[Analysis of 5 children with congenital thrombotic thrombocytopenic purpura].

Objective: To explore the clinical features and points of diagnosis and treatment for congenital thrombotic thrombocytopenic purpura (TTP) in children. Methods: The clinical manifestations, laboratory tests, genetic analysis and treatments of 5 children with congenital TTP hospitalized in Beijing Children's Hospital, Capital Medical University from February 2015 to July 2017 were analyzed retrospectively. Results: Among the 5 children with congenital TTP diagnosed by genetic monitoring and enzymology, there were 1 male and 4 females, 3 cases had suspicious positive family history, the age of onset was several hours after birth (range several hours after birth to 28 months). The main clinical manifestations were recurrent moderate to severe thrombocytopenia in 5 cases, mild to moderate hemolytic anemia in 4 cases, proteinuria or hematuria in 2 cases, and nervous system involvement in 1 case. The recurrence time was 1.5 (range 1.0 to 5.0) times per year and most of the inducing factors were respiratory and (or) digestive tract infections. Laboratory test showed that ADMATS13 enzyme activity were 0 in 4 cases, the enzyme activity was 100% in 1 case due to plasma infusion before examination. ADMATS13 enzyme antibody detection of all 5 cases were negative. Genetic analysis of all 5 children showed complex heterozygous mutations at different loci of ADAMTS13 gene, among which 8 loci were previously unreported, details are as follows: missense mutations in 4 cases (c.1564T>C(p.522C>R), c.1510G>T(p.504D>Y), c.4154A>C(p.1385Q>P) and c.G3854C (P.R1285P)); frameshift mutations in 3 cases(c.2875_2876insT (p.959Lfs29), c.2362_2363delGG (p.788G>Gfs56) and c.1335delC (p.F445fs)), shear mutation in one case(IVS21+1A>G). The patients in the acute phase were all treated with fresh frozen plasma infusion (10 ml/(kg·d)), continuous application for 7-14 days). Platelets gradually returned to normal and clinical symptoms improved. The follow-up time was 27 months (range 11-35 months). All the children survived, among whom 2 cases were treated with prophylaxis and monitoring platelet stability above 200×10(9)/L, 3 cases were treated on-demand only when platelet decreased and monitoring platelet stability above 100×10(9)/L. Conclusions: The main clinical manifestation of congenital TTP is recurrent thrombocytopenia with or without hemolytic anemia. The key point of treatment is plasma infusion. Genetic testing is helpful for early diagnosis.