and14 Manchester Royal Infirmary, Manchester, United Kingdom Key Points• In women presenting with an initial diagnosis of TTP during pregnancy, cTTP was more common than acquired TTP.• Active monitoring and management during pregnancy results in positive pregnancy outcomes.Pregnancy can precipitate thrombotic thrombocytopenic purpura (TTP). We present a prospective study of TTP cases from the United Kingdom Thrombotic Thrombocytopenic Purpura (UK TTP) Registry with clinical and laboratory data from the largest cohort of pregnancy-associated TTP and describe management through pregnancy, averting fetal loss and maternal complications. Thirty-five women presented with a first TTP episode during pregnancy: 23/47 with their first congenital TTP (cTTP) episode and 12/47 with acute acquired TTP in pregnancy. TTP presented primarily in the third trimester/ postpartum, but fetal loss was highest in the second trimester. Fetal loss occurred in 16/38 pregnancies before cTTP was diagnosed, but in none of the 15 subsequent managed pregnancies. Seventeen of 23 congenital cases had a missense mutation, C3178T, within exon 24 (R1060W). There were 8 novel mutations. In acquired TTP presentations, fetal loss occurred in 5/18 pregnancies and 2 terminations because of disease. We also present data on 12 women with a history of nonpregnancy-associated TTP: 18 subsequent pregnancies have been successfully managed, guided by ADAMTS13 levels. cTTP presents more frequently than acquired TTP during pregnancy and must be differentiated by ADAMTS13 analysis. Careful diagnosis, monitoring, and treatment in congenital and acquired TTP have assisted in excellent pregnancy outcomes. (Blood. 2014;124(2):211-219)

Background Current treatment for severe hemophilia A is replacement of deficient factor. Although replacement therapy has improved life expectancy and quality, limitations include frequent infusions and high costs. Gene therapy is a potential alternative that utilizes an adeno‐associated virus ( AAV ) vector containing the human genetic code for factor 8 ( FVIII ) that transduces the liver, enabling endogenous production of FVIII . Individuals with preexisting immunity to AAV serotypes may be less likely to benefit from this treatment. Objectives This study measured seroprevalence of antibodies to AAV 5 and 8 in an UK adult hemophilia A cohort. Patients/Methods Patients were recruited from seven hemophilia centres in the UK . Citrated plasma samples from 100 patients were tested for preexisting activities against AAV 5 and 8 using AAV transduction inhibition and total antibodies assays. Results Twent‐one percent of patients had antibodies against AAV 5 and 23% had antibodies against AAV 8. Twenty‐five percent and 38% of patients exhibited inhibitors of AAV 5 or AAV 8 cellular transduction respectively. Overall seroprevalence using either assay against AAV 5 was 30% and against AAV 8 was 40% in this cohort of hemophilia A patients. Seropositivity for both AAV 5 and AAV 8 was seen in 24% of participants. Conclusions Screening for preexisting immunity may be important in identifying patients most likely to benefit from gene therapy. Clinical studies may be needed to evaluate the impact of preexisting immunity on the safety and efficacy of AAV mediated gene therapy.

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