Approach to the patient with suspected TTP, HUS, or other thrombotic microangiopathy (TMA)
- James N George, MD
James N George, MD
- Professor of Medicine
- University of Oklahoma Health Sciences Center
- Carla Nester, MS, MD
Carla Nester, MS, MD
- Assistant Professor
- University of Iowa
The initial evaluation of a patient with suspected thrombotic thrombocytopenic purpura (TTP) or another primary thrombotic microangiopathy (TMA) syndrome must focus on distinguishing these primary syndromes from other systemic disorders that can present with microangiopathic hemolytic anemia (MAHA) and thrombocytopenia.
●The primary TMA syndromes include thrombotic thrombocytopenia purpura (TTP; hereditary or acquired), Shiga toxin-mediated HUS (hemolytic-uremic syndrome [ST-HUS]), drug-induced TMA (DITMA) syndromes, complement-mediated TMA (hereditary or acquired), and rare hereditary disorders of vitamin B12 metabolism or factors involved in hemostasis. These syndromes require urgent treatment directed at the TMA pathophysiology.
●Other systemic disorders that can present with MAHA and thrombocytopenia include pregnancy-associated syndromes (eg, severe preeclampsia/HELLP syndrome), severe hypertension, systemic infections and malignancies, autoimmune disorders such as systemic lupus erythematosus, and complications of hematopoietic stem cell or organ transplantation. Unlike the primary TMA syndromes, these systemic disorders require therapy directed at the underlying disorder rather than specific therapy for the TMA.
This topic review describes our initial approach to the child or adult with MAHA and thrombocytopenia for whom the etiology is uncertain. Details of the evaluation and management of specific, defined primary TMA syndromes including thrombotic thrombocytopenic purpura (TTP) are presented in separate topic reviews on these syndromes. (See 'Overview of primary TMA syndromes' below.)
The following terminology is used in this topic review:
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- Microangiopathic hemolytic anemia (MAHA)
- Thrombotic microangiopathy (TMA)
- OVERVIEW OF PRIMARY TMA SYNDROMES
- SYSTEMIC DISORDERS ASSOCIATED WITH MAHA AND THROMBOCYTOPENIA
- INITIAL EVALUATION (ALL PATIENTS)
- Verify MAHA and thrombocytopenia
- Exclude systemic disorders
- EVALUATION FOR PRIMARY TMA SYNDROMES
- Key distinguishing features among the primary TMA syndromes
- Features of individual primary TMAs
- Laboratory evaluation
- - All patients
- - Diarrhea/known infectious diarrhea exposure
- - Homocysteine and MMA testing
- - Role of complement testing
- - Role of molecular testing
- - Role of kidney biopsy
- IMMEDIATE MANAGEMENT DECISIONS
- Plasma exchange (PEX)
- Anti-complement therapy
- Additional therapies
- SUMMARY AND RECOMMENDATIONS