular ADAMTS13 replacement during pregnancy and postpartum, outcomes improve dramatically. Best practice includes:
- ADAMTS13 replacement at least every two weeks from pregnancy confirmation.
- Low-dose aspirin and thromboprophylaxis to prevent placental infarction.
- Specialized maternal-fetal medicine care with regular fetal scans and Doppler studies.
- Increased replacement frequency as pregnancy advances.
- Delivery typically at 37–38 weeks, with replacement continued for at least 8 weeks postpartum.
Future directions include shifting from fresh frozen plasma to recombinant ADAMTS13, which provides higher enzyme levels and improved outcomes.
Immune TTP in Pregnancy
Management of immune TTP (iTTP) requires close preconception and antenatal monitoring. Women should enter pregnancy with normalized ADAMTS13 levels, but levels may decline during gestation. When levels remain normal, outcomes are good and delivery can be individualized with the obstetric team. If ADAMTS13 falls, treatment may include corticosteroids, rituximab, plasma exchange, and in select late-pregnancy cases, caplacizumab.
Conclusion
Dr. Scully concludes that pregnancy-related conditions such as preeclampsia and HELLP, and pregnancy-associated TMAs such as TTP, differ in timing and persistence. Preeclampsia usually arises after 20 weeks, HELLP in the third trimester, while TTP may present at any time, including postpartum. The key differentiator is a severely reduced ADAMTS13 activity (<20%) in TTP. Routine labs may not distinguish these entities, but ADAMTS13 testing and attention to maternal end-organ damage guide diagnosis. Emerging therapies like including recombinant ADAMTS13 and targeted agents offer promising avenues for improving maternal and fetal outcomes.