Characterization and treatment of congenital thrombotic thrombocytopenic purpura.

Alwan, Ferras and Vendramin, Chiara and Liesner, Ri and Clark, Amanda and Lester, William and Dutt, Tina and Thomas, William and Gooding, Richard and Biss, Tina and Watson, H G and Cooper, Nichola and Rayment, Rachel and Cranfield, Tanya and van Veen, Joost J and Hill, Quentin A and Davis, Sarah and Motwani, Jayashree and Bhatnagar, Neha and Priddee, Nicole and David, Marianna and Crowley, Maeve P and Alamelu, Jayanthi and Lyall, Hamish and Westwood, John-Paul and Thomas, Mari and Scully, Marie (2019) Characterization and treatment of congenital thrombotic thrombocytopenic purpura. Blood. ISSN 1528-0020.

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Official URL: http://www.bloodjournal.org/content/early/2019/02/...

Abstract

Congenital Thrombotic Thrombocytopenic Purpura (cTTP) is an ultra rare thrombomicroangiopathy caused by an inherited deficiency of ADAMTS13. There is limited data on the genotype-phenotype correlation and no consensus on treatment. We reviewed the largest cohort of cTTP cases, diagnosed in the UK, over the past 15 years. 73 cases of cTTP were diagnosed, confirmed by genetic analysis. 93% were alive at the time of review. 36% had homozygous mutations and 64% compound heterozygous mutations. Two presentation peaks were seen, childhood (median diagnosis age 3.5 years) and adulthood, typically related to pregnancy (median diagnosis age 31 years). Genetic mutations differed by age of onset with pre-spacer mutations more likely to be associated with childhood-onset (p=0.0011). 69% of adult presentations were associated with pregnancy. Fresh Frozen Plasma (FFP) and intermediate purity factor VIII concentrate were used as treatment. 88% of patients with normal blood counts but headaches, lethargy or abdominal pain reported symptom resolution with prophylactic therapy although the most common currently used regimen of three weekly FFP proved insufficient for 70% of patients and weekly or fortnightly infusions were required. Stroke incidence was significantly reduced in patients receiving prophylactic therapy (2% versus 17%, p=0.04). Long term, there is a risk of end organ damage, seen in 75% of patients with a late diagnosis of cTTP. In conclusion, pre-spacer mutations are associated with earlier development of cTTP symptoms. Prophylactic ADAMTS13 replacement decreases the risk of end organ damage such as ischemic stroke and resolved previously unrecognized symptoms in patients with non-overt disease.

Item Type: Article
Subjects: WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Jennifer Manders
Date Deposited: 28 Feb 2019 12:02
Last Modified: 28 Feb 2019 12:02
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1851

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