Identifying patients with cTTP
The clinical presentation of congenital thrombotic thrombocytopenic purpura (cTTP) ranges from life-threatening, acute, overt thrombotic thrombocytopenic purpura (TTP) events to milder TTP manifestations, including thrombocytopenia, haemolytic anaemia, abdominal pain, headaches, and neurological symptoms.1 End-organ damage due to recurrent overt and non-overt TTP events, such as stroke, chronic kidney disease, or cardiac involvement, can develop.1
Although first symptom occurrence of cTTP has classically been described in childhood, presentation can occur at any age, with a notable peak in women during pregnancy.2
A review of cTTP cases found that genetic mutations differed by age of onset with prespacer mutations more likely to be associated with childhood onset. In this review, pregnancy was the most common trigger of adult-onset cTTP, accounting for 69% of adult presentations.2
Diagnosing TTP can be complex due to its various clinical symptoms, similarity to other thrombotic microangiopathies, and restricted access to ADAMTS13 testing.3,4
The rarity of cTTP and its variable phenotype may often delay the correct diagnosis. Diagnosis of TTP may be challenging too, due to the limited availability of ADAMTS13 testing.3,5 A high index of suspicion should be kept in mind for all patients presenting with an acute thrombotic microangiopathy, regardless of their age.5 Tests, such as ADAMTS13 activity assays, can then help to confirm TTP diagnoses.1,5 Among patients with severe thrombocytopenia and haemolytic anaemia of unknown cause, the reduction in ADAMTS13 levels to <10% of normal values confirms a diagnosis of TTP.1,6
A diagnosis of cTTP is then confirmed through genetic analysis and identification of causative ADAMTS13 mutations. Polymerase chain reaction (PCR) direct sequencing, can be used to analyse the patient's genes to detect ADAMTS13 mutations.6
Increased education of cTTP and wider availability of ADAMTS13 assays could lead to more accurate and timely diagnoses.2 When coupled with earlier treatments, greater understanding and clarity into the scientific basis and the clinical outcomes of cTTP could lead to better patient outcome.2
- Scully M, et al. N Engl J Med. 2024;390(17):1584-1596.
- Alwan F, et al. Blood. 2019;133(15):1644-1651.
- Chiasakul T, Cuker A. Hematology Am Soc Hematol Educ Program. 2018;2018(1):530-538.
- Matsumoto M, et al. Int J Hematol. 2023;118(5):529-546.
- Ferrari B, et al. J Thromb Haemost. 2019;17(4):666-669.
- Sakai K, Matsumoto M. J Clin Med. 2023;12(10):3365.
ADAMTS13, A disintegrin and metalloproteinase with thrombospondin motifs 13
cTTP, Congenital thrombotic thrombocytopenic purpura
PCR, Polymerase chain reaction
SmPC, Summary of product characteristics
TTP, Thrombotic thrombocytopenic purpura
