Upshaw-Schulman Syndrome Revealed by Pregnancy.

Background:

Thrombotic thrombocytopenic purpura (TTP) is a rare systemic disease. Its mechanism has been unclear for yeas. Recently, it has been reported that the deficiency of ADAMTS 13 (a disintegrin-like domain, and metalloprotease, with thrombospondin type1 motif 13) activity cause TTP. Congenital TTP (Upshaw-Schulman syndrome: USS) is caused by ADAMTS 13 gene mutation and secondary TTP is caused by anti-ADAMTS 13 antibody. Only five families of USS have been reported in Japan, previously. Here, we report a case of USS patient who has gene mutations.

Case report:

On 23 weeks of gestation, a Japanese pregnant woman was pointed out thrombocytopenia (8.2 x 10E7/mL), and was diagnosed as idiopathic thrombocytopenic purpura. On 31 weeks of gestation, she developed headache, vomiting, high grade fever, disorientation and additional vanishing fetal movement. Unfortunately, intrauterine fatal death was confirmed. The diagnosis of TTP was confirmed, plasma exchange, the administration of methylprednisolone, dipyridamole and high-dose intravenously immunoglobulin was started. She has recovered day by day and the stabilization of platelet count was obtained. Her ADAMTS 13 activity on admission day was lower than detection limit (< 3%), and her father, mother and sister’s low ADAMTS 13 activity (47.4%, 35.8% and 34.8%, respectively) was proved later. Because ADAMTS 13 inhibitor was not detected, she was diagnosed as USS and preventive FFP infusions were started. In accordance with the increase of ADAMTS 13 activity, the platelet count also has a tendency to increase. She has performed regular FFP infusions every two weeks at this time of reporting. This family’s ADAMTS 13 gene mutations were analyzed by DNA sequencing. Patient has compound heterozygote mutations; R193W from father and A606P from mother. Sister has Q606A too, and brother has normal gene.

Conclusion:

Clinical signs of TTP are often masqueraded as a simple thrombocytopenia until 20-30 weeks of gestation. USS is a life threatening disease to both mother and fetus, an early diagnosis is critical. Therefore, pregnant women developed thrombocytopenia need to be determined ADAMTS 13 activity routinely.