Subacute immune-mediated thrombotic thrombocytopenic purpura: prolonged prodromes and delayed diagnosis in 5 cases.
6 affiliations
- 1Department of Cardiovascular Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK.
- 2Department of Haematology, Staffordshire Thrombosis and Anticoagulation Service, University Hospitals North Midlands NHS Trust, Stoke-on-Trent, UK.
- 3Department of Haematology, Royal Wolverhampton NHS Foundation Trust, Wolverhampton, UK.
- 4Department of Haematology, The Dudley Group NHS Foundation Trust, Dudley, UK.
- 5Department of Haematology, University Hospitals of Derby and Burton, Burton On Trent, UK.
- 6Department of Haemostasis, Liaison Haematology and Transfusion, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Abstract
Background
Immune thrombotic thrombocytopenic purpura (iTTP) is caused by a deficiency in ADAMTS-13 activity and is classically an acute-onset disorder. A subset of patients, however, may experience a more insidious course. Comprehensive reports of these presentations are sparse, and delayed diagnosis has been associated with increased thrombotic complications and mortality.Objectives
To report on 5 cases of subacute iTTP presentations involving a prolonged prodromal period of nonspecific symptoms with gradual decline in platelet counts before acute deterioration and subsequent diagnosis.Methods
This retrospective case series identified delayed iTTP diagnoses in 5 patients with thrombocytopenia (platelets <150 ×10⁹/L) and ADAMTS-13 activity <10 IU/dL managed at a single UK specialist tertiary referral center between 2022 and 2024. Clinical data, laboratory results, treatments, and outcomes were obtained from medical records.Results
The median age was 52 years (range, 3-78), and 3 patients were female. Median time from first nonspecific symptom to diagnosis was 84 days (range, 60-120), compared with 22 days (range, 5-65) from the first documented evidence of microangiopathic hemolytic anemia or thrombotic microangiopathy. All patients were found to have severe thrombocytopenia and ADAMTS-13 activity <10 IU/dL, with 3 showing anti-ADAMTS-13 IgG positivity. All patients were treated with plasma exchange, corticosteroids, rituximab, and caplacizumab; 3 required obinutuzumab for relapsed/refractory low ADAMTS-13 levels.Conclusion
Insidious changes to blood count trends and prodromal symptoms risk being overlooked, delaying treatment and increasing morbidity and mortality. Broader awareness of subacute iTTP presentations outside hematology may improve timely diagnosis and management.
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BibTeX
@article{tehrani2026subacute,
title = {{Subacute immune-mediated thrombotic thrombocytopenic purpura: prolonged prodromes and delayed diagnosis in 5 cases.}},
author = {Tara G Tehrani and David J Sutton and Richard Whitmill and Muzna Aquil and Amir Shenouda and Aurangzeb Razzak and Humayun Ahmad and Malahat Saeed and Gillian C Lowe and Phillip L R Nicolson},
journal = {Research and practice in thrombosis and haemostasis},
year = {2026},
month = sep,
doi = {10.1016/j.rpth.2026.106972},
url = {https://europepmc.org/article/MED/42921460},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Subacute immune-mediated thrombotic thrombocytopenic purpura: prolonged prodromes and delayed diagnosis in 5 cases.
AU - Tara G Tehrani
AU - David J Sutton
AU - Richard Whitmill
AU - Muzna Aquil
AU - Amir Shenouda
AU - Aurangzeb Razzak
AU - Humayun Ahmad
AU - Malahat Saeed
AU - Gillian C Lowe
AU - Phillip L R Nicolson
PY - 2026
DA - 2026/09/18
JO - Research and practice in thrombosis and haemostasis
DO - 10.1016/j.rpth.2026.106972
UR - https://europepmc.org/article/MED/42921460
AB - Background Immune thrombotic thrombocytopenic purpura (iTTP) is caused by a deficiency in ADAMTS-13 activity and is classically an acute-onset disorder. A subset of patients, however, may experience a more insidious course. Comprehensive reports of these presentations are sparse, and delayed diagnosis has been associated with increased thrombotic complications and mortality.Objectives To report on 5 cases of subacute iTTP presentations involving a prolonged prodromal period of nonspecific symptoms with gradual decline in platelet counts before acute deterioration and subsequent diagnosis.Methods This retrospective case series identified delayed iTTP diagnoses in 5 patients with thrombocytopenia (platelets <150 ×10⁹/L) and ADAMTS-13 activity <10 IU/dL managed at a single UK specialist tertiary referral center between 2022 and 2024. Clinical data, laboratory results, treatments, and outcomes were obtained from medical records.Results The median age was 52 years (range, 3-78), and 3 patients were female. Median time from first nonspecific symptom to diagnosis was 84 days (range, 60-120), compared with 22 days (range, 5-65) from the first documented evidence of microangiopathic hemolytic anemia or thrombotic microangiopathy. All patients were found to have severe thrombocytopenia and ADAMTS-13 activity <10 IU/dL, with 3 showing anti-ADAMTS-13 IgG positivity. All patients were treated with plasma exchange, corticosteroids, rituximab, and caplacizumab; 3 required obinutuzumab for relapsed/refractory low ADAMTS-13 levels.Conclusion Insidious changes to blood count trends and prodromal symptoms risk being overlooked, delaying treatment and increasing morbidity and mortality. Broader awareness of subacute iTTP presentations outside hematology may improve timely diagnosis and management.
SN - 2475-0379
ER -