A Unique Case Involving a Female Patient with Upshaw-Schulman Syndrome: Low Titers of Antibodies against ADAMTS13 prior to Pregnancy Disappeared after Successful Delivery

Abstract

Background: Upshaw-Schulman syndrome (USS) is usually suspected based on severe deficiency of ADAMTS13 activity without ADAMTS13 antibody, but the definitive diagnosis is made by ADAMTS13 gene analysis. We present a unique case of USS with low titers of ADAMTS13 antibodies before pregnancy. Interestingly, titers of ADAMTS13 antibodies decreased to almost undetectable levels after delivery. Case Report: In patient LL4, the diagnosis of USS was confirmed at age 27 by ADAMTS13 gene analysis. She became pregnant at age 30. During the pregnancy, she received regular fresh frozen plasma (FFP) infusion. Plasma von Willebrand factor levels increase as pregnancy progresses. To prevent platelet thrombi, much more ADAMTS13 supplementation is necessary during late gestation in patients with USS. Therefore, we shortened the interval between and increased the volume of FFP infusions as pregnancy progressed. At 39 weeks, she delivered a healthy baby girl. Before pregnancy, she had low titers of both neutralizing and binding anti-ADAMTS13 antibodies. Despite frequent FFP infusions, titers of the antibodies did not increase, but rather decreased to almost undetectable levels during pregnancy. Conclusion: Both the neutralizing and binding antibodies against ADAMTS13 decreased to almost undetectable levels after delivery in this patient, which can be caused by an immunological reset.

Success and limitations of plasma treatment in pregnant women with congenital thrombotic thrombocytopenic purpura

“…The characteristics of these patients and babies are shown in Table 1, and for some of them the detailed clinical course during pregnancy was previously reported. 7,9,[17][18][19][20][21] Each mother's cTTP code corresponded to those in our previous reports. 3,7,9,11,22 We classified these 38 pregnancies into two groups.…”

“…Because early miscarriage sometimes occurs even in healthy women (10%‐15%), 16 we excluded miscarriages (n = 2) before 12 weeks of gestation. The characteristics of these patients and babies are shown in Table 1, and for some of them the detailed clinical course during pregnancy was previously reported 7,9,17‐21 . Each mother's cTTP code corresponded to those in our previous reports 3,7,9,11,22 …”

Anti-ADAMTS13 Antibodies and a Novel Heterozygous p.R1177Q Mutation in a Case of Pregnancy-Onset Immune-Mediated Thrombotic Thrombocytopenic Purpura

“…However, some rare cases of congenital TTP patients presenting with anti-ADAMTS13 autoantibodies have been described. 7 8 9 On the other hand, two sisters have been reported who had acquired immune-mediated TTP, although their familial history was suspicious for congenital TTP. 10 Hence, it was suggested that investigating the presence of both anti-ADAMTS13 autoantibodies and ADAMTS13 genetic variations is sometimes essential to improve the differential diagnosis between immune-mediated TTP and congenital TTP.…”