Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management.
Senthil SukumarBernhard LämmleSpero R CatalandPublished in: Journal of clinical medicine (2021)
Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. TTP results from a severe deficiency of the specific von Willebrand factor (VWF)-cleaving protease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). ADAMTS13 deficiency is most commonly acquired due to anti-ADAMTS13 autoantibodies. It can also be inherited in the congenital form as a result of biallelic mutations in the ADAMTS13 gene. In adults, the condition is most often immune-mediated (iTTP) whereas congenital TTP (cTTP) is often detected in childhood or during pregnancy. iTTP occurs more often in women and is potentially lethal without prompt recognition and treatment. Front-line therapy includes daily plasma exchange with fresh frozen plasma replacement and immunosuppression with corticosteroids. Immunosuppression targeting ADAMTS13 autoantibodies with the humanized anti-CD20 monoclonal antibody rituximab is frequently added to the initial therapy. If available, anti-VWF therapy with caplacizumab is also added to the front-line setting. While it is hypothesized that refractory TTP will be less common in the era of caplacizumab, in relapsed or refractory cases cyclosporine A, N-acetylcysteine, bortezomib, cyclophosphamide, vincristine, or splenectomy can be considered. Novel agents, such as recombinant ADAMTS13, are also currently under investigation and show promise for the treatment of TTP. Long-term follow-up after the acute episode is critical to monitor for relapse and to diagnose and manage chronic sequelae of this disease.
Keyphrases
- monoclonal antibody
- replacement therapy
- systemic lupus erythematosus
- multiple myeloma
- diffuse large b cell lymphoma
- acute myeloid leukemia
- physical activity
- drug induced
- early onset
- chronic kidney disease
- gene expression
- stem cells
- low dose
- acute lymphoblastic leukemia
- polycystic ovary syndrome
- intensive care unit
- combination therapy
- machine learning
- type diabetes
- genome wide
- skeletal muscle
- respiratory failure
- dna methylation
- transcription factor
- extracorporeal membrane oxygenation
- autism spectrum disorder
- young adults