Pathophysiology of acquired TTP and other primary thrombotic microangiopathies (TMAs)
- James N George, MD
James N George, MD
- Professor of Medicine
- University of Oklahoma Health Sciences Center
Thrombotic microangiopathy (TMA) describes a specific pathologic lesion in which abnormalities in the vessel wall of arterioles and capillaries lead to microvascular thrombosis. TMA is a pathologic diagnosis made by tissue biopsy. However, it is commonly inferred from the observation of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia in the appropriate clinical setting. Acquired thrombotic thrombocytopenic purpura (TTP) was the first of the primary TMAs to be described and is perhaps the best understood of the TMAs pathophysiologically. TTP is unique among the primary TMAs for minimal abnormalities of kidney function, despite microthrombi observed throughout the kidney.
The pathophysiology of acquired (autoimmune) TTP, complement-mediated TMA, Shiga toxin-induced TMA (hemolytic uremic syndrome [ST-HUS]), and some of the rare inherited TMAs will be reviewed here.
The pathophysiology of hereditary TTP and drug-induced TMA (also called drug-induced TTP) is presented separately. (See "Hereditary thrombotic thrombocytopenic purpura (TTP)", section on 'Genetics' and "Drug-induced thrombotic microangiopathy", section on 'Pathophysiology'.)
Separate topic reviews also discuss the general approach to the patient with a suspected TMA (see "Approach to the patient with suspected TTP, HUS, or other thrombotic microangiopathy (TMA)"), and diagnosis and management of specific conditions:
●Acquired TTP – (See "Acquired TTP: Clinical manifestations and diagnosis" and "Acquired TTP: Initial treatment".)
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- HISTOPATHOLOGY OF TMA
- Endothelial changes and microthrombi
- Hematologic findings
- TTP PATHOGENESIS
- Deficient ADAMTS13 activity
- Causes of ADAMTS13 deficiency
- - Inhibitory antibodies to ADAMTS13
- - ADAMTS13 gene mutations
- COMPLEMENT-MEDIATED TMA PATHOGENESIS
- Consequences of excessive complement activity
- Inhibitory antibodies to complement factor H
- Complement gene mutations
- Interactions between VWF and the alternative complement pathway
- SHIGA TOXIN-INDUCED TMA (ST-HUS)
- OTHER PRIMARY TMA PATHOGENESIS
- Mutations in coagulation regulators
- - DGKE
- - Thrombomodulin
- Vitamin B12 metabolism/MMACHC mutations
- Drug-induced TMA