Hereditary TTP and Hemolytic Anemia in Newborns

Hereditary thrombotic thrombocytopenic purpura (hTTP) is a thrombotic microangiopathy due to severe ADAMTS13 deficiency. hTTP typically presents in adulthood with thrombocytopenia, hemolytic anemia, and/or neurologic abnormalities. However, nearly half of the patients with hTTP are symptomatic at birth, most commonly presenting as severe jaundice secondary to hemolysis. Turbulent blood flow during birth puts neonates at high risk for thrombotic events and subsequent hemolytic anemia. We present a case series of 3 siblings with ADAMTS13 loss-of-function variants, all of whom required neonatal exchange transfusion. These siblings are now in their 30s and were diagnosed with hTTP between the ages of 13 and 18. One sibling experienced a neonatal stroke, while another sibling required a leukemia workup in her childhood because of hTTP. They remain in good health as adults. Two of them receive recombinant ADAMTS13 treatment for their deficiency. A recent report found that only 5% of patients with hTTP were correctly diagnosed at birth—underscoring the importance of having a high index of suspicion in the neonatal period for the anemic and thrombocytopenic newborn with nonimmune hemolytic anemia. With newly Food and Drug Administration–approved recombinant ADAMTS13 therapy and rapid diagnostic testing for ADAMTS13 levels, it is imperative that pediatricians and neonatologists recognize this rare but treatable form of recalcitrant jaundice. We propose a diagnostic algorithm to assist clinicians in neonatal diagnosis of hTTP in hopes of mitigating the need for exchange transfusions and extensive hematologic workups later in life. Timely diagnosis would prompt targeted treatment, which can prevent long-term neurologic and renal sequelae.