Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a potential diagnosis in any patient with hemolytic anemia and thrombocytopenia - 95% of cases are fatal if left untreated.

Symptoms are usually nonspecific, although half of patients have neurologic abnormalities. Pentad of fever, renal failure, hemolytic anemia, thrombocytopenia, and neurologic changes are often seen, although most patients do not have the entire pentad.

Examination of the peripheral smear is critical and shows evidence of microangiopathic hemolytic anemia with fragmented red blood cells (schistocytes) and thrombocytopenia.

An urgent hematology consultation is recommended for suspected cases.

Plasma-exchange therapy combined with corticosteroids is the mainstay of treatment for acute acquired (idiopathic) TTP. Caplacizumab may be prescribed as an adjunctive therapy in adults.

Renal and neurologic dysfunctions are the main complications.

TTP is a clinical syndrome characterized by microangiopathic hemolytic anemia and thrombocytopenic purpura.[1]Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017 Feb;15(2):312-22. https://www.doi.org/10.1111/jth.13571 http://www.ncbi.nlm.nih.gov/pubmed/27868334?tool=bestpractice.com Although the original descriptions included a pentad of microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic dysfunction, renal dysfunction, and fever, most patients do not have the entire pentad. There are no pathognomic features of TTP. Without treatment, TTP is typically fatal. Pathophysiology involves the absence of von Willebrand factor cleaving enzyme (ADAMTS-13), resulting in unusually large von Willebrand multimers that lead to platelet aggregation and subsequent thrombocytopenia and microthrombi. Some evidence suggests that at least 33% of patients with idiopathic TTP may have severe ADAMTS-13 deficiency.[2]Vesely SK, George JN, Lammle B, et al. ADAMTS-13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood. 2003;102:60-68. http://bloodjournal.hematologylibrary.org/content/102/1/60.full http://www.ncbi.nlm.nih.gov/pubmed/12637323?tool=bestpractice.com  For the diagnosis of TTP, ADAMTS-13 activity levels of <5% to 10% are diagnostic.[1]Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017 Feb;15(2):312-22. https://www.doi.org/10.1111/jth.13571 http://www.ncbi.nlm.nih.gov/pubmed/27868334?tool=bestpractice.com [3]Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-502. https://www.doi.org/10.1111/jth.15010 http://www.ncbi.nlm.nih.gov/pubmed/32914526?tool=bestpractice.com [4]Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012 Aug;158(3):323-35. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09167.x/full http://www.ncbi.nlm.nih.gov/pubmed/22624596?tool=bestpractice.com

The British Committee for Standards in Haematology has proposed the following subgroups of TTP:[4]Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012 Aug;158(3):323-35. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09167.x/full http://www.ncbi.nlm.nih.gov/pubmed/22624596?tool=bestpractice.com

Acute idiopathic TTP (the most common type of TTP, and the focus of this topic)

Congenital TTP

HIV-associated TTP

Pregnancy-associated TTP

Drug-associated TTP

Pancreatitis-associated TTP.

TTP has also been described with COVID-19 infection.[5]Tehrani HA, Darnahal M, Vaezi M, et al. COVID-19 associated thrombotic thrombocytopenic purpura (TTP); a case series and mini-review. Int Immunopharmacol. 2021 Apr;93:107397. http://www.ncbi.nlm.nih.gov/pubmed/33524803?tool=bestpractice.com [6]Altowyan E, Alnujeidi O, Alhujilan A, et al. COVID-19 presenting as thrombotic thrombocytopenic purpura (TTP). BMJ Case Rep. 2020 Dec 17;13(12):e238026. https://casereports.bmj.com/content/13/12/e238026.long http://www.ncbi.nlm.nih.gov/pubmed/33334760?tool=bestpractice.com

Hemolytic uremic syndrome is a similar syndrome but usually has a more pronounced renal component and is caused by Shiga toxin produced by certain E coli infections. Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated microangiopathy which clinically may masquerade as TTP, but is due to abnormalities in complement regulation.[1]Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017 Feb;15(2):312-22. https://www.doi.org/10.1111/jth.13571 http://www.ncbi.nlm.nih.gov/pubmed/27868334?tool=bestpractice.com [7]Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676-1687. http://www.ncbi.nlm.nih.gov/pubmed/19846853?tool=bestpractice.com See the BMJ Best Practice topic: “Hemolytic uremic syndrome” for more information on aHUS.