Why do secondary Thrombotic Microangiopathy (TMA) patients initially respond to plasmapheresis?

From the Guidelines

Secondary thrombotic microangiopathies (TMAs) initially respond to plasmapheresis because this procedure rapidly removes pathogenic factors from circulation that are driving the microangiopathic process, as supported by the most recent evidence from 2023 1.

Mechanism of Action

Plasmapheresis works by separating and removing plasma containing autoantibodies, immune complexes, cytokines, and other inflammatory mediators that contribute to endothelial damage and microvascular thrombosis.

• The process involves the extracorporeal separation of plasma from the cellular components of blood by use of membrane filtration or centrifugation, as described in a study from 2015 1.
• Blood is then reconstituted with exogenous albumin and/or fresh-frozen plasma or crystalloid and infused back into the patient.

Clinical Application

For secondary TMAs caused by conditions like autoimmune diseases, malignancies, medications, or infections, plasmapheresis provides immediate relief by clearing these harmful substances while simultaneously replacing normal plasma components that support healthy coagulation.

• The typical regimen involves daily plasmapheresis sessions with 1-1.5 plasma volume exchanges using fresh frozen plasma or cryosupernatant as replacement fluid, usually continued until platelet counts normalize and hemolysis resolves.
• However, this response is often temporary unless the underlying cause is addressed, as the pathogenic factors will continue to be produced, highlighting the importance of concurrent treatment of the underlying condition, as noted in a study from 2015 1.

Importance of Concurrent Treatment

Therefore, concurrent treatment of the underlying condition (such as immunosuppression for autoimmune disorders, discontinuation of offending medications, or treatment of infections) is essential for sustained improvement.

• Plasmapheresis serves as a bridge therapy that manages the acute manifestations while definitive treatment takes effect, as supported by the most recent evidence from 2023 1.
• It is crucial for patients with severe TMA to be evaluated at centers familiar with the diagnosis and treatment of TMA, given the specialized nature of the evaluation and treatment, which may require specific testing and treatment with plasma exchange that may not be widely available 1.

From the Research

Response to Secondary Thrombotic Microangiopathy (TMA) Patients

• Secondary TMA patients may initially respond to plasmapheresis due to the removal of autoantibodies and other harmful substances from the blood 2, 3.
• The use of plasmapheresis in secondary TMA has been shown to be effective in achieving complete remission, with similar results to primary TMA 2.
• The number of plasmapheresis sessions required to achieve complete remission can vary, with a median of 13 sessions reported in one study 2.
• The response to plasmapheresis may depend on the underlying cause of the secondary TMA, with malignancy being a common cause 2.
• Other treatments, such as rituximab, may be used in combination with plasmapheresis to achieve complete remission 4.

Mechanism of Plasmapheresis in Secondary TMA

• Plasmapheresis works by removing autoantibodies and other harmful substances from the blood, which can help to reduce the formation of blood clots and improve blood flow 5.
• The removal of these substances can help to improve the function of the endothelial cells, which line the blood vessels and play a critical role in maintaining blood flow 6.
• The use of plasmapheresis can also help to reduce the levels of ADAMTS13, a von Willebrand factor-cleaving protease, which can be low in patients with TTP 5.

Clinical Outcomes

• The clinical outcomes of secondary TMA patients treated with plasmapheresis can vary, with some patients achieving complete remission and others experiencing partial or no response 2, 3.
• The mortality rate for secondary TMA patients treated with plasmapheresis can be high, ranging from 13% to 35% 2, 3.
• Early diagnosis and treatment with plasmapheresis are critical in improving outcomes for secondary TMA patients 4.