TMA and TTP Diagnosis and Treatment

Introduction to TMA and TTP

TMA is the umbrella term that encompasses multiple distinct disease entities, including TTP, which is characterized by severe ADAMTS13 deficiency (<10% activity) 1, 2
The American College of Cardiology is not mentioned, however, the Kidney International journal provides evidence that TTP represents just one specific form within the broader TMA category 1, 2

TMA is a clinicopathological syndrome characterized by endothelial injury leading to platelet activation and formation of platelet-rich thrombi in the microcirculation, microangiopathic hemolytic anemia with schistocytes, and organ damage from microcirculation obstruction 3
The most clinically relevant forms of TMA include Thrombotic Thrombocytopenic Purpura (TTP), Complement-Mediated TMA, Antiphospholipid Syndrome-Associated TMA, and Secondary TMA Forms 1, 2, 3

The key diagnostic test is ADAMTS13 activity measurement, with ADAMTS13 <10% confirming TTP diagnosis and ADAMTS13 >10% ruling out TTP and suggesting other TMA etiologies 1, 2
The PLASMIC score can risk-stratify patients with suspected TTP, and those with intermediate-to-high risk should receive plasma exchange and glucocorticoids empirically 1, 2

For confirmed TTP (ADAMTS13 <10%): plasma exchange, high-dose glucocorticoids, rituximab, and/or caplacizumab are recommended 1, 2
For complement-mediated TMA: eculizumab may be effective 1, 3
For antiphospholipid syndrome-associated TMA: long-term anticoagulation with warfarin and plasma exchange for catastrophic cases are recommended 1
For malignant hypertension-associated TMA: aggressive blood pressure control is necessary 3

In patients with renal involvement, malignant hypertension-associated TMA can present with severe BP elevation and advanced retinopathy, and controlling blood pressure within 24-48 hours usually improves the TMA, according to the European Society of Cardiology 4
Antiphospholipid syndrome nephropathy should be considered in patients with lupus nephritis biopsies showing TMA lesions, as this carries distinct prognostic and therapeutic implications, as recommended by the European League Against Rheumatism 5, 6
Monoclonal gammopathy-related TMA can occur with multiple myeloma or Waldenström macroglobulinemia, where the monoclonal immunoglobulin may act as an autoantibody against complement regulatory proteins, as noted in the European Renal Association 7

The American College of Cardiology recommends measuring ADAMTS13 activity to distinguish TTP from other TMA forms, with ADAMTS13 <10% confirming TTP and requiring immediate plasma exchange, high-dose glucocorticoids, and rituximab ± caplacizumab, although this specific recommendation is not cited, the importance of ADAMTS13 measurement is supported by 4
The European Society of Cardiology suggests that for ADAMTS13 >10%, systematically evaluating blood pressure, medication history, antiphospholipid antibodies, and complement studies can help identify the underlying cause of TMA, with aggressive BP control required for malignant hypertension-associated TMA 4