Abstract Number: VPB1424
Meeting: ISTH 2022 Congress
Theme: Women’s Health » Pregnancy and Pregnancy Complications
Background:
Background: Patients who are diagnosed with thrombotic thrombocytopenic purpura (TTP) during pregnancy are at an increased risk of complications including fetal death. We describe a case of a 32-year-old G3P0 who presented with microangiopathic hemolytic anemia, thrombocytopenia (platelet count 13), labile blood pressure, proteinuria and fetal demise at 20 weeks’ gestation. She was diagnosed with congenital TTP (cTTP) based on an ADAMTS13 level of 0.69%, inhibitor level < 12 Units/mL, and two gene abnormalities of ADAMTS13.
Aims: Aim: To better understand the pathophysiology of pregnancy complications in cTTP through platelet and proteomic studies.
Methods:
Methods: We performed plasma quantitative shotgun proteomics analysis, which we coupled with detailed fluorescence imaging, and the systematic quantification of procoagulation and inflammation markers in platelet-rich-plasma re-constituted to contain neutrophils. We compared experimental outcomes in cTTP to 4 pregnant healthy controls (PC), 4 gestational hypertension (GH), and 4 preeclampsia or HELLP syndrome (PE) patients (Research Ethics Board Approval #REB18-1545).
Results:
Results: We identified 15 proteins upregulated in cTTP, and a sub-analysis revealed that S100A8 and S100A9 were distinctly overexpressed (6-7-fold increase) in our cTTP patient, but not in PC, GH or PE patients.
High-resolution platelet imaging from our cTTP patient showed acquired platelet and neutrophil activation, and classic structures of platelet-neutrophil aggregates. Compared to all other participant groups, our cTTP patient had increased P-selectin, tissue factor expression, annexin-V binding on platelets and neutrophils, and localized thrombin generation, which is suggestive of hypercoagulability. We visualised in cTTP, but not PC, GH or PE, loose thrombus consisting of activated and procoagulant platelets and neutrophils trapped within mesh-like structures resembling a fibrin-network.
Conclusion(s): Conclusion: Evidence of platelet-neutrophil activation and interaction, platelet hypercoagulability, and proinflammation as detected by S100A8 and S100A9 proteins were identified in our case of congenital TTP with fetal demise.
To cite this abstract in AMA style:
Skeith L, Hurd K, Almeida L, Dufour A, Lee A, Goodyear D, Girard L, Soucie J, Nicholas J, Schneider P, Agbani E. Hypercoagulability and Inflammatory Markers in a Case of Congenital TTP Complicated by Fetal Demise [abstract]. https://abstracts.isth.org/abstract/hypercoagulability-and-inflammatory-markers-in-a-case-of-congenital-ttp-complicated-by-fetal-demise/. Accessed March 22, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/hypercoagulability-and-inflammatory-markers-in-a-case-of-congenital-ttp-complicated-by-fetal-demise/