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Blood. 2019 Feb 15. pii: blood-2018-11-884700. doi: 10.1182/blood-2018-11-884700. [Epub ahead of print]

Characterization and treatment of congenital thrombotic thrombocytopenic purpura.

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Department of Haematology, University College London Hospital, London, United Kingdom;
Haemostasis Research Unit, University College London, London, United Kingdom.
Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital, London, United Kingdom.
Bristol Haemophilia Centre, University Hospitals Bristol Foundation Trust, Bristol, United Kingdom.
Department of Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Roald Dahl Haemostasis and Thrombosis Centre, Royal Liverpool University Hospital, Liverpool, United Kingdom.
Department of Haematology, Addenbrookes Hospital, Cambridge, United Kingdom.
Department of Haematology, University Hospitals of Leicester, Leicester, United Kingdom.
Department of Haematology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom.
Department of Haematology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
Centre for Haematology, Imperial College London, London, United Kingdom.
Department of Haematology, Cardiff and Vale University Health Board, Cardiff, United Kingdom.
Department of Haematology, Queen Alexandra Hospital, Portsmouth, United Kingdom.
Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
Department of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.
Department of Haematology, Milton Keynes University Hospital, Milton Keynes, United Kingdom.
Department of Haematology, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom.
Oxford Haemophilia and Thrombosis Comprehensive Care Centre, Oxford University Hospitals, Oxford, United Kingdom.
Department of Haematology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
Department of Haematology, James Cook University Hospital, Middlesborough, United Kingdom.
Department of Haemostasis and Thrombosis, Guy's and St Thomas' Hospital, London, United Kingdom.
Department of Paediatric Haemophilia and Thrombosis, Evelina London Children's Hospital, London, United Kingdom.
Department of Haematology, Norfolk and Norwich University Hospital, Norwich, United Kingdom.
Department of Haematology, University College London Hospital, London, United Kingdom.
National Institute for Health Research Cardiometabolic Programme, UCLH/UCL BRC, London, United Kingdom.


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.

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